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Sample records for aging brain function

  1. 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.

  2. Functional brain asymmetry, handedness and menarcheal age.

    PubMed

    Nikolova, P; Stoyanov, Z; Negrev, N

    1994-12-01

    Functional brain asymmetry influences many functions of the organism; the neuroendocrine axis is one that has received insufficient attention. In this study we set us as the goal of studying the link between functional brain asymmetry and menarcheal age in females with left versus right manual dominance. The appearance of the first menarche was used as a natural model of functioning of the hypothalamic-pituitary-gonadal (HPG) axis. 1695 females, aged between 16 and 25 years, were interviewed by questionnaire about manual dominance and menarcheal age. 182 women were selected and divided into 2 groups: all left-handers (n = 91), and a control group of 91 right-handers. We found a significantly lower average age of menarcheal appearance in the left-handers' age of 12.09 +/- 0.16 years compared to the right-handers' age of 13.32 +/- 0.12 years (p < 0.001). The earliest menarcheal age in left-handers was 8 years and the peak of appearance at age 13 (in 30.76% of the cases). In right-handers these values were 10 and 14 years (in 40.60% of the cases), respectively. The data allow us to accept the existence of a link between functional brain asymmetry and menarche, which causes earlier activation of the HPG axis in left-handed females.

  3. Functional interrelationship of brain aging and delirium.

    PubMed

    Rapazzini, Piero

    2016-02-01

    Theories on the development of delirium are complementary rather than competing and they may relate to each other. Here, we highlight that similar alterations in functional brain connectivity underlie both the observed age-related deficits and episodes of delirium. The default mode network (DMN) is a group of brain regions showing a greater level of activity at rest than during attention-based tasks. These regions include the posteromedial-anteromedial cortices and temporoparietal junctions. Evidence suggests that awareness is subserved through higher order neurons associated with the DMN. By using functional MRI disruption of DMN, connectivity and weaker task-induced deactivations of these regions are observed both in age-related cognitive impairment and during episodes of delirium. We can assume that an acute up-regulation of inhibitory tone within the brain acts to further disrupt network connectivity in vulnerable patients, who are predisposed by a reduced baseline connectivity, and triggers the delirium. PMID:25998952

  4. Functional interrelationship of brain aging and delirium.

    PubMed

    Rapazzini, Piero

    2016-02-01

    Theories on the development of delirium are complementary rather than competing and they may relate to each other. Here, we highlight that similar alterations in functional brain connectivity underlie both the observed age-related deficits and episodes of delirium. The default mode network (DMN) is a group of brain regions showing a greater level of activity at rest than during attention-based tasks. These regions include the posteromedial-anteromedial cortices and temporoparietal junctions. Evidence suggests that awareness is subserved through higher order neurons associated with the DMN. By using functional MRI disruption of DMN, connectivity and weaker task-induced deactivations of these regions are observed both in age-related cognitive impairment and during episodes of delirium. We can assume that an acute up-regulation of inhibitory tone within the brain acts to further disrupt network connectivity in vulnerable patients, who are predisposed by a reduced baseline connectivity, and triggers the delirium.

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

    PubMed

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

    2016-11-01

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

  7. Structural and functional imaging correlates for age-related changes in the brain.

    PubMed

    Tumeh, Paul C; Alavi, Abass; Houseni, Mohamed; Greenfield, Antje; Chryssikos, Timothy; Newberg, Andrew; Torigian, Drew A; Moonis, Gul

    2007-03-01

    In recent years, investigators have made significant progress in documenting brain structure and function as it relates to aging by using positron emission tomography, conventional magnetic resonance (MR) imaging, advanced MR techniques, and functional MR imaging. This review summarizes the latest advances in understanding physiologic maturation and aging as detected by these neuroimaging modalities. We also present our experience with MR volumetric and positron emission tomography analysis in separate cohorts of healthy subjects in the pediatric and adult age groups respectively. Our results are consistent with previous studies and include the following: total brain volume was found to increase with age (up to 20 years of age). Whole brain metabolism and frontal lobe metabolism both decrease significantly with age (38% and 42%, respectively), whereas cerebellar metabolism does not show a significant decline with age. Defining normal alterations in brain function and structure allows early detection of disorders such as Alzheimer's and Parkinson's diseases, which are commonly associated with normal aging. PMID:17289456

  8. A Brain-Wide Study of Age-Related Changes in Functional Connectivity.

    PubMed

    Geerligs, Linda; Renken, Remco J; Saliasi, Emi; Maurits, Natasha M; Lorist, Monicque M

    2015-07-01

    Aging affects functional connectivity between brain areas, however, a complete picture of how aging affects integration of information within and between functional networks is missing. We used complex network measures, derived from a brain-wide graph, to provide a comprehensive overview of age-related changes in functional connectivity. Functional connectivity in young and older participants was assessed during resting-state fMRI. The results show that aging has a large impact, not only on connectivity within functional networks but also on connectivity between the different functional networks in the brain. Brain networks in the elderly showed decreased modularity (less distinct functional networks) and decreased local efficiency. Connectivity decreased with age within networks supporting higher level cognitive functions, that is, within the default mode, cingulo-opercular and fronto-parietal control networks. Conversely, no changes in connectivity within the somatomotor and visual networks, networks implicated in primary information processing, were observed. Connectivity between these networks even increased with age. A brain-wide analysis approach of functional connectivity in the aging brain thus seems fundamental in understanding how age affects integration of information.

  9. 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.

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

    PubMed Central

    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.

    2013-01-01

    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 (1) an increased eating responses to fasting, a behavioral indicator of improvement in aged brain glucose sensing; (2) a longer latency to fall from an accelerating rotarod, a behavioral indicator of improved motor coordination; and (3) a higher serum active GLP-1. Third, 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 (1) dietary RS improves two important indicators of brain function: glucose sensing and motor coordination, and that (2) GLP-1 is important in the optimal feeding response to a fast. PMID:23818307

  11. 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.

  12. Age-Related Decline in Brain Resources Modulates Genetic Effects on Cognitive Functioning

    PubMed Central

    Lindenberger, Ulman; Nagel, Irene E.; Chicherio, Christian; Li, Shu-Chen; Heekeren, Hauke R.; Bäckman, Lars

    2008-01-01

    Individual differences in cognitive performance increase from early to late adulthood, likely reflecting influences of a multitude of factors. We hypothesize that losses in neurochemical and anatomical brain resources in normal aging modulate the effects of common genetic variations on cognitive functioning. Our hypothesis is based on the assumption that the function relating brain resources to cognition is nonlinear, so that genetic differences exert increasingly large effects on cognition as resources recede from high to medium levels in the course of aging. Direct empirical support for this hypothesis comes from a study by Nagel et al. (2008), who reported that the effects of the Catechol-O-Methyltransferase (COMT) gene on cognitive performance are magnified in old age and interacted with the Brain-Derived Neurotrophic Factor (BDNF) gene. We conclude that common genetic polymorphisms contribute to the increasing heterogeneity of cognitive functioning in old age. Extensions of the hypothesis to other polymorphisms are discussed. (150 of 150 words) PMID:19225597

  13. 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

  14. 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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2016-07-01

    Functional interactions in the brain are constrained by the underlying anatomical architecture, and structural and functional networks share network features such as modularity. Accordingly, age-related changes of structural connectivity (SC) may be paralleled by changes in functional connectivity (FC). We provide a detailed qualitative and quantitative characterization of the SC-FC coupling in human aging as inferred from resting-state blood oxygen-level dependent functional magnetic resonance imaging and diffusion-weighted imaging in a sample of 47 adults with an age range of 18-82. We revealed that SC and FC decrease with age across most parts of the brain and there is a distinct age-dependency of regionwise SC-FC coupling and network-level SC-FC relations. A specific pattern of SC-FC coupling predicts age more reliably than does regionwise SC or FC alone (r = 0.73, 95% CI = [0.7093, 0.8522]). Hence, our data propose that regionwise SC-FC coupling can be used to characterize brain changes in aging. Hum Brain Mapp 37:2645-2661, 2016. © 2016 Wiley Periodicals, Inc. PMID:27041212

  17. A Novel Brain Network Construction Method for Exploring Age-Related Functional Reorganization

    PubMed Central

    Li, Wei; Wang, Miao; Li, Yapeng; Huang, Yue; Chen, Xi

    2016-01-01

    The human brain undergoes complex reorganization and changes during aging. Using graph theory, scientists can find differences in topological properties of functional brain networks between young and elderly adults. However, these differences are sometimes significant and sometimes not. Several studies have even identified disparate differences in topological properties during normal aging or in age-related diseases. One possible reason for this issue is that existing brain network construction methods cannot fully extract the “intrinsic edges” to prevent useful signals from being buried into noises. This paper proposes a new subnetwork voting (SNV) method with sliding window to construct functional brain networks for young and elderly adults. Differences in the topological properties of brain networks constructed from the classic and SNV methods were consistent. Statistical analysis showed that the SNV method can identify much more statistically significant differences between groups than the classic method. Moreover, support vector machine was utilized to classify young and elderly adults; its accuracy, based on the SNV method, reached 89.3%, significantly higher than that with classic method. Therefore, the SNV method can improve consistency within a group and highlight differences between groups, which can be valuable for the exploration and auxiliary diagnosis of aging and age-related diseases. PMID:27057155

  18. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    PubMed

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity.

  19. Reorganization of brain networks in aging: a review of functional connectivity studies

    PubMed Central

    Sala-Llonch, Roser; Bartrés-Faz, David; Junqué, Carme

    2015-01-01

    Healthy aging (HA) is associated with certain declines in cognitive functions, even in individuals that are free of any process of degenerative illness. Functional magnetic resonance imaging (fMRI) has been widely used in order to link this age-related cognitive decline with patterns of altered brain function. A consistent finding in the fMRI literature is that healthy old adults present higher activity levels in some brain regions during the performance of cognitive tasks. This finding is usually interpreted as a compensatory mechanism. More recent approaches have focused on the study of functional connectivity, mainly derived from resting state fMRI, and have concluded that the higher levels of activity coexist with disrupted connectivity. In this review, we aim to provide a state-of-the-art description of the usefulness and the interpretations of functional brain connectivity in the context of HA. We first give a background that includes some basic aspects and methodological issues regarding functional connectivity. We summarize the main findings and the cognitive models that have been derived from task-activity studies, and we then review the findings provided by resting-state functional connectivity in HA. Finally, we suggest some future directions in this field of research. A common finding of the studies included is that older subjects present reduced functional connectivity compared to young adults. This reduced connectivity affects the main brain networks and explains age-related cognitive alterations. Remarkably, the default mode network appears as a highly compromised system in HA. Overall, the scenario given by both activity and connectivity studies also suggests that the trajectory of changes during task may differ from those observed during resting-state. We propose that the use of complex modeling approaches studying effective connectivity may help to understand context-dependent functional reorganizations in the aging process. PMID:26052298

  20. Changes in whole-brain functional networks and memory performance in aging.

    PubMed

    Sala-Llonch, Roser; Junqué, Carme; Arenaza-Urquijo, Eider M; Vidal-Piñeiro, Dídac; Valls-Pedret, Cinta; Palacios, Eva M; Domènech, Sara; Salvà, Antoni; Bargalló, Nuria; Bartrés-Faz, David

    2014-10-01

    We used resting-functional magnetic resonance imaging data from 98 healthy older adults to analyze how local and global measures of functional brain connectivity are affected by age, and whether they are related to differences in memory performance. Whole-brain networks were created individually by parcellating the brain into 90 cerebral regions and obtaining pairwise connectivity. First, we studied age-associations in interregional connectivity and their relationship with the length of the connections. Aging was associated with less connectivity in the long-range connections of fronto-parietal and fronto-occipital systems and with higher connectivity of the short-range connections within frontal, parietal, and occipital lobes. We also used the graph theory to measure functional integration and segregation. The pattern of the overall age-related correlations presented positive correlations of average minimum path length (r = 0.380, p = 0.008) and of global clustering coefficients (r = 0.454, p < 0.001), leading to less integrated and more segregated global networks. Main correlations in clustering coefficients were located in the frontal and parietal lobes. Higher clustering coefficients of some areas were related to lower performance in verbal and visual memory functions. In conclusion, we found that older participants showed lower connectivity of long-range connections together with higher functional segregation of these same connections, which appeared to indicate a more local clustering of information processing. Higher local clustering in older participants was negatively related to memory performance.

  1. Local brain atrophy accounts for functional activity differences in normal aging.

    PubMed

    Kalpouzos, Grégoria; Persson, Jonas; Nyberg, Lars

    2012-03-01

    Functional brain imaging studies of normal aging typically show age-related under- and overactivations during episodic memory tasks. Older individuals also undergo nonuniform gray matter volume (GMv) loss. Thus, age differences in functional brain activity could at least in part result from local atrophy. We conducted a series of voxel-based blood oxygen level-dependent (BOLD)-GMv analyses to highlight whether age-related under- and overrecruitment was accounted for by GMv changes. Occipital GMv loss accounted for underrecruitment at encoding. Efficiency reduction of sensory-perceptual mechanisms underpinned by these areas may partly be due to local atrophy. At retrieval, local GMv loss accounted for age-related overactivation of left dorsolateral prefrontal cortex, but not of left dorsomedial prefrontal cortex. Local atrophy also accounted for age-related overactivation in left lateral parietal cortex. Activity in these frontoparietal regions correlated with performance in the older group. Atrophy in the overrecruited regions was modest in comparison with other regions as shown by a between-group voxel-based morphometry comparison. Collectively, these findings link age-related structural differences to age-related functional under- as well as overrecruitment.

  2. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    PubMed

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-10-27

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias.

  3. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug

    PubMed Central

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J.; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B.; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D. Chichung; Abbracchio, Maria P.; Aigner, Ludwig

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood–brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias. PMID:26506265

  4. Structural and functional rejuvenation of the aged brain by an approved anti-asthmatic drug.

    PubMed

    Marschallinger, Julia; Schäffner, Iris; Klein, Barbara; Gelfert, Renate; Rivera, Francisco J; Illes, Sebastian; Grassner, Lukas; Janssen, Maximilian; Rotheneichner, Peter; Schmuckermair, Claudia; Coras, Roland; Boccazzi, Marta; Chishty, Mansoor; Lagler, Florian B; Renic, Marija; Bauer, Hans-Christian; Singewald, Nicolas; Blümcke, Ingmar; Bogdahn, Ulrich; Couillard-Despres, Sebastien; Lie, D Chichung; Abbracchio, Maria P; Aigner, Ludwig

    2015-01-01

    As human life expectancy has improved rapidly in industrialized societies, age-related cognitive impairment presents an increasing challenge. Targeting histopathological processes that correlate with age-related cognitive declines, such as neuroinflammation, low levels of neurogenesis, disrupted blood-brain barrier and altered neuronal activity, might lead to structural and functional rejuvenation of the aged brain. Here we show that a 6-week treatment of young (4 months) and old (20 months) rats with montelukast, a marketed anti-asthmatic drug antagonizing leukotriene receptors, reduces neuroinflammation, elevates hippocampal neurogenesis and improves learning and memory in old animals. By using gene knockdown and knockout approaches, we demonstrate that the effect is mediated through inhibition of the GPR17 receptor. This work illustrates that inhibition of leukotriene receptor signalling might represent a safe and druggable target to restore cognitive functions in old individuals and paves the way for future clinical translation of leukotriene receptor inhibition for the treatment of dementias. PMID:26506265

  5. The increase of the functional entropy of the human brain with age.

    PubMed

    Yao, Y; Lu, W L; Xu, B; Li, C B; Lin, C P; Waxman, D; Feng, J F

    2013-10-09

    We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy.

  6. Financial literacy is associated with medial brain region functional connectivity in old age.

    PubMed

    Han, S Duke; Boyle, Patricia A; Yu, Lei; Fleischman, Debra A; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A

    2014-01-01

    Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest (ROI) in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age.

  7. Financial Literacy is Associated with Medial Brain Region Functional Connectivity in Old Age

    PubMed Central

    Han, S. Duke; Boyle, Patricia A.; Yu, Lei; Fleischman, Debra A.; Arfanakis, Konstantinos; Leurgans, Sue; Bennett, David A.

    2014-01-01

    Financial literacy refers to the ability to access and utilize financial information in ways that promote better outcomes. In old age, financial literacy has been associated with a wide range of positive characteristics; however, the neural correlates remain unclear. Recent work has suggested greater co-activity between anterior-posterior medial brain regions is associated with better brain functioning. We hypothesized financial literacy would be associated with this pattern. We assessed whole-brain functional connectivity to a posterior cingulate cortex (PCC) seed region of interest in 138 participants of the Rush Memory and Aging Project. Results revealed financial literacy was associated with greater functional connectivity between the PCC and three regions: the right ventromedial prefrontal cortex (vmPFC), the left postcentral gyrus, and the right precuneus. Results also revealed financial literacy was associated negatively with functional connectivity between the PCC and left caudate. Post-hoc analyses showed the PCC-vmPFC relationship accounted for the most variance in a regression model adjusted for all four significant functional connectivity relationships, demographic factors, and global cognition. These findings provide information on the neural mechanisms associated with financial literacy in old age. PMID:24893911

  8. Nutrient biomarker patterns, cognitive function, and MRI measures of brain aging

    PubMed Central

    Silbert, L.C.; Howieson, D.; Dodge, H.H.; Traber, M.G.; Frei, B.; Kaye, J.A.; Shannon, J.; Quinn, J.F.

    2012-01-01

    Objective: To examine the cross-sectional relationship between nutrient status and psychometric and imaging indices of brain health in dementia-free elders. Methods: Thirty plasma biomarkers of diet were assayed in the Oregon Brain Aging Study cohort (n = 104). Principal component analysis constructed nutrient biomarker patterns (NBPs) and regression models assessed the relationship of these with cognitive and MRI outcomes. Results: Mean age was 87 ± 10 years and 62% of subjects were female. Two NBPs associated with more favorable cognitive and MRI measures: one high in plasma vitamins B (B1, B2, B6, folate, and B12), C, D, and E, and another high in plasma marine ω-3 fatty acids. A third pattern characterized by high trans fat was associated with less favorable cognitive function and less total cerebral brain volume. Depression attenuated the relationship between the marine ω-3 pattern and white matter hyperintensity volume. Conclusion: Distinct nutrient biomarker patterns detected in plasma are interpretable and account for a significant degree of variance in both cognitive function and brain volume. Objective and multivariate approaches to the study of nutrition in brain health warrant further study. These findings should be confirmed in a separate population. Neurology® 2012;78:241–249 PMID:22205763

  9. Reduced specificity of functional connectivity in the aging brain during task performance.

    PubMed

    Geerligs, Linda; Maurits, Natasha M; Renken, Remco J; Lorist, Monicque M

    2014-01-01

    The importance of studying connectivity in the aging brain is increasingly recognized. Recent studies have shown that connectivity within the default mode network is reduced with age and have demonstrated a clear relation of these changes with cognitive functioning. However, research on age-related changes in other functional networks is sparse and mainly focused on prespecified functional networks. Using functional magnetic resonance imaging, we investigated age-related changes in functional connectivity during a visual oddball task in a range of functional networks. It was found that compared with young participants, elderly showed a decrease in connectivity between areas belonging to the same functional network. This was found in the default mode network and the somatomotor network. Moreover, in all identified networks, elderly showed increased connectivity between areas within these networks and areas belonging to different functional networks. Decreased connectivity within functional networks was related to poorer cognitive functioning in elderly. The results were interpreted as a decrease in the specificity of functional networks in older participants.

  10. Fetal Functional Brain Age Assessed from Universal Developmental Indices Obtained from Neuro-Vegetative Activity Patterns

    PubMed Central

    Hoyer, Dirk; Tetschke, Florian; Jaekel, Susan; Nowack, Samuel; Witte, Otto W.; Schleußner, Ekkehard; Schneider, Uwe

    2013-01-01

    Fetal brain development involves the development of the neuro-vegetative (autonomic) control that is mediated by the autonomic nervous system (ANS). Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS) based on heart rate patterns. We analysed n = 113 recordings in quiet sleep, n = 286 in active sleep, and n = 29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4–40.3 weeks of gestation) preclassified in quiet sleep (n = 113, 63 females) and active sleep (n = 286, 145 females) state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5). The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R2 of training and validation set) of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications). We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA dependent f

  11. Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging.

    PubMed

    Boger, H A; Mannangatti, P; Samuvel, D J; Saylor, A J; Bender, T S; McGinty, J F; Fortress, A M; Zaman, V; Huang, P; Middaugh, L D; Randall, P K; Jayanthi, L D; Rohrer, B; Helke, K L; Granholm, A-C; Ramamoorthy, S

    2011-03-01

    Brain-derived neurotrophic factor (BDNF) is critical in synaptic plasticity and in the survival and function of midbrain dopamine neurons. In this study, we assessed the effects of a partial genetic deletion of BDNF on motor function and dopamine (DA) neurotransmitter measures by comparing Bdnf(+/-) with wildtype mice (WT) at different ages. Bdnf(+/-) and WT mice had similar body weights until 12 months of age; however, at 21 months, Bdnf(+/-) mice were significantly heavier than WT mice. Horizontal and vertical motor activity was reduced for Bdnf(+/-) compared to WT mice, but was not influenced by age. Performance on an accelerating rotarod declined with age for both genotypes and was exacerbated for Bdnf(+/-) mice. Body weight did not correlate with any of the three behavioral measures studied. Dopamine neurotransmitter markers indicated no genotypic difference in striatal tyrosine hydroxylase, DA transporter (DAT) or vesicular monoamine transporter 2 (VMAT2) immunoreactivity at any age. However, DA transport via DAT (starting at 12 months) and VMAT2 (starting at 3 months) as well as KCl-stimulated DA release were reduced in Bdnf(+/-) mice and declined with age suggesting an increasingly important role for BDNF in the release and uptake of DA with the aging process. These findings suggest that a BDNF expression deficit becomes more critical to dopaminergic dynamics and related behavioral activities with increasing age.

  12. Functional brain connectivity and cognition: effects of adult age and task demands.

    PubMed

    Chou, Ying-Hui; Chen, Nan-Kuei; Madden, David J

    2013-08-01

    Previous neuroimaging research has documented that patterns of intrinsic (resting state) functional connectivity (FC) among brain regions covary with individual measures of cognitive performance. Here, we examined the relation between intrinsic FC and a reaction time (RT) measure of performance, as a function of age group and task demands. We obtained filtered, event-related functional magnetic resonance imaging data, and RT measures of visual search performance, from 21 younger adults (19-29 years old) and 21 healthy, older adults (60-87 years old). Age-related decline occurred in the connectivity strength in multiple brain regions, consistent with previous findings. Among 8 pairs of regions, across somatomotor, orbitofrontal, and subcortical networks, increasing FC was associated with faster responding (lower RT). Relative to younger adults, older adults exhibited a lower strength of this RT-connectivity relation and greater disruption of this relation by a salient but irrelevant display item (color singleton distractor). Age-related differences in the covariation of intrinsic FC and cognitive performance vary as a function of task demands.

  13. Where the brain grows old: decline in anterior cingulate and medial prefrontal function with normal aging.

    PubMed

    Pardo, José V; Lee, Joel T; Sheikh, Sohail A; Surerus-Johnson, Christa; Shah, Hemant; Munch, Kristin R; Carlis, John V; Lewis, Scott M; Kuskowski, Michael A; Dysken, Maurice W

    2007-04-15

    Even healthy adults worry about declines in mental efficiency with aging. Subjective changes in mental flexibility, self-regulation, processing speed, and memory are often cited. We show here that focal decreases in brain activity occur with normal aging as measured with fluorodeoxyglucose and positron emission tomography. The largest declines localize to a medial network including the anterior cingulate/medial prefrontal cortex, dorsomedial thalamus, and sugenual cingulate/basal forebrain. Declining metabolism in this network correlates with declining cognitive function. The medial prefrontal metabolic changes with aging are similar in magnitude to the hypometabolism found in Mild Cognitive Impairment or Alzheimer's disease. These results converge with data from healthy elderly indicating dysfunction in the anterior attention system. The interaction of attention in the anterior cingulate cortex with memory in the medial temporal lobe may explain the global impairment that defines dementia. Despite the implications for an aging population, the neurophysiologic mechanisms of these metabolic decreases remain unknown. PMID:17321756

  14. Age-related changes in modular organization of human brain functional networks.

    PubMed

    Meunier, David; Achard, Sophie; Morcom, Alexa; Bullmore, Ed

    2009-02-01

    Graph theory allows us to quantify any complex system, e.g., in social sciences, biology or technology, that can be abstractly described as a set of nodes and links. Here we derived human brain functional networks from fMRI measurements of endogenous, low frequency, correlated oscillations in 90 cortical and subcortical regions for two groups of healthy (young and older) participants. We investigated the modular structure of these networks and tested the hypothesis that normal brain aging might be associated with changes in modularity of sparse networks. Newman's modularity metric was maximised and topological roles were assigned to brain regions depending on their specific contributions to intra- and inter-modular connectivity. Both young and older brain networks demonstrated significantly non-random modularity. The young brain network was decomposed into 3 major modules: central and posterior modules, which comprised mainly nodes with few inter-modular connections, and a dorsal fronto-cingulo-parietal module, which comprised mainly nodes with extensive inter-modular connections. The mean network in the older group also included posterior, superior central and dorsal fronto-striato-thalamic modules but the number of intermodular connections to frontal modular regions was significantly reduced, whereas the number of connector nodes in posterior and central modules was increased.

  15. Revitalizing the aged brain.

    PubMed

    Desai, Abhilash K

    2011-05-01

    Optimal cognitive and emotional function is vital to independence, productivity, and quality of life. Cognitive impairment without dementia may be seen in 16% to 33% of adults older than 65 years, and is associated with significant emotional distress. Cognitive and emotional well-being are inextricably linked. This article qualifies revitalizing the aged brain, discusses neuroplasticity, and suggests practical neuroplasticity-based strategies to improve the cognitive and emotional well-being of older adults.

  16. Visual Field Function in School-Aged Children with Spastic Unilateral Cerebral Palsy Related to Different Patterns of Brain Damage

    ERIC Educational Resources Information Center

    Jacobson, Lena; Rydberg, Agneta; Eliasson, Ann-Christin; Kits, Annika; Flodmark, Olof

    2010-01-01

    Aim: To relate visual field function to brain morphology in children with unilateral cerebral palsy (CP). Method: Visual field function was assessed using the confrontation technique and Goldmann perimetry in 29 children (15 males, 14 females; age range 7-17y, median age 11y) with unilateral CP classified at Gross Motor Function Classification…

  17. New insights into brain BDNF function in normal aging and Alzheimer disease.

    PubMed

    Tapia-Arancibia, Lucia; Aliaga, Esteban; Silhol, Michelle; Arancibia, Sandor

    2008-11-01

    The decline observed during aging involves multiple factors that influence several systems. It is the case for learning and memory processes which are severely reduced with aging. It is admitted that these cognitive effects result from impaired neuronal plasticity, which is altered in normal aging but mainly in Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus, cerebral cortex) and are considered as genuine molecular mediators of functional and morphological synaptic plasticity. Modification of BDNF and/or the expression of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal aging and Alzheimer disease. Interestingly, recent findings show that some physiologic or pathologic age-associated changes in the central nervous system could be offset by administration of exogenous BDNF and/or by stimulating its receptor expression. These molecules may thus represent a physiological reserve which could determine physiological or pathological aging. These data suggest that boosting the expression or activity of these endogenous protective systems may be a promising therapeutic alternative to enhance healthy aging.

  18. Cognitive activity, cognitive function, and brain diffusion characteristics in old age.

    PubMed

    Arfanakis, Konstantinos; Wilson, Robert S; Barth, Christopher M; Capuano, Ana W; Vasireddi, Anil; Zhang, Shengwei; Fleischman, Debra A; Bennett, David A

    2016-06-01

    The objective of this work was to test the hypotheses that a) more frequent cognitive activity in late life is associated with higher brain diffusion anisotropy and lower trace of the diffusion tensor, and b) brain diffusion characteristics partially mediate the association of late life cognitive activity with cognition. As part of a longitudinal cohort study, 379 older people without dementia rated their frequency of participation in cognitive activities, completed a battery of cognitive function tests, and underwent diffusion tensor imaging. We used tract-based spatial statistics to test the association between late life cognitive activity and brain diffusion characteristics. Clusters with statistically significant findings defined regions of interest in which we tested the hypothesis that diffusion characteristics partially mediate the association of late life cognitive activity with cognition. More frequent cognitive activity in late life was associated with higher level of global cognition after adjustment for age, sex, education, and indicators of early life cognitive enrichment (p = 0.001). More frequent cognitive activity was also related to higher fractional anisotropy in the left superior and inferior longitudinal fasciculi, left fornix, and corpus callosum, and lower trace in the thalamus (p < 0.05, FWE-corrected). After controlling for fractional anisotropy or trace from these regions, the regression coefficient for the association of late life cognitive activity with cognition was reduced by as much as 26 %. These findings suggest that the association of late life cognitive activity with cognition may be partially mediated by brain diffusion characteristics.

  19. Relationships between brain metabolism decrease in normal aging and changes in structural and functional connectivity.

    PubMed

    Chételat, Gaël; Landeau, Brigitte; Salmon, Eric; Yakushev, Igor; Bahri, Mohamed Ali; Mézenge, Florence; Perrotin, Audrey; Bastin, Christine; Manrique, Alain; Scheurich, Armin; Scheckenberger, Mathias; Desgranges, Béatrice; Eustache, Francis; Fellgiebel, Andreas

    2013-08-01

    Normal aging is characterized by brain glucose metabolism decline predominantly in the prefrontal cortex. The goal of the present study was to assess whether this change was associated with age-related alteration of white matter (WM) structural integrity and/or functional connectivity. FDG-PET data from 40 young and 57 elderly healthy participants from two research centers (n=49/48 in Center 1/2) were analyzed. WM volume from T1-weighted MRI (Center 1), fractional anisotropy from diffusion-tensor imaging (Center 2), and resting-state fMRI data (Center 1) were also obtained. Group comparisons were performed within each imaging modality. Then, positive correlations were assessed, within the elderly, between metabolism in the most affected region and the other neuroimaging modalities. Metabolism decline in the elderly predominated in the left inferior frontal junction (LIFJ). LIFJ hypometabolism was significantly associated with macrostructural and microstructural WM disturbances in long association fronto-temporo-occipital fibers, while no relationship was found with functional connectivity. The findings offer new perspectives to understand normal aging processes and open avenues for future studies to explore causality between age-related metabolism and connectivity changes. PMID:23518010

  20. The relevance of aging-related changes in brain function to rehabilitation in aging-related disease

    PubMed Central

    Crosson, Bruce; McGregor, Keith M.; Nocera, Joe R.; Drucker, Jonathan H.; Tran, Stella M.; Butler, Andrew J.

    2015-01-01

    The effects of aging on rehabilitation of aging-related diseases are rarely a design consideration in rehabilitation research. In this brief review we present strong coincidental evidence from these two fields suggesting that deficits in aging-related disease or injury are compounded by the interaction between aging-related brain changes and disease-related brain changes. Specifically, we hypothesize that some aphasia, motor, and neglect treatments using repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) in stroke patients may address the aging side of this interaction. The importance of testing this hypothesis and addressing the larger aging by aging-related disease interaction is discussed. Underlying mechanisms in aging that most likely are relevant to rehabilitation of aging-related diseases also are covered. PMID:26074807

  1. Aging, Brain Size, and IQ.

    ERIC Educational Resources Information Center

    Bigler, Erin D.; And Others

    1995-01-01

    Whether cross-sectional rates of decline for brain volume and the Performance Intellectual Quotient of the Wechsler Adult Intelligence Scale-Revised were equivalent over the years 16 to 65 was studied with 196 volunteers. Results indicate remarkably similar rates of decline in perceptual-motor functions and aging brain volume loss. (SLD)

  2. Functional correlates of brain aging: beta and gamma frequency band responses to age-related cortical changes.

    PubMed

    Christov, Mario; Dushanova, Juliana

    2016-01-01

    The brain as a system with gradually declined resources by age maximizes its performance by neural network reorganization for greater efficiency of neuronal oscillations in a given frequency band. Whether event-related high-frequency band responses are related to plasticity in neural recruitment contributed to the stability of sensory/cognitive mechanisms accompanying aging or are underlined pathological changes seen in aging brain remains unknown. Aged effect on brain electrical activity was studied in auditory discrimination task (low-frequency and high-frequency tone) at particular cortical locations in beta (β1: 12.5-20; β2: 20.5-30 Hz) and gamma frequency bands (γ1: 30.5-49; γ2: 52-69 Hz) during sensory (post-stimulus interval 0-250 ms) and cognitive processing (250-600 ms). Beta1 activity less affected by age during sensory processing. Reduced beta1 activity was more widespread during cognitive processing. This difference increased in fronto-parietal direction more expressed after high-frequency tone stimulation. Beta2 and gamma activity were more pronounced with progressive age during sensory processing. Reducing regional-process specificity with progressing age characterized age-related and tone-dependent beta2 changes during sensory, but not during cognitive processing. Beta2 and gamma activity diminished with age on cognitive processes, except the higher frontal tone-dependent gamma activity during cognitive processing. With increasing age, larger gamma2 activity was more expressed over the frontal brain areas to high tone discrimination and hand reaction choice. These gamma2 differences were shifted from posterior to anterior brain regions with advancing age. The aged influence was higher on cognitive processes than on perceptual ones. PMID:27373947

  3. Brain structure and function related to cognitive reserve variables in normal aging, mild cognitive impairment and Alzheimer's disease.

    PubMed

    Solé-Padullés, Cristina; Bartrés-Faz, David; Junqué, Carme; Vendrell, Pere; Rami, Lorena; Clemente, Imma C; Bosch, Beatriu; Villar, Amparo; Bargalló, Núria; Jurado, M Angeles; Barrios, Maite; Molinuevo, Jose Luis

    2009-07-01

    Cognitive reserve (CR) is the brain's capacity to cope with cerebral damage to minimize clinical manifestations. The 'passive model' considers head or brain measures as anatomical substrates of CR, whereas the 'active model' emphasizes the use of brain networks effectively. Sixteen healthy subjects, 12 amnestic mild cognitive impairment (MCI) and 16 cases with mild Alzheimer's disease (AD) were included to investigate the relationships between proxies of CR and cerebral measures considered in the 'passive' and 'active' models. CR proxies were inferred premorbid IQ (WAIS Vocabulary test), 'education-occupation', a questionnaire of intellectual and social activities and a composite CR measure. MRI-derived whole-brain volumes and brain activity by functional MRI during a visual encoding task were obtained. Among healthy elders, higher CR was related to larger brains and reduced activity during cognitive processing, suggesting more effective use of cerebral networks. In contrast, higher CR was associated with reduced brain volumes in MCI and AD and increased brain function in the latter, indicating more advanced neuropathology but that active compensatory mechanisms are still at work in higher CR patients. The right superior temporal gyrus (BA 22) and the left superior parietal lobe (BA 7) showed greatest significant differences in direction of slope with CR and activation between controls and AD cases. Finally, a regression analysis revealed that fMRI patterns were more closely related to CR proxies than brain volumes. Overall, inverse relationships for healthy and pathological aging groups emerged between brain structure and function and CR variables. PMID:18053618

  4. EEG Resting-State Brain Topological Reorganization as a Function of Age.

    PubMed

    Petti, Manuela; Toppi, Jlenia; Babiloni, Fabio; Cincotti, Febo; Mattia, Donatella; Astolfi, Laura

    2016-01-01

    Resting state connectivity has been increasingly studied to investigate the effects of aging on the brain. A reduced organization in the communication between brain areas was demonstrated by combining a variety of different imaging technologies (fMRI, EEG, and MEG) and graph theory. In this paper, we propose a methodology to get new insights into resting state connectivity and its variations with age, by combining advanced techniques of effective connectivity estimation, graph theoretical approach, and classification by SVM method. We analyzed high density EEG signals recorded at rest from 71 healthy subjects (age: 20-63 years). Weighted and directed connectivity was computed by means of Partial Directed Coherence based on a General Linear Kalman filter approach. To keep the information collected by the estimator, weighted and directed graph indices were extracted from the resulting networks. A relation between brain network properties and age of the subject was found, indicating a tendency of the network to randomly organize increasing with age. This result is also confirmed dividing the whole population into two subgroups according to the age (young and middle-aged adults): significant differences exist in terms of network organization measures. Classification of the subjects by means of such indices returns an accuracy greater than 80%. PMID:27006652

  5. The age-related posterior-anterior shift as revealed by voxelwise analysis of functional brain networks

    PubMed Central

    McCarthy, Paul; Benuskova, Lubica; Franz, Elizabeth A.

    2014-01-01

    The posterior-anterior shift in aging (PASA) is a commonly observed phenomenon in functional neuroimaging studies of aging, characterized by age-related reductions in occipital activity alongside increases in frontal activity. In this work we have investigated the hypothesis as to whether the PASA is also manifested in functional brain network measures such as degree, clustering coefficient, path length and local efficiency. We have performed statistical analysis upon functional networks derived from a fMRI dataset containing data from healthy young, healthy aged, and aged individuals with very mild to mild Alzheimer's disease (AD). Analysis of both task based and resting state functional network properties has indicated that the PASA can also be characterized in terms of modulation of functional network properties, and that the onset of AD appears to accentuate this modulation. We also explore the effect of spatial normalization upon the results of our analysis. PMID:25426065

  6. Flavonoids and the aging brain.

    PubMed

    Schmitt-Schillig, S; Schaffer, S; Weber, C C; Eckert, G P; Müller, W E

    2005-03-01

    Like in all other organs, the functional capacity of the human brain deteriorates over time. Pathological events such as oxidative stress, due to the elevated release of free radicals and reactive oxygen or nitrogen species, the subsequently enhanced oxidative modification of lipids, protein, and nucleic acids, and the modulation of apoptotic signaling pathways contribute to loss of brain function. The identification of neuroprotective food components is one strategy to facilitate healthy brain aging. Flavonoids were shown to activate key enzymes in mitochondrial respiration and to protect neuronal cells by acting as antioxidants, thus breaking the vicious cycle of oxidative stress and tissue damage. Furthermore, recent data indicate a favorable effect of flavonoids on neuro-inflammatory events. Whereas most of these effects have been shown in vitro, limited data in vivo are available, suggesting a rather low penetration of flavonoids into the brain. Nevertheless, several reports support the concept that flavonoid intake inhibits certain biochemical processes of brain aging, and might thus prevent to some extent the decline of cognitive functions with aging as well as the development or the course of neurodegenerative diseases. However, more data are needed to assess the true impact of flavonoids on brain aging.

  7. Sex hormones and brain aging.

    PubMed

    Veiga, Sergio; Melcangi, Roberto C; Doncarlos, Lydia L; Garcia-Segura, Luis M; Azcoitia, Iñigo

    2004-01-01

    Sex steroids exert pleiotropic effects in the nervous system, preserving neural function and promoting neuronal survival. Therefore, the age-related decrease in sex steroids may have a negative impact on neural function. Progesterone, testosterone and estradiol prevent neuronal loss in the central nervous system in different experimental animal models of neurodegeneration. Furthermore, progesterone and its reduced derivatives dihydroprogesterone and tetrahydroprogesterone reduce aging-associated morphological abnormalities of myelin and aging-associated myelin fiber loss in rat peripheral nerves. However, the results from hormone replacement studies in humans are thus far inconclusive. A possible alternative to hormonal replacement therapy is to increase local steroidogenesis by neural tissues, which express enzymes for steroid synthesis and metabolism. Proteins involved in the intramitochondrial trafficking of cholesterol, the first step in steroidogenesis, such as the peripheral-type benzodiazepine receptor and the steroidogenic acute regulatory protein, are up-regulated in the nervous system after injury. Furthermore, steroidogenic acute regulatory protein expression is increased in the brain of 24-month-old rats compared with young adult rats. This suggests that brain steroidogenesis may be modified in adaptation to neurodegenerative conditions and to the brain aging process. Furthermore, recent studies have shown that local formation of estradiol in the brain, by the enzyme aromatase, is neuroprotective. Therefore, steroidogenic acute regulatory protein, peripheral-type benzodiazepine receptor and aromatase are attractive pharmacological targets to promote neuroprotection in the aged brain. PMID:15582278

  8. Integrated Analysis and Visualization of Group Differences in Structural and Functional Brain Connectivity: Applications in Typical Ageing and Schizophrenia.

    PubMed

    Langen, Carolyn D; White, Tonya; Ikram, M Arfan; Vernooij, Meike W; Niessen, Wiro J

    2015-01-01

    Structural and functional brain connectivity are increasingly used to identify and analyze group differences in studies of brain disease. This study presents methods to analyze uni- and bi-modal brain connectivity and evaluate their ability to identify differences. Novel visualizations of significantly different connections comparing multiple metrics are presented. On the global level, "bi-modal comparison plots" show the distribution of uni- and bi-modal group differences and the relationship between structure and function. Differences between brain lobes are visualized using "worm plots". Group differences in connections are examined with an existing visualization, the "connectogram". These visualizations were evaluated in two proof-of-concept studies: (1) middle-aged versus elderly subjects; and (2) patients with schizophrenia versus controls. Each included two measures derived from diffusion weighted images and two from functional magnetic resonance images. The structural measures were minimum cost path between two anatomical regions according to the "Statistical Analysis of Minimum cost path based Structural Connectivity" method and the average fractional anisotropy along the fiber. The functional measures were Pearson's correlation and partial correlation of mean regional time series. The relationship between structure and function was similar in both studies. Uni-modal group differences varied greatly between connectivity types. Group differences were identified in both studies globally, within brain lobes and between regions. In the aging study, minimum cost path was highly effective in identifying group differences on all levels; fractional anisotropy and mean correlation showed smaller differences on the brain lobe and regional levels. In the schizophrenia study, minimum cost path and fractional anisotropy showed differences on the global level and within brain lobes; mean correlation showed small differences on the lobe level. Only fractional anisotropy

  9. Integrated Analysis and Visualization of Group Differences in Structural and Functional Brain Connectivity: Applications in Typical Ageing and Schizophrenia.

    PubMed

    Langen, Carolyn D; White, Tonya; Ikram, M Arfan; Vernooij, Meike W; Niessen, Wiro J

    2015-01-01

    Structural and functional brain connectivity are increasingly used to identify and analyze group differences in studies of brain disease. This study presents methods to analyze uni- and bi-modal brain connectivity and evaluate their ability to identify differences. Novel visualizations of significantly different connections comparing multiple metrics are presented. On the global level, "bi-modal comparison plots" show the distribution of uni- and bi-modal group differences and the relationship between structure and function. Differences between brain lobes are visualized using "worm plots". Group differences in connections are examined with an existing visualization, the "connectogram". These visualizations were evaluated in two proof-of-concept studies: (1) middle-aged versus elderly subjects; and (2) patients with schizophrenia versus controls. Each included two measures derived from diffusion weighted images and two from functional magnetic resonance images. The structural measures were minimum cost path between two anatomical regions according to the "Statistical Analysis of Minimum cost path based Structural Connectivity" method and the average fractional anisotropy along the fiber. The functional measures were Pearson's correlation and partial correlation of mean regional time series. The relationship between structure and function was similar in both studies. Uni-modal group differences varied greatly between connectivity types. Group differences were identified in both studies globally, within brain lobes and between regions. In the aging study, minimum cost path was highly effective in identifying group differences on all levels; fractional anisotropy and mean correlation showed smaller differences on the brain lobe and regional levels. In the schizophrenia study, minimum cost path and fractional anisotropy showed differences on the global level and within brain lobes; mean correlation showed small differences on the lobe level. Only fractional anisotropy

  10. Integrated Analysis and Visualization of Group Differences in Structural and Functional Brain Connectivity: Applications in Typical Ageing and Schizophrenia

    PubMed Central

    Langen, Carolyn D.; Ikram, M. Arfan; Vernooij, Meike W.

    2015-01-01

    Structural and functional brain connectivity are increasingly used to identify and analyze group differences in studies of brain disease. This study presents methods to analyze uni- and bi-modal brain connectivity and evaluate their ability to identify differences. Novel visualizations of significantly different connections comparing multiple metrics are presented. On the global level, “bi-modal comparison plots” show the distribution of uni- and bi-modal group differences and the relationship between structure and function. Differences between brain lobes are visualized using “worm plots”. Group differences in connections are examined with an existing visualization, the “connectogram”. These visualizations were evaluated in two proof-of-concept studies: (1) middle-aged versus elderly subjects; and (2) patients with schizophrenia versus controls. Each included two measures derived from diffusion weighted images and two from functional magnetic resonance images. The structural measures were minimum cost path between two anatomical regions according to the “Statistical Analysis of Minimum cost path based Structural Connectivity” method and the average fractional anisotropy along the fiber. The functional measures were Pearson’s correlation and partial correlation of mean regional time series. The relationship between structure and function was similar in both studies. Uni-modal group differences varied greatly between connectivity types. Group differences were identified in both studies globally, within brain lobes and between regions. In the aging study, minimum cost path was highly effective in identifying group differences on all levels; fractional anisotropy and mean correlation showed smaller differences on the brain lobe and regional levels. In the schizophrenia study, minimum cost path and fractional anisotropy showed differences on the global level and within brain lobes; mean correlation showed small differences on the lobe level. Only

  11. 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

  12. Polyphenols found in berry fruit improve age-associated changes in cognitive function and brain inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Research has demonstrated, in both human and animals, that cognitive functioning decreases with age, to include deficits in processing speed, executive function, memory, and spatial learning. The cause of these functional declines is not entirely understood; however, neuronal losses and the associat...

  13. Bottom up modeling of the connectome: linking structure and function in the resting brain and their changes in aging.

    PubMed

    Nakagawa, Tristan T; Jirsa, Viktor K; Spiegler, Andreas; McIntosh, Anthony R; Deco, Gustavo

    2013-10-15

    With the increasing availability of advanced imaging technologies, we are entering a new era of neuroscience. Detailed descriptions of the complex brain network enable us to map out a structural connectome, characterize it with graph theoretical methods, and compare it to the functional networks with increasing detail. To link these two aspects and understand how dynamics and structure interact to form functional brain networks in task and in the resting state, we use theoretical models. The advantage of using theoretical models is that by recreating functional connectivity and time series explicitly from structure and pre-defined dynamics, we can extract critical mechanisms by linking structure and function in ways not directly accessible in the real brain. Recently, resting-state models with varying local dynamics have reproduced empirical functional connectivity patterns, and given support to the view that the brain works at a critical point at the edge of a bifurcation of the system. Here, we present an overview of a modeling approach of the resting brain network and give an application of a neural mass model in the study of complexity changes in aging.

  14. Harnessing the power of gene microarrays for the study of brain aging and Alzheimer's disease: statistical reliability and functional correlation.

    PubMed

    Blalock, E M; Chen, K-C; Stromberg, A J; Norris, C M; Kadish, I; Kraner, S D; Porter, N M; Landfield, P W

    2005-11-01

    During normal brain aging, numerous alterations develop in the physiology, biochemistry and structure of neurons and glia. Aging changes occur in most brain regions and, in the hippocampus, have been linked to declining cognitive performance in both humans and animals. Age-related changes in hippocampal regions also may be harbingers of more severe decrements to come from neurodegenerative disorders such as Alzheimer's disease (AD). However, unraveling the mechanisms underlying brain aging, AD and impaired function has been difficult because of the complexity of the networks that drive these aging-related changes. Gene microarray technology allows massively parallel analysis of most genes expressed in a tissue, and therefore is an important new research tool that potentially can provide the investigative power needed to address the complexity of brain aging/neurodegenerative processes. However, along with this new analytic power, microarrays bring several major bioinformatics and resource problems that frequently hinder the optimal application of this technology. In particular, microarray analyses generate extremely large and unwieldy data sets and are subject to high false positive and false negative rates. Concerns also have been raised regarding their accuracy and uniformity. Furthermore, microarray analyses can result in long lists of altered genes, most of which may be difficult to evaluate for functional relevance. These and other problems have led to some skepticism regarding the reliability and functional usefulness of microarray data and to a general view that microarray data should be validated by an independent method. Given recent progress, however, we suggest that the major problem for current microarray research is no longer validity of expression measurements, but rather, the reliability of inferences from the data, an issue more appropriately redressed by statistical approaches than by validation with a separate method. If tested using statistically

  15. Preserving Brain Function in Aging: The Anti-glycative Potential of Berry Fruit.

    PubMed

    Thangthaeng, Nopporn; Poulose, Shibu M; Miller, Marshall G; Shukitt-Hale, Barbara

    2016-09-01

    Advanced glycation end products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produced when those foods are cooked at high temperatures. Studies have linked AGEs to various age-related physiological changes, including wrinkles, diabetic complications, and neurodegenerative disease, including Alzheimer's disease. Dietary berry fruits have been shown to reduce the severity or slow the progression of many physiological changes and disease pathologies that accompany aging. Emerging evidence has shown that the phytochemicals found in berry fruits exhibit anti-glycative activity. In this review, we briefly summarize the current evidence supporting the neuroprotective anti-glycative activity of berry fruits and their potential to preserve cognitive function during aging. PMID:27166828

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

    PubMed

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

    2015-08-01

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

  17. Functional connectivity in the developing brain: A longitudinal study from 4 to 9 months of age

    PubMed Central

    Damaraju, E.; Caprihan, A.; Lowe, J.R.; Allen, E.A.; Calhoun, V.D.; Phillips, J.P.

    2013-01-01

    We characterize the development of intrinsic connectivity networks (ICNs) from 4 to 9 months of age with resting state magnetic resonance imaging performed on sleeping infants without sedative medication. Data is analyzed with independent component analysis (ICA). Using both low (30 components) and high (100 components) ICA model order decompositions, we find that the functional network connectivity (FNC) map is largely similar at both 4 and 9 months. However at 9 months the connectivity strength decreases within local networks and increases between more distant networks. The connectivity within the default-mode network, which contains both local and more distant nodes, also increases in strength with age. The low frequency power spectrum increases with age only in the posterior cingulate cortex and posterior default mode network. These findings are consistent with a general developmental pattern of increasing longer distance functional connectivity over the first year of life and raise questions regarding the developmental importance of the posterior cingulate at this age. PMID:23994454

  18. [Can age-dependent cognitive functions be measured? P300 potentials--concept of brain aging--early diagnosis of dementia processes].

