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Sample records for reward-related brain function

  1. Circadian Misalignment, Reward-Related Brain Function, and Adolescent Alcohol Involvement

    PubMed Central

    Hasler, Brant P.; Clark, Duncan B.

    2013-01-01

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

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

    PubMed

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

    2015-03-01

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

  3. Divergent Effects of Genetic Variation in Endocannabinoid Signaling on Human Threat- and Reward-Related Brain Function

    PubMed Central

    Hariri, Ahmad R.; Gorka, Adam; Hyde, Luke W.; Kimak, Mark; Halder, Indrani; Ducci, Francesca; Ferrell, Robert E.; Goldman, David; Manuck, Stephen B.

    2011-01-01

    Background Fatty acid amide hydrolase (FAAH) is a key enzyme in regulating endocannabinoid (eCB) signaling. A common single nucleotide polymorphism (C385A) in the human FAAH gene has been associated with increased risk for addiction and obesity. Methods Using imaging genetics in 82 healthy adult volunteers, we examined the effects of FAAH C385A on threat- and reward-related human brain function. Results Carriers of FAAH 385A, associated with reduced enzyme and, possibly, increased eCB signaling, had decreased threat-related amygdala reactivity but increased reward-related ventral striatal reactivity in comparison to C385 homozygotes. Similar divergent effects of FAAH C385A genotype were manifest at the level of brain-behavior relationships. 385A carriers showed decreased correlation between amygdala reactivity and trait anxiety but increased correlation between ventral striatal reactivity and delay discounting, an index of impulsivity. Conclusions Our results parallel pharmacologic and genetic dissection of eCB signaling, are consistent with the psychotropic effects of Δ9-tetrahydrocannabinol and highlight specific neural mechanisms through which variability in eCB signaling impacts complex behavioral processes related to risk for addiction and obesity. PMID:19103437

  4. Weekend-weekday advances in sleep timing are associated with altered reward-related brain function in healthy adolescents

    PubMed Central

    Hasler, Brant P.; Dahl, Ronald E.; Holm, Stephanie M.; Jakubcak, Jennifer L.; Ryan, Neal D.; Silk, Jennifer S.; Phillips, Mary L.; Forbes, Erika E.

    2012-01-01

    Sleep timing shifts later during adolescence, thus conflicting with early school start times. This can lead to irregular weekday-weekend schedules and circadian misalignment, which have been linked to depression and substance abuse, consistent with disruptions in the processing of rewards. We tested associations between weekend-weekday shifts in sleep timing and the neural response to monetary reward in healthy adolescents, using actigraphy and a functional magnetic resonance imaging paradigm. Region-of-interest analyses focused on the medial prefrontal cortex (mPFC) and striatum, both of which are implicated in reward function. Analyses adjusted for pubertal stage, sex, and total sleep time. Greater weekend-weekday advances in midsleep were associated with decreased mPFC and striatal reactivity to reward, which could reflect reduced regulatory response and reward sensitivity. We speculate that circadian misalignment associated with weekend shifts in sleep timing may contribute to reward-related problems such as depression and substance abuse. PMID:22960270

  5. Pharmacological differentiation of opioid receptor antagonists by molecular and functional imaging of target occupancy and food reward-related brain activation in humans.

    PubMed

    Rabiner, E A; Beaver, J; Makwana, A; Searle, G; Long, C; Nathan, P J; Newbould, R D; Howard, J; Miller, S R; Bush, M A; Hill, S; Reiley, R; Passchier, J; Gunn, R N; Matthews, P M; Bullmore, E T

    2011-08-01

    Opioid neurotransmission has a key role in mediating reward-related behaviours. Opioid receptor (OR) antagonists, such as naltrexone (NTX), can attenuate the behaviour-reinforcing effects of primary (food) and secondary rewards. GSK1521498 is a novel OR ligand, which behaves as an inverse agonist at the μ-OR sub-type. In a sample of healthy volunteers, we used [(11)C]-carfentanil positron emission tomography to measure the OR occupancy and functional magnetic resonance imaging (fMRI) to measure activation of brain reward centres by palatable food stimuli before and after single oral doses of GSK1521498 (range, 0.4-100 mg) or NTX (range, 2-50 mg). GSK1521498 had high affinity for human brain ORs (GSK1521498 effective concentration 50 = 7.10 ng ml(-1)) and there was a direct relationship between receptor occupancy (RO) and plasma concentrations of GSK1521498. However, for both NTX and its principal active metabolite in humans, 6-β-NTX, this relationship was indirect. GSK1521498, but not NTX, significantly attenuated the fMRI activation of the amygdala by a palatable food stimulus. We thus have shown how the pharmacological properties of OR antagonists can be characterised directly in humans by a novel integration of molecular and functional neuroimaging techniques. GSK1521498 was differentiated from NTX in terms of its pharmacokinetics, target affinity, plasma concentration-RO relationships and pharmacodynamic effects on food reward processing in the brain. Pharmacological differentiation of these molecules suggests that they may have different therapeutic profiles for treatment of overeating and other disorders of compulsive consumption.