    PubMed

    Kügler, C

    1996-10-10

    Event related P300 potentials as the electrophysiological substrate of cognitive functions, such as the stimulus processing time (P300 latencies) and visual attention capacity (P300 amplitudes) are suitable for the analysis of age-related changes in cognitive human brain functions. P300 investigations carried out in a total of 330 test subjects aged between 18 and 98 years, showed an overall slight prolongation of the P300 latencies by 10 ms for each decade, as well as a discrete reduction in the P300 amplitudes of 1 microV. To describe the relationship between the P300 parameters and chronological age, polynomial regression models are more suitable than linear functions. This means that in middle-age, P300 potentials change only slightly while, from about the age of 60 upwards, a noticeable acceleration in the P300 changes takes place. An interesting observation was the fact that the acceleration in the P300 latency increase occurred some 10 years earlier in women than in men, beginning in the early postmenopausal period. The polynomial course of the regression function for the age-dependence of P300 potentials might reflect the positive influence of socio-cultural factors on the aging of cognitive functions. The true extent of the age-related changes in cognitive functions, however, can be determined only with the aid of intra-individual longitudinal studies. This is of considerable importance for the early diagnosis of both metabolic and primarily degenerative encephalopathies.

  19. Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes

    PubMed Central

    Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M.; Batista, Claudia Maria de Castro; Mattson, Mark P.; de Mello Coelho, Valeria

    2016-01-01

    We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN+ LLC. Some cortical NeuN+ neurons, GFAP+ glia limitans astrocytes, Iba-1+ microglia and S100β+ ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

  20. Lipid-laden cells differentially distributed in the aging brain are functionally active and correspond to distinct phenotypes.

    PubMed

    Shimabukuro, Marilia Kimie; Langhi, Larissa Gutman Paranhos; Cordeiro, Ingrid; Brito, José M; Batista, Claudia Maria de Castro; Mattson, Mark P; Mello Coelho, Valeria de

    2016-01-01

    We characterized cerebral Oil Red O-positive lipid-laden cells (LLC) of aging mice evaluating their distribution, morphology, density, functional activities and inflammatory phenotype. We identified LLC in meningeal, cortical and neurogenic brain regions. The density of cerebral LLC increased with age. LLC presenting small lipid droplets were visualized adjacent to blood vessels or deeper in the brain cortical and striatal parenchyma of aging mice. LLC with larger droplets were asymmetrically distributed in the cerebral ventricle walls, mainly located in the lateral wall. We also found that LLC in the subventricular region co-expressed beclin-1 or LC3, markers for autophagosome or autophagolysosome formation, and perilipin (PLIN), a lipid droplet-associated protein, suggesting lipophagic activity. Some cerebral LLC exhibited β galactosidase activity indicating a senescence phenotype. Moreover, we detected production of the pro-inflammatory cytokine TNF-α in cortical PLIN(+) LLC. Some cortical NeuN(+) neurons, GFAP(+) glia limitans astrocytes, Iba-1(+) microglia and S100β(+) ependymal cells expressed PLIN in the aging brain. Our findings suggest that cerebral LLC exhibit distinct cellular phenotypes and may participate in the age-associated neuroinflammatory processes. PMID:27029648

  1. Aluminium, iron and copper in human brain tissues donated to the Medical Research Council's Cognitive Function and Ageing Study.

    PubMed

    House, Emily; Esiri, Margaret; Forster, Gill; Ince, Paul G; Exley, Christopher

    2012-01-01

    Aluminium, iron and copper are all implicated in the aetiology of neurodegenerative diseases including Alzheimer's disease. However, there are very few large cohort studies of the content of these metals in aged human brains. We have used microwave digestion and TH GFAAS to measure aluminium, iron and copper in the temporal, frontal, occipital and parietal lobes of 60 brains donated to the Cognitive Function and Ageing Study. Every precaution was taken to reduce contamination of samples and acid digests to a minimum. Actual contamination was estimated by preparing a large number of (170+) method blanks which were interspersed within the full set of 700+ tissue digests. Subtraction of method blank values (MBV) from tissue digest values resulted in metal contents in all tissues in the range, MBV to 33 μg g(-1) dry wt. for aluminium, 112 to 8305 μg g(-1) dry wt. for iron and MBV to 384 μg g(-1) dry wt. for copper. While the median aluminium content for all tissues was 1.02 μg g(-1) dry wt. it was informative that 41 brains out of 60 included at least one tissue with an aluminium content which could be considered as potentially pathological (> 3.50 μg g(-1) dry wt.). The median content for iron was 286.16 μg g(-1) dry wt. and overall tissue iron contents were generally high which possibly reflected increased brain iron in ageing and in neurodegenerative disease. The median content for copper was 17.41 μg g(-1) dry wt. and overall tissue copper contents were lower than expected for aged brains but they were commensurate with aged brains showing signs of neurodegenerative disease. In this study we have shown, in particular, the value of carrying out significant numbers of method blanks to identify unknown sources of contamination. When these values are subtracted from tissue digest values the absolute metal contents could be considered as conservative and yet they may still reflect aspects of ageing and neurodegenerative disease in individual brains.

  2. 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.

  3. Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

    PubMed

    Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2015-12-01

    Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis.

  4. Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

    PubMed

    Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

    2015-12-01

    Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis. PMID:26318578

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

    PubMed

    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

  6. 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

  7. Age of acquisition effects on the functional organization of language in the adult brain.

    PubMed

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

    2011-10-01

    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 did not vary in relation to age of acquisition. For both tasks, a more left lateralized pattern of activation was observed, with activity for grammatical judgment being more anterior than that observed for phonemic-hand judgment, which was more posterior by comparison. Age of acquisition was linearly and negatively related to activation levels in anterior language regions and positively related to activation levels in posterior visual regions for both tasks.

  8. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis

    PubMed Central

    Karlsgodt, Katherine H.; van Erp, Theo G.M.; Bearden, Carrie E.; Cannon, Tyrone D.

    2014-01-01

    Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant. PMID:24144510

  9. Altered relationships between age and functional brain activation in adolescents at clinical high risk for psychosis.

    PubMed

    Karlsgodt, Katherine H; van Erp, Theo G M; Bearden, Carrie E; Cannon, Tyrone D

    2014-01-30

    Schizophrenia is considered a neurodevelopmental disorder, but whether the adolescent period, proximal to onset, is associated with aberrant development in individuals at clinical high risk (CHR) for psychosis is incompletely understood. While abnormal gray and white matter development has been observed, alterations in functional neuroimaging (fMRI) parameters during adolescence as related to conversion to psychosis have not yet been investigated. Twenty CHR individuals and 19 typically developing controls (TDC), (ages 14-21), were recruited from the Center for Assessment and Prevention of Prodromal States (CAPPS) at UCLA. Participants performed a Sternberg-style verbal working memory (WMem) task during fMRI and data were analyzed using a cross-sectional design to test the hypothesis that there is a deviant developmental trajectory in WMem associated neural circuitry in those at risk for psychosis. Eight of the CHR adolescents converted to psychosis within 2 years of initial assessment. A voxel-wise regression examining the relationship between age and activation revealed a significant group-by-age interaction. TDC showed a negative association between age and functional activation in the WMem circuitry while CHR adolescents showed a positive association. Moreover, CHR patients who later converted to overt psychosis showed a distinct pattern of abnormal age-associated activation in the frontal cortex relative to controls, while non-converters showed a more diffuse posterior pattern. Finding that age related variation in baseline patterns of neural activity differentiate individuals who subsequently convert to psychosis from healthy subjects suggests that these differences are likely to be clinically relevant. PMID:24144510

  10. Cognitive reserve is associated with the functional organization of the brain in healthy aging: a MEG study.

    PubMed

    López, María E; Aurtenetxe, Sara; Pereda, Ernesto; Cuesta, Pablo; Castellanos, Nazareth P; Bruña, Ricardo; Niso, Guiomar; Maestú, Fernando; Bajo, Ricardo

    2014-01-01

    The proportion of elderly people in the population has increased rapidly in the last century and consequently "healthy aging" is expected to become a critical area of research in neuroscience. Evidence reveals how healthy aging depends on three main behavioral factors: social lifestyle, cognitive activity, and physical activity. In this study, we focused on the role of cognitive activity, concentrating specifically on educational and occupational attainment factors, which were considered two of the main pillars of cognitive reserve (CR). Twenty-one subjects with similar rates of social lifestyle, physical and cognitive activity were selected from a sample of 55 healthy adults. These subjects were divided into two groups according to their level of CR; one group comprised subjects with high CR (9 members) and the other one contained those with low CR (12 members). To evaluate the cortical brain connectivity network, all participants were recorded by Magnetoencephalography (MEG) while they performed a memory task (modified version of the Sternberg's Task). We then applied two algorithms [Phase Locking Value (PLV) and Phase Lag Index (PLI)] to study the dynamics of functional connectivity. In response to the same task, the subjects with lower CR presented higher functional connectivity than those with higher CR. These results may indicate that participants with low CR needed a greater "effort" than those with high CR to achieve the same level of cognitive performance. Therefore, we conclude that CR contributes to the modulation of the functional connectivity patterns of the aging brain. PMID:24982632

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

    PubMed

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

    2016-01-01

    Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: "Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?" Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with

  12. Effect of Alzheimer Disease Risk on Brain Function During Self-Appraisal in Healthy Middle-Aged Adults

    PubMed Central

    Johnson, Sterling C.; Ries, Michele L.; Hess, Timothy M.; Carlsson, Cynthia M.; Gleason, Carey E.; Alexander, Andrew L.; Rowley, Howard A.; Asthana, Sanjay; Sager, Mark A.

    2009-01-01

    Context Recently asymptomatic middle-aged adult children of patients with Alzheimer Disease (AD) were found to exhibit fMRI deficits in the mesial temporal lobe during an encoding task. Whether this effect will be observed on other fMRI tasks is not yet known. This study examines the neural substrates of self-appraisal in people at risk for AD. Accurate appraisal of deficits is a problem for many AD patients, and prior fMRI studies of healthy young adults indicates that brain areas vulnerable to AD such as the anterior mesial temporal lobe and posterior cingulate are involved during self appraisal tasks. Objective To determine whether parental family history of AD (FH) or the ε4 allele of the Apolipoprotein E gene (APOE4) exert independent effects on brain function during self-appraisal. Design Cross-sectional factorial design in which APOE4 status (present/absent) was one factor, and FH status was the other. All participants received cognitive testing, genotyping and an fMRI task that required subjective self-appraisal (SA) decisions regarding trait adjective words in comparison to semantic decisions about the same words. Setting An academic medical center with a research-dedicated 3.0 Tesla MRI facility. Participants Cognitively normal middle-aged adults (N=110): 51 +FH; 59 −FH. Outcome measure Blood oxygen-dependent contrast measured with T2* weighted echo-planar imaging. Results FH and APOE4 status interacted in the posterior cingulate as well as left superior and medial frontal regions. There were main effects of FH (−FH > +FH) in left hippocampus, and ventral posterior cingulate. There were no main effects of APOE. Conclusion These results suggest that a parental history of AD may influence brain function during subjective self-appraisal in regions commonly affected by AD. Although these participants were asymptomatic and middle-aged, the findings suggest there may be subtle alterations in brain function attributable to AD risk factors. PMID:17909128

  13. Nutrients, Microglia Aging, and Brain Aging.

    PubMed

    Wu, Zhou; Yu, Janchun; Zhu, Aiqin; Nakanishi, Hiroshi

    2016-01-01

    As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging. PMID:26941889

  14. Preserving brain function in aging: The anti-glycative potential of berry fruit

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Advanced glycation end-products (AGEs) are naturally occurring macromolecules that are formed in vivo by the non-enzymatic modification of proteins, lipids, or nucleic acids by sugar, even in the absence of hyperglycemia. In the diet, AGEs are found in animal products, and additional AGEs are produc...

  15. NIH Conference. Brain imaging: aging and dementia

    SciTech Connect

    Cutler, N.R.; Duara, R.; Creasey, H.; Grady, C.L.; Haxby, J.V.; Schapiro, M.B.; Rapoport, S.I.

    1984-09-01

    The brain imaging techniques of positron emission tomography using (18F)-fluoro-2-deoxy-D-glucose, and computed tomography, together with neuropsychological tests, were used to examine overall brain function and anatomy in three study populations: healthy men at different ages, patients with presumptive Alzheimer's disease, and adults with Down's syndrome. Brain glucose use did not differ with age, whereas an age-related decrement in gray matter volume was found on computed tomographic assessment in healthy subjects. Memory deficits were found to precede significant reductions in brain glucose utilization in mild to moderate Alzheimer's dementia. Furthermore, differences between language and visuoconstructive impairments in patients with mild to moderate Alzheimer's disease were related to hemispheric asymmetry of brain metabolism. Brain glucose utilization was found to be significantly elevated in young adults with Down's syndrome, compared with controls. The importance of establishing strict criteria for selecting control subjects and patients is explained in relation to the findings.

  16. Arterial stiffness, pressure and flow pulsatility and brain structure and function: the Age, Gene/Environment Susceptibility--Reykjavik study.

    PubMed

    Mitchell, Gary F; van Buchem, Mark A; Sigurdsson, Sigurdur; Gotal, John D; Jonsdottir, Maria K; Kjartansson, Ólafur; Garcia, Melissa; Aspelund, Thor; Harris, Tamara B; Gudnason, Vilmundur; Launer, Lenore J

    2011-11-01

    Aortic stiffness increases with age and vascular risk factor exposure and is associated with increased risk for structural and functional abnormalities in the brain. High ambient flow and low impedance are thought to sensitize the cerebral microcirculation to harmful effects of excessive pressure and flow pulsatility. However, haemodynamic mechanisms contributing to structural brain lesions and cognitive impairment in the presence of high aortic stiffness remain unclear. We hypothesized that disproportionate stiffening of the proximal aorta as compared with the carotid arteries reduces wave reflection at this important interface and thereby facilitates transmission of excessive pulsatile energy into the cerebral microcirculation, leading to microvascular damage and impaired function. To assess this hypothesis, we evaluated carotid pressure and flow, carotid-femoral pulse wave velocity, brain magnetic resonance images and cognitive scores in participants in the community-based Age, Gene/Environment Susceptibility--Reykjavik study who had no history of stroke, transient ischaemic attack or dementia (n = 668, 378 females, 69-93 years of age). Aortic characteristic impedance was assessed in a random subset (n = 422) and the reflection coefficient at the aorta-carotid interface was computed. Carotid flow pulsatility index was negatively related to the aorta-carotid reflection coefficient (R = -0.66, P<0.001). Carotid pulse pressure, pulsatility index and carotid-femoral pulse wave velocity were each associated with increased risk for silent subcortical infarcts (hazard ratios of 1.62-1.71 per standard deviation, P<0.002). Carotid-femoral pulse wave velocity was associated with higher white matter hyperintensity volume (0.108 ± 0.045 SD/SD, P = 0.018). Pulsatility index was associated with lower whole brain (-0.127 ± 0.037 SD/SD, P<0.001), grey matter (-0.079 ± 0.038 SD/SD, P = 0.038) and white matter (-0.128 ± 0.039 SD/SD, P<0.001) volumes. Carotid-femoral pulse

  17. Load-related brain activation predicts spatial working memory performance in youth aged 9-12 and is associated with executive function at earlier ages.

    PubMed

    Huang, Anna S; Klein, Daniel N; Leung, Hoi-Chung

    2016-02-01

    Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9-12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders.

  18. Functional Brain Imaging

    PubMed Central

    2006-01-01

    Executive Summary Objective The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD). Clinical Need: Target Population and Condition Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be

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

    PubMed

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

    2016-01-01

    Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: "Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?" Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods with

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

    PubMed Central

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

    2016-01-01

    Age-related decline in gray and white brain matter goes together with cognitive depletion. To influence cognitive functioning in elderly, several types of physical exercise and nutritional intervention have been performed. This paper systematically reviews the potential additive and complementary effects of nutrition/nutritional supplements and physical exercise on cognition. The search strategy was developed for EMBASE, Medline, PubMed, Cochrane, CINAHL, and PsycInfo databases and focused on the research question: “Is the combination of physical exercise with nutrition/nutritional supplementation more effective than nutrition/nutritional supplementation or physical exercise alone in effecting on brain structure, metabolism, and/or function?” Both mammalian and human studies were included. In humans, randomized controlled trials that evaluated the effects of nutrition/nutritional supplements and physical exercise on cognitive functioning and associated parameters in healthy elderly (>65 years) were included. The systematic search included English and German language literature without any limitation of publication date. The search strategy yielded a total of 3129 references of which 67 studies met the inclusion criteria; 43 human and 24 mammalian, mainly rodent, studies. Three out of 43 human studies investigated a nutrition/physical exercise combination and reported no additive effects. In rodent studies, additive effects were found for docosahexaenoic acid supplementation when combined with physical exercise. Although feasible combinations of physical exercise/nutritional supplements are available for influencing the brain, only a few studies evaluated which possible combinations of nutrition/nutritional supplementation and physical exercise might have an effect on brain structure, metabolism and/or function. The reason for no clear effects of combinatory approaches in humans might be explained by the misfit between the combinations of nutritional methods

  1. Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age

    PubMed Central

    Laranjeira, António; Schulz, Joachim; Dotti, Carlos G.

    2016-01-01

    In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. In the current study, we set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. Here we report the age-dependent upregulation of genes involved in the metabolic process of fatty acid β-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. Our data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of β-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age. PMID:27518101

  2. Genes Related to Fatty Acid β-Oxidation Play a Role in the Functional Decline of the Drosophila Brain with Age.

    PubMed

    Laranjeira, António; Schulz, Joachim; Dotti, Carlos G

    2016-01-01

    In living organisms, ageing is widely considered to be the result of a multifaceted process consisting of the progressive accumulation of damage over time, having implications both in terms of function and survival. The study of ageing presents several challenges, from the different mechanisms implicated to the great diversity of systems affected over time. In the current study, we set out to identify genes involved in the functional decline of the brain with age and study its relevance in a tissue dependent manner using Drosophila melanogaster as a model system. Here we report the age-dependent upregulation of genes involved in the metabolic process of fatty acid β-oxidation in the nervous tissue of female wild-type flies. Downregulation of CG10814, dHNF4 and lipid mobilizing genes bmm and dAkh rescues the functional decline of the brain with age, both at the cellular and behaviour level, while over-expression worsens performance. Our data proposes the occurrence of a metabolic alteration in the fly brain with age, whereby the process of β-oxidation of fatty acids experiences a genetic gain-of-function. This event proved to be one of the main causes contributing to the functional decline of the brain with age. PMID:27518101

  3. The function of the NMDA-receptor during normal brain aging.

    PubMed

    Müller, W E; Stoll, S; Scheuer, K; Meichelböck, A

    1994-01-01

    Age-related changes of N-methyl-D-aspartate (NMDA) receptors have been found in cortical areas and in the hippocampus of many species. On the basis of a variety of experimental observations it has been suggested that the decrease of NMDA-receptor density might be one of the causative factors of the cognitive decline with aging. Based on these findings several strategies have been developed to improve cognition by compensating the NMDA-receptor deficits in aging. The most promising approaches are the indirect activation of glutamatergic neurotransmission by agonists of the glycine site or the restoration of the age-related deficit of receptor density by several nootropics. PMID:7897387

  4. Aberrant Brain Regional Homogeneity and Functional Connectivity in Middle-Aged T2DM Patients: A Resting-State Functional MRI Study

    PubMed Central

    Liu, Daihong; Duan, Shanshan; Zhang, Jiuquan; Zhou, Chaoyang; Liang, Minglong; Yin, Xuntao; Wei, Ping; Wang, Jian

    2016-01-01

    Type 2 diabetes mellitus (T2DM) has been associated with cognitive impairment. However, its neurological mechanism remains elusive. Combining regional homogeneity (ReHo) and functional connectivity (FC) analyses, the present study aimed to investigate brain functional alterations in middle-aged T2DM patients, which could provide complementary information for the neural substrates underlying T2DM-associated brain dysfunction. Twenty-five T2DM patients and 25 healthy controls were involved in neuropsychological testing and structural and resting-state functional magnetic resonance imaging (rs-fMRI) data acquisition. ReHo analysis was conducted to determine the peak coordinates of brain regions with abnormal local brain activity synchronization. Then, the identified brain regions were considered as seeds, and FC between these brain regions and global voxels was computed. Finally, the potential correlations between the imaging indices and neuropsychological data were also explored. Compared with healthy controls, T2DM patients exhibited higher ReHo values in the anterior cingulate gyrus (ACG) and lower ReHo in the right fusiform gyrus (FFG), right precentral gyrus (PreCG) and right medial orbit of the superior frontal gyrus (SFG). Considering these areas as seed regions, T2DM patients displayed aberrant FC, mainly in the frontal and parietal lobes. The pattern of FC alterations in T2DM patients was characterized by decreased connectivity and positive to negative or negative to positive converted connectivity. Digital Span Test (DST) forward scores revealed significant correlations with the ReHo values of the right PreCG (ρ = 0.527, p = 0.014) and FC between the right FFG and middle temporal gyrus (MTG; ρ = −0.437, p = 0.048). Our findings suggest that T2DM patients suffer from cognitive dysfunction related to spatially local and remote brain activity synchronization impairment. The patterns of ReHo and FC alterations shed light on the mechanisms underlying T2DM

  5. The effect of education on regional brain metabolism and its functional connectivity in an aged population utilizing positron emission tomography.

    PubMed

    Kim, Jaeik; Chey, Jeanyung; Kim, Sang-Eun; Kim, Hoyoung

    2015-05-01

    Education involves learning new information and acquiring cognitive skills. These require various cognitive processes including learning, memory, and language. Since cognitive processes activate associated brain areas, we proposed that the brains of elderly people with longer education periods would show traces of repeated activation as increased synaptic connectivity and capillary in brain areas involved in learning, memory, and language. Utilizing positron emission topography (PET), this study examined the effect of education in the human brain utilizing the regional cerebral glucose metabolism rates (rCMRglcs). 26 elderly women with high-level education (HEG) and 26 with low-level education (LEG) were compared with regard to their regional brain activation and association between the regions. Further, graphical theoretical analysis using rCMRglcs was applied to examine differences in the functional network properties of the brain. The results showed that the HEG had higher rCMRglc in the ventral cerebral regions that are mainly involved in memory, language, and neurogenesis, while the LEG had higher rCMRglc in apical areas of the cerebrum mainly involved in motor and somatosensory functions. Functional connectivity investigated with graph theoretical analysis illustrated that the brain of the HEG compared to those of the LEG were overall more efficient, more resilient, and characterized by small-worldness. This may be one of the brain's mechanisms mediating the reserve effects found in people with higher education.

  6. Online games training aging brains: limited transfer to cognitive control functions.

    PubMed

    van Muijden, Jesse; Band, Guido P H; Hommel, Bernhard

    2012-01-01

    The prevalence of age-related cognitive decline will increase due to graying of the global population. The goal of the present study was to test whether playing online cognitive training games can improve cognitive control (CC) in healthy older adults. Fifty-four older adults (age 60-77) played five different cognitive training games online for 30 min a day over a period of seven weeks (game group). Another group of 20 older adults (age 61-73) instead answered quiz questions about documentaries online (documentary group). Transfer was assessed by means of a cognitive test battery administered before and after the intervention. The test battery included measures of working memory updating, set shifting, response inhibition, attention, and inductive reasoning. Compared with the documentary group, the game group showed larger improvement of inhibition (Stop-Signal task) and inductive reasoning (Raven-SPM), whereas the documentary group showed more improvement in selective attention (UFoV-3). These effects qualify as transfer effects, because response inhibition, inductive reasoning and selective attention were not targeted by the interventions. However, because seven other indicators of CC did not show benefits of game training and some of those that did suffered from potential baseline differences, the study as a whole provides only modest support for the potential of videogame training to improve CC in healthy older adults. PMID:22912609

  7. Online games training aging brains: limited transfer to cognitive control functions

    PubMed Central

    van Muijden, Jesse; Band, Guido P. H.; Hommel, Bernhard

    2011-01-01

    The prevalence of age-related cognitive decline will increase due to graying of the global population. The goal of the present study was to test whether playing online cognitive training games can improve cognitive control (CC) in healthy older adults. Fifty-four older adults (age 60–77) played five different cognitive training games online for 30 min a day over a period of seven weeks (game group). Another group of 20 older adults (age 61–73) instead answered quiz questions about documentaries online (documentary group). Transfer was assessed by means of a cognitive test battery administered before and after the intervention. The test battery included measures of working memory updating, set shifting, response inhibition, attention, and inductive reasoning. Compared with the documentary group, the game group showed larger improvement of inhibition (Stop-Signal task) and inductive reasoning (Raven-SPM), whereas the documentary group showed more improvement in selective attention (UFoV-3). These effects qualify as transfer effects, because response inhibition, inductive reasoning and selective attention were not targeted by the interventions. However, because seven other indicators of CC did not show benefits of game training and some of those that did suffered from potential baseline differences, the study as a whole provides only modest support for the potential of videogame training to improve CC in healthy older adults. PMID:22912609

  8. Insulin-Like Growth Factor (IGF)-I Modulates Endothelial Blood-Brain Barrier Function in Ischemic Middle-Aged Female Rats.

    PubMed

    Bake, Shameena; Okoreeh, Andre K; Alaniz, Robert C; Sohrabji, Farida

    2016-01-01

    In comparison with young females, middle-aged female rats sustain greater cerebral infarction and worse functional recovery after stroke. These poorer stroke outcomes in middle-aged females are associated with an age-related reduction in IGF-I levels. Poststroke IGF-I treatment decreases infarct volume in older females and lowers the expression of cytokines in the ischemic hemisphere. IGF-I also reduces transfer of Evans blue dye to the brain, suggesting that this peptide may also promote blood-brain barrier function. To test the hypothesis that IGF-I may act at the blood-brain barrier in ischemic stroke, 2 approaches were used. In the first approach, middle-aged female rats were subjected to middle cerebral artery occlusion and treated with IGF-I after reperfusion. Mononuclear cells from the ischemic hemisphere were stained for CD4 or triple-labeled for CD4/CD25/FoxP3 and subjected to flow analyses. Both cohorts of cells were significantly reduced in IGF-I-treated animals compared with those in vehicle controls. Reduced trafficking of immune cells to the ischemic site suggests that blood-brain barrier integrity is better maintained in IGF-I-treated animals. The second approach directly tested the effect of IGF-I on barrier function of aging endothelial cells. Accordingly, brain microvascular endothelial cells from middle-aged female rats were cultured ex vivo and subjected to ischemic conditions (oxygen-glucose deprivation). IGF-I treatment significantly reduced the transfer of fluorescently labeled BSA across the endothelial monolayer as well as cellular internalization of fluorescein isothiocyanate-BSA compared with those in vehicle-treated cultures, Collectively, these data support the hypothesis that IGF-I improves blood-brain barrier function in middle-aged females.

  9. Light-sensitive brain pathways and aging.

    PubMed

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-03-15

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

  10. Light-sensitive brain pathways and aging.

    PubMed

    Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

    2016-01-01

    Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity. PMID:26980095

  11. Does transcranial direct current stimulation enhance cognitive and motor functions in the ageing brain? A systematic review and meta- analysis.

    PubMed

    Summers, Jeffery J; Kang, Nyeonju; Cauraugh, James H

    2016-01-01

    The use of transcranial direct current stimulation (tDCS) to enhance cognitive and motor functions has enjoyed a massive increase in popularity. Modifying neuroplasticity via non-invasive cortical stimulation has enormous potential to slow or even reverse declines in functions associated with ageing. The current meta-analysis evaluated the effects of tDCS on cognitive and motor performance in healthy older adults. Of the 81 studies identified, 25 qualified for inclusion. A random effects model meta-analysis revealed a significant overall standardized mean difference equal to 0.53 (SE=0.09; medium heterogeneity: I(2)=57.08%; and high fail-safe: N=448). Five analyses on moderator variables indicated significant tDCS beneficial effects: (a) on both cognitive and motor task performances, (b) across a wide-range of cognitive tasks, (c) on specific brain areas, (d) stimulation offline (before) or online (during) the cognitive and motor tasks. Although the meta-analysis revealed robust support for enhancing both cognitive and motor performance, we outline a number of caveats on the use of tDCS.

  12. The ageing brain: normal and abnormal memory.

    PubMed Central

    Albert, M S

    1997-01-01

    With advancing age, the majority of individuals experience declines in their ability to learn and remember. An examination of brain structure and function in healthy older persons across the age range indicates that there are substantial changes in the brain that appear to be related to alterations in memory. The nature of the cognitive and neurobiological alterations associated with age-related change is substantially different from that seen in the early stages of a dementing illness, such as Alzheimer's disease. These differences have implications for potential intervention strategies. PMID:9415922

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

    PubMed

    Semenova, O A; Machinskaya, R I

    2015-01-01

    A total number of 172 children aged 10-12 were electrophysiologically and neuropsychologically assessed in order to analyze the influence of the functioning of brain regulatory systems onto the voluntary regulation of cognitive performance during the preteen years. EEG patterns associated with the nonoptimal functioning of brain regulatory systems, particularly fronto-thalamic, limbic and fronto-striatal structures were significantly more often observed in children with learning and behavioral difficulties, as compared to the control group. Neuropsychological assessment showed that the nonoptimal functioning of different brain regulatory systems specifically affect the voluntary regulation of cognitive performance. Children with EEG patterns of fronto-thalamic nonoptimal functioning demonstrated poor voluntary regulation such as impulsiveness and difficulties in continuing the same algorithms. Children with EEG patterns of limbic nonoptimal functioning showed a less pronounced executive dysfunction manifested only in poor switching between program units within a task. Children with EEG patterns of fronto-striatal nonoptimal functioning struggled with such executive dysfunctions as motor and tactile perseverations and emotional-motivational deviations such as poor motivation and communicative skills. PMID:26601407

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

    PubMed

    Semenova, O A; Machinskaya, R I

    2015-01-01

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

  15. 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

  16. Metabolic drift in the aging brain

    PubMed Central

    Ivanisevic, Julijana; Stauch, Kelly L.; Petrascheck, Michael; Benton, H. Paul; Epstein, Adrian A.; Fang, Mingliang; Gorantla, Santhi; Tran, Minerva; Hoang, Linh; Kurczy, Michael E.; Boska, Michael D.; Gendelman, Howard E.; Fox, Howard S.; Siuzdak, Gary

    2016-01-01

    Brain function is highly dependent upon controlled energy metabolism whose loss heralds cognitive impairments. This is particularly notable in the aged individuals and in age-related neurodegenerative diseases. However, how metabolic homeostasis is disrupted in the aging brain is still poorly understood. Here we performed global, metabolomic and proteomic analyses across different anatomical regions of mouse brain at different stages of its adult lifespan. Interestingly, while severe proteomic imbalance was absent, global-untargeted metabolomics revealed an energy metabolic drift or significant imbalance in core metabolite levels in aged mouse brains. Metabolic imbalance was characterized by compromised cellular energy status (NAD decline, increased AMP/ATP, purine/pyrimidine accumulation) and significantly altered oxidative phosphorylation and nucleotide biosynthesis and degradation. The central energy metabolic drift suggests a failure of the cellular machinery to restore metabostasis (metabolite homeostasis) in the aged brain and therefore an inability to respond properly to external stimuli, likely driving the alterations in signaling activity and thus in neuronal function and communication. PMID:27182841

  17. Early Brain Response to Low-Dose Radiation Exposure Involves Molecular Networks and Pathways Associated with Cognitive Functions, Advanced Aging and Alzheimer's Disease

    SciTech Connect

    Lowe, Xiu R; Bhattacharya, Sanchita; Marchetti, Francesco; Wyrobek, Andrew J.

    2008-06-06

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

  18. Brain trace elements and aging

    NASA Astrophysics Data System (ADS)

    Hebbrecht, Geert; Maenhaut, Willy; Reuck, Jacques De

    1999-04-01

    Degenerative mechanisms involved in the aging process of the brain are to a certain extent counteracted by repair mechanisms. In both degenerative and recovery processes, trace elements are involved. The present study focused on the role of two minor (i.e., K and Ca) and six trace elements (i.e., Mn, Fe, Cu, Zn, Se and Rb) in the aging process. The elements were determined by PIXE in cerebral cortex and white matter, basal ganglia, brainstem and cerebellar cortex of 18 postmortem human brains, from persons without a history of neurologic or psychiatric disease who deceased between the age of 7 and 79. This age range allowed us to study the relationship between elemental concentrations and age. The most prominent findings were a concentration decrease for K and Rb and a concentration increase for the elements Ca, Fe, Zn and Se. The study supports recent findings that Ca and Fe are involved in brain degenerative processes initiated by oxygen free radicals, whereas Zn and Se are involved in immunological reactions counteracting the aging process.

  19. Cortical reorganization in the aging brain.

    PubMed

    Dinse, Hubert R

    2006-01-01

    Aging exerts major reorganization and remodeling at all levels of brain structure and function. Studies in aged animals and in human elderly individuals demonstrate that sensorimotor cortical representational maps undergo significant alterations. Because cortical reorganization is paralleled by a decline in perceptual and behavioral performance, this type of cortical remodeling differs from the plastic reorganization observed during learning processes in young individuals where map changes are associated with a gain in performance. It is now clear that brain plasticity is operational into old age; therefore, protocols for interventions such as training, exercising, practicing, and stimulation, which make use of neuroplasticity principles, are effective to ameliorate some forms of cortical and behavioral age-related changes, indicating that aging effects are not irreversible but treatable. However, old individuals cannot be rejuvenated, but restoration of function is possible through the emergence of new processing strategies. This implies that cortical reorganization in the aging brain occurs twice: during aging, and during treatment of age-related changes.

  20. The effects of Ginkgo biloba extract on cognitive functions in aged female rats: the role of oxidative stress and brain-derived neurotrophic factor.

    PubMed

    Belviranlı, Muaz; Okudan, Nilsel

    2015-02-01

    The aim of this study was to investigate the effects of Ginkgo biloba extract (GBE) on cognitive functions as well as oxidative stress and brain-derived neurotrophic factor (BDNF) levels in aged female rats. Rats were divided into 4 groups according to age (young vs. aged) and treatment (GBE vs. vehicle). GBE or vehicle was given for 30 d, and a series of behavioral tests were performed. Following behavioral testing, blood samples and brain tissues were obtained for analysis of BDNF, malondialdehyde (MDA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and glutathione levels, and superoxide dismutase activity. Locomotor activity and anxiety levels were lower in the aged rats. Based on Morris water maze probe trial findings, GBE supplementation increased the number of platform crossings in the aged rats. MDA and 8-OHdG levels were lower in the brain tissue, and BDNF levels were higher in plasma in the rates treated with GBE. Based on these findings, we concluded that GBE supplementation improved cognitive functions by decreasing oxidative damage and increasing the BDNF level in aged female rats.

  1. Executive dysfunction, brain aging, and political leadership.

    PubMed

    Fisher, Mark; Franklin, David L; Post, Jerrold M

    2014-01-01

    Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function.

  2. Executive dysfunction, brain aging, and political leadership.

    PubMed

    Fisher, Mark; Franklin, David L; Post, Jerrold M

    2014-01-01

    Decision-making is an essential component of executive function, and a critical skill of political leadership. Neuroanatomic localization studies have established the prefrontal cortex as the critical brain site for executive function. In addition to the prefrontal cortex, white matter tracts as well as subcortical brain structures are crucial for optimal executive function. Executive function shows a significant decline beginning at age 60, and this is associated with age-related atrophy of prefrontal cortex, cerebral white matter disease, and cerebral microbleeds. Notably, age-related decline in executive function appears to be a relatively selective cognitive deterioration, generally sparing language and memory function. While an individual may appear to be functioning normally with regard to relatively obvious cognitive functions such as language and memory, that same individual may lack the capacity to integrate these cognitive functions to achieve normal decision-making. From a historical perspective, global decline in cognitive function of political leaders has been alternatively described as a catastrophic event, a slowly progressive deterioration, or a relatively episodic phenomenon. Selective loss of executive function in political leaders is less appreciated, but increased utilization of highly sensitive brain imaging techniques will likely bring greater appreciation to this phenomenon. Former Israeli Prime Minister Ariel Sharon was an example of a political leader with a well-described neurodegenerative condition (cerebral amyloid angiopathy) that creates a neuropathological substrate for executive dysfunction. Based on the known neuroanatomical and neuropathological changes that occur with aging, we should probably assume that a significant proportion of political leaders over the age of 65 have impairment of executive function. PMID:25901887

  3. [Age-related changes of the brain].

    PubMed

    Paltsyn, A A; Komissarova, S V

    2015-01-01

    The first morphological signs of aging of the brain are found in the white matter already at a young age (20-40 years), and later (40-50 years) in a gray matter. After the 40-50 years appear and in subsequently are becoming more pronounced functional manifestations of morphological changes: the weakening of sensory-motor and cognitive abilities. While in principle this dynamic of age-related changes is inevitable, the rate of their development to a large extent determined by the genetic characteristics and lifestyle of the individual. According to modem concepts age-related changes in the number of nerve cells are different in different parts of the brain. However, these changes are not large and are not the main cause of senile decline brain. The main processes that contribute to the degradation of the brain develop as in the bodies of neurons and in neuropil. In the bodies of neurons--it is a damage (usually decrease) of the level of expression of many genes, and especially of the genes determining cell communication. In neuropil: reduction in the number of synapses and the strength of synaptic connections, reduction in the number of dendritic spines and axonal buttons, reduction in the number and thickness of the dendritic branches, demyelination of axons. As the result of these events, it becomes a violation of the rate of formation and rebuilding neuronal circuits. It is deplete associative ability, brain plasticity, and memory. PMID:27116888

  4. Aging and brain rejuvenation as systemic events

    PubMed Central

    Bouchard, Jill; Villeda, Saul A

    2015-01-01

    The effects of aging were traditionally thought to be immutable, particularly evident in the loss of plasticity and cognitive abilities occurring in the aged central nervous system (CNS). However, it is becoming increasingly apparent that extrinsic systemic manipulations such as exercise, caloric restriction, and changing blood composition by heterochronic parabiosis or young plasma administration can partially counteract this age-related loss of plasticity in the aged brain. In this review, we discuss the process of aging and rejuvenation as systemic events. We summarize genetic studies that demonstrate a surprising level of malleability in organismal lifespan, and highlight the potential for systemic manipulations to functionally reverse the effects of aging in the CNS. Based on mounting evidence, we propose that rejuvenating effects of systemic manipulations are mediated, in part, by blood-borne ‘pro-youthful’ factors. Thus, systemic manipulations promoting a younger blood composition provide effective strategies to rejuvenate the aged brain. As a consequence, we can now consider reactivating latent plasticity dormant in the aged CNS as a means to rejuvenate regenerative, synaptic, and cognitive functions late in life, with potential implications even for extending lifespan. PMID:25327899

  5. Association between Lifetime Physical Activity and Cognitive Functioning in Middle-Aged and Older Community Dwelling Adults: Results from the Brain in Motion Study.

    PubMed

    Gill, Stephanie J; Friedenreich, Christine M; Sajobi, Tolulope T; Longman, R Stewart; Drogos, Lauren L; Davenport, Margie H; Tyndall, Amanda V; Eskes, Gail A; Hogan, David B; Hill, Michael D; Parboosingh, Jillian S; Wilson, Ben J; Poulin, Marc J

    2015-11-01

    To determine if total lifetime physical activity (PA) is associated with better cognitive functioning with aging and if cerebrovascular function mediates this association. A sample of 226 (52.2% female) community dwelling middle-aged and older adults (66.5 ± 6.4 years) in the Brain in Motion Study, completed the Lifetime Total Physical Activity Questionnaire and underwent neuropsychological and cerebrovascular blood flow testing. Multiple robust linear regressions were used to model the associations between lifetime PA and global cognition after adjusting for age, sex, North American Adult Reading Test results (i.e., an estimate of premorbid intellectual ability), maximal aerobic capacity, body mass index and interactions between age, sex, and lifetime PA. Mediation analysis assessed the effect of cerebrovascular measures on the association between lifetime PA and global cognition. Post hoc analyses assessed past year PA and current fitness levels relation to global cognition and cerebrovascular measures. Better global cognitive performance was associated with higher lifetime PA (p=.045), recreational PA (p=.021), and vigorous intensity PA (p=.004), PA between the ages of 0 and 20 years (p=.036), and between the ages of 21 and 35 years (p.5), but partially mediated the relation between current fitness and global cognition. This study revealed significant associations between higher levels of PA (i.e., total lifetime, recreational, vigorous PA, and past year) and better cognitive function in later life. Current fitness levels relation to cognitive function may be partially mediated through current cerebrovascular function. PMID:26581793

  6. Functional Brain Activation Differences in School-Age Children with Speech Sound Errors: Speech and Print Processing

    ERIC Educational Resources Information Center

    Preston, Jonathan L.; Felsenfeld, Susan; Frost, Stephen J.; Mencl, W. Einar; Fulbright, Robert K.; Grigorenko, Elena L.; Landi, Nicole; Seki, Ayumi; Pugh, Kenneth R.

    2012-01-01

    Purpose: To examine neural response to spoken and printed language in children with speech sound errors (SSE). Method: Functional magnetic resonance imaging was used to compare processing of auditorily and visually presented words and pseudowords in 17 children with SSE, ages 8;6[years;months] through 10;10, with 17 matched controls. Results: When…

  7. 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

  8. Brain aging, Alzheimer's disease, and mitochondria

    PubMed Central

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the question of whether AD and brain aging should be conceptually lumped or split, the extent to which AD and brain aging potentially share common molecular mechanisms, whether beta amyloid should be primarily considered a marker of AD or simply brain aging, and the definition of AD itself. PMID:21920438

  9. Cognitive Skills and the Aging Brain: What to Expect.

    PubMed

    Howieson, Diane B

    2015-01-01

    Whether it's a special episode on the PBS series, "The Secret Life of the Brain" or an entire issue dedicated to the topic in the journal Science, a better understanding of the aging brain is viewed as a key to an improved quality of life in a world where people live longer. Despite dementia and other neurobiological disorders that are associated with aging, improved imaging has revealed that even into our seventies, our brains continue producing new neurons. Our author writes about how mental health functions react to the normal aging process, including why an aging brain may even form the basis for wisdom. PMID:27408669

  10. Exercise, cognitive function, and aging.

    PubMed

    Barnes, Jill N

    2015-06-01

    Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding potential adverse effects of aging on brain blood flow and cognition may help to determine effective strategies to mitigate these effects on the population. Exercise may be one strategy to prevent or delay cognitive decline. This review describes how aging is associated with cardiovascular disease risks, vascular dysfunction, and increasing Alzheimer's disease pathology. It will also discuss the possible effects of aging on cerebral vascular physiology, cerebral perfusion, and brain atrophy rates. Clinically, these changes will present as reduced cognitive function, neurodegeneration, and the onset of dementia. Regular exercise has been shown to improve cognitive function, and we hypothesize that this occurs through beneficial adaptations in vascular physiology and improved neurovascular coupling. This review highlights the potential interactions and ideas of how the age-associated variables may affect cognition and may be moderated by regular exercise. PMID:26031719

  11. [A study on functional plasticity of the brain in childhood. II. Speech development and intelligence after the damage of cerebral hemisphere under 1 year of age].

    PubMed

    Ichiba, N; Takigawa, H

    1992-11-01

    To investigate the functional plasticity of the brain in childhood, the speech development, the intelligence test and dichotic listening test were performed on 27 patients who had suffered from hemiplegia under 1 year of age. Among 13 patients with right hemiplegia, 7 to 24 years old, 11 patients showed a left ear dominance suggesting the lateralization of language in the right hemisphere. All 14 patients with left hemiplegia, 5 to 37 years old, showed a right ear dominance suggesting the lateralization of language in the left hemisphere. All 27 patients acquired speech function enough to converse with other people during daily life. There were no differences in speech development or intelligence scores between both groups of hemiplegia. Although there was no correlation between the speech development and the age of onset of hemiplegia, there was a correlation between the speech development and the intelligence score in both groups of hemiplegia. PMID:1419166

  12. A multi-ingredient dietary supplement abolishes large-scale brain cell loss, improves sensory function, and prevents neuronal atrophy in aging mice.

    PubMed

    Lemon, J A; Aksenov, V; Samigullina, R; Aksenov, S; Rodgers, W H; Rollo, C D; Boreham, D R

    2016-06-01

    Transgenic growth hormone mice (TGM) are a recognized model of accelerated aging with characteristics including chronic oxidative stress, reduced longevity, mitochondrial dysfunction, insulin resistance, muscle wasting, and elevated inflammatory processes. Growth hormone/IGF-1 activate the Target of Rapamycin known to promote aging. TGM particularly express severe cognitive decline. We previously reported that a multi-ingredient dietary supplement (MDS) designed to offset five mechanisms associated with aging extended longevity, ameliorated cognitive deterioration and significantly reduced age-related physical deterioration in both normal mice and TGM. Here we report that TGM lose more than 50% of cells in midbrain regions, including the cerebellum and olfactory bulb. This is comparable to severe Alzheimer's disease and likely explains their striking age-related cognitive impairment. We also demonstrate that the MDS completely abrogates this severe brain cell loss, reverses cognitive decline and augments sensory and motor function in aged mice. Additionally, histological examination of retinal structure revealed markers consistent with higher numbers of photoreceptor cells in aging and supplemented mice. We know of no other treatment with such efficacy, highlighting the potential for prevention or amelioration of human neuropathologies that are similarly associated with oxidative stress, inflammation and cellular dysfunction. Environ. Mol. Mutagen. 57:382-404, 2016. © 2016 Wiley Periodicals, Inc. PMID:27199101

  13. The Architecture of Cross-Hemispheric Communication in the Aging Brain: Linking Behavior to Functional and Structural Connectivity

    PubMed Central

    Kragel, James E.; Madden, David J.; Cabeza, Roberto

    2012-01-01

    Contralateral recruitment remains a controversial phenomenon in both the clinical and normative populations. To investigate the neural correlates of this phenomenon, we explored the tendency for older adults to recruit prefrontal cortex (PFC) regions contralateral to those most active in younger adults. Participants were scanned with diffusion tensor imaging and functional magnetic rresonance imaging during a lateralized word matching task (unilateral vs. bilateral). Cross-hemispheric communication was measured behaviorally as greater accuracy for bilateral than unilateral trials (bilateral processing advantage [BPA]) and at the neural level by functional and structural connectivity between contralateral PFC. Compared with the young, older adults exhibited 1) greater BPAs in the behavioral task, 2) greater compensatory activity in contralateral PFC during the bilateral condition, 3) greater functional connectivity between contralateral PFC during bilateral trials, and 4) a positive correlation between fractional anisotropy in the corpus callosum and both the BPA and the functional connectivity between contralateral PFC, indicating that older adults' ability to distribute processing across hemispheres is constrained by white matter integrity. These results clarify how older adults’ ability to recruit extra regions in response to the demands of aging is mediated by existing structural architecture, and how this architecture engenders corresponding functional changes that allow subjects to meet those task demands. PMID:21653286

  14. (Pre)diabetes, brain aging, and cognition.

    PubMed

    S Roriz-Filho, Jarbas; Sá-Roriz, Ticiana M; Rosset, Idiane; Camozzato, Ana L; Santos, Antonio C; Chaves, Márcia L F; Moriguti, Júlio César; Roriz-Cruz, Matheus

    2009-05-01

    Cognitive dysfunction and dementia have recently been proven to be common (and underrecognized) complications of diabetes mellitus (DM). In fact, several studies have evidenced that phenotypes associated with obesity and/or alterations on insulin homeostasis are at increased risk for developing cognitive decline and dementia, including not only vascular dementia, but also Alzheimer's disease (AD). These phenotypes include prediabetes, diabetes, and the metabolic syndrome. Both types 1 and 2 diabetes are also important risk factors for decreased performance in several neuropsychological functions. Chronic hyperglycemia and hyperinsulinemia primarily stimulates the formation of Advanced Glucose Endproducts (AGEs), which leads to an overproduction of Reactive Oxygen Species (ROS). Protein glycation and increased oxidative stress are the two main mechanisms involved in biological aging, both being also probably related to the etiopathogeny of AD. AD patients were found to have lower than normal cerebrospinal fluid levels of insulin. Besides its traditional glucoregulatory importance, insulin has significant neurothrophic properties in the brain. How can clinical hyperinsulinism be a risk factor for AD whereas lab experiments evidence insulin to be an important neurothrophic factor? These two apparent paradoxal findings may be reconciliated by evoking the concept of insulin resistance. Whereas insulin is clearly neurothrophic at moderate concentrations, too much insulin in the brain may be associated with reduced amyloid-beta (Abeta) clearance due to competition for their common and main depurative mechanism - the Insulin-Degrading Enzyme (IDE). Since IDE is much more selective for insulin than for Abeta, brain hyperinsulinism may deprive Abeta of its main clearance mechanism. Hyperglycemia and hyperinsulinemia seems to accelerate brain aging also by inducing tau hyperphosphorylation and amyloid oligomerization, as well as by leading to widespread brain microangiopathy

  15. [The Influence of the Functional State of Brain Regulatory Structures on the Programming, Selective Regulation and Control of Cognitive Activity in Children. Report I: Neuropsychological and EEG Analysis of Age-Related Changes in Brain Regulatory Functions in Children Aged 9-12 Years].

    PubMed

    Semenova, A; Machinskaya, R I; Lomakin, D I

    2015-01-01

    Age-related changes in brain regulatory functions in children aged from 9 to 12 years with typical development were studied by means of neuropsychological and EEG analysis. The participants of the study were 107 children without learning difficulties and behavior deviations; they were devided into three groups (9-10, 10-11 and 11-12 years). The neuropsychological tests revealed nonlinear age-related changes in different executive brain functions. The group of 10-11-year-old children showed better results in programming, in- hibition of impulsive reactions and in the perception of socially relevant information than the group of 9-10- year-old children. At the same time, these children had more difficulties with selective activity regulation as compared with the younger group. The difficulties were mainly caused by switching from one element of the program to another and by retention of learned sequence of actions. These children also showed a lower level of motivation for task performance. The children aged 11-12 years had less difficulties with selective activity regulation; however, impulsive behavior was more frequent; these children also had a higher level of task performance motivation than in children aged 10-11 years. The analysis of resting state EEG revealed age-related differences in deviated EEG patterns associated with non-optimal functioning of fronto-thalamic system and hypothalamic structures. The incidence of these two types of EEG patterns was significantly higher in children aged 10-11 years as compared with children aged 9-10 years. The EEG of the groups of 10-11 and 11-12-years-old children did not show any significant differences. PMID:26485784

  16. [The Influence of the Functional State of Brain Regulatory Structures on the Programming, Selective Regulation and Control of Cognitive Activity in Children. Report I: Neuropsychological and EEG Analysis of Age-Related Changes in Brain Regulatory Functions in Children Aged 9-12 Years].

    PubMed

    Semenova, A; Machinskaya, R I; Lomakin, D I

    2015-01-01

    Age-related changes in brain regulatory functions in children aged from 9 to 12 years with typical development were studied by means of neuropsychological and EEG analysis. The participants of the study were 107 children without learning difficulties and behavior deviations; they were devided into three groups (9-10, 10-11 and 11-12 years). The neuropsychological tests revealed nonlinear age-related changes in different executive brain functions. The group of 10-11-year-old children showed better results in programming, in- hibition of impulsive reactions and in the perception of socially relevant information than the group of 9-10- year-old children. At the same time, these children had more difficulties with selective activity regulation as compared with the younger group. The difficulties were mainly caused by switching from one element of the program to another and by retention of learned sequence of actions. These children also showed a lower level of motivation for task performance. The children aged 11-12 years had less difficulties with selective activity regulation; however, impulsive behavior was more frequent; these children also had a higher level of task performance motivation than in children aged 10-11 years. The analysis of resting state EEG revealed age-related differences in deviated EEG patterns associated with non-optimal functioning of fronto-thalamic system and hypothalamic structures. The incidence of these two types of EEG patterns was significantly higher in children aged 10-11 years as compared with children aged 9-10 years. The EEG of the groups of 10-11 and 11-12-years-old children did not show any significant differences.

  17. Infant Brain Structures, Executive Function, and Attention Deficit/Hyperactivity Problems at Preschool Age. A Prospective Study

    ERIC Educational Resources Information Center

    Ghassabian, Akhgar; Herba, Catherine M.; Roza, Sabine J.; Govaert, Paul; Schenk, Jacqueline J.; Jaddoe, Vincent W.; Hofman, Albert; White, Tonya; Verhulst, Frank C.; Tiemeier, Henning

    2013-01-01

    Background: Neuroimaging findings have provided evidence for a relation between variations in brain structures and Attention Deficit/Hyperactivity Disorder (ADHD). However, longitudinal neuroimaging studies are typically confined to children who have already been diagnosed with ADHD. In a population-based study, we aimed to characterize the…

  18. Plasticity of the aging brain: new directions in cognitive neuroscience.

    PubMed

    Gutchess, Angela

    2014-10-31

    Cognitive neuroscience has revealed aging of the human brain to be rich in reorganization and change. Neuroimaging results have recast our framework around cognitive aging from one of decline to one emphasizing plasticity. Current methods use neurostimulation approaches to manipulate brain function, providing a direct test of the ways that the brain differently contributes to task performance for younger and older adults. Emerging research into emotional, social, and motivational domains provides some evidence for preservation with age, suggesting potential avenues of plasticity, alongside additional evidence for reorganization. Thus, we begin to see that aging of the brain, amidst interrelated behavioral and biological changes, is as complex and idiosyncratic as the brain itself, qualitatively changing over the life span.

  19. Prediction of brain age suggests accelerated atrophy after traumatic brain injury

    PubMed Central

    Cole, James H; Leech, Robert; Sharp, David J

    2015-01-01

    Objective The long-term effects of traumatic brain injury (TBI) can resemble observed in normal ageing, suggesting that TBI may accelerate the ageing process. We investigate this using a neuroimaging model that predicts brain age in healthy individuals and then apply it to TBI patients. We define individuals' differences in chronological and predicted structural "brain age," and test whether TBI produces progressive atrophy and how this relates to cognitive function. Methods A predictive model of normal ageing was defined using machine learning in 1,537 healthy individuals, based on magnetic resonance imaging–derived estimates of gray matter (GM) and white matter (WM). This ageing model was then applied to test 99 TBI patients and 113 healthy controls to estimate brain age. Results The initial model accurately predicted age in healthy individuals (r * 0.92). TBI brains were estimated to be "older," with a mean predicted age difference (PAD) between chronological and estimated brain age of 4.66 years (±10.8) for GM and 5.97 years (±11.22) for WM. This PAD predicted cognitive impairment and correlated strongly with the time since TBI, indicating that brain tissue loss increases throughout the chronic postinjury phase. Interpretation TBI patients' brains were estimated to be older than their chronological age. This discrepancy increases with time since injury, suggesting that TBI accelerates the rate of brain atrophy. This may be an important factor in the increased susceptibility in TBI patients for dementia and other age-associated conditions, motivating further research into the age-like effects of brain injury and other neurological diseases. PMID:25623048

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

    PubMed

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

    2015-01-01

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

  1. Molecular aging of the brain, neuroplasticity, and vulnerability to depression and other brain-related disorders.

    PubMed

    Sibille, Etienne

    2013-03-01

    The increased risk for neurodegenerative and neuropsychiatric disorders associated with extended lifespan has long suggested mechanistic links between chronological age and brain-related disorders, including depression, Recent characterizations of age-dependent gene expression changes now show that aging of the human brain engages a specific set of biological pathways along a continuous lifelong trajectory, and that the same genes that are associated with normal brain aging are also frequently and similarly implicated in depression and other brain-related disorders. These correlative observations suggest a model of age-by-disease molecular interactions, in which brain aging promotes biological changes associated with diseases, and additional environmental factors and genetic variability contribute to defining disease risk or resiliency trajectories. Here we review the characteristic features of brain aging in terms of changes in gene function over time, and then focus on evidence supporting accelerated molecular aging in depression. This proposed age-by-disease biological interaction model addresses the current gap in research between "normal" brain aging and its connection to late-life diseases. The implications of this model are profound, as it provides an investigational framework for identifying critical moderating factors, outlines opportunities for early interventions or preventions, and may form the basis for a dimensional definition of diseases that goes beyond the current categorical system.

  2. Life and death of neurons in the aging brain

    NASA Technical Reports Server (NTRS)

    Morrison, J. H.; Hof, P. R.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    Neurodegenerative disorders are characterized by extensive neuron death that leads to functional decline, but the neurobiological correlates of functional decline in normal aging are less well defined. For decades, it has been a commonly held notion that widespread neuron death in the neocortex and hippocampus is an inevitable concomitant of brain aging, but recent quantitative studies suggest that neuron death is restricted in normal aging and unlikely to account for age-related impairment of neocortical and hippocampal functions. In this article, the qualitative and quantitative differences between aging and Alzheimer's disease with respect to neuron loss are discussed, and age-related changes in functional and biochemical attributes of hippocampal circuits that might mediate functional decline in the absence of neuron death are explored. When these data are viewed comprehensively, it appears that the primary neurobiological substrates for functional impairment in aging differ in important ways from those in neurodegenerative disorders such as Alzheimer's disease.

  3. Successful brain aging: plasticity, environmental enrichment, and lifestyle.

    PubMed

    Mora, Francisco

    2013-03-01

    Aging is a physiological process that can develop without the appearance of concurrent diseases. However, very frequently, older people suffer from memory loss and an accelerated cognitive decline. Studies of the neurobiology of aging are beginning to decipher the mechanisms underlying not only the physiology of aging of the brain but also the mechanisms that make people more vulnerable to cognitive dysfunction and neurodegenerative diseases. Today we know that the aging brain retains a considerable functional plasticity, and that this plasticity is positively promoted by genes activated by different lifestyle factors. In this article some of these lifestyle factors and their mechanisms of action are reviewed, including environmental enrichment and the importance of food intake and some nutrients. Aerobic physical exercise and reduction of chronic stress are also briefly reviewed. It is proposed that lifestyle factors are powerful instruments to promote healthy and successful aging of the brain and delay the appearance of age-related cognitive deficits in elderly people.

  4. Modeling the brain morphology distribution in the general aging population

    NASA Astrophysics Data System (ADS)

    Huizinga, W.; Poot, D. H. J.; Roshchupkin, G.; Bron, E. E.; Ikram, M. A.; Vernooij, M. W.; Rueckert, D.; Niessen, W. J.; Klein, S.

    2016-03-01

    Both normal aging and neurodegenerative diseases such as Alzheimer's disease cause morphological changes of the brain. To better distinguish between normal and abnormal cases, it is necessary to model changes in brain morphology owing to normal aging. To this end, we developed a method for analyzing and visualizing these changes for the entire brain morphology distribution in the general aging population. The method is applied to 1000 subjects from a large population imaging study in the elderly, from which 900 were used to train the model and 100 were used for testing. The results of the 100 test subjects show that the model generalizes to subjects outside the model population. Smooth percentile curves showing the brain morphology changes as a function of age and spatiotemporal atlases derived from the model population are publicly available via an interactive web application at agingbrain.bigr.nl.

  5. How age of bilingual exposure can change the neural systems for language in the developing brain: a functional near infrared spectroscopy investigation of syntactic processing in monolingual and bilingual children.

    PubMed

    Jasinska, K K; Petitto, L A

    2013-10-01

    Is the developing bilingual brain fundamentally similar to the monolingual brain (e.g., neural resources supporting language and cognition)? Or, does early-life bilingual language experience change the brain? If so, how does age of first bilingual exposure impact neural activation for language? We compared how typically-developing bilingual and monolingual children (ages 7-10) and adults recruit brain areas during sentence processing using functional Near Infrared Spectroscopy (fNIRS) brain imaging. Bilingual participants included early-exposed (bilingual exposure from birth) and later-exposed individuals (bilingual exposure between ages 4-6). Both bilingual children and adults showed greater neural activation in left-hemisphere classic language areas, and additionally, right-hemisphere homologues (Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus). However, important differences were observed between early-exposed and later-exposed bilinguals in their earliest-exposed language. Early bilingual exposure imparts fundamental changes to classic language areas instead of alterations to brain regions governing higher cognitive executive functions. However, age of first bilingual exposure does matter. Later-exposed bilinguals showed greater recruitment of the prefrontal cortex relative to early-exposed bilinguals and monolinguals. The findings provide fascinating insight into the neural resources that facilitate bilingual language use and are discussed in terms of how early-life language experiences can modify the neural systems underlying human language processing.

  6. Functional brain mapping of psychopathology

    PubMed Central

    Honey, G; Fletcher, P; Bullmore, E

    2002-01-01

    In this paper, we consider the impact that the novel functional neuroimaging techniques may have upon psychiatric illness. Functional neuroimaging has rapidly developed as a powerful tool in cognitive neuroscience and, in recent years, has seen widespread application in psychiatry. Although such studies have produced evidence for abnormal patterns of brain response in association with some pathological conditions, the core pathophysiologies remain unresolved. Although imaging techniques provide an unprecedented opportunity for investigation of physiological function of the living human brain, there are fundamental questions and assumptions which remain to be addressed. In this review we examine these conceptual issues under three broad sections: (1) characterising the clinical population of interest, (2) defining appropriate levels of description of normal brain function, and (3) relating these models to pathophysiological conditions. Parallel advances in each of these questions will be required before imaging techniques can impact on clinical decisions in psychiatry. PMID:11909899

  7. Understanding How Exercise Promotes Cognitive Integrity in the Aging Brain.

    PubMed

    Laitman, Benjamin M; John, Gareth R

    2015-01-01

    Alterations in the structure and organization of the aging central nervous system (CNS), and associated functional deficits, result in cognitive decline and increase susceptibility to neurodegeneration. Age-related changes to the neurovascular unit (NVU), and their consequences for cerebrovascular function, are implicated as driving cognitive impairment during aging as well as in neurodegenerative disease. The molecular events underlying these effects are incompletely characterized. Similarly, the mechanisms underlying effects of factors that reduce the impact of aging on the brain, such as physical exercise, are also opaque. A study in this issue of PLOS Biology links the NVU to cognitive decline in the aging brain and suggests a potential underlying molecular mechanism. Notably, the study further links the protective effects of chronic exercise on cognition to neurovascular integrity during aging.

  8. Lead poisoning and brain cell function

    SciTech Connect

    Goldstein, G.W. Kennedy Institute, Baltimore, MD )

    1990-11-01

    Exposure to excessive amounts of inorganic lead during the toddler years may produce lasting adverse effects upon brain function. Maximal ingestion of lead occurs at an age when major changes are occurring in the density of brain synaptic connections. The developmental reorganization of synapses is, in part, mediated by protein kinases, and these enzymes are particularly sensitive to stimulation by lead. By inappropriately activating specific protein kinases, lead poisoning may disrupt the development of neural networks without producing overt pathological alterations. The blood-brain barrier is another potential vulnerable site for the neurotoxic action of lead. protein kinases appear to regulate the development of brain capillaries and the expression of the blood-brain barrier properties. Stimulation of protein kinase by lead may disrupt barrier development and alter the precise regulation of the neuronal environment that is required for normal brain function. Together, these findings suggest that the sensitivity of protein kinases to lead may in part underlie the brain dysfunction observed in children poisoned by this toxicant.

  9. 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

    2010-03-01

    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/.

  10. 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

    2010-03-01

    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/. PMID

  11. Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

    PubMed Central

    Zamroziewicz, Marta K.; Barbey, Aron K.

    2016-01-01

    Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition's impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition—from entire diets to specific nutrients—affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i) methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns (NBPs), along with (ii) modern indices of brain health derived from high-resolution magnetic resonance imaging (MRI). By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging. PMID:27375409

  12. ShcC proteins: brain aging and beyond.

    PubMed

    Sagi, Orli; Budovsky, Arie; Wolfson, Marina; Fraifeld, Vadim E

    2015-01-01

    To date, most studies of Shc family of signaling adaptor proteins have been focused on the near-ubiquitously expressed ShcA, indicating its relevance to age-related diseases and longevity. Although the role of the neuronal ShcC protein is much less investigated, accumulated evidence suggests its importance for neuroprotection against such aging-associated conditions as brain ischemia and oxidative stress. Here, we summarize more than decade of studies on the ShcC expression and function in normal brain, age-related brain pathologies and immune disorders with a focus on the interactions of ShcC with signaling proteins/pathways, and the possible implications of these interactions for changes associated with aging.

  13. Progesterone Receptors: Form and Function in Brain

    PubMed Central

    Brinton, Roberta Diaz; Thompson, Richard F.; Foy, Michael R.; Baudry, Michel; Wang, JunMing; Finch, Caleb E; Morgan, Todd E.; Stanczyk, Frank Z.; Pike, Christian J.; Nilsen, Jon

    2008-01-01

    Emerging data indicate that progesterone has multiple non-reproductive functions in the central nervous system to regulate cognition, mood, inflammation, mitochondrial function, neurogenesis and regeneration, myelination and recovery from traumatic brain injury. Progesterone-regulated neural responses are mediated by an array of progesterone receptors (PR) that include the classic nuclear PRA and PRB receptors and splice variants of each, the seven transmembrane domain 7TMPRβ and the membrane-associated 25-Dx PR (PGRMC1). These PRs induce classic regulation of gene expression while also transducing signaling cascades that originate at the cell membrane and ultimately activate transcription factors. Remarkably, PRs are broadly expressed throughout the brain and can be detected in every neural cell type. The distribution of PRs beyond hypothalamic borders, suggests a much broader role of progesterone in regulating neural function. Despite the large body of evidence regarding progesterone regulation of reproductive behaviors and estrogen-inducible responses as well as effects of progesterone metabolite neurosteroids, much remains to be discovered regarding the functional outcomes resulting from activation of the complex array of PRs in brain by gonadally and / or glial derived progesterone. Moreover, the impact of clinically used progestogens and developing selective PR modulators for targeted outcomes in brain is a critical avenue of investigation as the non-reproductive functions of PRs have far-reaching implications for hormone therapy to maintain neurological health and function throughout menopausal aging. PMID:18374402

  14. The Impact of Traumatic Brain Injury on the Aging Brain.

    PubMed

    Young, Jacob S; Hobbs, Jonathan G; Bailes, Julian E

    2016-09-01

    Traumatic brain injury (TBI) has come to the forefront of both the scientific and popular culture. Specifically, sports-related concussions or mild TBI (mTBI) has become the center of scientific scrutiny with a large amount of research focusing on the long-term sequela of this type of injury. As the populace continues to age, the impact of TBI on the aging brain will become clearer. Currently, reports have come to light that link TBI to neurodegenerative disorders such as Alzheimer's and Parkinson's diseases, as well as certain psychiatric diseases. Whether these associations are causations, however, is yet to be determined. Other long-term sequelae, such as chronic traumatic encephalopathy (CTE), appear to be associated with repetitive injuries. Going forward, as we gain better understanding of the pathophysiological process involved in TBI and subclinical head traumas, and individual traits that influence susceptibility to neurocognitive diseases, a clearer, more comprehensive understanding of the connection between brain injury and resultant disease processes in the aging brain will become evident. PMID:27432348

  15. Altered Proteins in the Aging Brain

    PubMed Central

    Elobeid, Adila; Libard, Sylwia; Leino, Marina; Popova, Svetlana N.

    2016-01-01

    We assessed the prevalence of common altered brain proteins in 296 cognitively unimpaired subjects ranging from age 50 to 102 years. The incidence and the stage of hyperphosphorylated-τ (HPτ), β-amyloid, α-synuclein (αS), and transactive response DNA (TDP) binding protein 43 (TDP43)-immunoreactivity (-IR) increased with age. HPτ-IR was observed in 98% of the subjects; the locus coeruleus was solely affected in 46%, and 79% of the subjects were in Braak stages a to II. β-Amyloid was seen in 47% of subjects and the Thal phase correlated with the HPτ Braak stage and age. Intermediate Alzheimer disease-related pathology (ADRP) was seen in 12%; 52% of the subjects with HPτ-IR fulfilled criteria for definite primary age-related tauopathy (PART). The incidence of concomitant pathology (αS, TDP43) did not differ between those with PART and those with ADRP but the former were younger. TDP43-IR was observed in 36%; the most frequently affected region was the medulla; αS-IR was observed in 19% of subjects. In 41% of the subjects from 80 to 89 years at death, 3 altered proteins were seen in the brain. Thus, altered proteins are common in the brains of cognitively unimpaired aged subjects; this should be considered while developing diagnostic biomarkers, particularly for identifying subjects at early stages of neurodegenerative diseases. PMID:26979082

  16. Altered Proteins in the Aging Brain.

    PubMed

    Elobeid, Adila; Libard, Sylwia; Leino, Marina; Popova, Svetlana N; Alafuzoff, Irina

    2016-04-01

    We assessed the prevalence of common altered brain proteins in 296 cognitively unimpaired subjects ranging from age 50 to 102 years. The incidence and the stage of hyperphosphorylated-τ (HPτ), β-amyloid, α-synuclein (αS), and transactive response DNA (TDP) binding protein 43 (TDP43)-immunoreactivity (-IR) increased with age. HPτ-IR was observed in 98% of the subjects; the locus coeruleus was solely affected in 46%, and 79% of the subjects were in Braak stages a to II. β-Amyloid was seen in 47% of subjects and the Thal phase correlated with the HPτ Braak stage and age. Intermediate Alzheimer disease-related pathology (ADRP) was seen in 12%; 52% of the subjects with HPτ-IR fulfilled criteria for definite primary age-related tauopathy (PART). The incidence of concomitant pathology (αS, TDP43) did not differ between those with PART and those with ADRP but the former were younger. TDP43-IR was observed in 36%; the most frequently affected region was the medulla; αS-IR was observed in 19% of subjects. In 41% of the subjects from 80 to 89 years at death, 3 altered proteins were seen in the brain. Thus, altered proteins are common in the brains of cognitively unimpaired aged subjects; this should be considered while developing diagnostic biomarkers, particularly for identifying subjects at early stages of neurodegenerative diseases. PMID:26979082

  17. Comparing Aging and Fitness Effects on Brain Anatomy.

    PubMed

    Fletcher, Mark A; Low, Kathy A; Boyd, Rachel; Zimmerman, Benjamin; Gordon, Brian A; Tan, Chin H; Schneider-Garces, Nils; Sutton, Bradley P; Gratton, Gabriele; Fabiani, Monica

    2016-01-01

    Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain's atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55-87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors. PMID:27445740

  18. Comparing Aging and Fitness Effects on Brain Anatomy.

    PubMed

    Fletcher, Mark A; Low, Kathy A; Boyd, Rachel; Zimmerman, Benjamin; Gordon, Brian A; Tan, Chin H; Schneider-Garces, Nils; Sutton, Bradley P; Gratton, Gabriele; Fabiani, Monica

    2016-01-01

    Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain's atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55-87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors.

  19. A Preliminary Study of the Effects of an Arts Education Program on Executive Function, Behavior, and Brain Structure in a Sample of Nonclinical School-Aged Children.

    PubMed

    Park, Subin; Lee, Jong-Min; Baik, Young; Kim, Kihyun; Yun, Hyuk Jin; Kwon, Hunki; Jung, Yeon-Kyung; Kim, Bung-Nyun

    2015-11-01

    The authors examined the effects of arts education on cognition, behavior, and brain of children. Twenty-nine nonclinical children participated in a 15-week arts education program that was composed of either creative movement or musical arts. Children completed the Wisconsin Card Sorting Test, clinical scales, and brain magnetic resonance imaging before and after the intervention. Following program completion, performances on the Wisconsin Card Sorting Test, the Children's Depression Inventory scores, and conduct disorder scores were significantly improved. Furthermore, cortical thickness in the left postcentral gyrus and superior parietal lobule were increased, and the mean diffusivity values in the right posterior corona radiate and superior longitudinal fasciculus were decreased. Positive correlations between changes in cognitive measurements and changes in cortical thickness were observed. This preliminary study suggests a positive effect of arts education on executive functions in association with brain changes. However, these findings must be interpreted with caution due to the noncomparative study design.

  20. Advanced BrainAGE in older adults with type 2 diabetes mellitus.

    PubMed

    Franke, Katja; Gaser, Christian; Manor, Brad; Novak, Vera

    2013-01-01

    Aging alters brain structure and function and diabetes mellitus (DM) may accelerate this process. This study investigated the effects of type 2 DM on individual brain aging as well as the relationships between individual brain aging, risk factors, and functional measures. To differentiate a pattern of brain atrophy that deviates from normal brain aging, we used the novel BrainAGE approach, which determines the complex multidimensional aging pattern within the whole brain by applying established kernel regression methods to anatomical brain magnetic resonance images (MRI). The "Brain Age Gap Estimation" (BrainAGE) score was then calculated as the difference between chronological age and estimated brain age. 185 subjects (98 with type 2 DM) completed an MRI at 3Tesla, laboratory and clinical assessments. Twenty-five subjects (12 with type 2 DM) also completed a follow-up visit after 3.8 ± 1.5 years. The estimated brain age of DM subjects was 4.6 ± 7.2 years greater than their chronological age (p = 0.0001), whereas within the control group, estimated brain age was similar to chronological age. As compared to baseline, the average BrainAGE scores of DM subjects increased by 0.2 years per follow-up year (p = 0.034), whereas the BrainAGE scores of controls did not change between baseline and follow-up. At baseline, across all subjects, higher BrainAGE scores were associated with greater smoking and alcohol consumption, higher tumor necrosis factor alpha (TNFα) levels, lower verbal fluency scores and more severe deprepession. Within the DM group, higher BrainAGE scores were associated with longer diabetes duration (r = 0.31, p = 0.019) and increased fasting blood glucose levels (r = 0.34, p = 0.025). In conclusion, type 2 DM is independently associated with structural changes in the brain that reflect advanced aging. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of abnormal patterns of brain aging associated with type 2 DM

  1. Evolution of the Aging Brain Transcriptome and Synaptic Regulation

    PubMed Central

    Dakin, Kelly A.; Vann, James M.; Isaacs, Adrian; Geula, Chengiz; Wang, Jianbin; Pan, Ying; Gabuzda, Dana H.; Li, Cheng; Prolla, Tomas A.; Yankner, Bruce A.

    2008-01-01

    Alzheimer's disease and other neurodegenerative disorders of aging are characterized by clinical and pathological features that are relatively specific to humans. To obtain greater insight into how brain aging has evolved, we compared age-related gene expression changes in the cortex of humans, rhesus macaques, and mice on a genome-wide scale. A small subset of gene expression changes are conserved in all three species, including robust age-dependent upregulation of the neuroprotective gene apolipoprotein D (APOD) and downregulation of the synaptic cAMP signaling gene calcium/calmodulin-dependent protein kinase IV (CAMK4). However, analysis of gene ontology and cell type localization shows that humans and rhesus macaques have diverged from mice due to a dramatic increase in age-dependent repression of neuronal genes. Many of these age-regulated neuronal genes are associated with synaptic function. Notably, genes associated with GABA-ergic inhibitory function are robustly age-downregulated in humans but not in mice at the level of both mRNA and protein. Gene downregulation was not associated with overall neuronal or synaptic loss. Thus, repression of neuronal gene expression is a prominent and recently evolved feature of brain aging in humans and rhesus macaques that may alter neural networks and contribute to age-related cognitive changes. PMID:18830410

  2. The Dopaminergic System in the Aging Brain of Drosophila

    PubMed Central

    White, Katherine E.; Humphrey, Dickon M.; Hirth, Frank

    2010-01-01

    Drosophila models of Parkinson's disease are characterized by two principal phenotypes: the specific loss of dopaminergic (DA) neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype Drosophila is lacking. Here we analyzed the DA system and motor behavior in aging Drosophila. DA neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of TH > mCD8::GFP and cell type-specific MARCM clones revealed that DA neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, DA neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that Drosophila show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity, and exploration behavior, but not centrophobism increase at late stages of life. Analysis of TH > Dcr2, mCD8::GFP revealed a specific effect of Dcr2 expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct DA behaviors in Drosophila. Moreover, DA neurons were maintained between early- and late life, as quantified by TH > mCD8::GFP and anti-TH labeling, indicating that adult onset, age-related degeneration of DA neurons does not occur in the aging brain of Drosophila. Taken together, our data establish baseline parameters in Drosophila for the study of Parkinson's disease as well as other disorders affecting DA neurons and movement control. PMID:21165178

  3. Poststroke Cell Therapy of the Aged Brain.

    PubMed

    Popa-Wagner, Aurel; Filfan, Madalina; Uzoni, Adriana; Pourgolafshan, Pouya; Buga, Ana-Maria

    2015-01-01

    During aging, many neurodegenerative disorders are associated with reduced neurogenesis and a decline in the proliferation of stem/progenitor cells. The development of the stem cell (SC), the regenerative therapy field, gained tremendous expectations in the diseases that suffer from the lack of treatment options. Stem cell based therapy is a promising approach to promote neuroregeneration after brain injury and can be potentiated when combined with supportive pharmacological drug treatment, especially in the aged. However, the mechanism of action for a particular grafted cell type, the optimal delivery route, doses, or time window of administration after lesion is still under debate. Today, it is proved that these protections are most likely due to modulatory mechanisms rather than the expected cell replacement. Our group proved that important differences appear in the aged brain compared with young one, that is, the accelerated progression of ischemic area, or the delayed initiation of neurological recovery. In this light, these age-related aspects should be carefully evaluated in the clinical translation of neurorestorative therapies. This review is focused on the current perspectives and suitable sources of stem cells (SCs), mechanisms of action, and the most efficient delivery routes in neurorestoration therapies in the poststroke aged environment. PMID:26347826

  4. Secrets of aging: What does a normally aging brain look like?

    PubMed Central

    2011-01-01

    Over the past half century, remarkable progress has been made in understanding the biological basis of memory and how it changes over the lifespan. An important conceptual advance during this period was the realization that normative cognitive trajectories can exist independently of dementing illness. In fact, mammals as different as rats and monkeys, who do not spontaneously develop Alzheimer’s disease, show memory impairments at advanced ages in similar domains as those observed in older humans. Thus, animal models have been particularly helpful in revealing brain mechanisms responsible for the cognitive changes that occur in aging. During these past decades, a number of empirical and technical advances enabled the discoveries that began to link age-related changes in brain function to behavior. The pace of innovation continues to accelerate today, resulting in an expanded window through which the secrets of the aging brain are being deciphered. PMID:22003369

  5. Neurotransmitter precursors and brain function.

    PubMed

    Conlay, L A; Zeisel, S H

    1982-04-01

    Brain function can be affected by the availability of dietary precursors of neurotransmitters. This occurs because the rate-limiting synthetic enzymes are not "saturated" with substrate under normal circumstances. Tyrosine affects catecholaminergic neurons that fire rapidly, whether in the brain stem to decrease blood pressure in hypertension or in the adrenal gland to increase blood pressure in hypotension, and has been used in the treatment of Parkinson's disease and depression. Choline forms acetylcholine and has been used successfully in the treatment of tardive dyskinesia and memory disorders. Tryptophan, which forms serotonin, has been used for chronic pain therapy, sleep disorders, depression, and appetite control. Although these substances may lack the potency of traditionally used agonists, they offer an increase in specificity because the enzymes necessary to convert them to neurotransmitters are found only in neurons. Precursors are also "physiological"; they are consumed as foods and, therefore, should be relatively safe therapeutic agents. PMID:6124895

  6. Eloquent Brain, Ethical Challenges: Functional Brain Mapping in Neurosurgery.

    PubMed

    Klein, Eran

    2015-06-01

    Functional brain mapping is an increasingly relied upon tool in presurgical planning and intraoperative decision making. Mapping allows personalization of structure-function relationships when surgical or other treatment of pathology puts eloquent functioning like language or vision at risk. As an innovative technology, functional brain mapping holds great promise but also raises important ethical questions. In this article, recent work in neuroethics on functional imaging and functional neurosurgery is explored and applied to functional brain mapping. Specific topics discussed in this article are incidental findings, responsible innovation, and informed consent.

  7. Brain development and aging: overlapping and unique patterns of change.

    PubMed

    Tamnes, Christian K; Walhovd, Kristine B; Dale, Anders M; Østby, Ylva; Grydeland, Håkon; Richardson, George; Westlye, Lars T; Roddey, J Cooper; Hagler, Donald J; Due-Tønnessen, Paulina; Holland, Dominic; Fjell, Anders M

    2013-03-01

    Early-life development is characterized by dramatic changes, impacting lifespan function more than changes in any other period. Developmental origins of neurocognitive late-life functions are acknowledged, but detailed longitudinal magnetic resonance imaging studies of brain maturation and direct comparisons with aging are lacking. To these aims, a novel method was used to measure longitudinal volume changes in development (n=85, 8-22 years) and aging (n=142, 60-91 years). Developmental reductions exceeded 1% annually in much of the cortex, more than double to that seen in aging, with a posterior-to-anterior gradient. Cortical reductions were greater than the subcortical during development, while the opposite held in aging. The pattern of lateral cortical changes was similar across development and aging, but the pronounced medial temporal reduction in aging was not precast in development. Converging patterns of change in adolescents and elderly, particularly in the medial prefrontal areas, suggest that late developed cortices are especially vulnerable to atrophy in aging. A key question in future research will be to disentangle the neurobiological underpinnings for the differences and the similarities between brain changes in development and aging. PMID:23246860

  8. Attention, psychomotor functions and age.

    PubMed

    Kallus, Konrad Wolfgang; Schmitt, Jeroen A J; Benton, David

    2005-12-01

    Nutrition might play an important role to ameliorate or to buffer age-related declines in attention and psychomotor functions. The assessment of nutritional effects in aged subjects has to take into account that attention and psychomotor functions can be subdivided in different functions that are differentially affected by age. This paper gives an overview of changes in different facets of attention and psychomotor functions beyond fifty as well as assessment methods for attention and psychomotor performance. It also provides a review of models to explain the pattern of changes with increasing age, and discusses the problems of high performance variance and of age related confounding variables like health status. Two different approaches are discussed that analyse a performance profile and an experimentally oriented functional microanalysis of changes in performance with respect to the effects of nutrition on attention and psychomotor functions. Addressed are examples of missing age-related deficits or even age-related superiority. Caffeine and Ginseng are considered as examples to enhance performance in older persons. Results are in accordance with data on the positive role of physical fitness for mental performance in older persons. Performance of older persons can well be enhanced by functional food components or nutritional supplementation. The effects are comparable to the effects obtained in younger groups, while there is only weak evidence for specific compensatory effects in aged persons. Finally the role of nutrition for the processes of healthy aging is discussed.

  9. Heavy Drinking Can Harm the Aging Brain

    MedlinePlus

    ... in their attention or executive function (which includes reasoning and working memory), regardless of their age, the ... The study was published Sept. 22 in Alcoholism: Clinical and Experimental Research . SOURCES: Marc Gordon, M.D., ...

  10. Age-related hearing loss: ear and brain mechanisms.

    PubMed

    Frisina, Robert D

    2009-07-01

    Loss of sensory function in the aged has serious consequences for economic productivity, quality of life, and healthcare costs in the billions each year. Understanding the neural and molecular bases will pave the way for biomedical interventions to prevent, slow, or reverse these conditions. This chapter summarizes new information regarding age changes in the auditory system involving both the ear (peripheral) and brain (central). A goal is to provide findings that have implications for understanding some common biological underpinnings that affect sensory systems, providing a basis for eventual interventions to improve overall sensory functioning, including the chemical senses.

  11. Blueberries and the Aging Brain: Beyond Antioxidants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Wild blueberries, native to North America, have been evaluated as having anti-aging properties for nerve cells and nerve cell functions such as neuromotor skills and memory. Aged animals fed blueberries in their diets for eight weeks showed improvements in short-term memory, coordination, balance, m...

  12. Dynamic imaging of brain function

    PubMed Central

    Hyder, Fahmeed

    2013-01-01

    In recent years, there have been unprecedented methodological advances in the dynamic imaging of brain activities. Electrophysiological, optical, and magnetic resonance methods now allow mapping of functional activation (or deactivation) by measurement of neuronal activity (e.g., membrane potential, ion flux, neurotransmitter flux), energy metabolism (e.g., glucose consumption, oxygen consumption, creatine kinase flux), and functional hyperemia (e.g., blood oxygenation, blood flow, blood volume). Properties of the glutamatergic synapse are used as a model to reveal activities at the nerve terminal and their associated changes in energy demand and blood flow. This approach reveals that each method measures different tissue- and/or cell-specific components with specified spatiotemporal resolution. While advantages and disadvantages of different methods are apparent and often used to supersede one another in terms of specificity and/or sensitivity, no particular technique is the optimal dynamic brain imaging method because each method is unique in some respect. Because the demand for energy substrates is a fundamental requirement for function, energy-based methods may allow quantitative dynamic imaging in vivo. However there are exclusive neurobiological insights gained by combining some of these different dynamic imaging techniques. PMID:18839085

  13. Comparing Aging and Fitness Effects on Brain Anatomy

    PubMed Central

    Fletcher, Mark A.; Low, Kathy A.; Boyd, Rachel; Zimmerman, Benjamin; Gordon, Brian A.; Tan, Chin H.; Schneider-Garces, Nils; Sutton, Bradley P.; Gratton, Gabriele; Fabiani, Monica

    2016-01-01

    Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain’s atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55–87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors. PMID:27445740

  14. Expression profiling in the aging brain: a perspective.

    PubMed

    Galvin, James E; Ginsberg, Stephen D

    2005-11-01

    To evaluate molecular events associated with the aging process in animal models and human tissues, microarray analysis is performed at the regional and cellular levels to define transcriptional patterns or mosaics that may lead to better understanding of the mechanism(s) that drive senescence. In this review, we outline the experimental and analytical issues associated with high-throughput genomic analyses in aging brain and other tissues for a comprehensive evaluation of the current state of microarray analysis in aging paradigms. Ultimately, the goal of these studies is to apply functional genomics and proteomics approaches to aging research to develop new tools to assess age in cell- and tissue-specific manners in order to develop aging biomarkers for pharmacotherapeutic interventions and disease prevention.

  15. Alpha oscillatory correlates of motor inhibition in the aged brain

    PubMed Central

    Bönstrup, Marlene; Hagemann, Julian; Gerloff, Christian; Sauseng, Paul; Hummel, Friedhelm C.

    2015-01-01

    Exerting inhibitory control is a cognitive ability mediated by functions known to decline with age. The goal of this study is to add to the mechanistic understanding of cortical inhibition during motor control in aged brains. Based on behavioral findings of impaired inhibitory control with age we hypothesized that elderly will show a reduced or a lack of EEG alpha-power increase during tasks that require motor inhibition. Since inhibitory control over movements has been shown to rely on prior motor memory formation, we investigated cortical inhibitory processes at two points in time—early after learning and after an overnight consolidation phase and hypothesized an overnight increase of inhibitory capacities. Young and elderly participants acquired a complex finger movement sequence and in each experimental session brain activity during execution and inhibition of the sequence was recorded with multi-channel EEG. We assessed cortical processes of sustained inhibition by means of task-induced changes of alpha oscillatory power. During inhibition of the learned movement, young participants showed a significant alpha power increase at the sensorimotor cortices whereas elderly did not. Interestingly, for both groups, the overnight consolidation phase improved up-regulation of alpha power during sustained inhibition. This points to deficits in the generation and enhancement of local inhibitory mechanisms at the sensorimotor cortices in aged brains. However, the alpha power increase in both groups implies neuroplastic changes that strengthen the network of alpha power generation over time in young as well as elderly brains. PMID:26528179

  16. 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.

  17. Resveratrol attenuates peripheral and brain inflammation and reduces ischemic brain injury in aged female mice.

    PubMed

    Jeong, Sae Im; Shin, Jin A; Cho, Sunghee; Kim, Hye Won; Lee, Ji Yoon; Kang, Jihee Lee; Park, Eun-Mi

    2016-08-01

    Resveratrol is known to improve metabolic dysfunction associated with obesity. Visceral obesity is a sign of aging and is considered a risk factor for ischemic stroke. In this study, we investigated the effects of resveratrol on inflammation in visceral adipose tissue and the brain and its effects on ischemic brain injury in aged female mice. Mice treated with resveratrol (0.1 mg/kg, p.o.) for 10 days showed reduced levels of interleukin-1β and tumor necrosis factor-α, as well as a reduction in the size of adipocytes in visceral adipose tissue. Resveratrol also reduced interleukin-1β and tumor necrosis factor-α protein levels and immunoglobulin G extravasation in the brain. Mice treated with resveratrol demonstrated smaller infarct size, improved neurological function, and blunted peripheral inflammation at 3 days postischemic stroke. These results showed that resveratrol counteracted inflammation in visceral adipose tissue and in the brain and reduced stroke-induced brain injury and peripheral inflammation in aged female mice. Therefore, resveratrol administration can be a valuable strategy for the prevention of age-associated and disease-provoked inflammation in postmenopausal women.

  18. Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

    PubMed

    Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

    2016-08-01

    Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction.

  19. Non-invasive brain stimulation of the aging brain: State of the art and future perspectives.

    PubMed

    Tatti, Elisa; Rossi, Simone; Innocenti, Iglis; Rossi, Alessandro; Santarnecchi, Emiliano

    2016-08-01

    Favored by increased life expectancy and reduced birth rate, worldwide demography is rapidly shifting to older ages. The golden age of aging is not only an achievement but also a big challenge because of the load of the elderly on social and medical health care systems. Moreover, the impact of age-related decline of attention, memory, reasoning and executive functions on self-sufficiency emphasizes the need of interventions to maintain cognitive abilities at a useful degree in old age. Recently, neuroscientific research explored the chance to apply Non-Invasive Brain Stimulation (NiBS) techniques (as transcranial electrical and magnetic stimulation) to healthy aging population to preserve or enhance physiologically-declining cognitive functions. The present review will update and address the current state of the art on NiBS in healthy aging. Feasibility of NiBS techniques will be discussed in light of recent neuroimaging (either structural or functional) and neurophysiological models proposed to explain neural substrates of the physiologically aging brain. Further, the chance to design multidisciplinary interventions to maximize the efficacy of NiBS techniques will be introduced as a necessary future direction. PMID:27221544

  20. 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.

  1. Describing functional diversity of brain regions and brain networks

    PubMed Central

    Anderson, Michael L.; Kinnison, Josh; Pessoa, Luiz

    2013-01-01

    Despite the general acceptance that functional specialization plays an important role in brain function, there is little consensus about its extent in the brain. We sought to advance the understanding of this question by employing a data-driven approach that capitalizes on the existence of large databases of neuroimaging data. We quantified the diversity of activation in brain regions as a way to characterize the degree of functional specialization. To do so, brain activations were classified in terms of task domains, such as vision, attention, and language, which determined a region’s functional fingerprint. We found that the degree of diversity varied considerably across the brain. We also quantified novel properties of regions and of networks that inform our understanding of several task-positive and task-negative networks described in the literature, including defining functional fingerprints for entire networks and measuring their functional assortativity, namely the degree to which they are composed of regions with similar functional fingerprints. Our results demonstrate that some brain networks exhibit strong assortativity, whereas other networks consist of relatively heterogeneous parts. In sum, rather than characterizing the contributions of individual brain regions using task-based functional attributions, we instead quantified their dispositional tendencies, and related those to each region’s affiliative properties in both task-positive and task-negative contexts. PMID:23396162

  2. Dietary amino acids and brain function.

    PubMed

    Fernstrom, J D

    1994-01-01

    Two groups of amino acids--the aromatic and the acidic amino acids--are reputed to influence brain function when their ingestion in food changes the levels of these amino acids in the brain. The aromatic amino acids (tryptophan, tyrosine, phenylalanine) are the biosynthetic precursors for the neurotransmitters serotonin, dopamine, and norepinephrine. Single meals, depending on their protein content, can rapidly influence uptake of aromatic amino acid into the brain and, as a result, directly modify their conversion to neurotransmitters. Such alterations in the production of transmitters can directly modify their release from neurons and, thus, influence brain function. The acidic amino acids glutamate and aspartate are themselves brain neurotransmitters. However, they do not have ready access to the brain from the circulation or the diet. As a result, the ingestion of proteins, which are naturally rich in aspartate and glutamate, has no effect on the level of acidic amino acid in the brain (or, thus, on brain function by this mechanism). Nevertheless, the food additives monosodium glutamate and aspartame (which contains aspartate) have been reputed to raise the level of acidic amino acid in the brain (when ingested in enormous amounts), to modify brain function, and even to cause neuronal damage. Despite such claims, a substantial body of published evidence clearly indicates that the brain is not affected by ingestion of aspartame and is affected by glutamate only when the amino acid is administered alone in extremely large doses. Therefore, when consumed in the diet neither compound presents a risk to normal brain function.

  3. Exercise, Cognitive Function, and Aging

    ERIC Educational Resources Information Center

    Barnes, Jill N.

    2015-01-01

    Increasing the lifespan of a population is often a marker of a country's success. With the percentage of the population over 65 yr of age expanding, managing the health and independence of this population is an ongoing concern. Advancing age is associated with a decrease in cognitive function that ultimately affects quality of life. Understanding…

  4. Development and Aging of the Kisspeptin–GPR54 System in the Mammalian Brain: What are the Impacts on Female Reproductive Function?

    PubMed Central

    Franceschini, Isabelle; Desroziers, Elodie

    2012-01-01

    The prominent role of the G protein coupled receptor GPR54 and its peptide ligand kisspeptin in the progression of puberty has been extensively documented in many mammalian species including humans. Kisspeptins are very potent gonadotropin-releasing hormone secretagogues produced by two main populations of neurons located in two ventral forebrain regions, the preoptic area and the arcuate nucleus. Within the last 2 years a substantial amount of data has accumulated concerning the development of these neuronal populations and their timely regulation by central and peripheral factors during fetal, neonatal, and peripubertal stages of development. This review focuses on the development of the kisspeptin–GPR54 system in the brain of female mice, rats, sheep, monkeys, and humans. We will also discuss the notion that this system represents a major target through which signals from the environment early in life can reprogram reproductive function. PMID:23543285

  5. Brain Aging in the Oldest-Old

    PubMed Central

    von Gunten, A.; Ebbing, K.; Imhof, A.; Giannakopoulos, P.; Kövari, E.

    2010-01-01

    Nonagenarians and centenarians represent a quickly growing age group worldwide. In parallel, the prevalence of dementia increases substantially, but how to define dementia in this oldest-old age segment remains unclear. Although the idea that the risk of Alzheimer's disease (AD) decreases after age 90 has now been questioned, the oldest-old still represent a population relatively resistant to degenerative brain processes. Brain aging is characterised by the formation of neurofibrillary tangles (NFTs) and senile plaques (SPs) as well as neuronal and synaptic loss in both cognitively intact individuals and patients with AD. In nondemented cases NFTs are usually restricted to the hippocampal formation, whereas the progressive involvement of the association areas in the temporal neocortex parallels the development of overt clinical signs of dementia. In contrast, there is little correlation between the quantitative distribution of SP and AD severity. The pattern of lesion distribution and neuronal loss changes in extreme aging relative to the younger-old. In contrast to younger cases where dementia is mainly related to severe NFT formation within adjacent components of the medial and inferior aspects of the temporal cortex, oldest-old individuals display a preferential involvement of the anterior part of the CA1 field of the hippocampus whereas the inferior temporal and frontal association areas are relatively spared. This pattern suggests that both the extent of NFT development in the hippocampus as well as a displacement of subregional NFT distribution within the Cornu ammonis (CA) fields may be key determinants of dementia in the very old. Cortical association areas are relatively preserved. The progression of NFT formation across increasing cognitive impairment was significantly slower in nonagenarians and centenarians compared to younger cases in the CA1 field and entorhinal cortex. The total amount of amyloid and the neuronal loss in these regions were also

  6. Delayed progesterone treatment reduces brain infarction and improves functional outcomes after ischemic stroke: a time-window study in middle-aged rats

    PubMed Central

    Yousuf, Seema; Sayeed, Iqbal; Atif, Fahim; Tang, Huiling; Wang, Jun; Stein, Donald G

    2014-01-01

    We evaluated the neuroprotective effects of delayed progesterone (PROG) treatment against ischemic stroke-induced neuronal death, inflammation, and functional deficits. We induced transient focal cerebral ischemia in male rats and administered PROG (8 mg/kg) or vehicle intraperitoneally at 3, 6, or 24 hours post occlusion, subcutaneously 5 hours later and then every 24 hours for 7 days. Behavioral outcomes were evaluated over 22 days. Infarct size and other biomarkers of injury were evaluated by cresyl violet staining, and matrix metalloproteinase-9 (MMP-9), glial fibrillary acidic protein (GFAP), and vascular endothelial growth factor (VEGF) by immunofluorescence. Progesterone treatment started at 3 and 6 hours post occlusion significantly (P<0.05) improved behavioral performance at all time points (74.01%) and reduced infarction volume (61.68%) compared with vehicle. No significant difference was observed between the 3 and 6 hour PROG treatment groups. Matrix metalloproteinase-9 and VEGF were upregulated in the PROG groups compared with vehicle. Glial fibrillary acidic protein expression was increased in the vehicle group but markedly lower in the PROG groups. Treatment delayed for 24 hours did not significantly improve functional outcomes or reduce infarction volume. We conclude that, under the right treatment conditions, PROG treatment delayed up to 6 hours can improve functional deficits and reduce brain infarction, possibly by modulating GFAP, VEGF, and MMP-9 expression. PMID:24301297

  7. Can Endocrine Disruptors Influence Neuroplasticity In The Aging Brain?

    PubMed Central

    Weiss, Bernard

    2007-01-01

    Only within the last two decades has the adult mammalian brain been recognized for its ability to generate new nerve cells and other neural structures and in essence to rewire itself. Although hippocampal structures have received the greatest scrutiny, other sites, including the cerebral cortex, also display this potential. Such processes remain active in the aging brain, although to a lesser degree. Two of the factors known to induce neurogenesis are environmental enrichment and physical activity. Gonadal hormones, however, also play crucial roles. Androgens and estrogens are both required for the preservation of cognitive function during aging and apparently help counteract the risk of Alzheimer’s disease. One overlooked threat to hormonal adequacy that requires close examination is the abundance of environmental endocrine-disrupting chemicals that interfere with gonadal function. They come in the form of estrogenic mimics, androgen mimics, anti-estrogens, anti-androgens, and in a variety of other guises. Because our brains are in continuous transition throughout the lifespan, responding both to environmental circumstances and to changing levels of gonadal steroids, endocrine-disrupting chemicals possess the potential to impair neurogenesis, and represent a hazard for the preservation of cognitive function during the later stages of the life cycle. PMID:17350099

  8. Promoting motor function by exercising the brain.

    PubMed

    Perrey, Stephane

    2013-01-01

    Exercise represents a behavioral intervention that enhances brain health and motor function. The increase in cerebral blood volume in response to physical activity may be responsible for improving brain function. Among the various neuroimaging techniques used to monitor brain hemodynamic response during exercise, functional near-infrared spectroscopy could facilitate the measurement of task-related cortical responses noninvasively and is relatively robust with regard to the subjects' motion. Although the components of optimal exercise interventions have not been determined, evidence from animal and human studies suggests that aerobic exercise with sufficiently high intensity has neuroprotective properties and promotes motor function. This review provides an insight into the effect of physical activity (based on endurance and resistance exercises) on brain function for producing movement. Since most progress in the study of brain function has come from patients with neurological disorders (e.g., stroke and Parkinson's patients), this review presents some findings emphasizing training paradigms for restoring motor function. PMID:24961309

  9. Brain aging and mitochondria-targeted plastoquinone antioxidants of SkQ-type.

    PubMed

    Isaev, N K; Stelmashook, E V; Stelmashook, N N; Sharonova, I N; Skrebitsky, V G

    2013-03-01

    Normal brain aging leads to decrease in cognitive functions, shrink in brain volume, loss of nerve fibers and degenerating myelin, reduction in length and branching of dendrites, partial loss of synapses, and reduction in expression of genes that play central roles in synaptic plasticity, vesicular transport, and mitochondrial functioning. Impaired mitochondrial functions and mitochondrial reactive oxygen species can contribute to the damage of these genes in aging cerebral cortex. This review discusses the possibility of using mitochondria-targeted antioxidants to slow the processes of brain aging. PMID:23586724

  10. Social support, stress and the aging brain.

    PubMed

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress. PMID:26060327

  11. Social support, stress and the aging brain.

    PubMed

    Sherman, Stephanie M; Cheng, Yen-Pi; Fingerman, Karen L; Schnyer, David M

    2016-07-01

    Social support benefits health and well-being in older individuals, however the mechanism remains poorly understood. One proposal, the stress-buffering hypothesis states social support 'buffers' the effects of stress on health. Alternatively, the main effect hypothesis suggests social support independently promotes health. We examined the combined association of social support and stress on the aging brain. Forty healthy older adults completed stress questionnaires, a social network interview and structural MRI to investigate the amygdala-medial prefrontal cortex circuitry, which is implicated in social and emotional processing and negatively affected by stress. Social support was positively correlated with right medial prefrontal cortical thickness while amygdala volume was negatively associated with social support and positively related to stress. We examined whether the association between social support and amygdala volume varied across stress level. Stress and social support uniquely contribute to amygdala volume, which is consistent with the health benefits of social support being independent of stress.

  12. 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

  13. 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.

  14. The Influence of the Brain on Overpopulation, Ageing and Dependency.

    ERIC Educational Resources Information Center

    Cape, Ronald D. T.