  6. GLP-1 receptor activation modulates appetite- and reward-related brain areas in humans.

    PubMed

    van Bloemendaal, Liselotte; IJzerman, Richard G; Ten Kulve, Jennifer S; Barkhof, Frederik; Konrad, Robert J; Drent, Madeleine L; Veltman, Dick J; Diamant, Michaela

    2014-12-01

    Gut-derived hormones, such as GLP-1, have been proposed to relay information to the brain to regulate appetite. GLP-1 receptor agonists, currently used for the treatment of type 2 diabetes (T2DM), improve glycemic control and stimulate satiety, leading to decreases in food intake and body weight. We hypothesized that food intake reduction after GLP-1 receptor activation is mediated through appetite- and reward-related brain areas. Obese T2DM patients and normoglycemic obese and lean individuals (n = 48) were studied in a randomized, crossover, placebo-controlled trial. Using functional MRI, we determined the acute effects of intravenous administration of the GLP-1 receptor agonist exenatide, with or without prior GLP-1 receptor blockade using exendin 9-39, on brain responses to food pictures during a somatostatin pancreatic-pituitary clamp. Obese T2DM patients and normoglycemic obese versus lean subjects showed increased brain responses to food pictures in appetite- and reward-related brain regions (insula and amygdala). Exenatide versus placebo decreased food intake and food-related brain responses in T2DM patients and obese subjects (in insula, amygdala, putamen, and orbitofrontal cortex). These effects were largely blocked by prior GLP-1 receptor blockade using exendin 9-39. Our findings provide novel insights into the mechanisms by which GLP-1 regulates food intake and how GLP-1 receptor agonists cause weight loss.

  7. Repeated electrical stimulation of reward-related brain regions affects cocaine but not "natural" reinforcement.

    PubMed

    Levy, Dino; Shabat-Simon, Maytal; Shalev, Uri; Barnea-Ygael, Noam; Cooper, Ayelet; Zangen, Abraham

    2007-12-19

    Drug addiction is associated with long-lasting neuronal adaptations including alterations in dopamine and glutamate receptors in the brain reward system. Treatment strategies for cocaine addiction and especially the prevention of craving and relapse are limited, and their effectiveness is still questionable. We hypothesized that repeated stimulation of the brain reward system can induce localized neuronal adaptations that may either potentiate or reduce addictive behaviors. The present study was designed to test how repeated interference with the brain reward system using localized electrical stimulation of the medial forebrain bundle at the lateral hypothalamus (LH) or the prefrontal cortex (PFC) affects cocaine addiction-associated behaviors and some of the neuronal adaptations induced by repeated exposure to cocaine. Repeated high-frequency stimulation in either site influenced cocaine, but not sucrose reward-related behaviors. Stimulation of the LH reduced cue-induced seeking behavior, whereas stimulation of the PFC reduced both cocaine-seeking behavior and the motivation for its consumption. The behavioral findings were accompanied by glutamate receptor subtype alterations in the nucleus accumbens and the ventral tegmental area, both key structures of the reward system. It is therefore suggested that repeated electrical stimulation of the PFC can become a novel strategy for treating addiction.

  8. Functional states of rat cortical circuits during the unpredictable availability of a reward-related cue

    PubMed Central

    Fernández-Lamo, Iván; Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García M, José M.

    2016-01-01

    Proper performance of acquired abilities can be disturbed by the unexpected occurrence of external changes. Rats trained with an operant conditioning task (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1) schedule were subsequently placed in a Skinner box in which the lever could be removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1-medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC-basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT situations. While lever presses were accompanied by a significant increase in fPSP slopes at the five synapses, the unpredictable absence of the lever were accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral analysis of local field potentials (LFPs) recorded when the animal approached the corresponding area in the lever OUT situation presented lower spectral powers than during lever IN occasions for all recording sites, apart from CA1. Thus, the unpredictable availability of a reward-related cue modified the activity of cortical and subcortical areas related with the acquisition of operant learning tasks, suggesting an immediate functional reorganization of these neural circuits to address the changed situation and to modify ongoing behaviors accordingly. PMID:27869181

  9. Functional states of rat cortical circuits during the unpredictable availability of a reward-related cue.

    PubMed

    Fernández-Lamo, Iván; Sánchez-Campusano, Raudel; Gruart, Agnès; Delgado-García, José M