    1989-01-01

    With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

  15. The Bilingual Brain as Revealed by Functional Neuroimaging.

    ERIC Educational Resources Information Center

    Abutalebi, Jubin; Cappa, Stefano F.; Perani, Daniela

    2001-01-01

    Functional neuroimaging of bilinguals and monolinguals used in conjunction with experimental cognitive tasks has been successful in establishing functional specialization as a principle of brain organization in humans. Consistent results show that attained proficiency and possibly language exposure are more important than age of acquisition as a…

  16. AMPK Function in Aging Process.

    PubMed

    Ruiz, Rocío; Pérez-Villegas, Eva María; Manuel Carrión, Ángel

    2016-01-01

    Aging involves the progressive deterioration of physiological functions, diminishing the individual's capacity for survival. Indeed, aging is the main risk factor for cancer, diabetes, cardiovascular disorders and neurodegenerative diseases. The discovery that the rate of aging is controlled by conserved genetic and biochemical pathways represented an unprecedented advance in aging research. The AMPK protein is a metabolic sensor that acts as a qualified cellular housekeeper, as well as controlling energy homeostasis and resistance to stress. Thus, the correct regulation of this factor enhances health and survival. In this manuscript we will review the molecular pathways regulated by AMPK that are related to the aging process, paying special attention to mitochondrial dysfunction, metabolic deregulation, cell senescence and autophagy.

  17. Brain plasticity and motor practice in cognitive aging

    PubMed Central

    Cai, Liuyang; Chan, John S. Y.; Yan, Jin H.; Peng, Kaiping

    2014-01-01

    For more than two decades, there have been extensive studies of experience-based neural plasticity exploring effective applications of brain plasticity for cognitive and motor development. Research suggests that human brains continuously undergo structural reorganization and functional changes in response to stimulations or training. From a developmental point of view, the assumption of lifespan brain plasticity has been extended to older adults in terms of the benefits of cognitive training and physical therapy. To summarize recent developments, first, we introduce the concept of neural plasticity from a developmental perspective. Secondly, we note that motor learning often refers to deliberate practice and the resulting performance enhancement and adaptability. We discuss the close interplay between neural plasticity, motor learning and cognitive aging. Thirdly, we review research on motor skill acquisition in older adults with, and without, impairments relative to aging-related cognitive decline. Finally, to enhance future research and application, we highlight the implications of neural plasticity in skills learning and cognitive rehabilitation for the aging population. PMID:24653695

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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

  3. Efficiency and cost of economical brain functional networks.

    PubMed

    Achard, Sophie; Bullmore, Ed

    2007-02-01

    Brain anatomical networks are sparse, complex, and have economical small-world properties. We investigated the efficiency and cost of human brain functional networks measured using functional magnetic resonance imaging (fMRI) in a factorial design: two groups of healthy old (N = 11; mean age = 66.5 years) and healthy young (N = 15; mean age = 24.7 years) volunteers were each scanned twice in a no-task or "resting" state following placebo or a single dose of a dopamine receptor antagonist (sulpiride 400 mg). Functional connectivity between 90 cortical and subcortical regions was estimated by wavelet correlation analysis, in the frequency interval 0.06-0.11 Hz, and thresholded to construct undirected graphs. These brain functional networks were small-world and economical in the sense of providing high global and local efficiency of parallel information processing for low connection cost. Efficiency was reduced disproportionately to cost in older people, and the detrimental effects of age on efficiency were localised to frontal and temporal cortical and subcortical regions. Dopamine antagonism also impaired global and local efficiency of the network, but this effect was differentially localised and did not interact with the effect of age. Brain functional networks have economical small-world properties-supporting efficient parallel information transfer at relatively low cost-which are differently impaired by normal aging and pharmacological blockade of dopamine transmission.

  4. Oxidative Stress, Aging and CNS disease in the Canine Model of Human Brain Aging

    PubMed Central

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    SYNOPSIS Decline in cognitive functions that accompany aging in dogs may have a biological basis, and many of the disorders associated with aging in canines may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of both laboratory and clinical studies – antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs. However, determining all effective compounds and combinations, dosage ranges, as well as when to initiate intervention and long term effects constitute gaps in our current knowledge. PMID:18249248

  5. Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging.

    PubMed

    Head, Elizabeth; Rofina, Jaime; Zicker, Steven

    2008-01-01

    Decline in cognitive functions that accompany aging in dogs may have a biologic basis, and many of the disorders associated with aging in dogs may be mitigated through dietary modifications that incorporate specific nutraceuticals. Based on previous research and the results of laboratory and clinical studies, antioxidants may be one class of nutraceutical that provides benefits to aged dogs. Brains of aged dogs accumulate oxidative damage to proteins and lipids, which may lead to dysfunction of neuronal cells. The production of free radicals and lack of increase in compensatory antioxidant enzymes may lead to detrimental modifications to important macromolecules within neurons. Reducing oxidative damage through food ingredients rich in a broad spectrum of antioxidants significantly improves, or slows the decline of, learning and memory in aged dogs.

  6. 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)

  7. The Ageing Brain: Age-dependent changes in the electroencephalogram during propofol and sevoflurane general anaesthesia

    PubMed Central

    Purdon, P. L.; Pavone, K. J.; Akeju, O.; Smith, A. C.; Sampson, A. L.; Lee, J.; Zhou, D. W.; Solt, K.; Brown, E. N.

    2015-01-01

    Background Anaesthetic drugs act at sites within the brain that undergo profound changes during typical ageing. We postulated that anaesthesia-induced brain dynamics observed in the EEG change with age. Methods We analysed the EEG in 155 patients aged 18–90 yr who received propofol (n=60) or sevoflurane (n=95) as the primary anaesthetic. The EEG spectrum and coherence were estimated throughout a 2 min period of stable anaesthetic maintenance. Age-related effects were characterized by analysing power and coherence as a function of age using linear regression and by comparing the power spectrum and coherence in young (18- to 38-yr-old) and elderly (70- to 90-yr-old) patients. Results Power across all frequency bands decreased significantly with age for both propofol and sevoflurane; elderly patients showed EEG oscillations ∼2- to 3-fold smaller in amplitude than younger adults. The qualitative form of the EEG appeared similar regardless of age, showing prominent alpha (8–12 Hz) and slow (0.1–1 Hz) oscillations. However, alpha band dynamics showed specific age-related changes. In elderly compared with young patients, alpha power decreased more than slow power, and alpha coherence and peak frequency were significantly lower. Older patients were more likely to experience burst suppression. Conclusions These profound age-related changes in the EEG are consistent with known neurobiological and neuroanatomical changes that occur during typical ageing. Commercial EEG-based depth-of-anaesthesia indices do not account for age and are therefore likely to be inaccurate in elderly patients. In contrast, monitoring the unprocessed EEG and its spectrogram can account for age and individual patient characteristics. PMID:26174300

  8. The beneficial effects of tree nuts on the aging brain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary patterns may play an important role in protecting the brain from the cellular and cognitive dysfunction associated with the aging process and neurodegenerative diseases. Tree nuts are showing promise as possible dietary interventions for age-related brain dysfunction. Tree nuts are an impo...

  9. How age of acquisition influences brain architecture in bilinguals

    PubMed Central

    Wei, Miao; Joshi, Anand A.; Zhang, Mingxia; Mei, Leilei; Manis, Franklin R.; He, Qinghua; Beattie, Rachel L.; Xue, Gui; Shattuck, David W.; Leahy, Richard M.; Xue, Feng; Houston, Suzanne M.; Chen, Chuansheng; Dong, Qi; Lu, Zhong-Lin

    2016-01-01

    In the present study, we explored how Age of Acquisition (AoA) of L2 affected brain structures in bilingual individuals. Thirty-six native English speakers who were bilingual were scanned with high resolution MRI. After MRI signal intensity inhomogeneity correction, we applied both voxel-based morphometry (VBM) and surface-based morphometry (SBM) approaches to the data. VBM analysis was performed using FSL’s standard VBM processing pipeline. For the SBM analysis, we utilized a semi-automated sulci delineation procedure, registered the brains to an atlas, and extracted measures of twenty four pre-selected regions of interest. We addressed three questions: (1) Which areas are more susceptible to differences in AoA? (2) How do AoA, proficiency and current level of exposure work together in predicting structural differences in the brain? And (3) What is the direction of the effect of AoA on regional volumetric and surface measures? Both VBM and SBM results suggested that earlier second language exposure was associated with larger volumes in the right parietal cortex. Consistently, SBM showed that the cortical area of the right superior parietal lobule increased as AoA decreased. In contrast, in the right pars orbitalis of the inferior frontal gyrus, AoA, proficiency, and current level of exposure are equally important in accounting for the structural differences. We interpret our results in terms of current theory and research on the effects of L2 learning on brain structures and functions. PMID:27695193

  10. The role of the brain in female reproductive aging.

    PubMed

    Downs, Jodi L; Wise, Phyllis M

    2009-02-01

    In middle-aged women, follicular depletion is a critical factor mediating the menopausal transition; however, all levels of the hypothalamic-pituitary-gonadal (HPG) axis contribute to the age-related decline in reproductive function. To help elucidate the complex interactions between the ovary and brain during middle-age that lead to the onset of the menopause, we utilize animal models which share striking similarities in reproductive physiology. Our results show that during middle-age, prior to any overt irregularities in estrous cyclicity, the ability of 17beta-estradiol (E(2)) to modulate the cascade of neurochemical events required for preovulatory gonadotropin-releasing hormone (GnRH) release and a luteinizing hormone (LH) surge is diminished. Middle-aged female rats experience a delay in and an attenuation of LH release in response to E(2). Additionally, although we do not observe a decrease in GnRH neuron number until a very advanced age, E(2)-mediated GnRH neuronal activation declines during the earliest stages of age-related reproductive decline. Numerous hypothalamic neuropeptides and neurochemical stimulatory inputs (i.e., glutamate, norepinephrine (NE), and vasoactive intestinal peptide (VIP)) that drive the E(2)-mediated GnRH/LH surge appear to dampen with age or lack the precise temporal coordination required for a specific pattern of GnRH secretion, while inhibitory signals such as gamma-aminobutyric acid (GABA) and opioid peptides remain unchanged or elevated during the afternoon of proestrus. These changes, occurring at the level of the hypothalamus, lead to irregular estrous cycles and, ultimately, the cessation of reproductive function. Taken together, our studies indicate that the hypothalamus is an important contributor to age-related female reproductive decline.

  11. Age sensitivity of behavioral tests and brain substrates of normal aging in mice.

    PubMed

    Kennard, John A; Woodruff-Pak, Diana S

    2011-01-01

    Knowledge of age sensitivity, the capacity of a behavioral test to reliably detect age-related changes, has utility in the design of experiments to elucidate processes of normal aging. We review the application of these tests in studies of normal aging and compare and contrast the age sensitivity of the Barnes maze, eyeblink classical conditioning, fear conditioning, Morris water maze, and rotorod. These tests have all been implemented to assess normal age-related changes in learning and memory in rodents, which generalize in many cases to age-related changes in learning and memory in all mammals, including humans. Behavioral assessments are a valuable means to measure functional outcomes of neuroscientific studies of aging. Highlighted in this review are the attributes and limitations of these measures in mice in the context of age sensitivity and processes of brain aging. Attributes of these tests include reliability and validity as assessments of learning and memory, well-defined neural substrates, and sensitivity to neural and pharmacological manipulations and disruptions. These tests engage the hippocampus and/or the cerebellum, two structures centrally involved in learning and memory that undergo functional and anatomical changes in normal aging. A test that is less well represented in studies of normal aging, the context pre-exposure facilitation effect (CPFE) in fear conditioning, is described as a method to increase sensitivity of contextual fear conditioning to changes in the hippocampus. Recommendations for increasing the age sensitivity of all measures of normal aging in mice are included, as well as a discussion of the potential of the under-studied CPFE to advance understanding of subtle hippocampus-mediated phenomena.

  12. Simple models of human brain functional networks.

    PubMed

    Vértes, Petra E; Alexander-Bloch, Aaron F; Gogtay, Nitin; Giedd, Jay N; Rapoport, Judith L; Bullmore, Edward T

    2012-04-10

    Human brain functional networks are embedded in anatomical space and have topological properties--small-worldness, modularity, fat-tailed degree distributions--that are comparable to many other complex networks. Although a sophisticated set of measures is available to describe the topology of brain networks, the selection pressures that drive their formation remain largely unknown. Here we consider generative models for the probability of a functional connection (an edge) between two cortical regions (nodes) separated by some Euclidean distance in anatomical space. In particular, we propose a model in which the embedded topology of brain networks emerges from two competing factors: a distance penalty based on the cost of maintaining long-range connections; and a topological term that favors links between regions sharing similar input. We show that, together, these two biologically plausible factors are sufficient to capture an impressive range of topological properties of functional brain networks. Model parameters estimated in one set of functional MRI (fMRI) data on normal volunteers provided a good fit to networks estimated in a second independent sample of fMRI data. Furthermore, slightly detuned model parameters also generated a reasonable simulation of the abnormal properties of brain functional networks in people with schizophrenia. We therefore anticipate that many aspects of brain network organization, in health and disease, may be parsimoniously explained by an economical clustering rule for the probability of functional connectivity between different brain areas.

  13. Increased Learning and Brain Long-Term Potentiation in Aged Mice Lacking DNA Polymerase μ

    PubMed Central

    Lucas, Daniel; Delgado-García, José M.; Escudero, Beatriz; Albo, Carmen; Aza, Ana; Acín-Pérez, Rebeca; Torres, Yaima; Moreno, Paz; Enríquez, José Antonio; Samper, Enrique; Blanco, Luis; Fairén, Alfonso

    2013-01-01

    A definitive consequence of the aging process is the progressive deterioration of higher cognitive functions. Defects in DNA repair mechanisms mostly result in accelerated aging and reduced brain function. DNA polymerase µ is a novel accessory partner for the non-homologous end-joining DNA repair pathway for double-strand breaks, and its deficiency causes reduced DNA repair. Using associative learning and long-term potentiation experiments, we demonstrate that Polµ−/− mice, however, maintain the ability to learn at ages when wild-type mice do not. Expression and biochemical analyses suggest that brain aging is delayed in Polµ−/− mice, being associated with a reduced error-prone DNA oxidative repair activity and a more efficient mitochondrial function. This is the first example in which the genetic ablation of a DNA-repair function results in a substantially better maintenance of learning abilities, together with fewer signs of brain aging, in old mice. PMID:23301049

  14. Functional brain network changes associated with maintenance of cognitive function in multiple sclerosis.

    PubMed

    Helekar, Santosh A; Shin, Jae C; Mattson, Brandi J; Bartley, Krystle; Stosic, Milena; Saldana-King, Toni; Montague, P Read; Hutton, George J

    2010-01-01

    In multiple sclerosis (MS) functional changes in connectivity due to cortical reorganization could lead to cognitive impairment (CI), or reflect a re-adjustment to reduce the clinical effects of widespread tissue damage. Such alterations in connectivity could result in changes in neural activation as assayed by executive function tasks. We examined cognitive function in MS patients with mild to moderate CI and age-matched controls. We evaluated brain activity using functional magnetic resonance imaging (fMRI) during the successful performance of the Wisconsin card sorting (WCS) task by MS patients, showing compensatory maintenance of normal function, as measured by response latency and error rate. To assess changes in functional connectivity throughout the brain, we performed a global functional brain network analysis by computing voxel-by-voxel correlations on the fMRI time series data and carrying out a hierarchical cluster analysis. We found that during the WCS task there is a significant reduction in the number of smaller size brain functional networks, and a change in the brain areas representing the nodes of these networks in MS patients compared to age-matched controls. There is also a concomitant increase in the strength of functional connections between brain loci separated at intermediate-scale distances in these patients. These functional alterations might reflect compensatory neuroplastic reorganization underlying maintenance of relatively normal cognitive function in the face of white matter lesions and cortical atrophy produced by MS.

  15. Perspectives on Aging Vestibular Function.

    PubMed

    Anson, Eric; Jeka, John

    2015-01-01

    Much is known about age-related anatomical changes in the vestibular system. Knowledge regarding how vestibular anatomical changes impact behavior for older adults continues to grow, in line with advancements in diagnostic testing. However, despite advancements in clinical diagnostics, much remains unknown about the functional impact that an aging vestibular system has on daily life activities such as standing and walking. Modern diagnostic tests are very good at characterizing neural activity of the isolated vestibular system, but the tests themselves are artificial and do not reflect the multisensory aspects of natural human behavior. Also, the majority of clinical diagnostic tests are passively applied because active behavior can enhance performance. In this perspective paper, we review anatomical and behavioral changes associated with an aging vestibular system and highlight several areas where a more functionally relevant perspective can be taken. For postural control, a multisensory perturbation approach could be used to bring balance rehabilitation into the arena of precision medicine. For walking and complex gaze stability, this may result in less physiologically specific impairments, but the trade-off would be a greater understanding of how the aging vestibular system truly impacts the daily life of older adults. PMID:26779116

  16. Microglial cell dysregulation in brain aging and neurodegeneration

    PubMed Central

    von Bernhardi, Rommy; Eugenín-von Bernhardi, Laura; Eugenín, Jaime

    2015-01-01

    Aging is the main risk factor for neurodegenerative diseases. In aging, microglia undergoes phenotypic changes compatible with their activation. Glial activation can lead to neuroinflammation, which is increasingly accepted as part of the pathogenesis of neurodegenerative diseases, including Alzheimer’s disease (AD). We hypothesize that in aging, aberrant microglia activation leads to a deleterious environment and neurodegeneration. In aged mice, microglia exhibit an increased expression of cytokines and an exacerbated inflammatory response to pathological changes. Whereas LPS increases nitric oxide (NO) secretion in microglia from young mice, induction of reactive oxygen species (ROS) predominates in older mice. Furthermore, there is accumulation of DNA oxidative damage in mitochondria of microglia during aging, and also an increased intracellular ROS production. Increased ROS activates the redox-sensitive nuclear factor kappa B, which promotes more neuroinflammation, and can be translated in functional deficits, such as cognitive impairment. Mitochondria-derived ROS and cathepsin B, are also necessary for the microglial cell production of interleukin-1β, a key inflammatory cytokine. Interestingly, whereas the regulatory cytokine TGFβ1 is also increased in the aged brain, neuroinflammation persists. Assessing this apparent contradiction, we have reported that TGFβ1 induction and activation of Smad3 signaling after inflammatory stimulation are reduced in adult mice. Other protective functions, such as phagocytosis, although observed in aged animals, become not inducible by inflammatory stimuli and TGFβ1. Here, we discuss data suggesting that mitochondrial and endolysosomal dysfunction could at least partially mediate age-associated microglial cell changes, and, together with the impairment of the TGFβ1-Smad3 pathway, could result in the reduction of protective activation and the facilitation of cytotoxic activation of microglia, resulting in the promotion of

  17. Docosahexaenoic Acid and the Aging Brain1–3

    PubMed Central

    Lukiw, Walter J.; Bazan, Nicolas G.

    2008-01-01

    The dietary essential PUFA docosahexaenoic acid [DHA; 22:6(n-3)] is a critical contributor to cell structure and function in the nervous system, and deficits in DHA abundance are associated with cognitive decline during aging and in neurodegenerative disease. Recent studies underscore the importance of DHA-derived neuroprotectin D1 (NPD1) in the homeostatic regulation of brain cell survival and repair involving neurotrophic, antiapoptotic and antiinflammatory signaling. Emerging evidence suggests that NPD1 synthesis is activated by growth factors and neurotrophins. Evolving research indicates that NPD1 has important determinant and regulatory interactions with the molecular-genetic mechanisms affecting β-amyloid precursor protein (βAPP) and amyloid beta (Aβ) peptide neurobiology. Deficits in DHA or its peroxidation appear to contribute to inflammatory signaling, apoptosis, and neuronal dysfunction in Alzheimer disease (AD), a common and progressive age-related neurological disorder unique to structures and processes of the human brain. This article briefly reviews our current understanding of the interactions of DHA and NPD1 on βAPP processing and Aβ peptide signaling and how this contributes to oxidative and pathogenic processes characteristic of aging and AD pathology. PMID:19022980

  18. Forthergillian Lecture. Imaging human brain function.

    PubMed

    Frackowiak, R S

    The non-invasive brain scanning techniques introduced a quarter of a century ago have become crucial for diagnosis in clinical neurology. They have also been used to investigate brain function and have provided information about normal activity and pathogenesis. They have been used to investigate functional specialization in the brain and how specialized areas communicate to generate complex integrated functions such as speech, memory, the emotions and so on. The phenomenon of brain plasticity is poorly understood and yet clinical neurologists are aware, from everyday observations, that spontaneous recovery from brain lesions is common. An improved understanding of the mechanisms of recovery may generate new therapeutic strategies and indicate ways of modulating mechanisms that promote plastic compensation for loss of function. The main methods used to investigate these issues are positron emission tomography and magnetic resonance imaging (M.R.I.). M.R.I. is also used to map brain structure. The techniques of functional brain mapping and computational morphometrics depend on high performance scanners and a validated set of analytic statistical procedures that generate reproducible data and meaningful inferences from brain scanning data. The motor system presents a good paradigm to illustrate advances made by scanning towards an understanding of plasticity at the level of brain areas. The normal motor system is organized in a nested hierarchy. Recovery from paralysis caused by internal capsule strokes involves functional reorganization manifesting itself as changed patterns of activity in the component brain areas of the normal motor system. The pattern of plastic modification depends in part on patterns of residual or disturbed connectivity after brain injury. Therapeutic manipulations in patients with Parkinson's disease using deep brain stimulation, dopaminergic agents or fetal mesencephalic transplantation provide a means to examine mechanisms underpinning

  19. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    PubMed

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.

  20. Modeling of functional brain imaging data

    NASA Astrophysics Data System (ADS)

    Horwitz, Barry

    1999-03-01

    The richness and complexity of data sets obtained from functional neuroimaging studies of human cognitive behavior, using techniques such as positron emission tomography and functional magnetic resonance imaging, have until recently not been exploited by computational neural modeling methods. In this article, following a brief introduction to functional neuroimaging methodology, two neural modeling approaches for use with functional brain imaging data are described. One, which uses structural equation modeling, examines the effective functional connections between various brain regions during specific cognitive tasks. The second employs large-scale neural modeling to relate functional neuroimaging signals in multiple, interconnected brain regions to the underlying neurobiological time-varying activities in each region. These two modeling procedures are illustrated using a visual processing paradigm.

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

    PubMed Central

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

    2016-01-01

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

  2. HRT and its effect on normal ageing of the brain and dementia

    PubMed Central

    Compton, Jacqueline; van Amelsvoort, Therese; Murphy, Declan

    2001-01-01

    There are significant gender differences in human brain disease. For example, females are significantly more likely to suffer from Alzheimer's disease (AD) than men (even after correcting for differences in life expectancy), and females on hormone replacement therapy (HRT) are significantly less likely to suffer from Alzheimer's disease than women who do not take HRT. However the neurobiological basis to these differences in clinical brain disease were unknown until relatively recently. In this review we will discuss results of studies that show; (i) gender differences in human brain disease are most likely to be explained by gender differences in brain development and ageing; (ii) sex steroids have a significant effect on the brain; (iii) sex steroids are crucial to the development and ageing of brain regions affected in age-related brain diseases (for example AD); (iv) sex steroids interact with neuronal networks and chemical systems at many different levels; (v) sex steroids affect cognitive function in elderly women. Thus, the current literature supports the hypothesis that sex steroids can modulate brain ageing, and this provides a neurobiological explanation for the significantly higher prevalence of AD in females who do not take HRT, and may lead to new treatment approaches for age-related brain disease including AD. PMID:11736875

  3. 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.

  4. Redox proteomics and the dynamic molecular landscape of the aging brain.

    PubMed

    Perluigi, Marzia; Swomley, Aaron M; Butterfield, D Allan

    2014-01-01

    It is well established that the risk to develop neurodegenerative disorders increases with chronological aging. Accumulating studies contributed to characterize the age-dependent changes either at gene and protein expression level which, taken together, show that aging of the human brain results from the combination of the normal decline of multiple biological functions with environmental factors that contribute to defining disease risk of late-life brain disorders. Finding the "way out" of the labyrinth of such complex molecular interactions may help to fill the gap between "normal" brain aging and development of age-dependent diseases. To this purpose, proteomics studies are a powerful tool to better understand where to set the boundary line of healthy aging and age-related disease by analyzing the variation of protein expression levels and the major post translational modifications that determine "protein" physio/pathological fate. Increasing attention has been focused on oxidative modifications due to the crucial role of oxidative stress in aging, in addition to the fact that this type of modification is irreversible and may alter protein function. Redox proteomics studies contributed to decipher the complexity of brain aging by identifying the proteins that were increasingly oxidized and eventually dysfunctional as a function of age. The purpose of this review is to summarize the most important findings obtained by applying proteomics approaches to murine models of aging with also a brief overview of some human studies, in particular those related to dementia.

  5. Scale-Free Brain Functional Networks

    NASA Astrophysics Data System (ADS)

    Eguíluz, Victor M.; Chialvo, Dante R.; Cecchi, Guillermo A.; Baliki, Marwan; Apkarian, A. Vania

    2005-01-01

    Functional magnetic resonance imaging is used to extract functional networks connecting correlated human brain sites. Analysis of the resulting networks in different tasks shows that (a)the distribution of functional connections, and the probability of finding a link versus distance are both scale-free, (b)the characteristic path length is small and comparable with those of equivalent random networks, and (c)the clustering coefficient is orders of magnitude larger than those of equivalent random networks. All these properties, typical of scale-free small-world networks, reflect important functional information about brain states.

  6. Chronic Anticholinergic Use and the Aging Brain

    PubMed Central

    Cai, Xueya; Campbell, Noll; Khan, Babar; Callahan, Chris; Boustani, Malaz

    2012-01-01

    Background Older Americans are facing an epidemic of chronic diseases and are thus exposed to anticholinergics (AC) that might negatively affect their risk of developing mild cognitive impairment (MCI) or dementia. Objective Investigate the association between impairment in cognitive function and previous AC exposure. Design A retrospective cohort study. Setting Primary care clinics in Indianapolis, Indiana. Participants 3690 older adults who have undergone cognitive assessment and had a one-year medication dispensing record. Outcome Cognitive function was measured in two sequential steps; a two-step screening process followed by a formal diagnostic process for participants with positive screening results. Exposure Three patterns of AC exposure were defined by the duration of AC exposure, the number of AC medications dispensed at the same time, and the severity of AC effects as determined by the Anticholinergic Cognitive Burden List. Results In comparison to older adults with no anticholinergic exposure and after adjusting for age, race, gender, and underlying comorbidity, the odds ratio (OR) for having a diagnosis of MCI was 2.73 (95% confidence interval, CI; 1.27, 5.87) among older adults who were exposed to at least three possible anticholinergic for at least 90 days; and the OR for having dementia was 0.43 (95% CI; 0.10, 1.81). Conclusion Exposure to medications with severe anticholinergic cognitive burden may be a risk factor for developing MCI. PMID:23183138

  7. Developmental changes in brain activation and functional connectivity during response inhibition in the early childhood brain.

    PubMed

    Mehnert, Jan; Akhrif, Atae; Telkemeyer, Silke; Rossi, Sonja; Schmitz, Christoph H; Steinbrink, Jens; Wartenburger, Isabell; Obrig, Hellmuth; Neufang, Susanne

    2013-11-01

    Response inhibition is an attention function which develops relatively early during childhood. Behavioral data suggest that by the age of 3, children master the basic task requirements for the assessment of response inhibition but performance improves substantially until the age of 7. The neuronal mechanisms underlying these developmental processes, however, are not well understood. In this study, we examined brain activation patterns and behavioral performance of children aged between 4 and 6 years compared to adults by applying a go/no-go paradigm during near-infrared spectroscopy (NIRS) brain imaging. We furthermore applied task-independent functional connectivity measures to the imaging data to identify maturation of intrinsic neural functional networks. We found a significant group×condition related interaction in terms of inhibition-related reduced right fronto-parietal activation in children compared to adults. In contrast, motor-related activation did not differ between age groups. Functional connectivity analysis revealed that in the children's group, short-range coherence within frontal areas was stronger, and long-range coherence between frontal and parietal areas was weaker, compared to adults. Our findings show that in children aged from 4 to 6 years fronto-parietal brain maturation plays a crucial part in the cognitive development of response inhibition. PMID:23265620

  8. Role of walnuts in maintaining brain health with age.

    PubMed

    Poulose, Shibu M; Miller, Marshall G; Shukitt-Hale, Barbara

    2014-04-01

    Because of the combination of population growth and population aging, increases in the incidence of chronic neurodegenerative disorders have become a societal concern, both in terms of decreased quality of life and increased financial burden. Clinical manifestation of many of these disorders takes years, with the initiation of mild cognitive symptoms leading to behavioral problems, dementia and loss of motor functions, the need for assisted living, and eventual death. Lifestyle factors greatly affect the progression of cognitive decline, with high-risk behaviors including unhealthy diet, lack of exercise, smoking, and exposure to environmental toxins leading to enhanced oxidative stress and inflammation. Although there exists an urgent need to develop effective treatments for age-related cognitive decline and neurodegenerative disease, prevention strategies have been underdeveloped. Primary prevention in many of these neurodegenerative diseases could be achieved earlier in life by consuming a healthy diet, rich in antioxidant and anti-inflammatory phytochemicals, which offers one of the most effective and least expensive ways to address the crisis. English walnuts (Juglans regia L.) are rich in numerous phytochemicals, including high amounts of polyunsaturated fatty acids, and offer potential benefits to brain health. Polyphenolic compounds found in walnuts not only reduce the oxidant and inflammatory load on brain cells but also improve interneuronal signaling, increase neurogenesis, and enhance sequestration of insoluble toxic protein aggregates. Evidence for the beneficial effects of consuming a walnut-rich diet is reviewed in this article. PMID:24500933

  9. Exploring age-related brain degeneration in meditation practitioners.

    PubMed

    Luders, Eileen

    2014-01-01

    A growing body of research suggests that meditation practices are associated with substantial psychological as well as physiological benefits. In searching for the biological mechanisms underlying the beneficial impact of meditation, studies have revealed practice-induced alterations of neurotransmitters, brain activity, and cognitive abilities, just to name a few. These findings not only imply a close link between meditation and brain structure, but also suggest possible modulating effects of meditation on age-related brain atrophy. Given that normal aging is associated with significant loss of brain tissue, meditation-induced growth and/or preservation might manifest as a seemingly reduced brain age in meditators (i.e., cerebral measures characteristic of younger brains). Surprisingly, there are only three published studies that have addressed the question of whether meditation diminishes age-related brain degeneration. This paper reviews these three studies with respect to the brain attributes studied, the analytical strategies applied, and the findings revealed. The review concludes with an elaborate discussion on the significance of existing studies, implications and directions for future studies, as well as the overall relevance of this field of research.

  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. Entropy changes in brain function.

    PubMed

    Rosso, Osvaldo A

    2007-04-01

    The traditional way of analyzing brain electrical activity, on the basis of electroencephalography (EEG) records, relies mainly on visual inspection and years of training. Although it is quite useful, of course, one has to acknowledge its subjective nature that hardly allows for a systematic protocol. In the present work quantifiers based on information theory and wavelet transform are reviewed. The "relative wavelet energy" provides information about the relative energy associated with different frequency bands present in the EEG and their corresponding degree of importance. The "normalized total wavelet entropy" carries information about the degree of order-disorder associated with a multi-frequency signal response. Their application in the analysis and quantification of short duration EEG signals (event-related potentials) and epileptic EEG records are summarized.

  12. Peroxisomes in brain development and function.

    PubMed

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

    2016-05-01

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

  13. Peroxisomes in brain development and function.

    PubMed

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

    2016-05-01

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

  14. Functional brain changes in presymptomatic Huntington's disease.

    PubMed

    Reading, Sarah A J; Dziorny, Adam C; Peroutka, Laura A; Schreiber, Mathew; Gourley, Lisa M; Yallapragada, Venu; Rosenblatt, Adam; Margolis, Russell L; Pekar, James J; Pearlson, Godfrey D; Aylward, Elizabeth; Brandt, Jason; Bassett, Susan S; Ross, Christopher A

    2004-06-01

    Evidence suggests early structural brain changes in individuals with the Huntington's disease (HD) genetic mutation who are presymptomatic for the movement symptoms of the illness. The aim of this study was to investigate the presence of functional brain changes in this same population using functional magnetic resonance imaging. Subjects and matched controls underwent an functional magnetic resonance imaging "interference" protocol, a task known to be mediated in part by corticostriatal circuitry. In the setting of normal cognitive performance, presymptomatic HD subjects had significantly and specifically less activation in the left anterior cingulate cortex (BA 24, 32) compared with matched controls.

  15. 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?

  16. 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

  17. 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.

  18. Statistical Approaches for the Study of Cognitive and Brain Aging.

    PubMed

    Chen, Huaihou; Zhao, Bingxin; Cao, Guanqun; Proges, Eric C; O'Shea, Andrew; Woods, Adam J; Cohen, Ronald A

    2016-01-01

    Neuroimaging studies of cognitive and brain aging often yield massive datasets that create many analytic and statistical challenges. In this paper, we discuss and address several limitations in the existing work. (1) Linear models are often used to model the age effects on neuroimaging markers, which may be inadequate in capturing the potential nonlinear age effects. (2) Marginal correlations are often used in brain network analysis, which are not efficient in characterizing a complex brain network. (3) Due to the challenge of high-dimensionality, only a small subset of the regional neuroimaging markers is considered in a prediction model, which could miss important regional markers. To overcome those obstacles, we introduce several advanced statistical methods for analyzing data from cognitive and brain aging studies. Specifically, we introduce semiparametric models for modeling age effects, graphical models for brain network analysis, and penalized regression methods for selecting the most important markers in predicting cognitive outcomes. We illustrate these methods using the healthy aging data from the Active Brain Study. PMID:27486400

  19. Statistical Approaches for the Study of Cognitive and Brain Aging

    PubMed Central

    Chen, Huaihou; Zhao, Bingxin; Cao, Guanqun; Proges, Eric C.; O'Shea, Andrew; Woods, Adam J.; Cohen, Ronald A.

    2016-01-01

    Neuroimaging studies of cognitive and brain aging often yield massive datasets that create many analytic and statistical challenges. In this paper, we discuss and address several limitations in the existing work. (1) Linear models are often used to model the age effects on neuroimaging markers, which may be inadequate in capturing the potential nonlinear age effects. (2) Marginal correlations are often used in brain network analysis, which are not efficient in characterizing a complex brain network. (3) Due to the challenge of high-dimensionality, only a small subset of the regional neuroimaging markers is considered in a prediction model, which could miss important regional markers. To overcome those obstacles, we introduce several advanced statistical methods for analyzing data from cognitive and brain aging studies. Specifically, we introduce semiparametric models for modeling age effects, graphical models for brain network analysis, and penalized regression methods for selecting the most important markers in predicting cognitive outcomes. We illustrate these methods using the healthy aging data from the Active Brain Study. PMID:27486400

  20. Birth Size and Brain Function 75 Years Later

    PubMed Central

    Muller, Majon; Sigurdsson, Sigurdur; Kjartansson, Olafur; Jonsson, Palmi V.; Garcia, Melissa; von Bonsdorff, Mikaela B.; Gunnarsdottir, Ingibjorg; Thorsdottir, Inga; Harris, Tamara B.; van Buchem, Mark; Gudnason, Vilmundur

    2014-01-01

    BACKGROUND: There are several lines of evidence pointing to fetal and other early origins of diseases of the aging brain, but there are no data directly addressing the hypotheses in an older population. We investigated the association of fetal size to late-age measures of brain structure and function in a large cohort of older men and women and explored the modifying effect of education on these associations. METHODS: Within the AGES (Age Gene/Environment Susceptibility)-Reykjavik population-based cohort (born between 1907 and 1935), archived birth records were abstracted for 1254 men and women who ∼75 years later underwent an examination that included brain MRI and extensive cognitive assessment. RESULTS: Adjustment for intracranial volume, demographic and medical history characteristics, and lower Ponderal index at birth (per kg/m3), an indicator of third-trimester fetal wasting, was significantly associated with smaller volumes of total brain and white matter; βs (95% confidence intervals) were −1.0 (−1.9 to −0.0) and −0.5 (−1.0 to −0.0) mL. Furthermore, lower Ponderal index was associated with slower processing speed and reduced executive functioning but only in those with low education (β [95% confidence interval]: −0.136 [−0.235 to −0.036] and −0.077 [−0.153 to −0.001]). CONCLUSIONS: This first study of its kind provides clinical measures suggesting that smaller birth size, as an indicator of a suboptimal intrauterine environment, is associated with late-life alterations in brain tissue volume and function. In addition, it shows that the effects of a suboptimal intrauterine environment on late-life cognitive function were present only in those with lower educational levels. PMID:25180277

  1. Strengthening connections: functional connectivity and brain plasticity.

    PubMed

    Kelly, Clare; Castellanos, F Xavier

    2014-03-01

    The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist's toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypotheses for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology.

  2. Strengthening connections: functional connectivity and brain plasticity

    PubMed Central

    Kelly, Clare; Castellanos, F. Xavier

    2014-01-01

    The ascendancy of functional neuroimaging has facilitated the addition of network-based approaches to the neuropsychologist’s toolbox for evaluating the sequelae of brain insult. In particular, intrinsic functional connectivity (iFC) mapping of resting state fMRI (R-fMRI) data constitutes an ideal approach to measuring macro-scale networks in the human brain. Beyond the value of iFC mapping for charting how the functional topography of the brain is altered by insult and injury, iFC analyses can provide insights into effects of experience-dependent plasticity at the macro level of large-scale functional networks. Such insights are foundational to the design of training and remediation interventions that will best facilitate recovery of function. In this review, we consider what is currently known about the origin and function of iFC in the brain, and how this knowledge is informative in neuropsychological settings. We then summarize studies that have examined experience-driven plasticity of iFC in healthy control participants, and frame these findings in terms of a schema that may aid in the interpretation of results and the generation of hypothesis for rehabilitative studies. Finally, we outline some caveats to the R-fMRI approach, as well as some current developments that are likely to bolster the utility of the iFC paradigm for neuropsychology. PMID:24496903

  3. Determinants of iron accumulation in the normal aging brain.

    PubMed

    Pirpamer, Lukas; Hofer, Edith; Gesierich, Benno; De Guio, François; Freudenberger, Paul; Seiler, Stephan; Duering, Marco; Jouvent, Eric; Duchesnay, Edouard; Dichgans, Martin; Ropele, Stefan; Schmidt, Reinhold

    2016-07-01

    In a recent postmortem study, R2* relaxometry in gray matter (GM) of the brain has been validated as a noninvasive measure for iron content in brain tissue. Iron accumulation in the normal aging brain is a common finding and relates to brain maturation and degeneration. The goal of this study was to assess the determinants of iron accumulation during brain aging. The study cohort consisted of 314 healthy community-dwelling participants of the Austrian Stroke Prevention Study. Their age ranged from 38-82 years. Quantitative magnetic resonance imaging was performed on 3T and included R2* mapping, based on a 3D multi-echo gradient echo sequence. The median of R2* values was measured in all GM regions, which were segmented automatically using FreeSurfer. We investigated 25 possible determinants for cerebral iron deposition. These included demographics, brain volume, lifestyle factors, cerebrovascular risk factors, serum levels of iron, and single nucleotide polymorphisms related to iron regulating genes (rs1800562, rs3811647, rs1799945, and rs1049296). The body mass index (BMI) was significantly related to R2* in 15/32 analyzed brain regions with the strongest correlations found in the amygdala (p = 0.0091), medial temporal lobe (p = 0.0002), and hippocampus (p ≤ 0.0001). Further associations to R2* values were found in deep GM for age and smoking. No significant associations were found for gender, GM volume, serum levels of iron, or iron-associated genetic polymorphisms. In conclusion, besides age, the BMI and smoking are the only significant determinants of brain iron accumulation in normally aging subjects. Smoking relates to iron deposition in the basal ganglia, whereas higher BMI is associated with iron content in the neocortex following an Alzheimer-like distribution. PMID:27255824

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

    PubMed Central

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

    2014-01-01

    The ongoing 1000 brains study (1000BRAINS) is an epidemiological and neuroscientific investigation of structural and functional variability in the human brain during aging. The two recruitment sources are the 10-year follow-up cohort of the German Heinz Nixdorf Recall (HNR) Study, and the HNR MultiGeneration Study cohort, which comprises spouses and offspring of HNR subjects. The HNR is a longitudinal epidemiological investigation of cardiovascular risk factors, with a comprehensive collection of clinical, laboratory, socioeconomic, and environmental data from population-based subjects aged 45–75 years on inclusion. HNR subjects underwent detailed assessments in 2000, 2006, and 2011, and completed annual postal questionnaires on health status. 1000BRAINS accesses these HNR data and applies a separate protocol comprising: neuropsychological tests of attention, memory, executive functions and language; examination of motor skills; ratings of personality, life quality, mood and daily activities; analysis of laboratory and genetic data; and state-of-the-art magnetic resonance imaging (MRI, 3 Tesla) of the brain. The latter includes (i) 3D-T1- and 3D-T2-weighted scans for structural analyses and myelin mapping; (ii) three diffusion imaging sequences optimized for diffusion tensor imaging, high-angular resolution diffusion imaging for detailed fiber tracking and for diffusion kurtosis imaging; (iii) resting-state and task-based functional MRI; and (iv) fluid-attenuated inversion recovery and MR angiography for the detection of vascular lesions and the mapping of white matter lesions. The unique design of 1000BRAINS allows: (i) comprehensive investigation of various influences including genetics, environment and health status on variability in brain structure and function during aging; and (ii) identification of the impact of selected influencing factors on specific cognitive subsystems and their anatomical correlates. PMID:25071558

  5. Impact of hippocampal neuronal ablation on neurogenesis and cognition in the aged brain.

    PubMed

    Yeung, S T; Myczek, K; Kang, A P; Chabrier, M A; Baglietto-Vargas, D; Laferla, F M

    2014-02-14

    Neuronal loss is the most common and critical feature of a spectrum of brain traumas and neurodegenerative disorders such as Alzheimer's disease (AD). The capacity to generate new neurons in the central nervous system diminishes early during brain development and is restricted mainly to two brain areas in the mature brain: subventricular zone and subgranular zone. Extensive research on the impact of brain injury on endogenous neurogenesis and cognition has been conducted primarily using young animals, when neurogenesis is most active. However, a critical question remains to elucidate the effect of brain injury on endogenous neurogenesis and cognition in older animals, which is far more relevant for age-related neurodegenerative disorders such as AD. Therefore, we examined the impact of neuronal loss on endogenous neurogenesis in aged animals using CaM/Tet-DTA mice, a transgenic model of hippocampal cell loss. Additionally, we investigated whether the upregulation of adult neurogenesis could mitigate cognitive deficits following substantial hippocampal neuronal loss. Our findings demonstrate that aged CaM/Tet-DTA mice that sustain severe neuronal loss exhibit an upregulation of endogenous neurogenesis. However, despite this significant upregulation, neurogenesis alone is not able to mitigate the cognitive deficits observed. Our studies suggest that the aged brain has the capacity to stimulate neurogenesis post-injury; however, multiple therapeutic approaches, including upregulation of endogenous neurogenesis, will be necessary to recover brain function after severe neurodegeneration.

  6. Association of structural global brain network properties with intelligence in normal aging.

    PubMed

    Fischer, Florian U; Wolf, Dominik; Scheurich, Armin; Fellgiebel, Andreas

    2014-01-01

    Higher general intelligence attenuates age-associated cognitive decline and the risk of dementia. Thus, intelligence has been associated with cognitive reserve or resilience in normal aging. Neurophysiologically, intelligence is considered as a complex capacity that is dependent on a global cognitive network rather than isolated brain areas. An association of structural as well as functional brain network characteristics with intelligence has already been reported in young adults. We investigated the relationship between global structural brain network properties, general intelligence and age in a group of 43 cognitively healthy elderly, age 60-85 years. Individuals were assessed cross-sectionally using Wechsler Adult Intelligence Scale-Revised (WAIS-R) and diffusion-tensor imaging. Structural brain networks were reconstructed individually using deterministic tractography, global network properties (global efficiency, mean shortest path length, and clustering coefficient) were determined by graph theory and correlated to intelligence scores within both age groups. Network properties were significantly correlated to age, whereas no significant correlation to WAIS-R was observed. However, in a subgroup of 15 individuals aged 75 and above, the network properties were significantly correlated to WAIS-R. Our findings suggest that general intelligence and global properties of structural brain networks may not be generally associated in cognitively healthy elderly. However, we provide first evidence of an association between global structural brain network properties and general intelligence in advanced elderly. Intelligence might be affected by age-associated network deterioration only if a certain threshold of structural degeneration is exceeded. Thus, age-associated brain structural changes seem to be partially compensated by the network and the range of this compensation might be a surrogate of cognitive reserve or brain resilience.

  7. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    PubMed

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease. PMID:26590911

  8. Recent Developments in Understanding Brain Aging: Implications for Alzheimer's Disease and Vascular Cognitive Impairment.

    PubMed

    Deak, Ferenc; Freeman, Willard M; Ungvari, Zoltan; Csiszar, Anna; Sonntag, William E

    2016-01-01

    As the population of the Western world is aging, there is increasing awareness of age-related impairments in cognitive function and a rising interest in finding novel approaches to preserve cerebral health. A special collection of articles in The Journals of Gerontology: Biological Sciences and Medical Sciences brings together information of different aspects of brain aging, from latest developments in the field of neurodegenerative disorders to cerebral microvascular mechanisms of cognitive decline. It is emphasized that although the cellular changes that occur within aging neurons have been widely studied, more research is required as new signaling pathways are discovered that can potentially protect cells. New avenues for research targeting cellular senescence, epigenetics, and endocrine mechanisms of brain aging are also discussed. Based on the current literature it is clear that understanding brain aging and reducing risk for neurological disease with age requires searching for mechanisms and treatment options beyond the age-related changes in neuronal function. Thus, comprehensive approaches need to be developed that address the multiple, interrelated mechanisms of brain aging. Attention is brought to the importance of maintenance of cerebromicrovascular health, restoring neuroendocrine balance, and the pressing need for funding more innovative research into the interactions of neuronal, neuroendocrine, inflammatory and microvascular mechanisms of cognitive impairment, and Alzheimer's disease.

  9. Darwin's evolution theory, brain oscillations, and complex brain function in a new "Cartesian view".

    PubMed

    Başar, Erol; Güntekin, Bahar

    2009-01-01

    Comparatively analyses of electrophysiological correlates across species during evolution, alpha activity during brain maturation, and alpha activity in complex cognitive processes are presented to illustrate a new multidimensional "Cartesian System" brain function. The main features are: (1) The growth of the alpha activity during evolution, increase of alpha during cognitive processes, and decrease of the alpha entropy during evolution provide an indicator for evolution of brain cognitive performance. (2) Human children younger than 3 years are unable to produce higher cognitive processes and do not show alpha activity till the age of 3 years. The mature brain can perform higher cognitive processes and demonstrates regular alpha activity. (3) Alpha activity also is significantly associated with highly complex cognitive processes, such as the recognition of facial expressions. The neural activity reflected by these brain oscillations can be considered as constituent "building blocks" for a great number of functions. An overarching statement on the alpha function is presented by extended analyzes with multiple dimensions that constitute a "Cartesian Hyperspace" as the basis for oscillatory function. Theoretical implications are considered. PMID:18805445

  10. Darwin's evolution theory, brain oscillations, and complex brain function in a new "Cartesian view".

    PubMed

    Başar, Erol; Güntekin, Bahar

    2009-01-01

    Comparatively analyses of electrophysiological correlates across species during evolution, alpha activity during brain maturation, and alpha activity in complex cognitive processes are presented to illustrate a new multidimensional "Cartesian System" brain function. The main features are: (1) The growth of the alpha activity during evolution, increase of alpha during cognitive processes, and decrease of the alpha entropy during evolution provide an indicator for evolution of brain cognitive performance. (2) Human children younger than 3 years are unable to produce higher cognitive processes and do not show alpha activity till the age of 3 years. The mature brain can perform higher cognitive processes and demonstrates regular alpha activity. (3) Alpha activity also is significantly associated with highly complex cognitive processes, such as the recognition of facial expressions. The neural activity reflected by these brain oscillations can be considered as constituent "building blocks" for a great number of functions. An overarching statement on the alpha function is presented by extended analyzes with multiple dimensions that constitute a "Cartesian Hyperspace" as the basis for oscillatory function. Theoretical implications are considered.

  11. Age, Plasticity, and Homeostasis In Childhood Brain Disorders

    PubMed Central

    Dennis, Maureen; Spiegler, Brenda J.; Juranek, Jenifer J.; Bigler, Erin D.; Snead, O. Carter; Fletcher, Jack M.

    2013-01-01

    It has been widely accepted that the younger the age and/or immaturity of the organism, the greater the brain plasticity, the young age plasticity privilege. This paper examines the relation of a young age to plasticity, reviewing human pediatric brain disorders, as well as selected animal models, human developmental and adult brain disorder studies. As well, we review developmental and childhood acquired disorders that involve a failure of regulatory homeostasis. Our core arguments are: Plasticity is neutral with respect to outcome. Although the effects of plasticity are often beneficial, the outcome of plasticity may be adaptive or maladaptive.The young age plasticity privilege has been overstated.Plastic change operates in concert with homeostatic mechanisms regulating change at every point in the lifespan.The same mechanisms that propel developmental change expose the immature brain to adverse events, making it more difficult for the immature than for the mature brain to sustain equilibrium between plasticity and homeostasis.Poor outcome in many neurodevelopmental disorders and childhood acquired brain insults is related to disequilibrium between plasticity and homeostasis. PMID:24096190

  12. Histamine function in brain disorders.

    PubMed

    Fernández-Novoa, L; Cacabelos, R

    2001-10-15

    The neurotransmitter histamine (HA) has been implicated in the regulation of numerous and important activities of the central nervous system as arousal, cognition, circadian rhythms and neuroendocrine regulation. The data presented here indicate the participation of the histaminergic system in central nervous system disorders, such as Alzheimer's disease and schizophrenia. We also present experimental data on histamine in an animal model of neurodegeneration and the cytotoxic effects of histamine on cultured rat endothelial cells. More studies are needed to investigate the role of the histaminergic system in central nervous system disorders. Peripheral cellular studies in health and disease, molecular studies on receptors and in vivo pharmacological studies may help us to better understand the function of the histaminergic system in health and disease.

  13. Aging, plasticity and environmental enrichment: structural changes and neurotransmitter dynamics in several areas of the brain.

    PubMed

    Mora, Francisco; Segovia, Gregorio; del Arco, Alberto

    2007-08-01

    Cajal was probably the first neurobiologist to suggest that plasticity of nerve cells almost completely disappeared during aging. However, we know today that neural plasticity is still present in the brain during aging. In this review we suggest that aging is a physiological process that occurs asynchronously in different areas of the brain and that the rate of that process is modulated by environmental factors and related to the neuronal-synaptic-molecular substrates of each area. We review here some of the most recent results on aging of the brain in relation to the plastic changes that occur in young and aged animals as a result of living in an enriched environment. We highlight the results from our own laboratory on the dynamics of neurotransmitters in different areas of the brain. Specifically we review first the effects of aging on neurons, dendrites, synapses, and also on molecular and functional plasticity. Second, the effects of environmental enrichment on the brain of young and aged animals. And third the effects of an enriched environment on the age-related changes in neurogenesis and in the extracellular concentrations of glutamate and GABA in hippocampus, and on dopamine, acetylcholine, glutamate and GABA under a situation of acute mild stress in the prefrontal cortex.

  14. 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…

  15. 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

  16. 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.

  17. Beneficial effects of folic acid on enhancement of memory and antioxidant status in aged rat brain.

    PubMed

    Singh, Rashmi; Kanwar, Shalinder S; Sood, Pooja K; Nehru, Bimla

    2011-01-01

    As our population ages, diseases affecting memory and daily functioning will affect an increasing number of individuals, their families and the healthcare system. Therefore, there is a need to study and evaluate effects of certain conditions for anti-aging of the brain. Nutrient supplementation can modify the brain function. The chemistry and function of both the developing and the mature brain are influenced by diet (Fernstrom, Am J Clinical Nutrition 71:1669S-1673S, 2000). Clinical, biochemical, and pathological aspects have shown a correlation between mental symptoms, especially depression and cognitive decline, with high incidence of folate deficiency (Bottiglieri et al., J Neurol Neurosurg Psychiatry 69:562, 2000). In the present study, consequences of folic acid supplementation on brain dysfunction as a result of aging were studied in cerebral cortex, mid brain, and cerebellar regions of rat brain. This study was carried out on 6-, 11-, and 16-month-old rats, which received folic acid at a dose of 5 mg/kg body weight/day for a period of 8 weeks. Respective control groups of the same age groups were also taken. At the end of the treatment duration, behavioral studies were performed and later the animals were killed for various biochemical and histological investigations. Results indicated significant improvement in memory as assessed by active avoidance, passive avoidance, and plus maze tests in the folic acid supplemented aged animals. Significant improvement was also seen in the cellular protective mechanisms where by the activity of superoxide dismutase and catalase enzymes increased in folic acid supplemented group and so was the glutathione content. Increased lipid peroxidation content, a marker of aging, was also found to be decreased during folic acid supplementation in all the three regions of brain in our study. Thus, it can be concluded that folic acid helps in improving the memory status by reducing oxidative stress and maintaining the integrity of

  18. Aging impact on brain biomechanics with applications to hydrocephalus.

    PubMed

    Wilkie, K P; Drapaca, C S; Sivaloganathan, S

    2012-06-01

    Hydrocephalus is a neurological disorder whose clinical symptoms and treatment outcome are correlated with patient age. In Wilkie et al. (2010, A theoretical study of the effect of intraventricular pulsations on the pathogenesis of hydrocephalus. Appl. Math. Comput., 215, 3181-3191), the fractional Zener model was used to investigate the role of cerebrospinal fluid pressure pulsations in the development of hydrocephalus in infants and adults. In this paper, we determine the mechanical parameters of the fractional Zener model for the infant and adult brains using age-dependent shear complex modulus data (Thibault, K. L. & Margulies, S. S. (1998) Age-dependent material properties of the porcine cerebrum: effect on pediatric inertial head injury criteria. J. Biomech., 31, 1119-1126). The displacement of brain tissue under conditions representing the onset of hydrocephalus are then calculated. The infant brain was found to produce tissue displacements that are unphysical for our model geometry and a new boundary condition is proposed to replace the stress-free outer boundary condition used in Wilkie et al. (2010). The steadystate elastic modulus is identified as the parameter of interest in the development of hydrocephalus: it is found to increase from the infant value of 621 Pa to the young adult value of 955 Pa and we hypothesize that it then decreases with age. The low steady-state elastic modulus of the infant brain (and possibly the aged brain) increases the tissue's susceptibility to large deformations and thus to the ventricular expansion characteristic of hydrocephalus.

  19. Differential expression of sirtuins in the aging rat brain.

    PubMed

    Braidy, Nady; Poljak, Anne; Grant, Ross; Jayasena, Tharusha; Mansour, Hussein; Chan-Ling, Tailoi; Smythe, George; Sachdev, Perminder; Guillemin, Gilles J

    2015-01-01

    Although there are seven mammalian sirtuins (SIRT1-7), little is known about their expression in the aging brain. To characterize the change(s) in mRNA and protein expression of SIRT1-7 and their associated proteins in the brain of "physiologically" aged Wistar rats. We tested mRNA and protein expression levels of rat SIRT1-7, and the levels of associated proteins in the brain using RT-PCR and western blotting. Our data shows that SIRT1 expression increases with age, concurrently with increased acetylated p53 levels in all brain regions investigated. SIRT2 and FOXO3a protein levels increased only in the occipital lobe. SIRT3-5 expression declined significantly in the hippocampus and frontal lobe, associated with increases in superoxide and fatty acid oxidation levels, and acetylated CPS-1 protein expression, and a reduction in MnSOD level. While SIRT6 expression declines significantly with age acetylated H3K9 protein expression is increased throughout the brain. SIRT7 and Pol I protein expression increased in the frontal lobe. This study identifies previously unknown roles for sirtuins in regulating cellular homeostasis and healthy aging. PMID:26005404

  20. 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. PMID:25770126

  1. Impact of fatty acids on brain circulation, structure and function.

    PubMed

    Haast, Roy A M; Kiliaan, Amanda J

    2015-01-01

    The use of dietary intervention has evolved into a promising approach to prevent the onset and progression of brain diseases. The positive relationship between intake of omega-3 long chain polyunsaturated fatty acids (ω3-LCPUFAs) and decreased onset of disease- and aging-related deterioration of brain health is increasingly endorsed across epidemiological and diet-interventional studies. Promising results are found regarding to the protection of proper brain circulation, structure and functionality in healthy and diseased humans and animal models. These include enhanced cerebral blood flow (CBF), white and gray matter integrity, and improved cognitive functioning, and are possibly mediated through increased neurovascular coupling, neuroprotection and neuronal plasticity, respectively. Contrary, studies investigating diets high in saturated fats provide opposite results, which may eventually lead to irreversible damage. Studies like these are of great importance given the high incidence of obesity caused by the increased and decreased consumption of respectively saturated fats and ω3-LCPUFAs in the Western civilization. This paper will review in vivo research conducted on the effects of ω3-LCPUFAs and saturated fatty acids on integrity (circulation, structure and function) of the young, aging and diseased brain.

  2. Gestational Age and Neonatal Brain Microstructure in Term Born Infants: A Birth Cohort Study

    PubMed Central

    Broekman, Birit F. P.; Wang, Changqing; Li, Yue; Rifkin-Graboi, Anne; Saw, Seang Mei; Chong, Yap-Seng; Kwek, Kenneth; Gluckman, Peter D.; Fortier, Marielle V.; Meaney, Michael J.; Qiu, Anqi

    2014-01-01

    Objective Understanding healthy brain development in utero is crucial in order to detect abnormal developmental trajectories due to developmental disorders. However, in most studies neuroimaging was done after a significant postnatal period, and in those studies that performed neuroimaging on fetuses, the quality of data has been affected due to complications of scanning during pregnancy. To understand healthy brain development between 37–41 weeks of gestational age, our study assessed the in utero growth of the brain in healthy term born babies with DTI scanning soon after birth. Methods A cohort of 93 infants recruited from maternity hospitals in Singapore underwent diffusion tensor imaging between 5 to 17 days after birth. We did a cross-sectional examination of white matter microstructure of the brain among healthy term infants as a function of gestational age via voxel-based analysis on fractional anisotropy. Results Greater gestational age at birth in term infants was associated with larger fractional anisotropy values in early developing brain regions, when corrected for age at scan. Specifically, it was associated with a cluster located at the corpus callosum (corrected p<0.001), as well as another cluster spanning areas of the anterior corona radiata, anterior limb of internal capsule, and external capsule (corrected p<0.001). Conclusions Our findings show variation in brain maturation associated with gestational age amongst ‘term’ infants, with increased brain maturation when born with a relatively higher gestational age in comparison to those infants born with a relatively younger gestational age. Future studies should explore if these differences in brain maturation between 37 and 41 weeks of gestational age will persist over time due to development outside the womb. PMID:25535959

  3. Mutant alpha-synuclein causes age-dependent neuropathology in monkey brain.

    PubMed

    Yang, Weili; Wang, Guohao; Wang, Chuan-En; Guo, Xiangyu; Yin, Peng; Gao, Jinquan; Tu, Zhuchi; Wang, Zhengbo; Wu, Jing; Hu, Xintian; Li, Shihua; Li, Xiao-Jiang

    2015-05-27

    Parkinson's disease (PD) is an age-dependent neurodegenerative disease that often occurs in those over age 60. Although rodents and small animals have been used widely to model PD and investigate its pathology, their short life span makes it difficult to assess the aging-related pathology that is likely to occur in PD patient brains. Here, we used brain tissues from rhesus monkeys at 2-3, 7-8, and >15 years of age to examine the expression of Parkin, PINK1, and α-synuclein, which are known to cause PD via loss- or gain-of-function mechanisms. We found that α-synuclein is increased in the older monkey brains, whereas Parkin and PINK1 are decreased or remain unchanged. Because of the gain of toxicity of α-synuclein, we performed stereotaxic injection of lentiviral vectors expressing mutant α-synuclein (A53T) into the substantia nigra of monkeys and found that aging also increases the accumulation of A53T in neurites and its associated neuropathology. A53T also causes more extensive reactive astrocytes and axonal degeneration in monkey brain than in mouse brain. Using monkey brain tissues, we found that A53T interacts with neurofascin, an adhesion molecule involved in axon subcellular targeting and neurite outgrowth. Aged monkey brain tissues show an increased interaction of neurofascin with A53T. Overexpression of A53T causes neuritic toxicity in cultured neuronal cells, which can be attenuated by transfected neurofascin. These findings from nonhuman primate brains reveal age-dependent pathological and molecular changes that could contribute to the age-dependent neuropathology in PD.

  4. Metabolomics of human brain aging and age-related neurodegenerative diseases.

    PubMed

    Jové, Mariona; Portero-Otín, Manuel; Naudí, Alba; Ferrer, Isidre; Pamplona, Reinald

    2014-07-01

    Neurons in the mature human central nervous system (CNS) perform a wide range of motor, sensory, regulatory, behavioral, and cognitive functions. Such diverse functional output requires a great diversity of CNS neuronal and non-neuronal populations. Metabolomics encompasses the study of the complete set of metabolites/low-molecular-weight intermediates (metabolome), which are context-dependent and vary according to the physiology, developmental state, or pathologic state of the cell, tissue, organ, or organism. Therefore, the use of metabolomics can help to unravel the diversity-and to disclose the specificity-of metabolic traits and their alterations in the brain and in fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of aging and neurodegenerative diseases. Here, we review the current applications of metabolomics in studies of CNS aging and certain age-related neurodegenerative diseases such as Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Neurometabolomics will increase knowledge of the physiologic and pathologic functions of neural cells and will place the concept of selective neuronal vulnerability in a metabolic context.

  5. Benefits from dietary polyphenols for brain aging and Alzheimer's disease.

    PubMed

    Rossi, L; Mazzitelli, S; Arciello, M; Capo, C R; Rotilio, G

    2008-12-01

    Brain aging and the most diffused neurodegenerative diseases of the elderly are characterized by oxidative damage, redox metals homeostasis impairment and inflammation. Food polyphenols can counteract these alterations in vitro and are therefore suggested to have potential anti-aging and brain-protective activities, as also indicated by the results of some epidemiological studies. Despite the huge and increasing amount of the in vitro studies trying to unravel the mechanisms of action of dietary polyphenols, the research in this field is still incomplete, and questions about bioavailability, biotransformation, synergism with other dietary factors, mechanisms of the antioxidant activity, risks inherent to their possible pro-oxidant activities are still unanswered. Most of all, the capacity of the majority of these compounds to cross the blood-brain barrier and reach brain is still unknown. This commentary discusses recent data on these aspects, particularly focusing on effects of curcumin, resveratrol and catechins on Alzheimer's disease.

  6. Dissecting mechanisms of brain aging by studying the intrinsic excitability of neurons

    PubMed Central

    Rizzo, Valerio; Richman, Jeffrey; Puthanveettil, Sathyanarayanan V.

    2015-01-01

    Several studies using vertebrate and invertebrate animal models have shown aging associated changes in brain function. Importantly, changes in soma size, loss or regression of dendrites and dendritic spines and alterations in the expression of neurotransmitter receptors in specific neurons were described. Despite this understanding, how aging impacts intrinsic properties of individual neurons or circuits that govern a defined behavior is yet to be determined. Here we discuss current understanding of specific electrophysiological changes in individual neurons and circuits during aging. PMID:25610394

  7. Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents.

    PubMed

    Li, Wenjing; Li, Jianhong; Wang, Jieqiong; Zhou, Peng; Wang, Zhenchang; Xian, Junfang; He, Huiguang

    2016-01-01

    Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input. PMID:26819781

  8. Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents.

    PubMed

    Li, Wenjing; Li, Jianhong; Wang, Jieqiong; Zhou, Peng; Wang, Zhenchang; Xian, Junfang; He, Huiguang

    2016-01-01

    Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input.

  9. Functional Reorganizations of Brain Network in Prelingually Deaf Adolescents

    PubMed Central

    Li, Wenjing; Li, Jianhong; Wang, Jieqiong; Zhou, Peng; Wang, Zhenchang; Xian, Junfang; He, Huiguang

    2016-01-01

    Previous neuroimaging studies suggested structural or functional brain reorganizations occurred in prelingually deaf subjects. However, little is known about the reorganizations of brain network architectures in prelingually deaf adolescents. The present study aims to investigate alterations of whole-brain functional network using resting-state fMRI and graph theory analysis. We recruited 16 prelingually deaf adolescents (10~18 years) and 16 normal controls matched in age and gender. Brain networks were constructed from mean time courses of 90 regions. Widely distributed network was observed in deaf subjects, with increased connectivity between the limbic system and regions involved in visual and language processing, suggesting reinforcement of the processing for the visual and verbal information in deaf adolescents. Decreased connectivity was detected between the visual regions and language regions possibly due to inferior reading or speaking skills in deaf subjects. Using graph theory analysis, we demonstrated small-worldness property did not change in prelingually deaf adolescents relative to normal controls. However, compared with healthy adolescents, eight regions involved in visual, language, and auditory processing were identified as hubs only present in prelingually deaf adolescents. These findings revealed reorganization of brain functional networks occurred in prelingually deaf adolescents to adapt to deficient auditory input. PMID:26819781

  10. See the brain at work: intraoperative laser Doppler functional brain imaging

    NASA Astrophysics Data System (ADS)

    Martin-Williams, E. J.; Raabe, A.; Van De Ville, D.; Leutenegger, M.; Szelényi, A.; Hattingen, E.; Gerlach, R.; Seifert, V.; Hauger, C.; Lopez, A.; Leitgeb, R.; Unser, M.; Lasser, T.

    2009-07-01

    During open brain surgery we acquire perfusion images non-invasively using laser Doppler imaging. The regions of brain activity show a distinct signal in response to stimulation providing intraoperative functional brain maps of remarkably strong contrast.

  11. 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

  12. 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.

  13. 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.

  14. Homological scaffolds of brain functional networks.

    PubMed

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

    2014-12-01

    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.

  15. 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

  16. Homological scaffolds of brain functional networks.

    PubMed

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

    2014-12-01

    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

  17. Electroencephalographic imaging of higher brain function.

    PubMed Central

    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. PMID:10466140

  18. Ageing and gastrointestinal sensory function: altered colonic mechanosensory and chemosensory function in the aged mouse

    PubMed Central

    Keating, Christopher; Nocchi, Linda; Yu, Yang; Donovan, Jemma; Grundy, David

    2016-01-01

    Key points Remarkably little is known about how age affects the sensory signalling pathways in the gastrointestinal tract despite age‐related gastrointestinal dysfunction being a prime cause of morbidity amongst the elderly populationHigh‐threshold gastrointestinal sensory nerves play a key role in signalling distressing information from the gut to the brain.We found that ageing is associated with attenuated high‐threshold afferent mechanosensitivity in the murine colon, and associated loss of TRPV1 channel function.These units have the capacity to sensitise in response to injurious events, and their loss in ageing may predispose the elderly to lower awareness of GI injury or disease. Abstract Ageing has a profound effect upon gastrointestinal function through mechanisms that are poorly understood. Here we investigated the effect of age upon gastrointestinal sensory signalling pathways in order to address the mechanisms underlying these changes. In vitro mouse colonic and jejunal preparations with attached splanchnic and mesenteric nerves were used to study mechanosensory and chemosensory afferent function in 3‐, 12‐ and 24‐month‐old C57BL/6 animals. Quantitative RT‐PCR was used to investigate mRNA expression in colonic tissue and dorsal root ganglion (DRG) cells isolated from 3‐ and 24‐month animals, and immunohistochemistry was used to quantify the number of 5‐HT‐expressing enterochromaffin (EC) cells. Colonic and jejunal afferent mechanosensory function was attenuated with age and these effects appeared earlier in the colon compared to the jejunum. Colonic age‐related loss of mechanosensory function was more pronounced in high‐threshold afferents compared to low‐threshold afferents. Chemosensory function was attenuated in the 24‐month colon, affecting TRPV1 and serotonergic signalling pathways. High‐threshold mechanosensory afferent fibres and small‐diameter DRG neurons possessed lower functional TRPV1 receptor responses

  19. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease.

  20. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer's Disease.

    PubMed

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer's Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer's Disease. PMID:26937969

  1. MR brain image analysis in dementia: From quantitative imaging biomarkers to ageing brain models and imaging genetics.

    PubMed

    Niessen, Wiro J

    2016-10-01

    MR brain image analysis has constantly been a hot topic research area in medical image analysis over the past two decades. In this article, it is discussed how the field developed from the construction of tools for automatic quantification of brain morphology, function, connectivity and pathology, to creating models of the ageing brain in normal ageing and disease, and tools for integrated analysis of imaging and genetic data. The current and future role of the field in improved understanding of the development of neurodegenerative disease is discussed, and its potential for aiding in early and differential diagnosis and prognosis of different types of dementia. For the latter, the use of reference imaging data and reference models derived from large clinical and population imaging studies, and the application of machine learning techniques on these reference data, are expected to play a key role. PMID:27344937

  2. MR brain image analysis in dementia: From quantitative imaging biomarkers to ageing brain models and imaging genetics.

    PubMed

    Niessen, Wiro J

    2016-10-01

    MR brain image analysis has constantly been a hot topic research area in medical image analysis over the past two decades. In this article, it is discussed how the field developed from the construction of tools for automatic quantification of brain morphology, function, connectivity and pathology, to creating models of the ageing brain in normal ageing and disease, and tools for integrated analysis of imaging and genetic data. The current and future role of the field in improved understanding of the development of neurodegenerative disease is discussed, and its potential for aiding in early and differential diagnosis and prognosis of different types of dementia. For the latter, the use of reference imaging data and reference models derived from large clinical and population imaging studies, and the application of machine learning techniques on these reference data, are expected to play a key role.

  3. Estimating brain age using high-resolution pattern recognition: Younger brains in long-term meditation practitioners.

    PubMed

    Luders, Eileen; Cherbuin, Nicolas; Gaser, Christian

    2016-07-01

    Normal aging is known to be accompanied by loss of brain substance. The present study was designed to examine whether the practice of meditation is associated with a reduced brain age. Specific focus was directed at age fifty and beyond, as mid-life is a time when aging processes are known to become more prominent. We applied a recently developed machine learning algorithm trained to identify anatomical correlates of age in the brain translating those into one single score: the BrainAGE index (in years). Using this validated approach based on high-dimensional pattern recognition, we re-analyzed a large sample of 50 long-term meditators and 50 control subjects estimating and comparing their brain ages. We observed that, at age fifty, brains of meditators were estimated to be 7.5years younger than those of controls. In addition, we examined if the brain age estimates change with increasing age. While brain age estimates varied only little in controls, significant changes were detected in meditators: for every additional year over fifty, meditators' brains were estimated to be an additional 1month and 22days younger than their chronological age. Altogether, these findings seem to suggest that meditation is beneficial for brain preservation, effectively protecting against age-related atrophy with a consistently slower rate of brain aging throughout life. PMID:27079530

  4. Maintaining older brain functionality: A targeted review.

    PubMed

    Ballesteros, Soledad; Kraft, Eduard; Santana, Silvina; Tziraki, Chariklia

    2015-08-01

    The unprecedented growth in the number of older adults in our society is accompanied by the exponential increase in the number of elderly people who will suffer cognitive decline and dementia in the next decades. This will create an enormous cost for governments, families and individuals. Brain plasticity and its role in brain adaptation to the process of aging is influenced by other changes as a result of co-morbidities, environmental factors, personality traits (psychosocial variables) and genetic and epigenetic factors. This review summarizes recent findings obtained mostly from interventional studies that aim to prevent and/or delay age-related cognitive decline in healthy adults. There are a multitude of such studies. In this paper, we focused our review on physical activity, computerized cognitive training and social enhancement interventions on improving cognition, physical health, independent living and wellbeing of older adults. The methodological limitations of some of these studies, and the need for new multi-domain synergistic interventions, based on current advances in neuroscience and social-brain theories, are discussed. PMID:26054789

  5. Maintaining older brain functionality: A targeted review.

    PubMed

    Ballesteros, Soledad; Kraft, Eduard; Santana, Silvina; Tziraki, Chariklia

    2015-08-01

    The unprecedented growth in the number of older adults in our society is accompanied by the exponential increase in the number of elderly people who will suffer cognitive decline and dementia in the next decades. This will create an enormous cost for governments, families and individuals. Brain plasticity and its role in brain adaptation to the process of aging is influenced by other changes as a result of co-morbidities, environmental factors, personality traits (psychosocial variables) and genetic and epigenetic factors. This review summarizes recent findings obtained mostly from interventional studies that aim to prevent and/or delay age-related cognitive decline in healthy adults. There are a multitude of such studies. In this paper, we focused our review on physical activity, computerized cognitive training and social enhancement interventions on improving cognition, physical health, independent living and wellbeing of older adults. The methodological limitations of some of these studies, and the need for new multi-domain synergistic interventions, based on current advances in neuroscience and social-brain theories, are discussed.

  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. Individual diversity of functional brain network economy.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Ganger, Sebastian; Windischberger, Christian; Kasper, Siegfried; Lanzenberger, Rupert

    2015-04-01

    On average, brain network economy represents a trade-off between communication efficiency, robustness, and connection cost, although an analogous understanding on an individual level is largely missing. Evaluating resting-state networks of 42 healthy participants with seven Tesla functional magnetic resonance imaging and graph theory revealed that not even half of all possible connections were common across subjects. The strongest similarities among individuals were observed for interhemispheric and/or short-range connections, which may relate to the essential feature of the human brain to develop specialized systems within each hemisphere. Despite this marked variability in individual network architecture, all subjects exhibited equal small-world properties. Furthermore, interdependency between four major network economy metrics was observed across healthy individuals. The characteristic path length was associated with the clustering coefficient (peak correlation r=0.93), the response to network attacks (r=-0.97), and the physical connection cost in three-dimensional space (r=-0.62). On the other hand, clustering was negatively related to attack response (r=-0.75) and connection cost (r=-0.59). Finally, increased connection cost was associated with better response to attacks (r=0.65). This indicates that functional brain networks with high global information transfer also exhibit strong network resilience. However, it seems that these advantages come at the cost of decreased local communication efficiency and increased physical connection cost. Except for wiring length, the results were replicated on a subsample at three Tesla (n=20). These findings highlight the finely tuned interrelationships between different parameters of brain network economy. Moreover, the understanding of the individual diversity of functional brain network economy may provide further insights in the vulnerability to mental and neurological disorders.

  8. Vulnerable Neural Systems and the Borderland of Brain Aging and Neurodegeneration

    PubMed Central

    Jagust, William

    2013-01-01

    Brain aging is characterized by considerable heterogeneity, including varying degrees of dysfunction in specific brain systems, notably a medial temporal lobe memory system, and a frontostriatal executive system. These same systems are also affected by neurodegenerative diseases of late life. Recent work using techniques for presymptomatic detection of disease in cognitively normal older people has shown that some of the late life alterations in cognition, neural structure and function attributed to aging probably reflects early neurodegeneration. However, it has become clear that these same brain systems are also vulnerable to aging itself in the absence of even subtle disease. Thus, fundamental systemic limitations appear to confer vulnerability of these neural systems to a variety of insults, including those recognized as typical disease and those that are attributed to age. By focusing on the fundamental causes of neural system vulnerability, the prevention or treatment of a wide range of late-life neural dysfunction might be possible. PMID:23352159

  9. Centrophenoxine: effects on aging mammalian brain.

    PubMed

    Nandy, K

    1978-02-01

    A study was made of the effects of centrophenoxine on the learning and memory of old mice. The results were correlated with changes in neuronal lipofuscin in the cerebral cortex and hippocampus. Old female mice (11-12 months) were treated with centropheoxine for three months and their learning and memory were tested in a T-maze. The number of trials required to attain the criterion in the 20 treated old mice were compared with those for 20 untreated mice of the same age and for 20 younger untreated mice. The treated animals learned the task with significantly fewer trials, and also exhibited a reduction of neuronal lipofuscin pigment in both the cerebral cortex and the hippocampus. The changes in lipofuscin were demonstrated by study of the characteristic autofluorescence, and by histolchemical and ultrastructural (electron microscope) observations.

  10. Growth hormone, insulin-like growth factor-1 and the aging brain.

    PubMed

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan. PMID:25300732

  11. Growth hormone, insulin-like growth factor-1 and the aging brain.

    PubMed

    Ashpole, Nicole M; Sanders, Jessica E; Hodges, Erik L; Yan, Han; Sonntag, William E

    2015-08-01

    Growth hormone (GH) and insulin-like growth factor (IGF)-1 regulate the development and function of cells throughout the body. Several clinical diseases that result in a decline in physical and mental functions are marked by mutations that disrupt GH or IGF-1 signaling. During the lifespan there is a robust decrease in both GH and IGF-1. Because GH and IGF-1 are master regulators of cellular function, impaired GH and IGF-1 signaling in aging/disease states leads to significant alterations in tissue structure and function, especially within the brain. This review is intended to highlight the effects of the GH and IGF-1 on neuronal structure, function, and plasticity. Furthermore, we address several potential mechanisms through which the age-related reductions in GH and IGF-1 affect cognition. Together, the studies reviewed here highlight the importance of maintaining GH and IGF-1 signaling in order to sustain proper brain function throughout the lifespan.

  12. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression. PMID:26827786

  13. Brain atrophy in Alzheimer's Disease and aging.

    PubMed

    Pini, Lorenzo; Pievani, Michela; Bocchetta, Martina; Altomare, Daniele; Bosco, Paolo; Cavedo, Enrica; Galluzzi, Samantha; Marizzoni, Moira; Frisoni, Giovanni B

    2016-09-01

    Thanks to its safety and accessibility, magnetic resonance imaging (MRI) is extensively used in clinical routine and research field, largely contributing to our understanding of the pathophysiology of neurodegenerative disorders such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the main findings in AD and normal aging over the past twenty years, focusing on the patterns of gray and white matter changes assessed in vivo using MRI. Major progresses in the field concern the segmentation of the hippocampus with novel manual and automatic segmentation approaches, which might soon enable to assess also hippocampal subfields. Advancements in quantification of hippocampal volumetry might pave the way to its broader use as outcome marker in AD clinical trials. Patterns of cortical atrophy have been shown to accurately track disease progression and seem promising in distinguishing among AD subtypes. Disease progression has also been associated with changes in white matter tracts. Recent studies have investigated two areas often overlooked in AD, such as the striatum and basal forebrain, reporting significant atrophy, although the impact of these changes on cognition is still unclear. Future integration of different MRI modalities may further advance the field by providing more powerful biomarkers of disease onset and progression.

  14. When "altering brain function" becomes "mind control".

    PubMed

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. "Under what conditions does 'altering brain function' qualify as 'mind control'?" In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control.

  15. Brain surgery breathes new life into aging plants

    SciTech Connect

    Makansi, J.

    2006-04-15

    Unlike managing the human aging process, extending the life of a power plant often includes brain surgery, modernizing its control and automation system. Lately, such retrofits range from wholesale replacing of existing controls to the addition of specific control elements that help optimize performance. Pending revisions to safety codes and cybersecurity issues also need to be considered. 4 figs.

  16. Brain-Based Teaching in the Digital Age

    ERIC Educational Resources Information Center

    Sprenger, Marilee

    2010-01-01

    In the digital age, your students have the ways, means, and speed to gather any information they want. But they need your guidance more than ever. Discover how digital technology is actually changing your students' brains. Learn why this creates new obstacles for teachers, but also opens up potential new pathways for learning. You will understand…

  17. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain

    PubMed Central

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the “universal” language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID:26881224

  18. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain.

    PubMed

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the "universal" language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics. PMID:26881224

  19. Neurolinguistics: Structure, Function, and Connectivity in the Bilingual Brain.

    PubMed

    Wong, Becky; Yin, Bin; O'Brien, Beth

    2016-01-01

    Advances in neuroimaging techniques and analytic methods have led to a proliferation of studies investigating the impact of bilingualism on the cognitive and brain systems in humans. Lately, these findings have attracted much interest and debate in the field, leading to a number of recent commentaries and reviews. Here, we contribute to the ongoing discussion by compiling and interpreting the plethora of findings that relate to the structural, functional, and connective changes in the brain that ensue from bilingualism. In doing so, we integrate theoretical models and empirical findings from linguistics, cognitive/developmental psychology, and neuroscience to examine the following issues: (1) whether the language neural network is different for first (dominant) versus second (nondominant) language processing; (2) the effects of bilinguals' executive functioning on the structure and function of the "universal" language neural network; (3) the differential effects of bilingualism on phonological, lexical-semantic, and syntactic aspects of language processing on the brain; and (4) the effects of age of acquisition and proficiency of the user's second language in the bilingual brain, and how these have implications for future research in neurolinguistics.

  20. The Indirect Effect of Age Group on Switch Costs via Gray Matter Volume and Task-Related Brain Activity.

    PubMed

    Steffener, Jason; Gazes, Yunglin; Habeck, Christian; Stern, Yaakov

    2016-01-01

    Healthy aging simultaneously affects brain structure, brain function, and cognition. These effects are often investigated in isolation ignoring any relationships between them. It is plausible that age related declines in cognitive performance are the result of age-related structural and functional changes. This straightforward idea is tested in within a conceptual research model of cognitive aging. The current study tested whether age-related declines in task-performance were explained by age-related differences in brain structure and brain function using a task-switching paradigm in 175 participants. Sixty-three young and 112 old participants underwent MRI scanning of brain structure and brain activation. The experimental task was an executive context dual task with switch costs in response time as the behavioral measure. A serial mediation model was applied voxel-wise throughout the brain testing all pathways between age group, gray matter volume, brain activation and increased switch costs, worsening performance. There were widespread age group differences in gray matter volume and brain activation. Switch costs also significantly differed by age group. There were brain regions demonstrating significant indirect effects of age group on switch costs via the pathway through gray matter volume and brain activation. These were in the bilateral precuneus, bilateral parietal cortex, the left precentral gyrus, cerebellum, fusiform, and occipital cortices. There were also significant indirect effects via the brain activation pathway after controlling for gray matter volume. These effects were in the cerebellum, occipital cortex, left precentral gyrus, bilateral supramarginal, bilateral parietal, precuneus, middle cingulate extending to medial superior frontal gyri and the left middle frontal gyri. There were no significant effects through the gray matter volume alone pathway. These results demonstrate that a large proportion of the age group effect on switch costs can

  1. The Indirect Effect of Age Group on Switch Costs via Gray Matter Volume and Task-Related Brain Activity

    PubMed Central

    Steffener, Jason; Gazes, Yunglin; Habeck, Christian; Stern, Yaakov

    2016-01-01

    Healthy aging simultaneously affects brain structure, brain function, and cognition. These effects are often investigated in isolation ignoring any relationships between them. It is plausible that age related declines in cognitive performance are the result of age-related structural and functional changes. This straightforward idea is tested in within a conceptual research model of cognitive aging. The current study tested whether age-related declines in task-performance were explained by age-related differences in brain structure and brain function using a task-switching paradigm in 175 participants. Sixty-three young and 112 old participants underwent MRI scanning of brain structure and brain activation. The experimental task was an executive context dual task with switch costs in response time as the behavioral measure. A serial mediation model was applied voxel-wise throughout the brain testing all pathways between age group, gray matter volume, brain activation and increased switch costs, worsening performance. There were widespread age group differences in gray matter volume and brain activation. Switch costs also significantly differed by age group. There were brain regions demonstrating significant indirect effects of age group on switch costs via the pathway through gray matter volume and brain activation. These were in the bilateral precuneus, bilateral parietal cortex, the left precentral gyrus, cerebellum, fusiform, and occipital cortices. There were also significant indirect effects via the brain activation pathway after controlling for gray matter volume. These effects were in the cerebellum, occipital cortex, left precentral gyrus, bilateral supramarginal, bilateral parietal, precuneus, middle cingulate extending to medial superior frontal gyri and the left middle frontal gyri. There were no significant effects through the gray matter volume alone pathway. These results demonstrate that a large proportion of the age group effect on switch costs can

  2. Functional Brain Networks in Schizophrenia: A Review

    PubMed Central

    Calhoun, Vince D.; Eichele, Tom; Pearlson, Godfrey

    2009-01-01

    Functional magnetic resonance imaging (fMRI) has become a major technique for studying cognitive function and its disruption in mental illness, including schizophrenia. The major proportion of imaging studies focused primarily upon identifying regions which hemodynamic response amplitudes covary with particular stimuli and differentiate between patient and control groups. In addition to such amplitude based comparisons, one can estimate temporal correlations and compute maps of functional connectivity between regions which include the variance associated with event-related responses as well as intrinsic fluctuations of hemodynamic activity. Functional connectivity maps can be computed by correlating all voxels with a seed region when a spatial prior is available. An alternative are multivariate decompositions such as independent component analysis (ICA) which extract multiple components, each of which is a spatially distinct map of voxels with a common time course. Recent work has shown that these networks are pervasive in relaxed resting and during task performance and hence provide robust measures of intact and disturbed brain activity. This in turn bears the prospect of yielding biomarkers for schizophrenia, which can be described both in terms of disrupted local processing as well as altered global connectivity between large-scale networks. In this review we will summarize functional connectivity measures with a focus upon work with ICA and discuss the meaning of intrinsic fluctuations. In addition, examples of how brain networks have been used for classification of disease will be shown. We present work with functional network connectivity, an approach that enables the evaluation of the interplay between multiple networks and how they are affected in disease. We conclude by discussing new variants of ICA for extracting maximally group discriminative networks from data. In summary, it is clear that identification of brain networks and their inter

  3. Non-Invasive Brain-to-Brain Interface (BBI): Establishing Functional Links between Two Brains

    PubMed Central

    Yoo, Seung-Schik; Kim, Hyungmin; Filandrianos, Emmanuel; Taghados, Seyed Javid; Park, Shinsuk

    2013-01-01

    Transcranial focused ultrasound (FUS) is capable of modulating the neural activity of specific brain regions, with a potential role as a non-invasive computer-to-brain interface (CBI). In conjunction with the use of brain-to-computer interface (BCI) techniques that translate brain function to generate computer commands, we investigated the feasibility of using the FUS-based CBI to non-invasively establish a functional link between the brains of different species (i.e. human and Sprague-Dawley rat), thus creating a brain-to-brain interface (BBI). The implementation was aimed to non-invasively translate the human volunteer’s intention to stimulate a rat’s brain motor area that is responsible for the tail movement. The volunteer initiated the intention by looking at a strobe light flicker on a computer display, and the degree of synchronization in the electroencephalographic steady-state-visual-evoked-potentials (SSVEP) with respect to the strobe frequency was analyzed using a computer. Increased signal amplitude in the SSVEP, indicating the volunteer’s intention, triggered the delivery of a burst-mode FUS (350 kHz ultrasound frequency, tone burst duration of 0.5 ms, pulse repetition frequency of 1 kHz, given for 300 msec duration) to excite the motor area of an anesthetized rat transcranially. The successful excitation subsequently elicited the tail movement, which was detected by a motion sensor. The interface was achieved at 94.0±3.0% accuracy, with a time delay of 1.59±1.07 sec from the thought-initiation to the creation of the tail movement. Our results demonstrate the feasibility of a computer-mediated BBI that links central neural functions between two biological entities, which may confer unexplored opportunities in the study of neuroscience with potential implications for therapeutic applications. PMID:23573251

  4. Effects of non-pharmacological or pharmacological interventions on cognition and brain plasticity of aging individuals

    PubMed Central

    Pieramico, Valentina; Esposito, Roberto; Cesinaro, Stefano; Frazzini, Valerio; Sensi, Stefano L.

    2014-01-01

    Brain aging and aging-related neurodegenerative disorders are major health challenges faced by modern societies. Brain aging is associated with cognitive and functional decline and represents the favourable background for the onset and development of dementia. Brain aging is associated with early and subtle anatomo-functional physiological changes that often precede the appearance of clinical signs of cognitive decline. Neuroimaging approaches unveiled the functional correlates of these alterations and helped in the identification of therapeutic targets that can be potentially useful in counteracting age-dependent cognitive decline. A growing body of evidence supports the notion that cognitive stimulation and aerobic training can preserve and enhance operational skills in elderly individuals as well as reduce the incidence of dementia. This review aims at providing an extensive and critical overview of the most recent data that support the efficacy of non-pharmacological and pharmacological interventions aimed at enhancing cognition and brain plasticity in healthy elderly individuals as well as delaying the cognitive decline associated with dementia. PMID:25228860

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

    PubMed

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

    2013-03-01

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

  6. What have novel imaging techniques revealed about metabolism in the aging brain?

    PubMed

    Lin, Ai-Ling; Rothman, Douglas L

    2014-05-01

    Brain metabolism declines with age and do so in an accelerated manner in neurodegenerative disorders. Noninvasive neuroimaging techniques have played an important role to identify the metabolic biomarkers in aging brain. Particularly, PET with fluorine-18 ((18)F)-labeled 2-fluoro-2-deoxy-d-glucose tracer and proton magnetic resonance spectroscopy (MRS) have been widely used to monitor changes in brain metabolism over time, identify the risk for Alzheimer's disease (AD) and predict the conversion from mild cognitive impairment to AD. Novel techniques, including PET carbon-11 Pittsburgh compound B, carbon-13 and phosphorus-31 MRS, have also been introduced to determine Aβ plaques deposition, mitochondrial functions and brain bioenergetics in aging brain and neurodegenerative disorders. Here, we introduce the basic principle of the imaging techniques, review the findings from 2-fluoro-2-deoxy-d-glucose-PET, Pittsburgh compound B PET, proton, carbon-13 and phosphorus-31 MRS on changes in metabolism in normal aging brain, mild cognitive impairment and AD, and discuss the potential of neuroimaging to identify effective interventions and treatment efficacy for neurodegenerative disorders.

  7. Perinatal choline influences brain structure and function.

    PubMed

    Zeisel, Steven H; Niculescu, Mihai D

    2006-04-01

    Choline is derived not only from the diet, but also from de novo synthesis. It is important for methyl-group metabolism, the formation of membranes, kidney function, and neurotransmission. When deprived of dietary choline, most adult men and postmenopausal women develop signs of organ dysfunction (fatty liver or muscle damage) and have a decreased capacity to convert homocysteine to methionine. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain structure and function (memory is permanently enhanced in rodents exposed to choline during the latter part of gestation). PMID:16673755

  8. Aging and Gene Expression in the Primate Brain

    SciTech Connect

    Fraser, Hunter B.; Khaitovich, Philipp; Plotkin, Joshua B.; Paabo, Svante; Eisen, Michael B.

    2005-02-18

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

  9. The Big Five default brain: functional evidence.

    PubMed

    Sampaio, Adriana; Soares, José Miguel; Coutinho, Joana; Sousa, Nuno; Gonçalves, Óscar F

    2014-11-01

    Recent neuroimaging studies have provided evidence that different dimensions of human personality may be associated with specific structural neuroanatomic correlates. Identifying brain correlates of a situation-independent personality structure would require evidence of a stable default mode of brain functioning. In this study, we investigated the correlates of the Big Five personality dimensions (Extraversion, Neuroticism, Openness/Intellect, Agreeableness, and Conscientiousness) and the default mode network (DMN). Forty-nine healthy adults completed the NEO-Five Factor. The results showed that the Extraversion (E) and Agreeableness (A) were positively correlated with activity in the midline core of the DMN, whereas Neuroticism (N), Openness (O), and Conscientiousness (C) were correlated with the parietal cortex system. Activity of the anterior cingulate cortex was positively associated with A and negatively with C. Regions of the parietal lobe were differentially associated with each personality dimension. The present study not only confirms previous functional correlates regarding the Big Five personality dimensions, but it also expands our knowledge showing the association between different personality dimensions and specific patterns of brain activation at rest.

  10. (n-6) and (n-3) Polyunsaturated fatty acids and the aging brain: food for thought.

    PubMed

    Whelan, Jay

    2008-12-01

    Over the last decade, the role of dietary PUFA in growth, development, and cognitive function in the infant has been a topic at numerous national and international meetings. Only recently has the role of PUFA been more seriously examined as they relate to the aging brain. In fact, a search of the literature reveals very few randomized control trials exploring this research area. However, the literature reveals growing mechanistic evidence that cognitive function of the aging brain can be preserved, or loss of function can be diminished with docosahexaenoic acid, a long-chain (n-3) PUFA. Furthermore, no symposia have taken a serious look at the impact of (n-6) PUFA on the brain, in particular arachidonic acid (AA), the most highly concentrated (n-6) PUFA in the brain. This symposium explores the role of AA metabolism in the brain as it relates to neurological mood disorders. To that end, this symposium was designed to highlight the potential effects of dietary PUFA on the adult brain, an important issue given the growing elderly population in this country and the growing problems with neurological disorders (dementia, Alzheimer disease, Parkinson disease, bipolar disorders, etc.).

  11. The impact of aging and gender on brain viscoelasticity.

    PubMed

    Sack, Ingolf; Beierbach, Bernd; Wuerfel, Jens; Klatt, Dieter; Hamhaber, Uwe; Papazoglou, Sebastian; Martus, Peter; Braun, Jürgen

    2009-07-01

    Viscoelasticity is a sensitive measure of the microstructural constitution of soft biological tissue and is increasingly used as a diagnostic marker, e.g. in staging liver fibrosis or characterizing breast tumors. In this study, multifrequency magnetic resonance elastography was used to investigate the in vivo viscoelasticity of healthy human brain in 55 volunteers (23 females) ranging in age from 18 to 88 years. The application of four vibration frequencies in an acoustic range from 25 to 62.5 Hz revealed for the first time how physiological aging changes the global viscosity and elasticity of the brain. Using the rheological springpot model, viscosity and elasticity are combined in a parameter mu that describes the solid-fluid behavior of the tissue and a parameter alpha related to the tissue's microstructure. It is shown that the healthy adult brain undergoes steady parenchymal 'liquefaction' characterized by a continuous decline in mu of 0.8% per year (P<0.001), whereas alpha remains unchanged. Furthermore, significant sex differences were found with female brains being on average 9% more solid-like than their male counterparts rendering women more than a decade 'younger' than men with respect to brain mechanics (P=0.016). These results set the background for using cerebral multifrequency elastography in diagnosing subtle neurodegenerative processes not detectable by other diagnostic methods.

  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. Clinton Woolsey: Functional Brain Mapping Pioneer

    PubMed Central

    Lyon, Will; Mehta, Tej I.; Pointer, Kelli B.; Walden, Daniel; Elmayan, Ardem; Swanson, Kyle I.; Kuo, John S.

    2014-01-01

    Dr. Clinton Woolsey was a leading twentieth century neuroscientist for almost four decades. His most significant achievements were the novel use and refinement of evoked potential techniques to functionally map mammalian brains, the discovery of secondary cortical areas, and a wide repertoire of comparative neurofunctional studies across many species. We discuss his life and work through a historical context with contemporaries, highlight the primitive state of brain mapping before Woolsey, and his involvement in advancing its rapid development through work at both Johns Hopkins University and University of Wisconsin in Madison. Dr. Woolsey’s lasting impact on basic and clinical neuroscience, neurosurgery, and neurology and his important roles as a scientific mentor and leader are also described. PMID:25105696

  14. Decreased myeloperoxidase expressing cells in the aged rat brain after excitotoxic damage.

    PubMed

    Campuzano, Oscar; Castillo-Ruiz, Maria del Mar; Acarin, Laia; Gonzalez, Berta; Castellano, Bernardo

    2011-09-01

    Brain aging is associated to several morphological and functional alterations that influence the evolution and outcome of CNS damage. Acute brain injury such as an excitotoxic insult induces initial tissue damage followed by associated inflammation and oxidative stress, partly attributed to neutrophil recruitment and the expression of oxidative enzymes such as myeloperoxidase (MPO), among others. However, to date, very few studies have focused on how age can influence neutrophil infiltration after acute brain damage. Therefore, to evaluate the age-dependent pattern of neutrophil cell infiltration following an excitotoxic injury, intrastriatal injection of N-methyl-d-aspartate was performed in young and aged male Wistar rats. Animals were sacrificed at different times between 12h post-lesion (hpl) to 14 days post-lesion (dpl). Cryostat sections were processed for myeloperoxidase (MPO) immunohistochemistry, and double labeling for either neuronal cells (NeuN), astrocytes (GFAP), perivascular macrophages (ED-2), or microglia/macrophages (tomato lectin histochemistry). Our observations showed that MPO + cells were observed in the injured striatum from 12 hpl (when maximum values were found) until 7 dpl, when cell density was strongly diminished. However, at all survival times analyzed, the overall density of MPO + cells was lower in the aged versus the adult injured striatum. MPO + cells were mainly identified as neutrophils (especially at 12 hpl and 1 dpl), but it should be noted that MPO + neurons and microglia/macrophages were also found. MPO + neurons were most commonly observed at 12 hpl and reduced in the aged. MPO + microglia/macrophages were the main population expressing MPO from 3 dpl, when density was also reduced in aged subjects. These results point to neutrophil infiltration as another important factor contributing to the different responses of the adult and aged brain to damage, highlighting the need of using aged animals for the study of acute age

  15. Effects of age on testicular function.

    PubMed

    Tsitouras, P D

    1987-12-01

    Although frequency of sexual activity declines dramatically with age, most investigators have been able to define rather small physiologic function (hormonal and spermatogenic) changes with advancing age. Despite the development of subtle intrinsic age-related defects at all levels of the hypothalamic-pituitary-testicular axis, reproductive capacity is maintained in healthy elderly men.

  16. Age differences in brain activity related to unsuccessful declarative memory retrieval.

    PubMed

    Grady, Cheryl L; St-Laurent, Marie; Burianová, Hana

    2015-07-01

    Although memory recall is known to be reduced with normal aging, little is known about the patterns of brain activity that accompany these recall failures. By assessing faulty memory, we can identify the brain regions engaged during retrieval attempts in the absence of successful memory and determine the impact of aging on this functional activity. We used functional magnetic resonance imaging to examine age differences in brain activity associated with memory failure in three memory retrieval tasks: autobiographical (AM), episodic (EM) and semantic (SM). Compared to successful memory retrieval, both age groups showed more activity when they failed to recall a memory in regions consistent with the salience network (SLN), a brain network also associated with non-memory errors. Both groups also showed strong functional coupling among SLN regions during incorrect trials and in intrinsic patterns of functional connectivity. In comparison to young adults, older adults demonstrated (1) less activity within the SLN during unsuccessful AM trials; (2) weaker intrinsic functional connectivity between SLN nodes and dorsolateral prefrontal cortex; and (3) less differentiation of SLN functional connectivity during incorrect trials across memory conditions. These results suggest that the SLN is engaged during recall failures, as it is for non-memory errors, which may be because errors in general have particular salience for adapting behavior. In older adults, the dedifferentiation of functional connectivity within the SLN across memory conditions and the reduction of functional coupling between it and prefrontal cortex may indicate poorer inter-network communication and less flexible use of cognitive control processes, either while retrieval is attempted or when monitoring takes place after retrieval has failed. This article is part of a Special Issue entitled SI: Memory & Aging.

  17. 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…

  18. 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.

  19. Age related diastolic function in amateur athletes.

    PubMed

    Santoro, Amato; Alvino, Federico; Antonelli, Giovanni; Cassano, Francesco Emmanuel; De Vito, Raffaella; Cameli, Matteo; Mondillo, Sergio

    2015-03-01

    Diastolic function get worse with increasing age. Aim of this study was to investigate the impact of aerobic training on diastolic function with increasing age with speckle tracking echocardiography. We enrolled 125 amateur swimmers (AG), divided in three groups at increasing age: young athletes, adult athletes (AG2), old athletes (AG3). We enrolled 95 sedentary controls (SG) age-matched with athletes and divided into three groups: young sedentary group, adult sedentary group (SG2) and old sedentary group (SG3). AG had better diastolic function than SG. AG showed lower left ventricular twist than controls. E/A ratio got worse at increasing of age in all population (r = -0.34; p < 0.001); particularly in SG2 and SG3 there was a worsening of diastolic function respect to diastolic function of AG2 and AG3; in fact E/A ratio decreased with aging. Furthermore in SG E/A ratio showed a linear correlation with age (r = -0.54; p < 0.001); in AG this correlation was lost. Therefore the training and age were independent predictor of E/A (respectively β = -0.27; p = 0.004; β = -0.24, p = 0.008). Regular and aerobic training may minimize aging changes of diastolic function. This training-effect may play a key role to preserve diastolic filling in older athletes. PMID:25795025

  20. Stimulation of functional vision in children with perinatal brain damage.

    PubMed

    Alimović, Sonja; Mejaski-Bosnjak, Vlatka

    2011-01-01

    Cerebral visual impairment (CVI) is one of the most common causes of bilateral visual loss, which frequently occurs due to perinatal brain injury. Vision in early life has great impact on acquisition of basic comprehensions which are fundamental for further development. Therefore, early detection of visual problems and early intervention is necessary. The aim of the present study is to determine specific visual functioning of children with perinatal brain damage and the influence of visual stimulation on development of functional vision at early age of life. We initially assessed 30 children with perinatal brain damage up to 3 years of age, who were reffered to our pediatric low vision cabinet in "Little house" from child neurologists, ophthalmologists Type and degree of visual impairment was determined according to functional vision assessment of each child. On the bases of those assessments different kind of visual stimulations were carried out with children who have been identified to have a certain visual impairment. Through visual stimulation program some of the children were stimulated with light stimulus, some with different materials under the ultraviolet (UV) light, and some with bright color and high contrast materials. Children were also involved in program of early stimulation of overall sensory motor development. Goals and methods of therapy were determined individually, based on observation of child's possibilities and need. After one year of program, reassessment was done. Results for visual functions and functional vision were compared to evaluate the improvement of the vision development. These results have shown that there was significant improvement in functional vision, especially in visual attention and visual communication.

  1. Young Children's Changing Conceptualizations of Brain Function: Implications for Teaching Neuroscience in Early Elementary Settings

    ERIC Educational Resources Information Center

    Marshall, Peter J.; Comalli, Christina E.

    2012-01-01

    Research Findings: Two exploratory studies explored young children's views of brain function and whether these views can be modified through exposure to a brief classroom intervention. In Study 1, children aged 4-13 years reported that the brain is used for "thinking," although older children were more likely than younger children to also endorse…

  2. Dynamic Functional Brain Connectivity for Face Perception

    PubMed Central

    Yang, Yuan; Qiu, Yihong; Schouten, Alfred C.

    2015-01-01

    Face perception is mediated by a distributed brain network comprised of the core system at occipito-temporal areas and the extended system at other relevant brain areas involving bilateral hemispheres. In this study we explored how the brain connectivity changes over the time for face-sensitive processing. We investigated the dynamic functional connectivity in face perception by analyzing time-dependent EEG phase synchronization in four different frequency bands: theta (4–7 Hz), alpha (8–14 Hz), beta (15–24 Hz), and gamma (25–45 Hz) bands in the early stages of face processing from 30 to 300 ms. High-density EEG were recorded from subjects who were passively viewing faces, buildings, and chairs. The dynamic connectivity within the core system and between the extended system were investigated. Significant differences between faces and non-faces mainly appear in theta band connectivity: (1) at the time segment of 90–120 ms between parietal area and occipito-temporal area in the right hemisphere, and (2) at the time segment of 150–180 ms between bilateral occipito-temporal areas. These results indicate (1) the importance of theta-band connectivity in the face-sensitive processing, and (2) that different parts of network are involved for the initial stage of face categorization and the stage of face structural encoding. PMID:26696870

  3. Brain Dynamics, Chaos and Bessel Functions

    NASA Astrophysics Data System (ADS)

    Freeman, W. J.; Capolupo, A.; Kozma, R.; Olivares del Campo, A.; Vitiello, G.

    2015-07-01

    By resorting to Freeman's observations showing that the distribution functions of impulse responses of cortex to sensory stimuli resemble Bessel functions, we study brain dynamics by considering the equivalence of spherical Bessel equation, in a given parametrization, to two oscillator equations, one damped and one amplified oscillator. The study of such a couple of equations, which are at the basis of the formulation of the dissipative many-body model, reveals the structure of the root loci of poles and zeros of solutions of Bessel equations, which are consistent with results obtained using ordinary differential equation techniques. We analyze stable and unstable limit cycles and consider thermodynamic features of brain functioning, which in this way may be described in terms of transitions between chaotic gas-like and ordered liquid-like behaviors. Nonlinearity dominates the dynamical critical transition regimes. Linear behavior, on the other hand, characterizes superpositions within self-organized neuronal domains in each dynamical phase. The formalism is consistent with the observed coexistence in circular causality of pulse density fields and wave density fields.

  4. Differential age-related changes in mitochondrial DNA repair activities in mouse brain regions

    PubMed Central

    Gredilla, Ricardo; Garm, Christian; Holm, Rikke; Bohr, Vilhelm A.; Stevnsner, Tinna

    2008-01-01

    Aging in the brain is characterized by increased susceptibility to neuronal loss and functional decline, and mitochondrial DNA (mtDNA) mutations are thought to play an important role in these processes. Due to the proximity of mtDNA to the main sites of mitochondrial free radical generation, oxidative stress is a major source of DNA mutations in mitochondria. The base excision repair (BER) pathway removes oxidative lesions from mtDNA, thereby constituting an important mechanism to avoid accumulation of mtDNA mutations. The complexity of the brain implies that exposure and defence against oxidative stress varies among brain regions and hence some regions may be particularly prone to accumulation of mtDNA damages. In the current study we investigated the efficiency of the BER pathway throughout the murine lifespan in mitochondria from cortex and hippocampus, regions that are central in mammalian cognition, and which are severely affected during aging and in neurodegenerative diseases. A regional specific regulation of mitochondrial DNA repair activities was observed with aging. In cortical mitochondria, DNA glycosylase activities peaked at middle-age followed by a significant drop at old age. However, only minor changes were observed in hippocampal mitochondria during the whole lifespan of the animals. Furthermore, DNA glycosylase activities were lower in hippocampal than in cortical mitochondria. Mitochondrial AP endonuclease activity increased in old animals in both brain regions. Our data suggest an important regional specific regulation of mitochondrial BER during aging. PMID:18701195

  5. Cell biology of normal brain aging: synaptic plasticity-cell death.

    PubMed

    Dorszewska, Jolanta

    2013-04-01

    Senescence of the brain seems to be related to increased levels of free oxygen radical (FOR). FOR may damage macromolecular compounds such as: proteins, lipids, and DNA. In the aging brain, increased FOR levels damage DNA, mitochondrial DNA (mtDNA), and nuclear DNA (nDNA). In DNA they damage single and double strands, leading to mutations in mtDNA and nDNA. Damage to mtDNA seems to result in decay of mitochondria, decreased production of ATP, and in the activation of the apoptotic process. In the aging brain, apoptosis does not seem to be activated in wild-type p53-expressing cells because the elevated levels of the p53 protein are no longer accompanied by decreased levels of the Bcl-2 protein and increased levels of the Bax protein. It seems that, in the aging brain, changes in the metabolism of neurons may lead to their decreased numbers in the cerebral and cerebellar cortex, hippocampus, basal nucleus of Meynert, locus ceruleus, and substantia nigra, as well as to decreased numbers of synapses and disturbed stimulation of synaptic plasticity in the senescent brain. Simultaneously, a decrease in neurogenesis in the aging brain may lead to a decline in the maintenance of tissue integrity, function, and regenerative response. Environmental enrichment and physical activity may improve hippocampal neurogenesis and induce neuronal plasticity. The morphological lesions in the senescent brain are undoubtedly followed by a disturbed balance between various types of neurons in the CNS. Nevertheless, the high plasticity of the CNS in humans most probably does not allow for the development of abnormalities in higher functions. PMID:23740630

  6. Diffusional anisotropy of the human brain assessed with diffusion-weighted MR: Relation with normal brain development and aging

    SciTech Connect

    Nomura, Toshiyuki; Sakuma, Hajime; Takeda, Kan; Tagami, Tomoyasu; Okuda, Yasuyuki; Nakagawa, Tsuyoshi )

    1994-02-01

    To analyze diffusional anisotropy in frontal and occipital white matter of human brain quantitatively as a function of age by using diffusion-weighted MR imaging. Ten neonates (<1 month), 13 infants (1-10 months), 9 children (1-11 years), and 16 adults (20-79 years) were examined. After taking axial spin-echo images of the brain, diffusion-sensitive gradients were added parallel or perpendicular to the orientation of nerve fibers. The apparent diffusion coefficient parallel to the nerve fibers (0) and that perpendicular to the fibers (90) were computed. The anisotropic ratio (90/0) was calculated as a function of age. Anisotropic ratios of frontal white matter were significantly larger in neonates as compared with infants, children, or adults. The ratios showed rapid decrease until 6 months and thereafter were identical in all subjects. In the occipital lobe, the ratios were also greater in neonates, but the differences from other age groups were not so prominent as in the frontal lobe. Comparing anisotropic ratios between frontal and occipital lobes, a significant difference was observed only in neonates. Diffusion-weighted images demonstrated that the myelination process starts earlier in the occipital lobe than in the frontal lobe. The changes of diffusional anisotropy in white matter are completed within 6 months after birth. Diffusion-weighted imaging provides earlier detection of brain myelination compared with the conventional T1- and T2-weighted images. 18 refs., 6 figs., 1 tab.

  7. Age Differences in Brain Activity Related to Unsuccessful Declarative Memory Retrieval

    PubMed Central

    Grady, Cheryl L.; St-Laurent, Marie; Burianová, Hana

    2016-01-01

    Although memory recall is known to be reduced with normal aging, little is known about the patterns of brain activity that accompany these recall failures. By assessing faulty memory, we can identify the brain regions engaged during retrieval attempts in the absence of successful memory and determine the impact of aging on this functional activity. We used functional magnetic resonance imaging to examine age differences in brain activity associated with memory failure in three memory retrieval tasks: autobiographical (AM), episodic (EM) and semantic (SM). Compared to successful memory retrieval, both age groups showed more activity when they failed to recall a memory in regions consistent with the salience network (SLN), a brain network also associated with non-memory errors. Both groups also showed strong functional coupling among SLN regions during incorrect trials and in intrinsic patterns of functional connectivity. In comparison to young adults, older adults demonstrated (1) less activity within the SLN during unsuccessful AM trials; (2) weaker intrinsic functional connectivity between SLN nodes and dorsolateral prefrontal cortex; and (3) less differentiation of SLN functional connectivity during incorrect trials across memory conditions. These results suggest that the SLN is engaged during recall failures, as it is for non-memory errors, which may be because errors in general have particular salience for adapting behavior. In older adults, the dedifferentiation of functional connectivity within the SLN across memory conditions and the reduction of functional coupling between it and prefrontal cortex may indicate poorer internetwork communication and less flexible use of cognitive control processes, either while retrieval is attempted or when monitoring takes place after retrieval has failed. PMID:25541365

  8. Functional recovery in aging mice after experimental stroke.

    PubMed

    Manwani, Bharti; Liu, Fudong; Xu, Yan; Persky, Rebecca; Li, Jun; McCullough, Louise D

    2011-11-01

    Aging is a non-modifiable risk factor for stroke. Since not all strokes can be prevented, a major emerging area of research is the development of effective strategies to enhance functional recovery after stroke. However, in the vast majority of pre-clinical stroke studies, the behavioral tests used to assess functional recovery have only been validated for use in young animals, or are designed for rats. Mice are increasingly utilized in stroke models but well validated behavioral tests designed for rats are not necessarily reproducible in mice. We examined a battery of behavioral tests to evaluate functional recovery in an aging murine model of stroke. We found that the vertical pole, hanging wire and open field can accurately assess acute behavioral impairments after stroke in both young and aging male mice, but animals recover rapidly on these tasks. The corner test can accurately and repeatedly differentiate stroke from sham animals up to 30 days post stroke and can be performed reliably in aging mice. Aging male mice had significantly worse behavioral impairment compared to young male mice in the first two weeks after stroke but eventually recovered to the same degree as young mice. In contrast, chronic infarct size, as measured by ipsilateral cerebral atrophy, was significantly lower in aging male mice compared to young male mice. Reactive gliosis, formation of glial scar, and an enhanced innate immune response was seen in the aging brain and may contribute to the delayed behavioral recovery seen in the aging animals.

  9. Long-term food restriction prevents aging-associated sphingolipid turnover dysregulation in the brain.

    PubMed

    Babenko, Nataliya A; Shakhova, Elena G

    2014-01-01

    Abnormalities of sphingolipid turnover in the brain during normal aging and age-related neurological disorders were associated with the neurons loss and cognitive malfunction. Calorie restriction (CR) prevented age-related deficits in hippocampal long-term potentiation and improved cognitive function at old age. In the paper we investigated the ceramide and sphingomyelin (SM) levels in the brain regions, which are critical for learning and memory of 3- and 24-month-old rats, as well as the correction of sphingolipid turnover in the brain of old rats, by means of the CR diet and modulators of SM turnover. Using the [methyl-(14)C-choline]SM, the neutral, but not the acid SMase activity has been observed to increase in both the hippocampus and brain cortex of 24-month-old rats with respect to 3-month-old animals. Age-dependent changes of neutral SMase activities were associated with ceramide accumulation and SM level drop in the brain structures studied. Treatment of the rats with the CR diet or N-acetylcysteine (NAC) or α-tocopherol acetate, but not an inhibitor of acid SMase imipramine, reduced the ceramide content and neutral SMase activity in the hippocampus of 24-month-old animals with respect to control rats of the same age. These results suggest that redox-sensitive neutral SMase plays important role in SM turnover dysregulation in both the hippocampus and neocortex at old age and that the CR diet can prevent the age-dependent accumulation of ceramide mainly via neutral SMase targeting.

  10. The choroid plexus and the paradox of interferons in the aging brain.

    PubMed

    Dhib-Jalbut, Suhayl

    2015-02-01

    The choroid plexus (CP) function is largely viewed as the source of cerebrospinal fluid (CSF) and as a barrier between the blood and the CSF. Other functions of the CP are becoming increasingly recognized as in the recent publication by Baruch et. al. who demonstrate increased expression of interferon type I mRNA signature (irf7, ifnß and ifit1) in CP of aged brains compared to younger brains, whereas interferon type II dependent genes (icam1, cxcl10, and ccl17) are reduced in the aging CP. The authors speculate an IFN-dependent mechanism that plays a role in the aging process and cognitive decline. This short communication summarizes the findings by the authors and highlights the seemingly paradoxical roles of IFN type I and type II in neuroinflammation.

  11. 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.

  12. 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.

  13. Lucid dreaming: an age-dependent brain dissociation.

    PubMed

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation. PMID:22639960

  14. Lucid dreaming: an age-dependent brain dissociation.

    PubMed

    Voss, Ursula; Frenzel, Clemens; Koppehele-Gossel, Judith; Hobson, Allan

    2012-12-01

    The current study focused on the distribution of lucid dreams in school children and young adults. The survey was conducted on a large sample of students aged 6-19 years. Questions distinguished between past and current experience with lucid dreams. Results suggest that lucid dreaming is quite pronounced in young children, its incidence rate drops at about age 16 years. Increased lucidity was found in those attending higher level compared with lower level schools. Taking methodological issues into account, we feel confident to propose a link between the natural occurrence of lucid dreaming and brain maturation.

  15. The impact of age on oncogenic potential: tumor-initiating cells and the brain microenvironment.

    PubMed

    Stoll, Elizabeth A; Horner, Philip J; Rostomily, Robert C

    2013-10-01

    Paradoxically, aging leads to both decreased regenerative capacity in the brain and an increased risk of tumorigenesis, particularly the most common adult-onset brain tumor, glioma. A shared factor contributing to both phenomena is thought to be age-related alterations in neural progenitor cells (NPCs), which function normally to produce new neurons and glia, but are also considered likely cells of origin for malignant glioma. Upon oncogenic transformation, cells acquire characteristics known as the hallmarks of cancer, including unlimited replication, altered responses to growth and anti-growth factors, increased capacity for angiogenesis, potential for invasion, genetic instability, apoptotic evasion, escape from immune surveillance, and an adaptive metabolic phenotype. The precise molecular pathogenesis and temporal acquisition of these malignant characteristics is largely a mystery. Recent studies characterizing NPCs during normal aging, however, have begun to elucidate mechanisms underlying the age-associated increase in their malignant potential. Aging cells are dependent upon multiple compensatory pathways to maintain cell cycle control, normal niche interactions, genetic stability, programmed cell death, and oxidative metabolism. A few multi-functional proteins act as 'critical nodes' in the coordination of these various cellular activities, although both intracellular signaling and elements within the brain environment are critical to maintaining a balance between senescence and tumorigenesis. Here, we provide an overview of recent progress in our understanding of how mechanisms underlying cellular aging inform on glioma pathogenesis and malignancy. PMID:23711239

  16. 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

  17. 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. PMID:27462210

  18. [Functional brain plasticity associated with motor learning].

    PubMed

    Doyon, Julien; Orban, Pierre; Barakat, Marc; Debas, Karen; Lungu, Ovidiu; Albouy, Geneviève; Fogel, Stuart; Proulx, Sébastien; Laventure, Samuel; Deslauriers, Jonathan; Duchesne, Catherine; Carrier, Julie; Benali, Habib

    2011-04-01

    This review presents the results of studies carried out in our laboratory that aim to investigate, through functional magnetic resonance imaging (fMRI), the brain plasticity associated with motor sequence learning, defined as our ability to integrate simple stereotyped movements into a single motor representation. Following a brief description of Doyon and colleagues' model (2002, 2005, 2009) of motor skill learning that has guided this work, we then describe the functional changes that occur at the different (rapid, slow, automatization) acquisition phases, and propose specific roles that the putamen, the cerebellum and their motor-related cortical areas, play in this form of motor behavior. Finally, we put forward evidence that post-training, non-REM sleep (and spindles in Stage 2 sleep, in particular) contributes to the consolidation of a motor sequence memory trace, and that increased activity within the striatum and/or the hippocampus mediates this mnemonic process.

  19. Healthy brain aging: role of exercise and physical activity.

    PubMed

    Rolland, Yves; Abellan van Kan, Gabor; Vellas, Bruno

    2010-02-01

    There is increasing evidence to suggest that physical activity has a protective effect on brain functioning in older people. To date, no randomized controlled trial (RCT) has shown that regular physical activity prevents dementia, but recent RCTs suggests an improvement of cognitive functioning in persons involved in aerobic programs, and evidence is accumulating from basic research. Future prevention of Alzheimer disease may depend on lifestyle habits such as physical activity.

  20. Regional and Gender Study of Neuronal Density in Brain during Aging and in Alzheimer's Disease

    PubMed Central

    Martínez-Pinilla, Eva; Ordóñez, Cristina; del Valle, Eva; Navarro, Ana; Tolivia, Jorge

    2016-01-01

    Background: Learning processes or language development are only some of the cognitive functions that differ qualitatively between men and women. Gender differences in the brain structure seem to be behind these variations. Indeed, this sexual dimorphism at neuroanatomical level is accompanied unequivocally by differences in the way that aging and neurodegenerative diseases affect men and women brains. Objective: The aim of this study is the analysis of neuronal density in four areas of the hippocampus, and entorhinal and frontal cortices to analyze the possible gender influence during normal aging and in Alzheimer's disease (AD). Methods: Human brain tissues of different age and from both sexes, without neurological pathology and with different Braak's stages of AD, were studied. Neuronal density was quantified using the optical dissector. Results: Our results showed the absence of a significant neuronal loss during aging in non-pathological brains in both sexes. However, we have demonstrated specific punctual significant variations in neuronal density related with the age and gender in some regions of these brains. In fact, we observed a higher neuronal density in CA3 and CA4 hippocampal areas of non-pathological brains of young men compared to women. During AD, we observed a negative correlation between Braak's stages and neuronal density in hippocampus, specifically in CA1 for women and CA3 for men, and in frontal cortex for both, men and women. Conclusion: Our data demonstrated a sexual dimorphism in the neuronal vulnerability to degeneration suggesting the need to consider the gender of the individuals in future studies, regarding neuronal loss in aging and AD, in order to avoid problems in interpreting data.

  1. Regional and Gender Study of Neuronal Density in Brain during Aging and in Alzheimer's Disease

    PubMed Central

    Martínez-Pinilla, Eva; Ordóñez, Cristina; del Valle, Eva; Navarro, Ana; Tolivia, Jorge

    2016-01-01

    Background: Learning processes or language development are only some of the cognitive functions that differ qualitatively between men and women. Gender differences in the brain structure seem to be behind these variations. Indeed, this sexual dimorphism at neuroanatomical level is accompanied unequivocally by differences in the way that aging and neurodegenerative diseases affect men and women brains. Objective: The aim of this study is the analysis of neuronal density in four areas of the hippocampus, and entorhinal and frontal cortices to analyze the possible gender influence during normal aging and in Alzheimer's disease (AD). Methods: Human brain tissues of different age and from both sexes, without neurological pathology and with different Braak's stages of AD, were studied. Neuronal density was quantified using the optical dissector. Results: Our results showed the absence of a significant neuronal loss during aging in non-pathological brains in both sexes. However, we have demonstrated specific punctual significant variations in neuronal density related with the age and gender in some regions of these brains. In fact, we observed a higher neuronal density in CA3 and CA4 hippocampal areas of non-pathological brains of young men compared to women. During AD, we observed a negative correlation between Braak's stages and neuronal density in hippocampus, specifically in CA1 for women and CA3 for men, and in frontal cortex for both, men and women. Conclusion: Our data demonstrated a sexual dimorphism in the neuronal vulnerability to degeneration suggesting the need to consider the gender of the individuals in future studies, regarding neuronal loss in aging and AD, in order to avoid problems in interpreting data. PMID:27679571

  2. 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

  3. Brain Na+, K+-ATPase Activity In Aging and Disease

    PubMed Central

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    Na+/K+ pump or sodium- and potassium-activated adenosine 5’-triphosphatase (Na+, K+-ATPase), its enzymatic version, is a crucial protein responsible for the electrochemical gradient across the cell membranes. It is an ion transporter, which in addition to exchange cations, is the ligand for cardenolides. This enzyme regulates the entry of K+ with the exit of Na+ from cells, being the responsible for Na+/K+ equilibrium maintenance through neuronal membranes. This transport system couples the hydrolysis of one molecule of ATP to exchange three sodium ions for two potassium ions, thus maintaining the normal gradient of these cations in animal cells. Oxidative metabolism is very active in brain, where large amounts of chemical energy as ATP molecules are consumed, mostly required for the maintenance of the ionic gradients that underlie resting and action potentials which are involved in nerve impulse propagation, neurotransmitter release and cation homeostasis. Protein phosphorylation is a key process in biological regulation. At nervous system level, protein phosphorylation is the major molecular mechanism through which the function of neural proteins is modulted in response to extracellular signals, including the response to neurotransmitter stimuli. It is the major mechanism of neural plasticity, including memory processing. The phosphorylation of Na+, K+-ATPase catalytic subunit inhibits enzyme activity whereas the inhibition of protein kinase C restores the enzyme activity. The dephosphorylation of neuronal Na+, K+-ATPase is mediated by calcineurin, a serine / threonine phosphatase. The latter enzyme is involved in a wide range of cellular responses to Ca2+ mobilizing signals, in the regulation of neuronal excitability by controlling the activity of ion channels, in the release of neurotransmitters and hormones, as well as in synaptic plasticity and gene transcription. In the present article evidence showing Na+, K+-ATPase involvement in signaling pathways

  4. Low-frequency transcranial magnetic stimulation is beneficial for enhancing synaptic plasticity in the aging brain

    PubMed Central

    Zhang, Zhan-chi; Luan, Feng; Xie, Chun-yan; Geng, Dan-dan; Wang, Yan-yong; Ma, Jun

    2015-01-01

    In the aging brain, cognitive function gradually declines and causes a progressive reduction in the structural and functional plasticity of the hippocampus. Transcranial magnetic stimulation is an emerging and novel neurological and psychiatric tool used to investigate the neurobiology of cognitive function. Recent studies have demonstrated that low-frequency transcranial magnetic stimulation (≤1 Hz) ameliorates synaptic plasticity and spatial cognitive deficits in learning-impaired mice. However, the mechanisms by which this treatment improves these deficits during normal aging are still unknown. Therefore, the current study investigated the effects of transcranial magnetic stimulation on the brain-derived neurotrophic factor signal pathway, synaptic protein markers, and spatial memory behavior in the hippocampus of normal aged mice. The study also investigated the downstream regulator, Fyn kinase, and the downstream effectors, synaptophysin and growth-associated protein 43 (both synaptic markers), to determine the possible mechanisms by which transcranial magnetic stimulation regulates cognitive capacity. Transcranial magnetic stimulation with low intensity (110% average resting motor threshold intensity, 1 Hz) increased mRNA and protein levels of brain-derived neurotrophic factor, tropomyosin receptor kinase B, and Fyn in the hippocampus of aged mice. The treatment also upregulated the mRNA and protein expression of synaptophysin and growth-associated protein 43 in the hippocampus of these mice. In conclusion, brain-derived neurotrophic factor signaling may play an important role in sustaining and regulating structural synaptic plasticity induced by transcranial magnetic stimulation in the hippocampus of aging mice, and Fyn may be critical during this regulation. These responses may change the structural plasticity of the aging hippocampus, thereby improving cognitive function. PMID:26199608

  5. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing.

  6. Dehydration affects brain structure and function in healthy adolescents.

    PubMed

    Kempton, Matthew J; Ettinger, Ulrich; Foster, Russell; Williams, Steven C R; Calvert, Gemma A; Hampshire, Adam; Zelaya, Fernando O; O'Gorman, Ruth L; McMorris, Terry; Owen, Adrian M; Smith, Marcus S

    2011-01-01

    It was recently observed that dehydration causes shrinkage of brain tissue and an associated increase in ventricular volume. Negative effects of dehydration on cognitive performance have been shown in some but not all studies, and it has also been reported that an increased perceived effort may be required following dehydration. However, the effects of dehydration on brain function are unknown. We investigated this question using functional magnetic resonance imaging (fMRI) in 10 healthy adolescents (mean age = 16.8, five females). Each subject completed a thermal exercise protocol and nonthermal exercise control condition in a cross-over repeated measures design. Subjects lost more weight via perspiration in the thermal exercise versus the control condition (P < 0.0001), and lateral ventricle enlargement correlated with the reduction in body mass (r = 0.77, P = 0.01). Dehydration following the thermal exercise protocol led to a significantly stronger increase in fronto-parietal blood-oxygen-level-dependent (BOLD) response during an executive function task (Tower of London) than the control condition, whereas cerebral perfusion during rest was not affected. The increase in BOLD response after dehydration was not paralleled by a change in cognitive performance, suggesting an inefficient use of brain metabolic activity following dehydration. This pattern indicates that participants exerted a higher level of neuronal activity in order to achieve the same performance level. Given the limited availability of brain metabolic resources, these findings suggest that prolonged states of reduced water intake may adversely impact executive functions such as planning and visuo-spatial processing. PMID:20336685

  7. Challenges of multimorbidity of the aging brain: a critical update.

    PubMed

    Jellinger, Kurt A; Attems, Johannes

    2015-04-01

    A major problem in elderly patients is the high incidence of multiple pathologies, referred to as multimorbidity, in the aging brain. It has been increasingly recognized that co-occurrence of neurodegenerative proteinopathies and other pathologies including cerebrovascular disorders is a frequent event in the brains of both cognitively intact and impaired aged subjects. Although clinical and neuropathological diagnostic criteria of the major neurodegenerative diseases have been improved, major challenges arise from cerebral multimorbidity, and the thresholds to cause clinical overt dementia are ill defined. More than 80% of aged human brains show neurodegenerative non-Alzheimer type proteinopathies and other pathologies which, however, frequently have been missed clinically and are even difficult to identify at neuropathological examination. Autopsy studies differ in selection criteria and the applied evaluation methods. Therefore, irrespective of the clinical symptoms, the frequency of cerebral pathologies vary considerably: Alzheimer-related pathology is seen in 19-100%, with "pure" Alzheimer's disease (AD) in 17-72%, Lewy pathology in 6-39% (AD + Lewy disease 9-28%), vascular pathologies in 28-93% (10.7-78% "pure" vascular dementia), TDP-43 proteinopathy in 6-39%, hippocampal sclerosis in 8-1%, and mixed pathologies in 10-93%. These data clearly suggest that pathologically deposited proteins in neurodegenerating diseases mutually interact and are influenced by other factors, in particular cardiovascular and cerebrovascular ones, to promote cognitive decline and other clinical symptoms. It is obvious that cognitive and other neuropsychiatric impairment in the aged result from a multimorbid condition in the CNS rather than from a single disease and that the number of complex pathologies progresses with increasing age. These facts have implications for improvement of the clinical diagnosis and prognosis, the development of specific biomarkers, preventive strategies

  8. A look inside the diabetic brain: Contributors to diabetes-induced brain aging.

    PubMed

    Wrighten, Shayna A; Piroli, Gerardo G; Grillo, Claudia A; Reagan, Lawrence P

    2009-05-01

    Central nervous system (CNS) complications resulting from diabetes is a problem that is gaining more acceptance and attention. Recent evidence suggests morphological, electrophysiological and cognitive changes, often observed in the hippocampus, in diabetic individuals. Many of the CNS changes observed in diabetic patients and animal models of diabetes are reminiscent of the changes seen in normal aging. The central commonalities between diabetes-induced and age-related CNS changes have led to the theory of advanced brain aging in diabetic patients. This review summarizes the findings of the literature as they relate to the relationship between diabetes and dementia and discusses some of the potential contributors to diabetes-induced CNS impairments.

  9. Influence of age on neurotransmitter function.

    PubMed

    Simpkins, J W; Millard, W J

    1987-12-01

    Regulation by neurotransmitters of anterior pituitary hormone secretion is complex and a thorough understanding of their normal role in hormone secretion is a prerequisite to understanding their involvement in age-related changes in endocrine function. To date, uncertainties far out-number demonstrated causative relationships between alterations in neurotransmitter release and resulting age-associated changes in hormone secretion. The best demonstrated relationships are the following. First, a decline in function of the TIDA system is responsible, in part, for the age-related elevation in prolactin secretion and may be involved in the decline in LH secretion. Second, the age-related decrease in hypothalamic norepinephrine turnover plays a role in the decline in LH and GH secretion and may be involved in alterations in TSH secretion during aging. Third, the decline in circadian activity of suprachiasmatic nucleus serotoninergic neurons may account for the blunting of circadian rhythms in the secretions of several anterior pituitary hormones in old animals. Fourth, evidence exists for an age-related decline in function of LHRH neurons, which may contribute to the observation of blunted LH secretion in old animals. Finally, somatostatin release may be increased in old animals, which likely contributes to the age-related decline in GH secretion. Other hypothalamic-releasing hormones have only recently been isolated and characterized; thus, little research on their age-related alterations has been done. Research on these neuropeptides will contribute further to our understanding of the role of neurotransmitters in age-related alterations in hormone secretion.

  10. 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.

  11. Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store

    PubMed Central

    Thibault, Olivier; Gant, John C; Landfield, Philip W

    2007-01-01

    Evidence accumulated over more than two decades has implicated Ca2+ dysregulation in brain aging and Alzheimer's disease (AD), giving rise to the Ca2+ hypothesis of brain aging and dementia. Electrophysiological, imaging, and behavioral studies in hippocampal or cortical neurons of rodents and rabbits have revealed aging-related increases in the slow afterhyperpolarization, Ca2+ spikes and currents, Ca2+ transients, and L-type voltage-gated Ca2+ channel (L-VGCC) activity. Several of these changes have been associated with age-related deficits in learning or memory. Consequently, one version of the Ca2+ hypothesis has been that increased L-VGCC activity drives many of the other Ca2+-related biomarkers of hippocampal aging. In addition, other studies have reported aging- or AD model-related alterations in Ca2+ release from ryanodine receptors (RyR) on intracellular stores. The Ca2+-sensitive RyR channels amplify plasmalemmal Ca2+ influx by the mechanism of Ca2+-induced Ca2+ release (CICR). Considerable evidence indicates that a preferred functional link is present between L-VGCCs and RyRs which operate in series in heart and some brain cells. Here, we review studies implicating RyRs in altered Ca2+ regulation in cell toxicity, aging, and AD. A recent study from our laboratory showed that increased CICR plays a necessary role in the emergence of Ca2+-related biomarkers of aging. Consequently, we propose an expanded L-VGCC/Ca2+ hypothesis, in which aging/pathological changes occur in both L-type Ca2+ channels and RyRs, and interact to abnormally amplify Ca2+ transients. In turn, the increased transients result in dysregulation of multiple Ca2+-dependent processes and, through somewhat different pathways, in accelerated functional decline during aging and AD. PMID:17465978

  12. Indestructible plastic: the neuroscience of the new aging brain

    PubMed Central

    Holman, Constance; de Villers-Sidani, Etienne

    2014-01-01

    In recent years, research on experience-dependent plasticity has provided valuable insight on adaptation to environmental input across the lifespan, and advances in understanding the minute cellular changes underlying the brain’s capacity for self-reorganization have opened exciting new possibilities for treating illness and injury. Ongoing work in this line of inquiry has also come to deeply influence another field: cognitive neuroscience of the normal aging. This complex process, once considered inevitable or beyond the reach of treatment, has been transformed into an arena of intense investigation and strategic intervention. However, important questions remain about this characterization of the aging brain, and the assumptions it makes about the social, cultural, and biological space occupied by cognition in the older individual and body. The following paper will provide a critical examination of the move from basic experiments on the neurophysiology of experience-dependent plasticity to the growing market for (and public conception of) cognitive aging as a medicalized space for intervention by neuroscience-backed technologies. Entangled with changing concepts of normality, pathology, and self-preservation, we will argue that this new understanding, led by personalized cognitive training strategies, is approaching a point where interdisciplinary research is crucial to provide a holistic and nuanced understanding of the aging process. This new outlook will allow us to move forward in a space where our knowledge, like our new conception of the brain, is never static. PMID:24782746

  13. The effects of age, sex, and hormones on emotional conflict-related brain response during adolescence.

    PubMed

    Cservenka, Anita; Stroup, Madison L; Etkin, Amit; Nagel, Bonnie J

    2015-10-01

    While cognitive and emotional systems both undergo development during adolescence, few studies have explored top-down inhibitory control brain activity in the context of affective processing, critical to informing adolescent psychopathology. In this study, we used functional magnetic resonance imaging to examine brain response during an Emotional Conflict (EmC) Task across 10-15-year-old youth. During the EmC Task, participants indicated the emotion of facial expressions, while disregarding emotion-congruent and incongruent words printed across the faces. We examined the relationships of age, sex, and gonadal hormones with brain activity on Incongruent vs. Congruent trials. Age was negatively associated with middle frontal gyrus activity, controlling for performance and movement confounds. Sex differences were present in occipital and parietal cortices, and were driven by activation in females, and deactivation in males to Congruent trials. Testosterone was negatively related with frontal and striatal brain response in males, and cerebellar and precuneus response in females. Estradiol was negatively related with fronto-cerebellar, cingulate, and precuneus brain activity in males, and positively related with occipital response in females. To our knowledge, this is the first study reporting the effects of age, sex, and sex steroids during an emotion-cognition task in adolescents. Further research is needed to examine longitudinal development of emotion-cognition interactions and deviations in psychiatric disorders in adolescence.

  14. Heritability of human brain functioning as assessed by electroencephalography

    SciTech Connect

    Beijsterveldt, C.E.M. van; Geus, E.J.C. de; Boomsma, D.I.

    1996-03-01

    To study the genetic and environmental contributions to individual differences in CNS functioning, the electroencephalogram (EEG) was measured in 213 twin pairs age 16 years. EEG was measured in 91 MZ and 122 DZ twins. To quantify sex differences in the genetic architecture, EEG was measured in female and male same-sex twins and in opposite-sex twins. EEG was recorded on 14 scalp positions during quiet resting with eyes closed. Spectral powers were calculated for four frequency bands: delta, theta, alpha, and beta. Twin correlations pointed toward high genetic influences for all these powers and scalp locations. Model fitting confirmed these findings; the largest part of the variance of the EEG is explained by additive genetic factors. The averaged heritabilities for the delta, theta, alpha, and beta frequencies was 76%, 89%, 89%, and 86%, respectively. Multivariate analyses suggested that the same genes for EEG alpha rhythm were expressed in different brain areas in the left and right hemisphere. This study shows that brain functioning, as indexed by rhythmic brain-electrical activity, is one of the most heritable characteristics in humans. 44 refs., 5 figs., 4 tabs.

  15. Early Shifts of Brain Metabolism by Caloric Restriction Preserve White Matter Integrity and Long-Term Memory in Aging Mice

    PubMed Central

    Guo, Janet; Bakshi, Vikas; Lin, Ai-Ling

    2015-01-01

    Preservation of brain integrity with age is highly associated with lifespan determination. Caloric restriction (CR) has been shown to increase longevity and healthspan in various species; however, its effects on preserving living brain functions in aging remain largely unexplored. In the study, we used multimodal, non-invasive neuroimaging (PET/MRI/MRS) to determine in vivo brain glucose metabolism, energy metabolites, and white matter structural integrity in young and old mice fed with either control or 40% CR diet. In addition, we determined the animals’ memory and learning ability with behavioral assessments. Blood glucose, blood ketone bodies, and body weight were also measured. We found distinct patterns between normal aging and CR aging on brain functions – normal aging showed reductions in brain glucose metabolism, white matter integrity, and long-term memory, resembling human brain aging. CR aging, in contrast, displayed an early shift from glucose to ketone bodies metabolism, which was associated with preservations of brain energy production, white matter integrity, and long-term memory in aging mice. Among all the mice, we found a positive correlation between blood glucose level and body weight, but an inverse association between blood glucose level and lifespan. Our findings suggest that CR could slow down brain aging, in part due to the early shift of energy metabolism caused by lower caloric intake, and we were able to identify the age-dependent effects of CR non-invasively using neuroimaging. These results provide a rationale for CR-induced sustenance of brain health with extended longevity. PMID:26617514

  16. Superior longitudinal fasciculus and language functioning in healthy aging.

    PubMed

    Madhavan, Kiely M; McQueeny, Tim; Howe, Steven R; Shear, Paula; Szaflarski, Jerzy

    2014-05-01

    Structural deterioration of brain tissue in older adults is thought to be responsible for the majority of age-related cognitive decline. Disruption of widespread cortical networks due to a loss of axonal integrity may also play an important role. Research examining correlations between structural change and functional decline has focused heavily on working memory, processing speed, and executive processes while other aspects of cognition, such as language functioning, have received less attention. The current study aimed to determine whether age-related changes in the superior longitudinal fasciculus (SLF), are responsible for the deterioration in language functioning associated with age. Subjects included 112 right-handed volunteers (ages 19-76). For each subject, the SLF of the left hemisphere was reconstructed from diffusion tensor images (DTI). Mean fractional anisotropy (FA) values were extracted from parietal (SLFp) and temporal (SLFt) bundles. Language functioning was measured using the Peabody Picture Vocabulary Test (PPVT), Boston Naming Test (BNT), Controlled Oral Word Association Test (COWAT), and Semantic Fluency Test (SFT). Regression analyses revealed that males and females showed a different pattern of decline in FA across adulthood. For males, greater SLFt FA was significantly associated with increased COWAT performance, and there was a positive relationship between both age and SLFp FA with BNT scores. In females, greater SLFp FA was related to lower COWAT performance. Taken together, the results suggest that white matter integrity of the SLF follows a different pattern of decline in adulthood for males and females, and this decline differentially affects language functioning.

  17. Brain regions essential for improved lexical access in an aged aphasic patient: a case report

    PubMed Central

    Meinzer, Marcus; Flaisch, Tobias; Obleser, Jonas; Assadollahi, Ramin; Djundja, Daniela; Barthel, Gabriela; Rockstroh, Brigitte

    2006-01-01

    Background The relationship between functional recovery after brain injury and concomitant neuroplastic changes is emphasized in recent research. In the present study we aimed to delineate brain regions essential for language performance in aphasia using functional magnetic resonance imaging and acquisition in a temporal sparse sampling procedure, which allows monitoring of overt verbal responses during scanning. Case presentation An 80-year old patient with chronic aphasia (2 years post-onset) was investigated before and after intensive language training using an overt picture naming task. Differential brain activation in the right inferior frontal gyrus for correct word retrieval and errors was found. Improved language performance following therapy was mirrored by increased fronto-thalamic activation while stability in more general measures of attention/concentration and working memory was assured. Three healthy age-matched control subjects did not show behavioral changes or increased activation when tested repeatedly within the same 2-week time interval. Conclusion The results bear significance in that the changes in brain activation reported can unequivocally be attributed to the short-term training program and a language domain-specific plasticity process. Moreover, it further challenges the claim of a limited recovery potential in chronic aphasia, even at very old age. Delineation of brain regions essential for performance on a single case basis might have major implications for treatment using transcranial magnetic stimulation. PMID:16916464

  18. The Gompertz function does not measure ageing.

    PubMed

    Driver, C

    2001-01-01

    The Gompertz transform of the distribution function for the age at death expresses mortality in a form R = R0e(alphat) where R0 is the mortality at time zero and alpha is the rate of increase of mortality, frequently taken as the rate of ageing. The slope of the line alpha is frequently used as a measure of the rate of ageing. It is argued that it is incorrect to use alpha in this way. To support this contention, a paradox is produced whereby selection for longevity increases alpha, which could lead to the absurd conclusion that selection for longevity increases the rate of ageing.

  19. Granulovacuolar degeneration in the ageing brain and in dementia.

    PubMed

    Ball, M J; Lo, P

    1977-05-01

    Quantitative morphometry with a sampling stage light microscope was performed to determine the severity of granulovacuolar degeneration of hippocampal neurones in serially sectioned temporal lobe from mentally normal subjects of different ages and from demented patients. The degree of granulovacuolar change in control brains increased slightly with increasing age; the "granulovacuolar index" of cases with Alzheimer's disease exceeded by many times that of age-matched controls. This significant difference was demonstrable whether the granulovacuolar severity was expressed as number of affected cells per volume of cortex analysed, or as the percentage involvement of total neurones counted in the hippocampus. The posterior half of each dement's hippocampus was found to be more susceptible to this augmented granulovacuolar degeneration than the anterior half, a selectivity already observed for neurofibrillary tangel formation in the same material.

  20. [Hunger-driven modulation in brain functions].

    PubMed

    Hirano, Yukinori; Saitoe, Minoru

    2014-01-01

    \\All organisms must obtain nutrition in order to survive and produce their progeny. In the natural environment, however, adequate nutrition or food is not always available. Thus, all organisms are equipped with mechanisms by which their nutritional condition alters their internal activities. In animals, the loss of nutritional intake (fasting) alters not only metabolism, but also behavior in a manner dependent on hormones such as insulin, glucagon, leptin, and ghrelin. As a result, animals are able to maintain their blood sugar level, and are motivated to crave food upon fasting. Moreover, our recent study revealed a novel role of hunger, which facilitates long-term memory (LTM) formation, and its molecular mechanism in the fruit fly, Drosophila. Here, we review the overall effect of fasting, and how fasting affects brain function. I then introduce our finding in which mild fasting facilitates LTM formation, and discuss its biological significance. PMID:24371130

  1. [Hunger-driven modulation in brain functions].

    PubMed

    Hirano, Yukinori; Saitoe, Minoru

    2014-01-01

    \\All organisms must obtain nutrition in order to survive and produce their progeny. In the natural environment, however, adequate nutrition or food is not always available. Thus, all organisms are equipped with mechanisms by which their nutritional condition alters their internal activities. In animals, the loss of nutritional intake (fasting) alters not only metabolism, but also behavior in a manner dependent on hormones such as insulin, glucagon, leptin, and ghrelin. As a result, animals are able to maintain their blood sugar level, and are motivated to crave food upon fasting. Moreover, our recent study revealed a novel role of hunger, which facilitates long-term memory (LTM) formation, and its molecular mechanism in the fruit fly, Drosophila. Here, we review the overall effect of fasting, and how fasting affects brain function. I then introduce our finding in which mild fasting facilitates LTM formation, and discuss its biological significance.

  2. Apolipoprotein E and cholesterol in aging and disease in the brain

    PubMed Central

    de Chaves, Elena Posse; Narayanaswami, Vasanthy

    2008-01-01

    Cholesterol can be detrimental or vital, and must be present in the right place at the right time and in the right amount. This is well known in the heart and the vascular system. However, in the CNS cholesterol is still an enigma, although several of its fundamental functions in the brain have been identified. Brain cholesterol has attracted additional attention owing to its close connection to ApoE, a key polymorphic transporter of extracellular cholesterol in humans. Indeed, both cholesterol and ApoE are so critical to fundamental activities of the brain, that the brain regulates their synthesis autonomously. Yet, similar control mechanisms of ApoE and cholesterol homeostasis may exist on either sides of the blood–brain barrier. One indication is that the APOE ε4 allele is associated with hypercholesterolemia and a proatherogenic profile on the vascular side and with increased risk of Alzheimer’s disease on the CNS side. In this review, we draw attention to the association between cholesterol and ApoE in the aging and diseased brain, and to the behavior of the ApoE4 protein at the molecular level. The attempt to correlate in vivo and in vitro observations is challenging but crucial for developing future strategies to address ApoE-related aberrations in cholesterol metabolism selectively in the brain. PMID:19649144

  3. Human neurologic function and the aging process.

    PubMed

    Potvin, A R; Syndulko, K; Tourtellotte, W W; Lemmon, J A; Potvin, J H

    1980-01-01

    Sixty-one normal men whose ages ranged from 20 to 80 years were evaluated on two occasions by means of a comprehensive series of 128 instrumented tests of neurologic function. The tests measured cognition, vision, strength, steadiness, reactions, speed, coordination, fatigue, gait, station, sensations, and tasks of daily living. The reliability of each test measured was determined, and any measure found unreliable (r less than or equal to 0.41) was not further analyzed. Significant age-related linear decreases were found for almost all neurologic functions. The declines over the age span varied from less than 10 percent to more than 90 percent for different functions. For the upper extremities, the largest declines (greater than 50 percent) were in hand-force steadiness, speed of hand-arm movements, and vibration sense; for the lower extremities, the largest declines were in one-legged balance with eyes closed and in vibration sense. For 13 of 14 tests in which significant dominant body-side effects were found, larger re-testing 7-10 days later, the subjects improved their scores by more than 5 percent on only 17 tests, 9 of which concerned the activities of daily living. No significant differential learning effects were found across age groups. The results point to the importance of developing a data bank on age-based neurologic function so that therapeutic effects can be evaluated in terms of age- and sex-matched normal functioning.

  4. Aging, mitochondria and male reproductive function.

    PubMed

    Amaral, Sandra; Ramalho-Santos, João

    2009-12-01

    The rise in life expectancy over the last century, together with higher maternal and paternal ages and have highlighted the issue of reduced fertility with advancing age. Aging of the male reproductive system is incited by multi-factorial changes at molecular, cellular and regulatory levels, and individual characteristics are highly variable, although strongly influenced by lifestyle and environmental factors. Damage accumulated with age leads to progressive deregulation of the hypothalamic-pituitary-gonadal axis and of local auto/paracrine interactions, thereby inducing changes in target organs such as the testis, penis and prostate. Elderly human males produce less testosterone, have fewer motile sperm and a higher incidence of erectile dysfunction and prostate disorders, all of which contribute to lower fertility. Cellular aging can manifest itself at several levels. Aging cells progressively accumulate "waste" products, resulting in a decreased functionally. Changes to mitochondria are among the most remarkable features observed in aging cells and several theories place mitochondria at the hub of cellular events related to aging, namely in terms of the accumulation of oxidative damage to cells and tissues, a process in which these organelles may play a prominent role, although alternative theories have also emerged. Furthermore, mitochondrial energy metabolism is also crucial for male reproductive function and mitochondria may therefore constitute a common link between aging and fertility loss.

  5. 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.

  6. Effects of the diet on brain function

    NASA Astrophysics Data System (ADS)

    Fernstrom, John D.

    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 neurotransmitter products.

  7. Neurogenetic Effects on Cognition in Aging Brains: A Window of Opportunity for Intervention?

    PubMed Central

    Reinvang, Ivar; Deary, Ian J.; Fjell, Anders M.; Steen, Vidar M.; Espeseth, Thomas; Parasuraman, Raja

    2010-01-01

    Knowledge of genetic influences on cognitive aging can constrain and guide interventions aimed at limiting age-related cognitive decline in older adults. Progress in understanding the neural basis of cognitive aging also requires a better understanding of the neurogenetics of cognition. This selective review article describes studies aimed at deriving specific neurogenetic information from three parallel and interrelated phenotype-based approaches: psychometric constructs, cognitive neuroscience-based processing measures, and brain imaging morphometric data. Developments in newer genetic analysis tools, including genome wide association, are also described. In particular, we focus on models for establishing genotype–phenotype associations within an explanatory framework linking molecular, brain, and cognitive levels of analysis. Such multiple-phenotype approaches indicate that individual variation in genes central to maintaining synaptic integrity, neurotransmitter function, and synaptic plasticity are important in affecting age-related changes in brain structure and cognition. Investigating phenotypes at multiple levels is recommended as a means to advance understanding of the neural impact of genetic variants relevant to cognitive aging. Further knowledge regarding the mechanisms of interaction between genetic and preventative procedures will in turn help in understanding the ameliorative effect of various experiential and lifestyle factors on age-related cognitive decline. PMID:21103005

  8. Age-associated differences on structural brain MRI in nondemented individuals from 71 to 103 years.

    PubMed

    Yang, Zixuan; Wen, Wei; Jiang, Jiyang; Crawford, John D; Reppermund, Simone; Levitan, Charlene; Slavin, Melissa J; Kochan, Nicole A; Richmond, Robyn L; Brodaty, Henry; Trollor, Julian N; Sachdev, Perminder S

    2016-04-01

    Successful brain aging in the oldest old (≥90 years) is underexplored. This study examined cross-sectional brain morphological differences from 8th to 11th decades of life in nondemented individuals by high-resolution magnetic resonance imaging. Two hundred seventy-seven nondemented community-dwelling participants (71-103 years) from Sydney Memory and Ageing Study and Sydney Centenarian Study comprised the sample, including a subsample of 160 cognitively high-functioning elders. Relationships between age and magnetic resonance imaging-derived measurements were studied using general linear models; and structural profiles of the ≥90 years were delineated. In full sample and the subsample, significant linear negative relationship of gray matter with age was found, with the greatest age effects in the medial temporal lobe and parietal and occipital cortices. This pattern was further confirmed by comparing directly the ≥90 years to the 71-89 years groups. Significant quadratic age effects on total white matter and white matter hyperintensities were observed. Our study demonstrated heterogeneous differences across brain regions between the oldest old and young old, with an emphasis on hippocampus, temporoposterior cortex, and white matter hyperintensities. PMID:26973107

  9. Working memory in middle-aged males: age-related brain activation changes and cognitive fatigue effects.

    PubMed

    Klaassen, Elissa B; Evers, Elisabeth A T; de Groot, Renate H M; Backes, Walter H; Veltman, Dick J; Jolles, Jelle

    2014-02-01

    We examined the effects of aging and cognitive fatigue on working memory (WM) related brain activation using functional magnetic resonance imaging. Age-related differences were investigated in 13 young and 16 middle-aged male school teachers. Cognitive fatigue was induced by sustained performance on cognitively demanding tasks (compared to a control condition). Results showed a main effect of age on left dorsolateral prefrontal and superior parietal cortex activation during WM encoding; greater activation was evident in middle-aged than young adults regardless of WM load or fatigue condition. An interaction effect was found in the dorsomedial prefrontal cortex (DMPFC); WM load-dependent activation was elevated in middle-aged compared to young in the control condition, but did not differ in the fatigue condition due to a reduction in activation in middle-aged in contrast to an increase in activation in the young group. These findings demonstrate age-related activation differences and differential effects of fatigue on activation in young and middle-aged adults.

  10. Age-related changes in brain support cells: Implications for stroke severity.

    PubMed

    Sohrabji, Farida; Bake, Shameena; Lewis, Danielle K

    2013-10-01

    Stroke is one of the leading causes of adult disability and the fourth leading cause of mortality in the US. Stroke disproportionately occurs among the elderly, where the disease is more likely to be fatal or lead to long-term supportive care. Animal models, where the ischemic insult can be controlled more precisely, also confirm that aged animals sustain more severe strokes as compared to young animals. Furthermore, the neuroprotection usually seen in younger females when compared to young males is not observed in older females. The preclinical literature thus provides a valuable resource for understanding why the aging brain is more susceptible to severe infarction. In this review, we discuss the hypothesis that stroke severity in the aging brain may be associated with reduced functional capacity of critical support cells. Specifically, we focus on astrocytes, that are critical for detoxification of the brain microenvironment and endothelial cells, which play a crucial role in maintaining the blood brain barrier. In view of the sex difference in stroke severity, this review also discusses studies of middle-aged acyclic females as well as the effects of the estrogen on astrocytes and endothelial cells.

  11. The Perimenopausal Aging Transition in the Female Rat Brain: Decline in Bioenergetic Systems and Synaptic Plasticity

    PubMed Central

    Yin, Fei; Yao, Jia; Sancheti, Harsh; Feng, Tao; Melcangi, Roberto C.; Morgan, Todd E.; Finch, Caleb E.; Pike, Christian J.; Mack, Wendy J.; Cadenas, Enrique; Brinton, Roberta D.

    2015-01-01

    The perimenopause is an aging transition unique to the female that leads to reproductive senescence which can be characterized by multiple neurological symptoms. To better understand potential underlying mechanisms of neurological symptoms of perimenopause, the current study determined genomic, biochemical, brain metabolic and electrophysiological transformations that occur during this transition using a rat model recapitulating fundamental characteristics of the human perimenopause. Gene expression analyses indicated two distinct aging programs: chronological and endocrine. A critical period emerged during the endocrine transition from regular to irregular cycling characterized by decline in bioenergetic gene expression, confirmed by deficits in FDG-PET brain metabolism, mitochondrial function, and long-term potentiation. Bioinformatic analysis predicted insulin/IGF1 and AMPK/PGC1α signaling pathways as upstream regulators. Onset of acyclicity was accompanied by a rise in genes required for fatty acid metabolism, inflammation, and mitochondrial function. Subsequent chronological aging resulted in decline of genes required for mitochondrial function and β-amyloid degradation. Emergence of glucose hypometabolism and impaired synaptic function in brain provide plausible mechanisms of neurological symptoms of perimenopause and may be predictive of later life vulnerability to hypometabolic conditions such as Alzheimer’s. PMID:25921624

  12. Heterogeneous Aging Effects on Functional Connectivity in Different Cortical Regions: A Resting-State Functional MRI Study Using Functional Data Analysis

    PubMed Central

    Chen, Pin-Yu; Chiou, Jeng-Min; Yang, Ya-Fang; Chen, Yu-Ting; Hsieh, Hsin-Long; Chang, Yu-Ling; Tseng, Wen-Yih I.

    2016-01-01

    Brain aging is a complex and heterogeneous process characterized by the selective loss and preservation of brain functions. This study examines the normal aging effects on the cerebral cortex by characterizing changes in functional connectivity using resting-state fMRI data. Previous resting-state fMRI studies on normal aging have examined specific networks of the brain, whereas few studies have examined cortical-cortical connectivities across the entire brain. To characterize the effects of normal aging on the cerebral cortex, we proposed the Pearson functional product-moment correlation coefficient for measuring functional connectivity, which has advantages over the traditional correlation coefficient. The distinct patterns of changes in functional connectivity within and among the four cerebral lobes clarified the effects of normal aging on cortical function. Besides, the advantages of the proposed approach over other methods considered were demonstrated through simulation comparisons. The results showed heterogeneous changes in functional connectivity in normal aging. Specifically, the elderly group exhibited enhanced inter-lobe connectivity between the frontal lobe and the other lobes. Inter-lobe connectivity decreased between the temporal and parietal lobes. The results support the frontal aging hypothesis proposed in behavioral and structural MRI studies. In conclusion, functional correlation analysis enables differentiation of changes in functional connectivities and characterizes the heterogeneous aging effects in different cortical regions. PMID:27658309

  13. 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.

  14. The Aging Brain Care Medical Home: Preliminary Data.

    PubMed

    LaMantia, Michael A; Alder, Catherine A; Callahan, Christopher M; Gao, Sujuan; French, Dustin D; Austrom, Mary G; Boustany, Karim; Livin, Lee; Bynagari, Bharath; Boustani, Malaz A

    2015-06-01

    The Aging Brain Care (ABC) Medical Home aims to improve the care, health outcomes, and medical costs of Medicare beneficiaries with dementia or depression across central Indiana. This population health management program, funded by the Centers for Medicare and Medicaid Services Innovation Center, expanded an existing collaborative dementia and depression care program to serve 1,650 older adults in a local safety-net hospital system. During the first year, 20 full-time clinical staff were hired, trained, and deployed to deliver a collaborative care intervention. In the first 18 months, an average of 13 visits was provided per person. Thirty percent of the sample had a diagnosis of dementia, and 77% had a diagnosis of depression. Sixty-six percent of participants with high depression scores (Patient Health Questionnaire-9 score ≥14) had at least a 50% reduction in their depressive symptoms. Fifty-one percent of caregivers of individuals with dementia had at least a 50% reduction in caregiver stress symptoms (measured by the Healthy Aging Brain Care Monitor-Caregiver Version). After 18 months, the ABC Medical Home has demonstrated progress toward improving the health of older adults with dementia and depression. Scalable and practical models like this show initial promise for answering the challenges posed by the nation's rapidly aging population. PMID:26096394

  15. Neural Plastic Effects of Cognitive Training on Aging Brain

    PubMed Central

    Leung, Natalie T. Y.; Tam, Helena M. K.; Chu, Leung W.; Kwok, Timothy C. Y.; Chan, Felix; Lam, Linda C. W.; Woo, Jean; Lee, Tatia M. C.

    2015-01-01

    Increasing research has evidenced that our brain retains a capacity to change in response to experience until late adulthood. This implies that cognitive training can possibly ameliorate age-associated cognitive decline by inducing training-specific neural plastic changes at both neural and behavioral levels. This longitudinal study examined the behavioral effects of a systematic thirteen-week cognitive training program on attention and working memory of older adults who were at risk of cognitive decline. These older adults were randomly assigned to the Cognitive Training Group (n = 109) and the Active Control Group (n = 100). Findings clearly indicated that training induced improvement in auditory and visual-spatial attention and working memory. The training effect was specific to the experience provided because no significant difference in verbal and visual-spatial memory between the two groups was observed. This pattern of findings is consistent with the prediction and the principle of experience-dependent neuroplasticity. Findings of our study provided further support to the notion that the neural plastic potential continues until older age. The baseline cognitive status did not correlate with pre- versus posttraining changes to any cognitive variables studied, suggesting that the initial cognitive status may not limit the neuroplastic potential of the brain at an old age. PMID:26417460

  16. Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

    PubMed Central

    Daugherty, Ana M; Raz, Naftali

    2015-01-01

    Age-related increase in frailty is accompanied by a fundamental shift in cellular iron homeostasis. By promoting oxidative stress, the intracellular accumulation of non-heme iron outside of binding complexes contributes to chronic inflammation and interferes with normal brain metabolism. In the absence of direct non-invasive biomarkers of brain oxidative stress, iron accumulation estimated in vivo may serve as its proxy indicator. Hence, developing reliable in vivo measurements of brain iron content via magnetic resonance imaging (MRI) is of significant interest in human neuroscience. To date, by estimating brain iron content through various MRI methods, significant age differences and age-related increases in iron content of the basal ganglia have been revealed across multiple samples. Less consistent are the findings that pertain to the relationship between elevated brain iron content and systemic indices of vascular and metabolic dysfunction. Only a handful of cross-sectional investigations have linked high iron content in various brain regions and poor performance on assorted cognitive tests. The even fewer longitudinal studies indicate that iron accumulation may precede shrinkage of the basal ganglia and thus predict poor maintenance of cognitive functions. This rapidly developing field will benefit from introduction of higher-field MRI scanners, improvement in iron-sensitive and -specific acquisition sequences and post-processing analytic and computational methods, as well as accumulation of data from long-term longitudinal investigations. This review describes the potential advantages and promises of MRI-based assessment of brain iron, summarizes recent findings and highlights the limitations of the current methodology. PMID:26248580

  17. Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods.

    PubMed

    Daugherty, Ana M; Raz, Naftali

    2015-09-01

    Age-related increase in frailty is accompanied by a fundamental shift in cellular iron homeostasis. By promoting oxidative stress, the intracellular accumulation of non-heme iron outside of binding complexes contributes to chronic inflammation and interferes with normal brain metabolism. In the absence of direct non-invasive biomarkers of brain oxidative stress, iron accumulation estimated in vivo may serve as its proxy indicator. Hence, developing reliable in vivo measurements of brain iron content via magnetic resonance imaging (MRI) is of significant interest in human neuroscience. To date, by estimating brain iron content through various MRI methods, significant age differences and age-related increases in iron content of the basal ganglia have been revealed across multiple samples. Less consistent are the findings that pertain to the relationship between elevated brain iron content and systemic indices of vascular and metabolic dysfunction. Only a handful of cross-sectional investigations have linked high iron content in various brain regions and poor performance on assorted cognitive tests. The even fewer longitudinal studies indicate that iron accumulation may precede shrinkage of the basal ganglia and thus predict poor maintenance of cognitive functions. This rapidly developing field will benefit from introduction of higher-field MRI scanners, improvement in iron-sensitive and -specific acquisition sequences and post-processing analytic and computational methods, as well as accumulation of data from long-term longitudinal investigations. This review describes the potential advantages and promises of MRI-based assessment of brain iron, summarizes recent findings and highlights the limitations of the current methodology.

  18. [Normal aging of frontal lobe functions].

    PubMed

    Calso, Cristina; Besnard, Jérémy; Allain, Philippe

    2016-03-01

    Normal aging in individuals is often associated with morphological, metabolic and cognitive changes, which particularly concern the cerebral frontal regions. Starting from the "frontal lobe hypothesis of cognitive aging" (West, 1996), the present review is based on the neuroanatomical model developed by Stuss (2008), introducing four categories of frontal lobe functions: executive control, behavioural and emotional self-regulation and decision-making, energization and meta-cognitive functions. The selected studies only address the changes of one at least of these functions. The results suggest a deterioration of several cognitive frontal abilities in normal aging: flexibility, inhibition, planning, verbal fluency, implicit decision-making, second-order and affective theory of mind. Normal aging seems also to be characterised by a general reduction in processing speed observed during neuropsychological assessment (Salthouse, 1996). Nevertheless many cognitive functions remain preserved such as automatic or non-conscious inhibition, specific capacities of flexibility and first-order theory of mind. Therefore normal aging doesn't seem to be associated with a global cognitive decline but rather with a selective change in some frontal systems, conclusion which should be taken into account for designing caring programs in normal aging. PMID:27005339

  19. Sexual function of the ageing male.

    PubMed

    Corona, Giovanni; Rastrelli, Giulia; Maseroli, Elisa; Forti, Gianni; Maggi, Mario

    2013-08-01

    With the progressive increase in the proportion of older people, there is an increasing interest in characterizing the modifications of sexual health and the effect of its perturbations as a function of the aging process. The aim of this review is to summarize the available evidence regarding the age-dependent modifications of male sexual function and their interaction with general health and age-dependent modification of endocrine function. Elderly patients are often affected by multiple organic diseases which can interfere with sexual function. Despite this evidence, several studies have indicated that, with advancing age, normal erections are not an absolute prerequisite to remain sexually active. Good physical health, the availability of a partner, and a regular and stable pattern of sexual activity earlier in life predict the maintenance of sexual activity in old age. Conversely, there are no convincing data that hormonal changes, associated with aging, have a primary role in underlying changes in sexual function in healthy aging men. Nonetheless, sexual dysfunctions especially in elderly people are poor investigated. Asking about sexual health remains difficult or embarrassing for many primary care physicians. In addition, many patients find it difficult to raise sexual issues with their doctor. This situation often results in sexual issues not being adequately addressed thus resulting in depression, social withdrawal and delayed diagnosis of underlying medical conditions often resulting in forthcoming cardiovascular events. Education and permission from a health care professional may help to alter such misconceptions. Information from physicians regarding normal age-related changes in sexuality and encouragement, together with advice on how to continue meaningful sexual relations, may play a key role in altering such negative attitudes. PMID:24054932

  20. Serum metabolites from walnut-fed aged rats attenuate stress-induced neurotoxicity in brain cells in vitro

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The shift in equilibrium towards excess reactive oxygen or nitrogen species production from innate antioxidant defense in brain is a critical factor in the declining neural functions and cognitive deficits accompanying age. In aging, there are noticeable alterations in the membrane microenvironment,...

  1. Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

    PubMed

    Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

    2013-06-01

    Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

  2. Using autopsy brain tissue to study alcohol-related brain damage in the genomic age.

    PubMed

    Sutherland, Greg T; Sheedy, Donna; Kril, Jillian J

    2014-01-01

    The New South Wales Tissue Resource Centre at the University of Sydney, Australia, is one of the few human brain banks dedicated to the study of the effects of chronic alcoholism. The bank was affiliated in 1994 as a member of the National Network of Brain Banks and also focuses on schizophrenia and healthy control tissue. Alcohol abuse is a major problem worldwide, manifesting in such conditions as fetal alcohol syndrome, adolescent binge drinking, alcohol dependency, and alcoholic neurodegeneration. The latter is also referred to as alcohol-related brain damage (ARBD). The study of postmortem brain tissue is ideally suited to determining the effects of long-term alcohol abuse, but it also makes an important contribution to understanding pathogenesis across the spectrum of alcohol misuse disorders and potentially other neurodegenerative diseases. Tissue from the bank has contributed to 330 peer-reviewed journal articles including 120 related to alcohol research. Using the results of these articles, this review chronicles advances in alcohol-related brain research since 2003, the so-called genomic age. In particular, it concentrates on transcriptomic approaches to the pathogenesis of ARBD and builds on earlier reviews of structural changes (Harper et al. Prog Neuropsychopharmacol Biol Psychiatry 2003;27:951) and proteomics (Matsumoto et al. Expert Rev Proteomics 2007;4:539).

  3. Disrupted Brain Functional Network Architecture in Chronic Tinnitus Patients

    PubMed Central

    Chen, Yu-Chen; Feng, Yuan; Xu, Jin-Jing; Mao, Cun-Nan; Xia, Wenqing; Ren, Jun; Yin, Xindao

    2016-01-01

    Purpose: Resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated the disruptions of multiple brain networks in tinnitus patients. Nonetheless, several studies found no differences in network processing between tinnitus patients and healthy controls (HCs). Its neural bases are poorly understood. To identify aberrant brain network architecture involved in chronic tinnitus, we compared the resting-state fMRI (rs-fMRI) patterns of tinnitus patients and HCs. Materials and Methods: Chronic tinnitus patients (n = 24) with normal hearing thresholds and age-, sex-, education- and hearing threshold-matched HCs (n = 22) participated in the current study and underwent the rs-fMRI scanning. We used degree centrality (DC) to investigate functional connectivity (FC) strength of the whole-brain network and Granger causality to analyze effective connectivity in order to explore directional aspects involved in tinnitus. Results: Compared to HCs, we found significantly increased network centrality in bilateral superior frontal gyrus (SFG). Unidirectionally, the left SFG revealed increased effective connectivity to the left middle orbitofrontal cortex (OFC), left posterior lobe of cerebellum (PLC), left postcentral gyrus, and right middle occipital gyrus (MOG) while the right SFG exhibited enhanced effective connectivity to the right supplementary motor area (SMA). In addition, the effective connectivity from the bilateral SFG to the OFC and SMA showed positive correlations with tinnitus distress. Conclusions: Rs-fMRI provides a new and novel method for identifying aberrant brain network architecture. Chronic tinnitus patients have disrupted FC strength and causal connectivity mostly in non-auditory regions, especially the prefrontal cortex (PFC). The current findings will provide a new perspective for understanding the neuropathophysiological mechanisms in chronic tinnitus. PMID:27458377

  4. Mapping brain function in freely moving subjects

    PubMed Central

    Holschneider, Daniel P.; Maarek, Jean-Michel I.

    2014-01-01

    Expression of many fundamental mammalian behaviors such as, for example, aggression, mating, foraging or social behaviors, depend on locomotor activity. A central dilemma in the functional neuroimaging of these behaviors has been the fact that conventional neuroimaging techniques generally rely on immobilization of the subject, which extinguishes all but the simplest activity. Ideally, imaging could occur in freely moving subjects, while presenting minimal interference with the subject’s natural behavior. Here we provide an overview of several approaches that have been undertaken in the past to achieve this aim in both tethered and freely moving animals, as well as in nonrestrained human subjects. Applications of specific radiotracers to single photon emission computed tomography and positron emission tomography are discussed in which brain activation is imaged after completion of the behavioral task and capture of the tracer. Potential applications to clinical neuropsychiatry are discussed, as well as challenges inherent to constraint-free functional neuroimaging. Future applications of these methods promise to increase our understanding of the neural circuits underlying mammalian behavior in health and disease. PMID:15465134

  5. Age and Gender Related Changes in the Normal Human Brain using Hybrid Diffusion Imaging (HYDI)

    PubMed Central

    Wu, Yu-Chien; Field, Aaron S.; Whalen, Paul J.; Alexander, Andrew L.

    2011-01-01

    Diffusion tensor imaging has been widely used to study brain diseases, disorders, development and aging. However, few studies have explored the effects of aging on diffusion imaging measures with higher b-values. Further the water diffusion in biological tissues appears bi-exponential although this also has not been explored with aging. In this study, hybrid diffusion imaging (HYDI) was used to study fifty-two healthy subjects with an age range from 18 to 72 years. The HYDI diffusion-encoding scheme consisted of five concentric q-space shells with b-values raging from 0 to 9375 s/mm2. Quantitative diffusion measures were investigated as a function of age and gender using both region-of-interest (whole brain white matter, genu and splenium of corpus callosum, posterior limb of the internal capsule) and whole-brain voxel based analyses. Diffusion measures included measures of the diffusion probability density function (zero displacement probability, and mean squared displacement), bi-exponential diffusion (i.e. volume fractions of fast/slow diffusion compartments and fast/slow diffusivities), and DTI measures (fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity). The bi-exponential volume fraction, the fast diffusivity, and the axial diffusivity measures (f1, D1 and Da) were found to be more sensitive to normal aging than the restricted, slow and radial diffusion measures (Po, D2 and Dr). The bi-exponential volume fraction, f1, showed the most widespread age-dependence in the voxel-based analyses although both FA and mean diffusivity did show changes in frontal white matter regions that may be associated with age-related decline. PMID:20932911

  6. Mitochondrial Energy Metabolism and Redox Signaling in Brain Aging and Neurodegeneration

    PubMed Central

    Yin, Fei; Boveris, Alberto

    2014-01-01

    Abstract Significance: The mitochondrial energy-transducing capacity is essential for the maintenance of neuronal function, and the impairment of energy metabolism and redox homeostasis is a hallmark of brain aging, which is particularly accentuated in the early stages of neurodegenerative diseases. Recent Advances: The communications between mitochondria and the rest of the cell by energy- and redox-sensitive signaling establish a master regulatory device that controls cellular energy levels and the redox environment. Impairment of this regulatory devise is critical for aging and the early stages of neurodegenerative diseases. Critical Issues: This review focuses on a coordinated metabolic network—cytosolic signaling, transcriptional regulation, and mitochondrial function—that controls the cellular energy levels and redox status as well as factors which impair this metabolic network during brain aging and neurodegeneration. Future Directions: Characterization of mitochondrial function and mitochondria-cytosol communications will provide pivotal opportunities for identifying targets and developing new strategies aimed at restoring the mitochondrial energy-redox axis that is compromised in brain aging and neurodegeneration. Antioxid. Redox Signal. 20, 353–371. PMID:22793257

  7. 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…

  8. Age Related Changes in Autonomic Functions

    PubMed Central

    Amir, Mohammed; Pakhare, Abhijit; Rathi, Preeti; Chaudhary, Lalita

    2016-01-01

    Introduction Autonomic Nervous System (ANS) imbalance may trigger or enhance pathology in different organ systems that varies in different age groups hence objective of present study was to evaluate association of different Age-groups with autonomic functions. Materials and Methods A cross-sectional study was conducted in 62 healthy volunteers in Department of Physiology LLRM Medical College Meerut, India. Volunteers were divided into three groups as younger (15-45 years), middle (45-60) and elder age (above 60), Autonomic functions were tested in three domains viz. Cardio-vagal, adrenergic and sudomotor functions. Numerical data was summarized as mean and standard deviation and categorical data as count and percentage. ANOVA and Chi-square test were used to find difference among groups, p<0.05 was considered statistically significant. Results Mean ± standard deviation OHT(Orthostatic Hypotension Test) among of younger, middle and elder age groups were 8.80±2.28, 13.40±4.64 and 21.82±6.04 respectively which represent decrease in sympathetic functions with age (p<0.001). Cardio-vagal or parasympathetic responses indicated by DBT (Deep Breathing Test) Valsalva and 30:15 ratio of HR response to standing tests has shown statistically significant (p<0.001) decrease in mean response with increasing age. Sudomotor response appeared normal in younger and middle group but was interrupted in more than half of elderly people (p<0.001). Conclusion Sympathetic responses & para-sympathetic responses have shown the significant decline with increasing age group. Sudomotor responses were partially interrupted in elderly age group. PMID:27134865

  9. An evaluation of the left-brain vs. right-brain hypothesis with resting state functional connectivity magnetic resonance imaging.

    PubMed

    Nielsen, Jared A; Zielinski, Brandon A; Ferguson, Michael A; Lainhart, Janet E; Anderson, Jeffrey S

    2013-01-01

    Lateralized brain regions subserve functions such as language and visuospatial processing. It has been conjectured that individuals may be left-brain dominant or right-brain dominant based on personality and cognitive style, but neuroimaging data has not provided clear evidence whether such phenotypic differences in the strength of left-dominant or right-dominant networks exist. We evaluated whether strongly lateralized connections covaried within the same individuals. Data were analyzed from publicly available resting state scans for 1011 individuals between the ages of 7 and 29. For each subject, functional lateralization was measured for each pair of 7266 regions covering the gray matter at 5-mm resolution as a difference in correlation before and after inverting images across the midsagittal plane. The difference in gray matter density between homotopic coordinates was used as a regressor to reduce the effect of structural asymmetries on functional lateralization. Nine left- and 11 right-lateralized hubs were identified as peaks in the degree map from the graph of significantly lateralized connections. The left-lateralized hubs included regions from the default mode network (medial prefrontal cortex, posterior cingulate cortex, and temporoparietal junction) and language regions (e.g., Broca Area and Wernicke Area), whereas the right-lateralized hubs included regions from the attention control network (e.g., lateral intraparietal sulcus, anterior insula, area MT, and frontal eye fields). Left- and right-lateralized hubs formed two separable networks of mutually lateralized regions. Connections involving only left- or only right-lateralized hubs showed positive correlation across subjects, but only for connections sharing a node. Lateralization of brain connections appears to be a local rather than global property of brain networks, and our data are not consistent with a whole-brain phenotype of greater "left-brained" or greater "right-brained" network strength

  10. Triggers and Effectors of Oxidative Stress at Blood-Brain Barrier Level: Relevance for Brain Ageing and Neurodegeneration

    PubMed Central

    2013-01-01

    As fundamental research advances, it is becoming increasingly clear that a clinically expressed disease implies a mixture of intertwining molecular disturbances. Oxidative stress is one of such pathogenic pathways involved in virtually all central nervous system pathologies, infectious, inflammatory, or degenerative in nature. Since brain homeostasis largely depends on integrity of blood-brain barrier (BBB), many studies focused lately on BBB alteration in a wide spectrum of brain diseases. The proper two-way molecular transfer through BBB depends on several factors, including the functional status of its tight junction (TJ) complexes of proteins sealing neighbour endothelial cells. Although there is abundant experimental work showing that oxidative stress associates BBB permeability alteration, less is known about its implications, at molecular level, in TJ protein expression or TJ-related cell signalling. In this paper, oxidative stress is presented as a common pathway for different brain pathogenic mechanisms which lead to BBB dysregulation. We revise here oxidative-induced molecular mechanisms of BBB disruption and TJ protein expression alteration, in relation to ageing and neurodegeneration. PMID:23533687

  11. Impact of diabetes on cognitive function and brain structure.

    PubMed

    Moheet, Amir; Mangia, Silvia; Seaquist, Elizabeth R

    2015-09-01

    Both type 1 and type 2 diabetes have been associated with reduced performance on multiple domains of cognitive function and with structural abnormalities in the brain. With an aging population and a growing epidemic of diabetes, central nervous system-related complications of diabetes are expected to rise and could have challenging future public health implications. In this review, we will discuss the brain structural and functional changes that have been associated with type 1 and type 2 diabetes. Diabetes duration and glycemic control may play important roles in the development of cognitive impairment in diabetes, but the exact underlying pathophysiological mechanisms causing these changes in cognition and structure are not well understood. Future research is needed to better understand the natural history and the underlying mechanisms, as well as to identify risk factors that predict who is at greatest risk of developing cognitive impairment. This information will lead to the development of new strategies to minimize the impact of diabetes on cognitive function.

  12. Age-related shifts in brain activity dynamics during task switching.

    PubMed

    Jimura, Koji; Braver, Todd S

    2010-06-01

    Cognitive aging studies have suggested that older adults show declines in both sustained and transient cognitive control processes. However, previous neuroimaging studies have primarily focused on age-related change in the magnitude, but not temporal dynamics, of brain activity. The present study compared brain activity dynamics in healthy old and young adults during task switching. A mixed blocked/event-related functional magnetic resonance imaging design enabled separation of transient and sustained neural activity associated with cognitive control. Relative to young adults, older adults exhibited not only decreased sustained activity in the anterior prefrontal cortex (aPFC) during task-switching blocks but also increased transient activity on task-switch trials. Another pattern of age-related shift in dynamics was present in the lateral PFC (lPFC) and posterior parietal cortex (PPC), with younger adults showing a cue-related response during task-switch trials in lPFC and PPC, whereas older adults exhibited switch-related activation during the cue period in PPC only. In all 3 regions, these qualitatively distinct patterns of brain activity predicted qualitatively distinct patterns of behavioral performance across the 2 age groups. Together, these results suggest that older adults may shift from a proactive to reactive cognitive control strategy as a means of retaining relatively preserved behavioral performance in the face of age-related neurocognitive changes. PMID:19805420

  13. Docosahexaenoic acid homeostasis, brain aging and Alzheimer's disease: Can we reconcile the evidence?

    PubMed

    Cunnane, Stephen C; Chouinard-Watkins, Raphael; Castellano, Christian A; Barberger-Gateau, Pascale

    2013-01-01

    A crossroads has been reached on research into docosahexaenoic acid (DHA) and Alzheimer's disease (AD). On the one hand, several prospective observational studies now clearly indicate a protective effect of higher fish and DHA intake against risk of AD. On the other hand, once AD is clinically evident, supplementation trials demonstrate essentially no benefit of DHA in AD. Despite apparently low DHA intake in AD, brain DHA levels are frequently the same as in controls, suggesting that low DHA intake results in low plasma DHA but does not necessarily reduce brain DHA in humans. Animal models involving dietary omega-3 fatty acid deficiency to deplete brain DHA may therefore not be appropriate in AD research. Studies in the healthy elderly suggest that DHA homeostasis changes during aging. Tracer methodology now permits estimation of DHA half-life in the human brain and whole body. Apolipoprotein E alleles have an important impact not only on AD but also on DHA homeostasis in humans. We therefore encourage further development of innovative approaches to the study of DHA metabolism and its role in human brain function. A better understanding of DHA metabolism in humans will hopefully help explain how higher habitual DHA intake protects against the risk of deteriorating cognition during aging and may eventually give rise to a breakthrough in the treatment of AD. PMID:22575581

  14. Aging and response conflict solution: Behavioural and functional connectivity changes

    PubMed Central

    Cieslik, Edna C.; Behrwind, Simone D.; Roski, Christian; Caspers, Svenja; Amunts, Katrin; Eickhoff, Simon B.

    2014-01-01

    Healthy aging has been found associated with less efficient response conflict solution, but the cognitive and neural mechanisms remain elusive. In a two-experiment study, we first examined the behavioural consequences of this putative age-related decline for conflicts induced by spatial stimulus–response incompatibility. We then used resting-state functional magnetic resonance imaging data from a large, independent sample of adults (n = 399; 18–85 years) to investigate age differences in functional connectivity between the nodes of a network previously found associated with incompatibility-induced response conflicts in the very same paradigm. As expected, overcoming interference from conflicting response tendencies took longer in older adults, even after accounting for potential mediator variables (general response speed and accuracy, motor speed, visuomotor coordination ability, and cognitive flexibility). Experiment 2 revealed selective age-related decreases in functional connectivity between bilateral anterior insula, pre-supplementary motor area, and right dorsolateral prefrontal cortex. Importantly, these age effects persisted after controlling for regional gray-matter atrophy assessed by voxel-based morphometry. Meta-analytic functional profiling using the BrainMap database showed these age-sensitive nodes to be more strongly linked to highly abstract cognition, as compared with the remaining network nodes, which in turn were more strongly linked to action-related processing. These findings indicate changes in interregional coupling with age among task-relevant network nodes that are not specifically associated with conflict resolution per se. Rather, our behavioural and neural data jointly suggest that healthy aging is associated with difficulties in properly activating non-dominant but relevant task schemata necessary to exert efficient cognitive control over action. PMID:24718622

  15. The modular and integrative functional architecture of the human brain.

    PubMed

    Bertolero, Maxwell A; Yeo, B T Thomas; D'Esposito, Mark

    2015-12-01

    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.

  16. The modular and integrative functional architecture of the human brain.

    PubMed

    Bertolero, Maxwell A; Yeo, B T Thomas; D'Esposito, Mark

    2015-12-01

    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

  17. 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

  18. The Role of Mitochondria in Brain Aging and the Effects of Melatonin

    PubMed Central

    Escames, Germaine; López, Ana; García, José Antonio; García, Laura; Acuña-Castroviejo, Darío; García, José Joaquín; López, Luis Carlos

    2010-01-01

    Melatonin is an endogenous indoleamine present in different tissues, cellular compartments and organelles including mitochondria. When melatonin is administered orally, it is readily available to the brain where it counteracts different processes that occur during aging and age-related neurodegenerative disorders. These aging processes include oxidative stress and oxidative damage, chronic and acute inflammation, mitochondrial dysfunction and loss of neural regeneration. This review summarizes age related changes in the brain and the importance of oxidative/nitrosative stress and mitochondrial dysfunction in brain aging. The data and mechanisms of action of melatonin in relation to aging of the brain are reviewed as well. PMID:21358969

  19. 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.

  20. Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging.

    PubMed

    Head, E; Nukala, V N; Fenoglio, K A; Muggenburg, B A; Cotman, C W; Sullivan, P G

    2009-11-01

    Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with behavioral enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (vitamins E and C, fruits and vegetables) and mitochondrial cofactors (lipoic acid and carnitine). Behavioral enrichment consisted of physical exercise, social enrichment, and cognitive training. We hypothesized that the antioxidant treatment improved neuronal function through increased mitochondrial function. Thus, we measured reactive oxygen species (ROS) production and bioenergetics in mitochondria isolated from young, aged, and treated aged animals. Aged canine brain mitochondria show significant increases in ROS production and a reduction in NADH-linked respiration. Mitochondrial function (ROS and NADH-linked respiration) was improved selectively in aged dogs treated with an antioxidant diet. In contrast, behavioral enrichment had no effect on any mitochondrial parameters. These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by behavioral enrichment.

  1. Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging.

    PubMed

    Head, E; Nukala, V N; Fenoglio, K A; Muggenburg, B A; Cotman, C W; Sullivan, P G

    2009-11-01

    Dogs develop cognitive decline and a progressive accumulation of oxidative damage. In a previous longitudinal study, we demonstrated that aged dogs treated with either an antioxidant diet or with behavioral enrichment show cognitive improvement. The antioxidant diet included cellular antioxidants (vitamins E and C, fruits and vegetables) and mitochondrial cofactors (lipoic acid and carnitine). Behavioral enrichment consisted of physical exercise, social enrichment, and cognitive training. We hypothesized that the antioxidant treatment improved neuronal function through increased mitochondrial function. Thus, we measured reactive oxygen species (ROS) production and bioenergetics in mitochondria isolated from young, aged, and treated aged animals. Aged canine brain mitochondria show significant increases in ROS production and a reduction in NADH-linked respiration. Mitochondrial function (ROS and NADH-linked respiration) was improved selectively in aged dogs treated with an antioxidant diet. In contrast, behavioral enrichment had no effect on any mitochondrial parameters. These results suggest that an antioxidant diet improves cognition by maintaining mitochondrial homeostasis, which may be an independent molecular pathway not engaged by behavioral enrichment. PMID:19703441

  2. Lack of serotonin1B receptor expression leads to age-related motor dysfunction, early onset of brain molecular aging and reduced longevity

    PubMed Central

    Sibille, E; Su, J; Leman, S; Le Guisquet, AM; Ibarguen-Vargas, Y; Joeyen-Waldorf, J; Glorioso, C; Tseng, GC; Pezzone, M; Hen, R; Belzung, C

    2008-01-01

    Normal aging of the brain differs from pathological conditions and is associated with increased risk for psychiatric and neurological disorders. In addition to its role in the etiology and treatment of mood disorders, altered serotonin (5-HT) signaling is considered a contributing factor to aging; however, no causative role has been identified in aging. We hypothesized that a deregulation of the 5-HT system would reveal its contribution to age-related processes and investigated behavioral and molecular changes throughout adult life in mice lacking the regulatory presynaptic 5-HT1B receptor (5-HT1BR), a candidate gene for 5-HT-mediated age-related functions. We show that the lack of 5-HT1BR (Htr1bKO mice) induced an early age-related motor decline and resulted in decreased longevity. Analysis of life-long transcriptome changes revealed an early and global shift of the gene expression signature of aging in the brain of Htr1bKO mice. Moreover, molecular changes reached an apparent maximum effect at 18-months in Htr1bKO mice, corresponding to the onset of early death in that group. A comparative analysis with our previous characterization of aging in the human brain revealed a phylogenetic conservation of age-effect from mice to humans, and confirmed the early onset of molecular aging in Htr1bKO mice. Potential mechanisms appear independent of known central mechanisms (Bdnf, inflammation), but may include interactions with previously identified age-related systems (IGF-1, sirtuins). In summary, our findings suggest that the onset of age-related events can be influenced by altered 5-HT function, thus identifying 5-HT as a modulator of brain aging, and suggesting age-related consequences to chronic manipulation of 5-HT. PMID:17420766

  3. Brain network characterization of high-risk preterm-born school-age children

    PubMed Central

    Fischi-Gomez, Elda; Muñoz-Moreno, Emma; Vasung, Lana; Griffa, Alessandra; Borradori-Tolsa, Cristina; Monnier, Maryline; Lazeyras, François; Thiran, Jean-Philippe; Hüppi, Petra S.

    2016-01-01

    Higher risk for long-term cognitive and behavioral impairments is one of the hallmarks of extreme prematurity (EP) and pregnancy-associated fetal adverse conditions such as intrauterine growth restriction (IUGR). While neurodevelopmental delay and abnormal brain function occur in the absence of overt brain lesions, these conditions have been recently associated with changes in microstructural brain development. Recent imaging studies indicate changes in brain connectivity, in particular involving the white matter fibers belonging to the cortico-basal ganglia-thalamic loop. Furthermore, EP and IUGR have been related to altered brain network architecture in childhood, with reduced network global capacity, global efficiency and average nodal strength. In this study, we used a connectome analysis to characterize the structural brain networks of these children, with a special focus on their topological organization. On one hand, we confirm the reduced averaged network node degree and strength due to EP and IUGR. On the other, the decomposition of the brain networks in an optimal set of clusters remained substantially different among groups, talking in favor of a different network community structure. However, and despite the different community structure, the brain networks of these high-risk school-age children maintained the typical small-world, rich-club and modularity characteristics in all cases. Thus, our results suggest that brain reorganizes after EP and IUGR, prioritizing a tight modular structure, to maintain the small-world, rich-club and modularity characteristics. By themselves, both extreme prematurity and IUGR bear a similar risk for neurocognitive and behavioral impairment, and the here defined modular network alterations confirm similar structural changes both by IUGR and EP at school age compared to control. Interestingly, the combination of both conditions (IUGR + EP) does not result in a worse outcome. In such cases, the alteration in network

  4. Brain network characterization of high-risk preterm-born school-age children.

    PubMed

    Fischi-Gomez, Elda; Muñoz-Moreno, Emma; Vasung, Lana; Griffa, Alessandra; Borradori-Tolsa, Cristina; Monnier, Maryline; Lazeyras, François; Thiran, Jean-Philippe; Hüppi, Petra S

    2016-01-01

    Higher risk for long-term cognitive and behavioral impairments is one of the hallmarks of extreme prematurity (EP) and pregnancy-associated fetal adverse conditions such as intrauterine growth restriction (IUGR). While neurodevelopmental delay and abnormal brain function occur in the absence of overt brain lesions, these conditions have been recently associated with changes in microstructural brain development. Recent imaging studies indicate changes in brain connectivity, in particular involving the white matter fibers belonging to the cortico-basal ganglia-thalamic loop. Furthermore, EP and IUGR have been related to altered brain network architecture in childhood, with reduced network global capacity, global efficiency and average nodal strength. In this study, we used a connectome analysis to characterize the structural brain networks of these children, with a special focus on their topological organization. On one hand, we confirm the reduced averaged network node degree and strength due to EP and IUGR. On the other, the decomposition of the brain networks in an optimal set of clusters remained substantially different among groups, talking in favor of a different network community structure. However, and despite the different community structure, the brain networks of these high-risk school-age children maintained the typical small-world, rich-club and modularity characteristics in all cases. Thus, our results suggest that brain reorganizes after EP and IUGR, prioritizing a tight modular structure, to maintain the small-world, rich-club and modularity characteristics. By themselves, both extreme prematurity and IUGR bear a similar risk for neurocognitive and behavioral impairment, and the here defined modular network alterations confirm similar structural changes both by IUGR and EP at school age compared to control. Interestingly, the combination of both conditions (IUGR + EP) does not result in a worse outcome. In such cases, the alteration in network

  5. Exercise-Related Changes of Networks in Aging and Mild Cognitive Impairment Brain.

    PubMed

    Huang, Pei; Fang, Rong; Li, Bin-Yin; Chen, Sheng-Di

    2016-01-01

    Aging and mild cognitive impairment (MCI) are accompanied by decline of cognitive functions. Meanwhile, the most common form of dementia is Alzheimer's disease (AD), which is characterized by loss of memory and other intellectual abilities serious to make difficulties for patients in their daily life. MCI is a transition period between normal aging and dementia, which has been used for early detection of emerging dementia. It converts to dementia with an annual rate of 5-15% as compared to normal aging with 1% rate. Small decreases in the conversion rate of MCI to AD might significantly reduce the prevalence of dementia. Thus, it is important to intervene at the preclinical stage. Since there are still no effective drugs to treat AD, non-drug intervention is crucial for the prevention and treatment of cognitive decline in aging and MCI populations. Previous studies have found some cognitive brain networks disrupted in aging and MCI population, and physical exercise (PE) could effectively remediate the function of these brain networks. Understanding the exercise-related mechanisms is crucial to design efficient and effective PE programs for treatment/intervention of cognitive decline. In this review, we provide an overview of the neuroimaging studies on physical training in normal aging and MCI to identify the potential mechanisms underlying current physical training procedures. Studies of functional magnetic resonance imaging, electroencephalography, magnetoencephalography and positron emission tomography on brain networks were all included. Based on our review, the default mode network, fronto-parietal network and fronto-executive network are probably the three most valuable targets for efficiency evaluation of interventions. PMID:27014055

  6. Exercise-Related Changes of Networks in Aging and Mild Cognitive Impairment Brain

    PubMed Central

    Huang, Pei; Fang, Rong; Li, Bin-Yin; Chen, Sheng-Di

    2016-01-01

    Aging and mild cognitive impairment (MCI) are accompanied by decline of cognitive functions. Meanwhile, the most common form of dementia is Alzheimer’s disease (AD), which is characterized by loss of memory and other intellectual abilities serious to make difficulties for patients in their daily life. MCI is a transition period between normal aging and dementia, which has been used for early detection of emerging dementia. It converts to dementia with an annual rate of 5–15% as compared to normal aging with 1% rate. Small decreases in the conversion rate of MCI to AD might significantly reduce the prevalence of dementia. Thus, it is important to intervene at the preclinical stage. Since there are still no effective drugs to treat AD, non-drug intervention is crucial for the prevention and treatment of cognitive decline in aging and MCI populations. Previous studies have found some cognitive brain networks disrupted in aging and MCI population, and physical exercise (PE) could effectively remediate the function of these brain networks. Understanding the exercise-related mechanisms is crucial to design efficient and effective PE programs for treatment/intervention of cognitive decline. In this review, we provide an overview of the neuroimaging studies on physical training in normal aging and MCI to identify the potential mechanisms underlying current physical training procedures. Studies of functional magnetic resonance imaging, electroencephalography, magnetoencephalography and positron emission tomography on brain networks were all included. Based on our review, the default mode network, fronto-parietal network and fronto-executive network are probably the three most valuable targets for efficiency evaluation of interventions. PMID:27014055

  7. The Effect of the APOE Genotype on Individual BrainAGE in Normal Aging, Mild Cognitive Impairment, and Alzheimer's Disease.

    PubMed

    Löwe, Luise Christine; Gaser, Christian; Franke, Katja

    2016-01-01

    In our aging society, diseases in the elderly come more and more into focus. An important issue in research is Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) with their causes, diagnosis, treatment, and disease prediction. We applied the Brain Age Gap Estimation (BrainAGE) method to examine the impact of the Apolipoprotein E (APOE) genotype on structural brain aging, utilizing longitudinal magnetic resonance image (MRI) data of 405 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. We tested for differences in neuroanatomical aging between carrier and non-carrier of APOE ε4 within the diagnostic groups and for longitudinal changes in individual brain aging during about three years follow-up. We further examined whether a combination of BrainAGE and APOE status could improve prediction accuracy of conversion to AD in MCI patients. The influence of the APOE status on conversion from MCI to AD was analyzed within all allelic subgroups as well as for ε4 carriers and non-carriers. The BrainAGE scores differed significantly between normal controls, stable MCI (sMCI) and progressive MCI (pMCI) as well as AD patients. Differences in BrainAGE changing rates over time were observed for APOE ε4 carrier status as well as in the pMCI and AD groups. At baseline and during follow-up, BrainAGE scores correlated significantly with neuropsychological test scores in APOE ε4 carriers and non-carriers, especially in pMCI and AD patients. Prediction of conversion was most accurate using the BrainAGE score as compared to neuropsychological test scores, even when the patient's APOE status was unknown. For assessing the individual risk of coming down with AD as well as predicting conversion from MCI to AD, the BrainAGE method proves to be a useful and accurate tool even if the information of the patient's APOE status is missing. PMID:27410431

  8. Mitochondrial Complex 1 Activity Measured by Spectrophotometry Is Reduced across All Brain Regions in Ageing and More Specifically in Neurodegeneration

    PubMed Central

    Chakrabarti, Lisa

    2016-01-01

    Mitochondrial function, in particular complex 1 of the electron transport chain (ETC), has been shown to decrease during normal ageing and in neurodegenerative disease. However, there is some debate concerning which area of the brain has the greatest complex 1 activity. It is important to identify the pattern of activity in order to be able to gauge the effect of age or disease related changes. We determined complex 1 activity spectrophotometrically in the cortex, brainstem and cerebellum of middle aged mice (70–71 weeks), a cerebellar ataxic neurodegeneration model (pcd5J) and young wild type controls. We share our updated protocol on the measurements of complex1 activity and find that mitochondrial fractions isolated from frozen tissues can be measured for robust activity. We show that complex 1 activity is clearly highest in the cortex when compared with brainstem and cerebellum (p<0.003). Cerebellum and brainstem mitochondria exhibit similar levels of complex 1 activity in wild type brains. In the aged brain we see similar levels of complex 1 activity in all three-brain regions. The specific activity of complex 1 measured in the aged cortex is significantly decreased when compared with controls (p<0.0001). Both the cerebellum and brainstem mitochondria also show significantly reduced activity with ageing (p<0.05). The mouse model of ataxia predictably has a lower complex 1 activity in the cerebellum, and although reductions are measured in the cortex and brain stem, the remaining activity is higher than in the aged brains. We present clear evidence that complex 1 activity decreases across the brain with age and much more specifically in the cerebellum of the pcd5j mouse. Mitochondrial impairment can be a region specific phenomenon in disease, but in ageing appears to affect the entire brain, abolishing the pattern of higher activity in cortical regions. PMID:27333203

  9. Estimating functional brain networks by incorporating a modularity prior.

    PubMed

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

    2016-11-01

    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.

  10. Estimating functional brain networks by incorporating a modularity prior.

    PubMed

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

    2016-11-01

    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

  11. 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…

  12. Monozygotic Twins with Asperger Syndrome: Differences in Behaviour Reflect Variations in Brain Structure and Function

    ERIC Educational Resources Information Center

    Belmonte, Matthew K.; Carper, Ruth A.

    2006-01-01

    A pair of monozygotic twins discordant for symptoms of Asperger syndrome was evaluated at the age of 13.45 years using psychometric, morphometric, behavioural, and functional imaging methods. The lower-functioning twin had a smaller brain overall, a smaller right cerebellum, and a disproportionately large left frontal lobe, and manifested almost…

  13. Decreased Functional Brain Activation in Friedreich Ataxia Using the Simon Effect Task

    ERIC Educational Resources Information Center

    Georgiou-Karistianis, N.; Akhlaghi, H.; Corben, L. A.; Delatycki, M. B.; Storey, E.; Bradshaw, J. L.; Egan, G. F.

    2012-01-01

    The present study applied the Simon effect task to examine the pattern of functional brain reorganization in individuals with Friedreich ataxia (FRDA), using functional magnetic resonance imaging (fMRI). Thirteen individuals with FRDA and 14 age and sex matched controls participated, and were required to respond to either congruent or incongruent…

  14. Brain white matter damage in aging and cognitive ability in youth and older age.

    PubMed

    Valdés Hernández, Maria Del C; Booth, Tom; Murray, Catherine; Gow, Alan J; Penke, Lars; Morris, Zoe; Maniega, Susana Muñoz; Royle, Natalie A; Aribisala, Benjamin S; Bastin, Mark E; Starr, John M; Deary, Ian J; Wardlaw, Joanna M

    2013-12-01

    Cerebral white matter hyperintensities (WMH) reflect accumulating white matter damage with aging and impair cognition. The role of childhood intelligence is rarely considered in associations between cognitive impairment and WMH. We studied community-dwelling older people all born in 1936, in whom IQ had been assessed at age 11 years. We assessed medical histories, current cognitive ability and quantified WMH on MR imaging. Among 634 participants, mean age 72.7 (SD 0.7), age 11 IQ was the strongest predictor of late life cognitive ability. After accounting for age 11 IQ, greater WMH load was significantly associated with lower late life general cognitive ability (β = -0.14, p < 0.01) and processing speed (β = -0.19, p < 0.001). WMH were also associated independently with lower age 11 IQ (β = -0.08, p < 0.05) and hypertension. In conclusion, having more WMH is significantly associated with lower cognitive ability, after accounting for prior ability, age 11IQ. Early-life IQ also influenced WMH in later life. Determining how lower IQ in youth leads to increasing brain damage with aging is important for future successful cognitive aging.

  15. Childhood cognitive ability accounts for associations between cognitive ability and brain cortical thickness in old age.

    PubMed

    Karama, S; Bastin, M E; Murray, C; Royle, N A; Penke, L; Muñoz Maniega, S; Gow, A J; Corley, J; Valdés Hernández, M del C; Lewis, J D; Rousseau, M-É; Lepage, C; Fonov, V; Collins, D L; Booth, T; Rioux, P; Sherif, T; Adalat, R; Starr, J M; Evans, A C; Wardlaw, J M; Deary, I J

    2014-05-01

    Associations between brain cortical tissue volume and cognitive function in old age are frequently interpreted as suggesting that preservation of cortical tissue is the foundation of successful cognitive aging. However, this association could also, in part, reflect a lifelong association between cognitive ability and cortical tissue. We analyzed data on 588 subjects from the Lothian Birth Cohort 1936 who had intelligence quotient (IQ) scores from the same cognitive test available at both 11 and 70 years of age as well as high-resolution brain magnetic resonance imaging data obtained at approximately 73 years of age. Cortical thickness was estimated at 81 924 sampling points across the cortex for each subject using an automated pipeline. Multiple regression was used to assess associations between cortical thickness and the IQ measures at 11 and 70 years. Childhood IQ accounted for more than two-third of the association between IQ at 70 years and cortical thickness measured at age 73 years. This warns against ascribing a causal interpretation to the association between cognitive ability and cortical tissue in old age based on assumptions about, and exclusive reference to, the aging process and any associated disease. Without early-life measures of cognitive ability, it would have been tempting to conclude that preservation of cortical thickness in old age is a foundation for successful cognitive aging when, instead, it is a lifelong association. This being said, results should not be construed as meaning that all studies on aging require direct measures of childhood IQ, but as suggesting that proxy measures of prior cognitive function can be useful to take into consideration.

  16. Concord grape juice supplementation and neurocognitive function in human aging.

    PubMed

    Krikorian, Robert; Boespflug, Erin L; Fleck, David E; Stein, Amanda L; Wightman, Jolynne D; Shidler, Marcelle D; Sadat-Hossieny, Sara

    2012-06-13

    Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline. PMID:22468945

  17. Inputs to prefrontal cortex support visual recognition in the aging brain.

    PubMed

    Gilbert, Jessica R; Moran, Rosalyn J

    2016-01-01

    Predictive coding models of brain function propose that top-down cortical signals promote efficient neural codes by carrying predictions of upcoming sensory events. We hypothesized that older brains would employ these codes more prominently given their longer repertoire of sensory experience. We measured the connectivity underlying stimulus-evoked responses in cortical visual networks using electroencephalography and dynamic causal modeling and found that in young adults with reported normal or corrected-to-normal vision, signals propagated from early visual regions and reverberated along reciprocal connections to temporal, parietal and frontal cortices, while in contrast, the network was driven by both early visual and prefrontal inputs in older adults with reported normal or corrected-to-normal vision. Previously thought of as exceptions to the rule of bottom-up signal propagation, our results demonstrate a prominent role for prefrontal inputs in driving vision in aged brains in line with lifespan-dependent predictive neural codes. PMID:27550752

  18. Inputs to prefrontal cortex support visual recognition in the aging brain

    PubMed Central

    Gilbert, Jessica R.; Moran, Rosalyn J.

    2016-01-01

    Predictive coding models of brain function propose that top-down cortical signals promote efficient neural codes by carrying predictions of upcoming sensory events. We hypothesized that older brains would employ these codes more prominently given their longer repertoire of sensory experience. We measured the connectivity underlying stimulus-evoked responses in cortical visual networks using electroencephalography and dynamic causal modeling and found that in young adults with reported normal or corrected-to-normal vision, signals propagated from early visual regions and reverberated along reciprocal connections to temporal, parietal and frontal cortices, while in contrast, the network was driven by both early visual and prefrontal inputs in older adults with reported normal or corrected-to-normal vision. Previously thought of as exceptions to the rule of bottom-up signal propagation, our results demonstrate a prominent role for prefrontal inputs in driving vision in aged brains in line with lifespan-dependent predictive neural codes. PMID:27550752

  19. Brief Report: Brain Mechanisms in Autism: Functional and Structural Abnormalities.

    ERIC Educational Resources Information Center

    Minshew, Nancy J.

    1996-01-01

    This paper summarizes results of research on functional and structural abnormalities of the brain in autism. The current concept of causation is seen to involve multiple biologic levels. A consistent profile of brain function and dysfunction across methods has been found and specific neuropathologic findings have been found; but some research…

  20. Recovery of cognitive functions following nonprogressive brain injury.

    PubMed

    Wilson, B A

    1998-04-01

    It has recently become clear that the adult human brain is capable of more plasticity than previously thought. Investigations into the natural history of change following brain injury demonstrate that partial recovery of function can and does occur. Furthermore, there is increasing evidence that intervention through re-training or provision of compensatory memory aids can result in improved cognitive functioning.

  1. Sex hormones and brain dopamine functions.

    PubMed

    Sotomayor-Zarate, Ramon; Cruz, Gonzalo; Renard, Georgina M; Espinosa, Pedro; Ramirez, Victor D

    2014-01-01

    Sex hormones exert differential effects on a variety of sensitive tissues like the reproductive tract, gonads, liver, bone and adipose tissue, among others. In the brain, sex hormones act as neuroactive steroids regulating the function of neuroendocrine diencephalic structures like the hypothalamus. In addition, steroids can exert physiological effects upon cortical, limbic and midbrain structures, influencing different behaviors such as memory, learning, mood and reward. In the last three decades, the role of sex hormones on monoamine neurotransmitters in extra-hypothalamic areas related to motivated behaviors, learning and locomotion has been the focus of much research. The purpose of this thematic issue is to present the state of art concerning the effects of sex hormones on the neurochemical regulation of dopaminergic midbrain areas involved in neurobiological and pathological processes, such as addiction to drugs of abuse. We also discuss evidence of how neonatal exposure to sex hormones or endocrine disrupting chemicals can produce long-term changes on the neurochemical regulation of dopaminergic neurons in the limbic and midbrain areas. PMID:25540983

  2. 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.

  3. Acute brain slice methods for adult and aging animals: application of targeted patch clampanalysis and optogenetics

    PubMed Central

    Daigle, Tanya L.; Chen, Qian; Feng, Guoping

    2014-01-01

    Summary The development of the living acute brain slice preparation for analyzing synaptic function roughly a half century ago was a pivotal achievement that greatly influenced the landscape of modern neuroscience. Indeed, many neuroscientists regard brain slices as the gold-standard model system for detailed cellular, molecular, and circuitry level analysis and perturbation of neuronal function. A critical limitation of this model system is the difficulty in preparing slices from adult and aging animals, and over the past several decades few substantial methodological improvements have emerged to facilitate patch clamp analysis in the mature adult stage. In this chapter we describe a robust and practical protocol for preparing brain slices from mature adult mice that are suitable for patch clamp analysis. This method reduces swelling and damage in superficial layers of the slices and improves the success rate for targeted patch clamp recordings, including recordings from fluorescently labeled populations in slices derived from transgenic mice. This adult brain slice method is suitable for diverse experimental applications, including both monitoring and manipulating neuronal activity with genetically encoded calcium indicators and optogenetic actuators, respectively. We describe the application of this adult brain slice platform and associated methods for screening kinetic properties of Channelrhodopsin (ChR) variants expressed in genetically-defined neuronal subtypes. PMID:25023312

  4. 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.

  5. Dietary and behavioral interventions protect against age related activation of caspase cascades in the canine brain.

    PubMed

    Snigdha, Shikha; Berchtold, Nicole; Astarita, Giuseppe; Saing, Tommy; Piomelli, Daniele; Cotman, Carl W

    2011-01-01

    Lifestyle interventions such as diet, exercise, and cognitive training represent a quietly emerging revolution in the modern approach to counteracting age-related declines in brain health. Previous studies in our laboratory have shown that long-term dietary supplementation with antioxidants and mitochondrial cofactors (AOX) or behavioral enrichment with social, cognitive, and exercise components (ENR), can effectively improve cognitive performance and reduce brain pathology of aged canines, including oxidative damage and Aβ accumulation. In this study, we build on and extend our previous findings by investigating if the interventions reduce caspase activation and ceramide accumulation in the aged frontal cortex, since caspase activation and ceramide accumulation are common convergence points for oxidative damage and Aβ, among other factors associated with the aged and AD brain. Aged beagles were placed into one of four treatment groups: CON--control environment/control diet, AOX--control environment/antioxidant diet, ENR--enriched environment/control diet, AOX/ENR--enriched environment/antioxidant diet for 2.8 years. Following behavioral testing, brains were removed and frontal cortices were analyzed to monitor levels of active caspase 3, active caspase 9 and their respective cleavage products such as tau and semaphorin7a, and ceramides. Our results show that levels of activated caspase-3 were reduced by ENR and AOX interventions with the largest reduction occurring with combined AOX/ENR group. Further, reductions in caspase-3 correlated with reduced errors in a reversal learning task, which depends on frontal cortex function. In addition, animals treated with an AOX arm showed reduced numbers of cells expressing active caspase 9 or its cleavage product semaphorin 7A, while ENR (but not AOX) reduced ceramide levels. Overall, these data demonstrate that lifestyle interventions curtail activation of pro-degenerative pathways to improve cellular health and are the

  6. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

    ... and Updates 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 ...

  7. Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions

    PubMed Central

    Morita, Tomoyo; Asada, Minoru; Naito, Eiichi

    2016-01-01

    Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of “structure” and “function” because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future. PMID:27695409

  8. Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions

    PubMed Central

    Morita, Tomoyo; Asada, Minoru; Naito, Eiichi

    2016-01-01

    Humans experience significant physical and mental changes from birth to adulthood, and a variety of perceptual, cognitive and motor functions mature over the course of approximately 20 years following birth. To deeply understand such developmental processes, merely studying behavioral changes is not sufficient; simultaneous investigation of the development of the brain may lead us to a more comprehensive understanding. Recent advances in noninvasive neuroimaging technologies largely contribute to this understanding. Here, it is very important to consider the development of the brain from the perspectives of “structure” and “function” because both structure and function of the human brain mature slowly. In this review, we first discuss the process of structural brain development, i.e., how the structure of the brain, which is crucial when discussing functional brain development, changes with age. Second, we introduce some representative studies and the latest studies related to the functional development of the brain, particularly for visual, facial recognition, and social cognition functions, all of which are important for humans. Finally, we summarize how brain science can contribute to developmental study and discuss the challenges that neuroimaging should address in the future.

  9. The connection between rhythmicity and brain function.

    PubMed

    Thaut, M H; Kenyon, G P; Schauer, M L; McIntosh, G C

    1999-01-01

    endeavor with important ramifications for the study of brain function, sensory perception, and motor behavior. One of the most exciting findings in this research, however, may be the evidence that the interaction between auditory rhythm and physical response can be effectively harnessed for specific therapeutic purposes in the rehabilitation of persons with movement disorders. PMID:10101675

  10. The connection between rhythmicity and brain function.

    PubMed

    Thaut, M H; Kenyon, G P; Schauer, M L; McIntosh, G C

    1999-01-01

    endeavor with important ramifications for the study of brain function, sensory perception, and motor behavior. One of the most exciting findings in this research, however, may be the evidence that the interaction between auditory rhythm and physical response can be effectively harnessed for specific therapeutic purposes in the rehabilitation of persons with movement disorders.

  11. Structural and functional connectivity in traumatic brain injury

    PubMed Central

    Xiao, Hui; Yang, Yang; Xi, Ji-hui; Chen, Zi-qian

    2015-01-01

    Traumatic brain injury survivors often experience cognitive deficits and neuropsychiatric symptoms. However, the neurobiological mechanisms underlying specific impairments are not fully understood. Advances in neuroimaging techniques (such as diffusion tensor imaging and functional MRI) have given us new insights on structural and functional connectivity patterns of the human brain in both health and disease. The connectome derived from connectivity maps reflects the entire constellation of distributed brain networks. Using these powerful neuroimaging approaches, changes at the microstructural level can be detected through regional and global properties of neuronal networks. Here we will review recent developments in the study of brain network abnormalities in traumatic brain injury, mainly focusing on structural and functional connectivity. Some connectomic studies have provided interesting insights into the neurological dysfunction that occurs following traumatic brain injury. These techniques could eventually be helpful in developing imaging biomarkers of cognitive and neurobehavioral sequelae, as well as predicting outcome and prognosis. PMID:26889200

  12. 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…

  13. Exercise benefits for the aging brain depend on the accompanying cognitive load: insights from sleep electroencephalogram.

    PubMed

    Horne, Jim

    2013-11-01

    Although exercise clearly offsets aging effects on the body, its benefits for the aging brain are likely to depend on the extent that physical activity (especially locomotion) facilitates multisensory encounters, curiosity, and interactions with novel environments; this is especially true for exploratory activity, which occupies much of wakefulness for most mammals in the wild. Cognition is inseparable from physical activity, with both interlinked to promote neuroplasticity and more successful brain aging. In these respects and for humans, exercising in a static, featureless, artificially lit indoor setting contrasts with exploratory outdoor walking within a novel environment during daylight. However, little is known about the comparative benefits for the aging brain of longer-term daily regimens of this latter nature including the role of sleep, to the extent that sleep enhances neuroplasticity as shown in short-term laboratory studies. More discerning analyses of sleep electroencephalogram (EEG) slow-wave activity especially 0.5-2-Hz activity would provide greater insights into use-dependent recovery processes during longer-term tracking of these regimens and complement slower changing waking neuropsychologic and resting functional magnetic resonance imaging (fMRI) measures, including those of the brain's default mode network. Although the limited research only points to ephemeral small sleep EEG effects of pure exercise, more enduring effects seem apparent when physical activity incorporates cognitive challenges. In terms of "use it or lose it," curiosity-driven "getting out and about," encountering, interacting with, and enjoying novel situations may well provide the brain with its real exercise, further reflected in changes to the dynamics of sleep. PMID:24051117

  14. Exercise benefits for the aging brain depend on the accompanying cognitive load: insights from sleep electroencephalogram.

    PubMed

    Horne, Jim

    2013-11-01

    Although exercise clearly offsets aging effects on the body, its benefits for the aging brain are likely to depend on the extent that physical activity (especially locomotion) facilitates multisensory encounters, curiosity, and interactions with novel environments; this is especially true for exploratory activity, which occupies much of wakefulness for most mammals in the wild. Cognition is inseparable from physical activity, with both interlinked to promote neuroplasticity and more successful brain aging. In these respects and for humans, exercising in a static, featureless, artificially lit indoor setting contrasts with exploratory outdoor walking within a novel environment during daylight. However, little is known about the comparative benefits for the aging brain of longer-term daily regimens of this latter nature including the role of sleep, to the extent that sleep enhances neuroplasticity as shown in short-term laboratory studies. More discerning analyses of sleep electroencephalogram (EEG) slow-wave activity especially 0.5-2-Hz activity would provide greater insights into use-dependent recovery processes during longer-term tracking of these regimens and complement slower changing waking neuropsychologic and resting functional magnetic resonance imaging (fMRI) measures, including those of the brain's default mode network. Although the limited research only points to ephemeral small sleep EEG effects of pure exercise, more enduring effects seem apparent when physical activity incorporates cognitive challenges. In terms of "use it or lose it," curiosity-driven "getting out and about," encountering, interacting with, and enjoying novel situations may well provide the brain with its real exercise, further reflected in changes to the dynamics of sleep.

  15. Hippocampal glucocorticoid receptor activation enhances voltage-dependent Ca2+ conductances: relevance to brain aging.

    PubMed Central

    Kerr, D S; Campbell, L W; Thibault, O; Landfield, P W

    1992-01-01

    Glucocorticoids (GCs) activate several biochemical/molecular processes in the hippocampus through two receptor types. In addition, GCs influence cognitive behaviors and hippocampal neural activity and can also increase the rate of aging-dependent cell loss in the hippocampus. However, the ionic mechanisms through which GCs modulate hippocampal neuronal function are not well understood. We report here direct evidence that activation of cytosolic steroid receptors, specifically of the type II GC receptor, can enhance voltage-dependent Ca2+ conductances in brain neurons. Ca2+ current was assessed by current-clamp measures of Ca2+ action potentials and by sharp electrode voltage-clamp analyses of voltage-sensitive currents in cesium-, tetrodotoxin-, and tetraethylammonium-treated CA1 neurons in hippocampal slices. Both Ca2+ action potentials and voltage-activated Ca2+ currents (N- and L-like) were increased by 2-hr exposure to the synthetic GC receptor agonist, RU 28362. This effect of RU 28362 was blocked by coincubation with cycloheximide, indicating that the GC receptor-Ca2+ channel interaction depends on de novo protein synthesis. Dysregulated calcium homeostasis is also viewed as a candidate mechanism in brain aging. Thus, present results are consistent with the hypothesis that excessive GC-receptor activation and resultant increased Ca2+ influx may be two sequential phases of a brain-aging process that results initially in impairment of function and eventually in neuronal loss. PMID:1528857

  16. Spatiotemporal Dependency of Age-Related Changes in Brain Signal Variability

    PubMed Central

    McIntosh, A. R.; Vakorin, V.; Kovacevic, N.; Wang, H.; Diaconescu, A.; Protzner, A. B.

    2014-01-01

    Recent theoretical and empirical work has focused on the variability of network dynamics in maturation. Such variability seems to reflect the spontaneous formation and dissolution of different functional networks. We sought to extend these observations into healthy aging. Two different data sets, one EEG (total n = 48, ages 18–72) and one magnetoencephalography (n = 31, ages 20–75) were analyzed for such spatiotemporal dependency using multiscale entropy (MSE) from regional brain sources. In both data sets, the changes in MSE were timescale dependent, with higher entropy at fine scales and lower at more coarse scales with greater age. The signals were parsed further into local entropy, related to information processed within a regional source, and distributed entropy (information shared between two sources, i.e., functional connectivity). Local entropy increased for most regions, whereas the dominant change in distributed entropy was age-related reductions across hemispheres. These data further the understanding of changes in brain signal variability across the lifespan, suggesting an inverted U-shaped curve, but with an important qualifier. Unlike earlier in maturation, where the changes are more widespread, changes in adulthood show strong spatiotemporal dependence. PMID:23395850

  17. 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.

  18. 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

  19. Exercise enhances memory consolidation in the aging brain

    PubMed Central

    Snigdha, Shikha; de Rivera, Christina; Milgram, Norton W.; Cotman, Carl W.

    2014-01-01

    Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long-term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise), post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 min on a treadmill) on memory consolidation in aged canines both right after, an hour after, and 24 h after acute exercise training in concurrent discrimination, object location memory (OLM), and novel object recognition tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at 24 h post-exercise and not right after or 1 h after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days) on OLM or till criterion were reached (for reversal learning task). We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise. PMID:24550824

  20. Exercise enhances memory consolidation in the aging brain.

    PubMed

    Snigdha, Shikha; de Rivera, Christina; Milgram, Norton W; Cotman, Carl W

    2014-01-01

    Exercise has been shown to reduce age-related losses in cognitive function including learning and memory, but the mechanisms underlying this effect remain poorly understood. Memory formation occurs in stages that include an initial acquisition phase, an intermediate labile phase, and then a process of consolidation which leads to long-term memory formation. An effective way to examine the mechanism by which exercise improves memory is to introduce the intervention (exercise), post-acquisition, making it possible to selectively examine memory storage and consolidation. Accordingly we evaluated the effects of post-trial exercise (10 min on a treadmill) on memory consolidation in aged canines both right after, an hour after, and 24 h after acute exercise training in concurrent discrimination, object location memory (OLM), and novel object recognition tasks. Our study shows that post-trial exercise facilitates memory function by improving memory consolidation in aged animals in a time-dependent manner. The improvements were significant at 24 h post-exercise and not right after or 1 h after exercise. Aged animals were also tested following chronic exercise (10 min/day for 14 consecutive days) on OLM or till criterion were reached (for reversal learning task). We found improvements from a chronic exercise design in both the object location and reversal learning tasks. Our studies suggest that mechanisms to improve overall consolidation and cognitive function remain accessible even with progressing age and can be re-engaged by both acute and chronic exercise.

  1. Medial Temporal Lobe Contributions to Intra-Item Associative Recognition Memory in the Aging Brain

    PubMed Central

    Dalton, Marshall Axel; Tu, Sicong; Hornberger, Michael; Hodges, John Russel; Piguet, Olivier

    2014-01-01

    Aging is associated with a decline in episodic memory function. This is accompanied by degradation of and functional changes in the medial temporal lobe (MTL) which subserves mnemonic processing. To date no study has investigated age-related functional change in MTL substructures during specific episodic memory processes such as intra-item associative memory. The aim of this study was to characterize age-related change in the neural correlates of intra-item associative memory processing. Sixteen young and 10 older subjects participated in a compound word intra-item associative memory task comprising a measure of associative recognition memory and a measure of recognition memory. There was no difference in performance between groups on the associative memory measure but each group recruited different MTL regions while performing the task. The young group recruited the left anterior hippocampus and posterior parahippocampal gyrus whereas the older participants recruited the hippocampus bilaterally. In contrast, recognition memory was significantly worse in the older subjects. The left anterior hippocampus was recruited in the young group during successful recognition memory whereas the older group recruited a more posterior region of the left hippocampus and showed a more bilateral activation of frontal brain regions than was observed in the young group. Our results suggest a reorganization of the neural correlates of intra-item associative memory in the aging brain. PMID:24427127

  2. Therapeutics with SPION-labeled stem cells for the main diseases related to brain aging: a systematic review

    PubMed Central

    Alvarim, Larissa T; Nucci, Leopoldo P; Mamani, Javier B; Marti, Luciana C; Aguiar, Marina F; Silva, Helio R; Silva, Gisele S; Nucci-da-Silva, Mariana P; DelBel, Elaine A; Gamarra, Lionel F

    2014-01-01

    The increase in clinical trials assessing the efficacy of cell therapy for structural and functional regeneration of the nervous system in diseases related to the aging brain is well known. However, the results are inconclusive as to the best cell type to be used or the best methodology for the homing of these stem cells. This systematic review analyzed published data on SPION (superparamagnetic iron oxide nanoparticle)-labeled stem cells as a therapy for brain diseases, such as ischemic stroke, Parkinson’s disease, amyotrophic lateral sclerosis, and dementia. This review highlights the therapeutic role of stem cells in reversing the aging process and the pathophysiology of brain aging, as well as emphasizing nanotechnology as an important tool to monitor stem cell migration in affected regions of the brain. PMID:25143726

  3. Centrality of Social Interaction in Human Brain Function.

    PubMed

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

    2015-10-01

    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.

  4. The Dynamic Dielectric at a Brain Functional Site and an EM Wave Approach to Functional Brain Imaging

    PubMed Central

    Li, X. P.; Xia, Q.; Qu, D.; Wu, T. C.; Yang, D. G.; Hao, W. D.; Jiang, X.; Li, X. M.

    2014-01-01

    Functional brain imaging has tremendous applications. The existing methods for functional brain imaging include functional Magnetic Resonant Imaging (fMRI), scalp electroencephalography (EEG), implanted EEG, magnetoencephalography (MEG) and Positron Emission Tomography (PET), which have been widely and successfully applied to various brain imaging studies. To develop a new method for functional brain imaging, here we show that the dielectric at a brain functional site has a dynamic nature, varying with local neuronal activation as the permittivity of the dielectric varies with the ion concentration of the extracellular fluid surrounding neurons in activation. Therefore, the neuronal activation can be sensed by a radiofrequency (RF) electromagnetic (EM) wave propagating through the site as the phase change of the EM wave varies with the permittivity. Such a dynamic nature of the dielectric at a brain functional site provides the basis for an RF EM wave approach to detecting and imaging neuronal activation at brain functional sites, leading to an RF EM wave approach to functional brain imaging. PMID:25367217

  5. The dynamic dielectric at a brain functional site and an EM wave approach to functional brain imaging.

    PubMed

    Li, X P; Xia, Q; Qu, D; Wu, T C; Yang, D G; Hao, W D; Jiang, X; Li, X M

    2014-11-04

    Functional brain imaging has tremendous applications. The existing methods for functional brain imaging include functional Magnetic Resonant Imaging (fMRI), scalp electroencephalography (EEG), implanted EEG, magnetoencephalography (MEG) and Positron Emission Tomography (PET), which have been widely and successfully applied to various brain imaging studies. To develop a new method for functional brain imaging, here we show that the dielectric at a brain functional site has a dynamic nature, varying with local neuronal activation as the permittivity of the dielectric varies with the ion concentration of the extracellular fluid surrounding neurons in activation. Therefore, the neuronal activation can be sensed by a radiofrequency (RF) electromagnetic (EM) wave propagating through the site as the phase change of the EM wave varies with the permittivity. Such a dynamic nature of the dielectric at a brain functional site provides the basis for an RF EM wave approach to detecting and imaging neuronal activation at brain functional sites, leading to an RF EM wave approach to functional brain imaging.

  6. The Impact of Diabetes on Brain Function in Childhood and Adolescence.

    PubMed

    Cameron, Fergus J

    2015-08-01

    A constant supply of glucose to the brain is critical for normal cerebral metabolism. The dysglycemia of type 1 diabetes (T1D) can affect activity, survival, and function of neural cells. Clinical studies in T1D have shown impairments in brain morphology and function. The most neurotoxic milieu seems to be young age and/or diabetic ketoacidosis at onset, severe hypoglycemia under the age of 6 years followed by chronic hyperglycemia. Adverse cognitive outcomes seem to be associated with poorer mental health outcomes. It is imperative to improve outcomes by investigating the mechanisms of injury so that neuroprotective strategies independent of glycemia can be identified.

  7. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer’s Disease

    PubMed Central

    Klöppel, Stefan; Koutsouleris, Nikolaos; Sauer, Heinrich

    2013-01-01

    Alzheimer’s disease (AD), the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI)-based biomarker that predicts the individual progression of mild cognitive impairment (MCI) to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE) score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%). The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF). With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07–1.13]). Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options. PMID:23826273

  8. Non-injurious neonatal hypoxia confers resistance to brain senescence in aged male rats.

    PubMed

    Martin, Nicolas; Bossenmeyer-Pourié, Carine; Koziel, Violette; Jazi, Rozat; Audonnet, Sandra; Vert, Paul; Guéant, Jean-Louis; Daval, Jean-Luc; Pourié, Grégory

    2012-01-01

    Whereas brief acute or intermittent episodes of hypoxia have been shown to exert a protective role in the central nervous system and to stimulate neurogenesis, other studies suggest that early hypoxia may constitute a risk factor that influences the future development of mental disorders. We therefore investigated the effects of a neonatal "conditioning-like" hypoxia (100% N₂, 5 min) on the brain and the cognitive outcomes of rats until 720 days of age (physiologic senescence). We confirmed that such a short hypoxia led to brain neurogenesis within the ensuing weeks, along with reduced apoptosis in the hippocampus involving activation of Erk1/2 and repression of p38 and death-associated protein (DAP) kinase. At 21 days of age, increased thicknesses and cell densities were recorded in various subregions, with strong synapsin activation. During aging, previous exposure to neonatal hypoxia was associated with enhanced memory retrieval scores specifically in males, better preservation of their brain integrity than controls, reduced age-related apoptosis, larger hippocampal cell layers, and higher expression of glutamatergic and GABAergic markers. These changes were accompanied with a marked expression of synapsin proteins, mainly of their phosphorylated active forms which constitute major players of synapse function and plasticity, and with increases of their key regulators, i.e. Erk1/2, the transcription factor EGR-1/Zif-268 and Src kinase. Moreover, the significantly higher interactions between PSD-95 scaffolding protein and NMDA receptors measured in the hippocampus of 720-day-old male animals strengthen the conclusion of increased synaptic functional activity and plasticity associated with neonatal hypoxia. Thus, early non-injurious hypoxia may trigger beneficial long term effects conferring higher resistance to senescence in aged male rats, with a better preservation of cognitive functions.

  9. Prion Protein Accumulation in Lipid Rafts of Mouse Aging Brain

    PubMed Central

    Agostini, Federica; Dotti, Carlos G.; Pérez-Cañamás, Azucena; Ledesma, Maria Dolores; Benetti, Federico; Legname, Giuseppe

    2013-01-01

    The cellular form of the prion protein (PrPC) is a normal constituent of neuronal cell membranes. The protein misfolding causes rare neurodegenerative disorders known as transmissible spongiform encephalopathies or prion diseases. These maladies can be sporadic, genetic or infectious. Sporadic prion diseases are the most common form mainly affecting aging people. In this work, we investigate the biochemical environment in which sporadic prion diseases may develop, focusing our attention on the cell membrane of neurons in the aging brain. It is well established that with aging the ratio between the most abundant lipid components of rafts undergoes a major change: while cholesterol decreases, sphingomyelin content rises. Our results indicate that the aging process modifies the compartmentalization of PrPC. In old mice, this change favors PrPC accumulation in detergent-resistant membranes, particularly in hippocampi. To confirm the relationship between lipid content changes and PrPC translocation into detergent-resistant membranes (DRMs), we looked at PrPC compartmentalization in hippocampi from acid sphingomyelinase (ASM) knockout (KO) mice and synaptosomes enriched in sphingomyelin. In the presence of high sphingomyelin content, we observed a significant increase of PrPC in DRMS. This process is not due to higher levels of total protein and it could, in turn, favor the onset of sporadic prion diseases during aging as it increases the PrP intermolecular contacts into lipid rafts. We observed that lowering sphingomyelin in scrapie-infected cells by using fumonisin B1 led to a 50% decrease in protease-resistant PrP formation. This may suggest an involvement of PrP lipid environment in prion formation and consequently it may play a role in the onset or development of sporadic forms of prion diseases. PMID:24040215

  10. Age of Onset of Marijuana Use and Executive Function

    PubMed Central

    Gruber, Staci A.; Sagar, Kelly A.; Dahlgren, Mary Kathryn; Racine, Megan; Lukas, Scott E.

    2012-01-01

    Marijuana (MJ) remains the most widely abused illicit substance in the United States, and in recent years, a decline in perceived risk of MJ use has been accompanied by a simultaneous increase in rates of use among adolescents. In the current study, we hypothesized that chronic MJ smokers would perform cognitive tasks, specifically those that require executive function more poorly than control subjects, and that individuals who started smoking MJ regularly prior to age 16 (early onset) would have more difficulty than those who started after age 16 (late onset). Thirty-four chronic, heavy MJ smokers separated into early and late onset groups and 28 non-MJ smoking controls completed a battery of neurocognitive measures. As hypothesized, MJ smokers performed more poorly than controls on several measures of executive function. Age of onset analyses revealed that these between-group differences were largely attributed to the early onset group, who were also shown to smoke twice as often and nearly three times as much MJ per week relative to the late onset smokers. Age of onset, frequency and magnitude of MJ use were all shown to impact cognitive performance. Findings suggest that earlier MJ onset is related to poorer cognitive function and increased frequency and magnitude of MJ use relative to later MJ onset. Exposure to MJ during a period of neurodevelopmental vulnerability, such as adolescence, may result in altered brain development and enduring neuropsychological changes. PMID:22103843

  11. Regional white matter hyperintensities: aging, AD risk, and cognitive function

    PubMed Central

    Birdsill, Alex C; Koscik, Rebecca L; Jonaitis, Erin M; Johnson, Sterling C; Okonkwo, Ozioma C; Hermann, Bruce P; LaRue, Asenath; Sager, Mark A; Bendlin, Barbara B

    2013-01-01

    White matter hyperintensities (WMH) of presumed vascular origin as seen on T2-weighted fluid attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI), are known to increase with age and are elevated in Alzheimer’s disease (AD). The cognitive implications of these common markers are not well understood. Previous research has primarily focused on global measures of WMH burden and broad localizations that contain multiple white matter tracts. The aims of this study were to determine the pattern of WMH accumulation with age, risk for AD, and the relationship with cognitive function utilizing a voxel-wise analysis capable of identifying specific white matter regions. Three hundred and forty-nine participants underwent T1-weighted and high-resolution T2FLAIR MRI and neuropsychological testing. Increasing age and lower cognitive speed and flexibility (a component of executive function), were both significantly associated with regional WMH throughout the brain. When age was controlled, lower cognitive speed and flexibility was independently associated with WMH in the superior corona radiata. APOE4 and parental family history of AD were not associated with higher burden of WMH. The results contribute to a larger body of literature suggesting that white matter measures are linked with processing speed, and illustrate the utility of voxel-wise analysis in understanding the effect of lesion location on cognitive function. PMID:24199958

  12. Beta-amyloid deposition and the aging brain.

    PubMed

    Rodrigue, Karen M; Kennedy, Kristen M; Park, Denise C

    2009-12-01

    A central issue in cognitive neuroscience of aging research is pinpointing precise neural mechanisms that determine cognitive outcome in late adulthood as well as identifying early markers of less successful cognitive aging. One promising biomarker is beta amyloid (Abeta) deposition. Several new radiotracers have been developed that bind to fibrillar Abeta providing sensitive estimates of amyloid deposition in various brain regions. Abeta imaging has been primarily used to study patients with Alzheimer's Disease (AD) and individuals with Mild Cognitive Impairment (MCI); however, there is now building data on Abeta deposition in healthy controls that suggest at least 20% and perhaps as much as a third of healthy older adults show significant deposition. Considerable evidence suggests amyloid deposition precedes declines in cognition and may be the initiator in a cascade of events that indirectly leads to age-related cognitive decline. We review studies of Abeta deposition imaging in AD, MCI, and normal adults, its cognitive consequences, and the role of genetic risk and cognitive reserve.

  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. PMID:26438800

  14. Social Determinants, Race, and Brain Health Outcomes: Findings from the Chicago Health and Aging Project.

    PubMed

    Aggarwal, Neelum T; Everson-Rose, Susan A; Evans, Denis A

    2015-01-01

    The broad spectrum of economic and cultural diversity in the U.S. population correlates with and affects the study of behavioral aspects of health. The purpose of this article is to provide a selective overview of research findings from the Chicago Health and Aging Project (CHAP), which covers a socio-demographically diverse population in Chicago, with a focus on role-related psychosocial factors and observed racial/ethnic differences in aging outcomes. CHAP is a longitudinal, epidemiological study of common chronic conditions of aging with an emphasis on medical, psychosocial, and environmental risk factors for the decline in cognitive function across the older adult lifespan. We briefly summarize the study design and methods used in the CHAP study and characterize the study population and describe the psychosocial data, noting black-white associations as they relate to three common brain health outcomes: cognitive function and Alzheimer's Disease, stroke, and subclinical vascular disease as noted on neuroimaging. PMID:26239039

  15. Social Determinants, Race, and Brain Health Outcomes: Findings from the Chicago Health and Aging Project.

    PubMed

    Aggarwal, Neelum T; Everson-Rose, Susan A; Evans, Denis A

    2015-01-01

    The broad spectrum of economic and cultural diversity in the U.S. population correlates with and affects the study of behavioral aspects of health. The purpose of this article is to provide a selective overview of research findings from the Chicago Health and Aging Project (CHAP), which covers a socio-demographically diverse population in Chicago, with a focus on role-related psychosocial factors and observed racial/ethnic differences in aging outcomes. CHAP is a longitudinal, epidemiological study of common chronic conditions of aging with an emphasis on medical, psychosocial, and environmental risk factors for the decline in cognitive function across the older adult lifespan. We briefly summarize the study design and methods used in the CHAP study and characterize the study population and describe the psychosocial data, noting black-white associations as they relate to three common brain health outcomes: cognitive function and Alzheimer's Disease, stroke, and subclinical vascular disease as noted on neuroimaging.

  16. Tail pinch induces fos immunoreactivity within several regions of the male rat brain: effects of age.

    PubMed

    Smith, W J; Stewart, J; Pfaus, J G

    1997-05-01

    Brief, intermittent stressors, such as low-level foot shock or tail pinch, induce a general excitement and autonomic arousal in rats that increases their sensitivity to external incentives. Such stimulation can facilitate a variety of behaviors, including feeding, aggression, sexual activity, parental behavior, and drug taking if the appropriate stimuli exist in the environment. However, the ability of tail pinch to induce general arousal and incentive motivation appears to diminish with age. Here we report on the ability of tail pinch to induce Fos immunoreactivity within several brain regions as a function of age. Young (2-3 months) and middle-aged (12-13 months) male rats were administered either five tail pinches (one every 2 min), one tail pinch, or zero (sham) tail pinches (n = 4 per stimulation condition). Rats were sacrificed 75 min following the onset of stimulation, and their brains were prepared for immunocytochemical detection of Fos protein. Fos immunoreactivity was induced by one and five tail pinches in several brain regions, including the anterior medial preoptic area (mPOA), paraventricular nucleus of the hypothalamus (PVN), paraventricular nucleus of the thalamus (PV-Thal), medial amygdala (MEA), basolateral amygdala (BLA), lateral habenula (LHab), and ventral tegmental area (VTA), of young rats compared with those that received zero tail pinches. In contrast to young rats, middle-aged rats had significantly less Fos induced by one and five tail pinches in the mPOA, PVN, MEA, BLA, and VTA, but an equivalent amount induced in the LHab. Fos immunoreactivity was not found within the medial prefrontal cortex, nucleus accumbens, striatum, lateral septum, or locus coeruleus in either young or old rats. Tail pinch appears to activate regions of the brain known to be involved in behavioral responses to both incentive cues and stressors. The lower level of cellular reactivity to tail pinch in middle-aged rats suggests a diminished neural responsiveness to

  17. Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging.

    PubMed

    Singh, Ram Harsh; Narsimhamurthy, K; Singh, Girish

    2008-12-01

    Ayurveda is the oldest system of Medicine in the world, its antiquity going back to the Vedas. It adapts a unique holistic approach to the entire science of life, health and cure. The areas of special consideration in Ayurveda are geriatrics, rejuvenation, nutrition, immunology, genetics and higher consciousness. The Ayurvedic texts describe a set of rejuvenative measures to impart biological sustenance to the bodily tissues. These remedies are called Rasayana which are claimed to act as micronutrients. Some of these Rasayanas are organ and tissue specific. Those specific to brain tissue are called Medhya Rasayana. Such Rasayanas retard brain aging and help in regeneration of neural tissues besides producing antistress, adaptogenic and memory enhancing effect. In addition to the long tradition of textual and experience-based evidence for their efficacy, certain recent studies conducted on these traditional remedies on scientific parameters have shown promising results which have been reviewed in this paper for providing lead for further studies. The popular Medhya Rasayanas are Ashwagandha (Withania somnifera Dunal), Brahmi (Bacopa monnieri Linn), Mandukaparni (Centella asiatica Linn) and Sankhapuspi (Convolvulus pluricaulis Chois). PMID:18931935

  18. Dedifferentiation of emotion regulation strategies in the aging brain

    PubMed Central

    Ponzio, Allison; Velasco, Ricardo; Kaplan, Jonas; Mather, Mara

    2015-01-01

    Different emotion regulation strategies are distinctly represented in the brains of younger adults. Decreasing a reaction to a negative situation by reinterpreting it (reappraisal) relies on cognitive control regions in the prefrontal cortex, while distracting away from a stressor involves more posterior medial structures. In this study, we used Multi-Voxel pattern analyses (MVPA) to examine whether reappraisal and distraction strategies have distinct representations in the older adult brain, or whether emotion regulation strategies become more dedifferentiated in later life. MVPA better differentiated the two emotion regulation strategies for younger adults than for older adults, and revealed the greatest age-related differences in differentiation in the posterior medial cortex (PMC). Univariate analyses revealed equal PMC recruitment across strategies for older adults, but greater activity during distraction than reappraisal for younger adults. The PMC is central to self-focused processing, and thus our findings are consistent with the possibility that focusing on the self may be a default mechanism across emotion regulation strategies for older people. PMID:25380765

  19. Imaging local brain function with emission computed tomography

    SciTech Connect

    Kuhl, D.E.

    1984-03-01

    Positron emission tomography (PET) using /sup 18/F-fluorodeoxyglucose (FDG) was used to map local cerebral glucose utilization in the study of local cerebral function. This information differs fundamentally from structural assessment by means of computed tomography (CT). In normal human volunteers, the FDG scan was used to determine the cerebral metabolic response to conrolled sensory stimulation and the effects of aging. Cerebral metabolic patterns are distinctive among depressed and demented elderly patients. The FDG scan appears normal in the depressed patient, studded with multiple metabolic defects in patients with multiple infarct dementia, and in the patients with Alzheimer disease, metabolism is particularly reduced in the parietal cortex, but only slightly reduced in the caudate and thalamus. The interictal FDG scan effectively detects hypometabolic brain zones that are sites of onset for seizures in patients with partial epilepsy, even though these zones usually appear normal on CT scans. The future prospects of PET are discussed.

  20. Cognitive dysfunction syndrome: a disease of canine and feline brain aging.

    PubMed

    Landsberg, Gary M; Nichol, Jeff; Araujo, Joseph A

    2012-07-01

    Brain aging is a degenerative process manifest by impairment of cognitive function; although not all pets are affected at the same level, once cognitive decline begins it is generally a progressive disorder. Diagnosis of cognitive dysfunction syndrome (CDS) is based on recognition of behavioral signs and exclusion of other medical causes that might mimic CDS or complicate its diagnosis. Drugs, diets, and supplements are now available that might slow CDS progression by various mechanisms including reducing oxidative stress and inflammation or improving mitochondrial and neuronal function. Moreover, available therapeutics may provide some level of improvement in cognitive and clinical signs of CDS. PMID:22720812

  1. 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].

  2. Age, Intelligence, and Event-Related Brain Potentials during Late Childhood: A Longitudinal Study.

    ERIC Educational Resources Information Center

    Stauder, Johannes E. A.; van der Molen, Maurits W.; Molenaar, Peter C. M.

    2003-01-01

    Studied the relationship between event-related brain activity, age, and intelligence using a visual oddball task presented to girls at 9, 10, and 11 years of age. Findings for 26 girls suggest a qualitative shift in the relation between event-related brain activity and intelligence between 9 and 10 years of age. (SLD)

  3. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains

    PubMed Central

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-01-01

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains. PMID:27032368

  4. Functional brain imaging in 14 patients with dissociative amnesia reveals right inferolateral prefrontal hypometabolism.

    PubMed

    Brand, Matthias; Eggers, Carsten; Reinhold, Nadine; Fujiwara, Esther; Kessler, Josef; Heiss, Wolf-Dieter; Markowitsch, Hans J

    2009-10-30

    Dissociative amnesia is a condition usually characterized by severely impaired retrograde memory functioning in the absence of structural brain damage. Recent case studies nevertheless found functional brain changes in patients suffering from autobiographical-episodic memory loss in the cause of dissociative amnesia. Functional changes were demonstrated in both resting state and memory retrieval conditions. In addition, some but not all cases also showed other neuropsychological impairments beyond retrograde memory deficits. However, there is no group study available that examined potential functional brain abnormalities and accompanying neuropsychological deteriorations in larger samples of patients with dissociative retrograde amnesia. We report functional imaging and neuropsychological data acquired in 14 patients with dissociative amnesia following stressful or traumatic events. All patients suffered from autobiographical memory loss. In addition, approximately half of the patients had deficits in anterograde memory and executive functioning. Accompanying functional brain changes were measured by [18F]fluorodeoxyglucose positron emission tomography (FDG-PET). Regional glucose utilization of the patients was compared with that of 19 healthy subjects, matched for age and gender. We found significantly decreased glucose utilization in the right inferolateral prefrontal cortex in the patients. Hypometabolism in this brain region, known to be involved in retrieval of autobiographical memories and self-referential processing, may be a functional brain correlate of dissociative amnesia.

  5. A Systematic Investigation into Aging Related Genes in Brain and Their Relationship with Alzheimer’s Disease

    PubMed Central

    Meng, Guofeng; Zhong, Xiaoyan; Mei, Hongkang

    2016-01-01

    Aging, as a complex biological process, is accompanied by the accumulation of functional loses at different levels, which makes age to be the biggest risk factor to many neurological diseases. Even following decades of investigation, the process of aging is still far from being fully understood, especially at a systematic level. In this study, we identified aging related genes in brain by collecting the ones with sustained and consistent gene expression or DNA methylation changes in the aging process. Functional analysis with Gene Ontology to these genes suggested transcriptional regulators to be the most affected genes in the aging process. Transcription regulation analysis found some transcription factors, especially Specificity Protein 1 (SP1), to play important roles in regulating aging related gene expression. Module-based functional analysis indicated these genes to be associated with many well-known aging related pathways, supporting the validity of our approach to select aging related genes. Finally, we investigated the roles of aging related genes on Alzheimer’s Disease (AD). We found that aging and AD related genes both involved some common pathways, which provided a possible explanation why aging made the brain more vulnerable to Alzheimer’s Disease. PMID:26937969

  6. Improving memory in Parkinson's disease: a healthy brain ageing cognitive training program.

    PubMed

    Naismith, Sharon L; Mowszowski, Loren; Diamond, Keri; Lewis, Simon J G

    2013-07-01

    This study aimed to evaluate the efficacy of a multifactorial 'healthy brain ageing cognitive training program' for Parkinson's disease. Using a single-blinded waitlist control design, 50 participants with Parkinson's disease were recruited from the Brain & Mind Research Institute, Sydney, Australia. The intervention encompassed both psychoeducation and cognitive training; each component lasted 1-hour. The 2-hour sessions were delivered in a group format, twice-weekly over a 7-week period. Multifactorial psychoeducation was delivered by a range of health professionals. In addition to delivering cognitive strategies, it targeted depression, anxiety, sleep, vascular risk factors, diet, and exercise. Cognitive training was computer-based and was conducted by clinical neuropsychologists. The primary outcome was memory. Secondary outcomes included other aspects of cognition and knowledge pertaining to the psychoeducation material. Results demonstrated that cognitive training was associated with significant improvements in learning and memory corresponding to medium to large effect sizes. Treatment was also associated with medium effect size improvements in knowledge. Although the study was limited by the lack of randomized allocation to treatment and control groups, these findings suggest that a healthy brain ageing cognitive training program may be a viable tool to improve memory and/or slow cognitive decline in people with Parkinson's disease. It also appeared successful for increasing awareness of adaptive and/or compensatory cognitive strategies, as well as modifiable risk factors to optimize brain functioning.

  7. Biondi ring tangles in the choroid plexus of Alzheimer's disease and normal aging brains: a quantitative study.

    PubMed

    Wen, G Y; Wisniewski, H M; Kascsak, R J

    1999-06-19

    The choroid plexus (CP) performs the vital function of producing up to 90% (450-1000 ml/day) of cerebrospinal fluid (CSF) to nourish and to protect the brain in the CSF suspension. The CP also acts as a selective barrier between blood and CSF to regulate ions and other essential molecules. However, the accumulation of intracellular inclusions called Biondi ring tangles (BRTs) in CP cells of Alzheimer's disease (AD)/aging brains may affect these vital functions of the CP. Statistical analysis of quantitative data on the numbers of CP cells containing BRTs from 54 brains (29 AD and 25 normal control), age range 1-100 years, indicated a significant difference (p<0.00004) between AD and control brains, using analysis of covariance (ANCOVA) with age as covariate. This study compiled the first set of archives to reveal the distribution pattern of BRTs in the CP of AD brains at various ages. Electron microscopy of negatively stained isolated BRTs revealed that these tangles are made of tightly packed bundles of long filaments with diameter around 10 nm that are morphologically distinct from the more loosely packed/shorter bundles of 6-8 nm amyloid fibrils of neuritic plaques (NPs) and from the 24 nm paired helical filaments of neurofibrillary tangles (NFTs) in AD brain. These data suggest that BRTs may represent a significant and measurable biomarker for AD in addition to NPs and NFTs. PMID:10375650

  8. Biondi ring tangles in the choroid plexus of Alzheimer's disease and normal aging brains: a quantitative study.

    PubMed

    Wen, G Y; Wisniewski, H M; Kascsak, R J

    1999-06-19

    The choroid plexus (CP) performs the vital function of producing up to 90% (450-1000 ml/day) of cerebrospinal fluid (CSF) to nourish and to protect the brain in the CSF suspension. The CP also acts as a selective barrier between blood and CSF to regulate ions and other essential molecules. However, the accumulation of intracellular inclusions called Biondi ring tangles (BRTs) in CP cells of Alzheimer's disease (AD)/aging brains may affect these vital functions of the CP. Statistical analysis of quantitative data on the numbers of CP cells containing BRTs from 54 brains (29 AD and 25 normal control), age range 1-100 years, indicated a significant difference (p<0.00004) between AD and control brains, using analysis of covariance (ANCOVA) with age as covariate. This study compiled the first set of archives to reveal the distribution pattern of BRTs in the CP of AD brains at various ages. Electron microscopy of negatively stained isolated BRTs revealed that these tangles are made of tightly packed bundles of long filaments with diameter around 10 nm that are morphologically distinct from the more loosely packed/shorter bundles of 6-8 nm amyloid fibrils of neuritic plaques (NPs) and from the 24 nm paired helical filaments of neurofibrillary tangles (NFTs) in AD brain. These data suggest that BRTs may represent a significant and measurable biomarker for AD in addition to NPs and NFTs.

  9. Default mode network functional and structural connectivity after traumatic brain injury.

    PubMed

    Sharp, David J; Beckmann, Christian F; Greenwood, Richard; Kinnunen, Kirsi M; Bonnelle, Valerie; De Boissezon, Xavier; Powell, Jane H; Counsell, Serena J; Patel, Maneesh C; Leech, Robert

    2011-08-01

    Traumatic brain injury often results in cognitive impairments that limit recovery. The underlying pathophysiology of these impairments is uncertain, which restricts clinical assessment and management. Here, we use magnetic resonance imaging to test the hypotheses that: (i) traumatic brain injury results in abnormalities of functional connectivity within key cognitive networks; (ii) these changes are correlated with cognitive performance; and (iii) functional connectivity within these networks is influenced by underlying changes in structural connectivity produced by diffuse axonal injury. We studied 20 patients in the chronic phase after traumatic brain injury compared with age-matched controls. Network function was investigated in detail using functional magnetic resonance imaging to analyse both regional brain activation, and the interaction of brain regions within a network (functional connectivity). We studied patients during performance of a simple choice-reaction task and at 'rest'. Since functional connectivity reflects underlying structural connectivity, diffusion tensor imaging was used to quantify axonal injury, and test whether structural damage correlated with functional change. The patient group showed typical impairments in information processing and attention, when compared with age-matched controls. Patients were able to perform the task accurately, but showed slow and variable responses. Brain regions activated by the task were similar between the groups, but patients showed greater deactivation within the default mode network, in keeping with an increased cognitive load. A multivariate analysis of 'resting' state functional magnetic resonance imaging was then used to investigate whether changes in network function were present in the absence of explicit task performance. Overall, default mode network functional connectivity was increased in the patient group. Patients with the highest functional connectivity had the least cognitive impairment. In

  10. Estimating the brain pathological age of Alzheimer’s disease patients from MR image data based on the separability distance criterion

    NASA Astrophysics Data System (ADS)

    Li, Yongming; Li, Fan; Wang, Pin; Zhu, Xueru; Liu, Shujun; Qiu, Mingguo; Zhang, Jingna; Zeng, Xiaoping

    2016-10-01

    Traditional age estimation methods are based on the same idea that uses the real age as the training label. However, these methods ignore that there is a deviation between the real age and the brain age due to accelerated brain aging. This paper considers this deviation and searches for it by maximizing the separability distance value rather than by minimizing the difference between the estimated brain age and the real age. Firstly, set the search range of the deviation as the deviation candidates according to prior knowledge. Secondly, use the support vector regression (SVR) as the age estimation model to minimize the difference between the estimated age and the real age plus deviation rather than the real age itself. Thirdly, design the fitness function based on the separability distance criterion. Fourthly, conduct age estimation on the validation dataset using the trained age estimation model, put the estimated age into the fitness function, and obtain the fitness value of the deviation candidate. Fifthly, repeat the iteration until all the deviation candidates are involved and get the optimal deviation with maximum fitness values. The real age plus the optimal deviation is taken as the brain pathological age. The experimental results showed that the separability was apparently improved. For normal control-Alzheimer’s disease (NC-AD), normal control-mild cognition impairment (NC-MCI), and MCI-AD, the average improvements were 0.178 (35.11%), 0.033 (14.47%), and 0.017 (39.53%), respectively. For NC-MCI-AD, the average improvement was 0.2287 (64.22%). The estimated brain pathological age could be not only more helpful to the classification of AD but also more precisely reflect accelerated brain aging. In conclusion, this paper offers a new method for brain age estimation that can distinguish different states of AD and can better reflect the extent of accelerated aging.

  11. 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

    2011-12-01

    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. PMID:21664231

  12. 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

  13. 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