    2016-11-21

    Proper performance of acquired abilities can be disturbed by the unexpected occurrence of external changes. Rats trained with an operant conditioning task (to press a lever in order to obtain a food pellet) using a fixed-ratio (1:1) schedule were subsequently placed in a Skinner box in which the lever could be removed randomly. Field postsynaptic potentials (fPSPs) were chronically evoked in perforant pathway-hippocampal CA1 (PP-CA1), CA1-subiculum (CA1-SUB), CA1-medial prefrontal cortex (CA1-mPFC), mPFC-nucleus accumbens (mPFC-NAc), and mPFC-basolateral amygdala (mPFC-BLA) synapses during lever IN and lever OUT situations. While lever presses were accompanied by a significant increase in fPSP slopes at the five synapses, the unpredictable absence of the lever were accompanied by decreased fPSP slopes in all, except PP-CA1 synapses. Spectral analysis of local field potentials (LFPs) recorded when the animal approached the corresponding area in the lever OUT situation presented lower spectral powers than during lever IN occasions for all recording sites, apart from CA1. Thus, the unpredictable availability of a reward-related cue modified the activity of cortical and subcortical areas related with the acquisition of operant learning tasks, suggesting an immediate functional reorganization of these neural circuits to address the changed situation and to modify ongoing behaviors accordingly.

  10. Relation of Dietary Restraint Scores to Activation of Reward-Related Brain Regions in Response to Food Intake, Anticipated Intake, and Food Pictures

    PubMed Central

    Burger, Kyle S.; Stice, Eric

    2010-01-01

    Prospective studies indicate that individuals with elevated dietary restraint scores are at increased risk for future bulimic symptom onset, suggesting that these individuals may show hyper-responsivity of reward regions to food and food cues. Thus, we used functional magnetic resonance imaging (fMRI) to examine the relation of dietary restraint scores to activation of reward-related brain regions in response to receipt and anticipated receipt of chocolate milkshake and exposure to pictures of appetizing foods in 39 female adolescents (mean age = 15.5 ± 0.94). Dietary restraint scores were positively correlated with activation in the right orbitofrontal cortex (OFC) and bilateral dorsolateral prefrontal cortex (DLPFC) in response to milkshake receipt. However, dietary restraint scores did not correlate with activation in response to anticipated milkshake receipt or exposure to food pictures. Results indicate that individuals who report high dietary restraint have a hyper-responsivity in reward-related brain regions when food intake is occurring, which may increase risk for overeating and binge eating. PMID:21147234

  11. Brain mechanisms for perceptual and reward-related decision-making.

    PubMed

    Deco, Gustavo; Rolls, Edmund T; Albantakis, Larissa; Romo, Ranulfo

    2013-04-01

    Phenomenological models of decision-making, including the drift-diffusion and race models, are compared with mechanistic, biologically plausible models, such as integrate-and-fire attractor neuronal network models. The attractor network models show how decision confidence is an emergent property; and make testable predictions about the neural processes (including neuronal activity and fMRI signals) involved in decision-making which indicate that the medial prefrontal cortex is involved in reward value-based decision-making. Synaptic facilitation in these models can help to account for sequential vibrotactile decision-making, and for how postponed decision-related responses are made. The randomness in the neuronal spiking-related noise that makes the decision-making probabilistic is shown to be increased by the graded firing rate representations found in the brain, to be decreased by the diluted connectivity, and still to be significant in biologically large networks with thousands of synapses onto each neuron. The stability of these systems is shown to be influenced in different ways by glutamatergic and GABAergic efficacy, leading to a new field of dynamical neuropsychiatry with applications to understanding schizophrenia and obsessive-compulsive disorder. The noise in these systems is shown to be advantageous, and to apply to similar attractor networks involved in short-term memory, long-term memory, attention, and associative thought processes.

  12. Higher resting-state activity in reward-related brain circuits in obese versus normal-weight females independent of food intake

    PubMed Central

    Hogenkamp, P S; Zhou, W; Dahlberg, L S; Stark, J; Larsen, A L; Olivo, G; Wiemerslage, L; Larsson, E-M; Sundbom, M; Benedict, C; Schiöth, H B

    2016-01-01

    Background: In response to food cues, obese vs normal-weight individuals show greater activation in brain regions involved in the regulation of food intake under both fasted and sated conditions. Putative effects of obesity on task-independent low-frequency blood-oxygenation-level-dependent signals—that is, resting-state brain activity—in the context of food intake are, however, less well studied. Objective: To compare eyes closed, whole-brain low-frequency BOLD signals between severely obese and normal-weight females, as assessed by functional magnetic resonance imaging (fMRI). Methods: Fractional amplitude of low-frequency fluctuations were measured in the morning following an overnight fast in 17 obese (age: 39±11 years, body mass index (BMI): 42.3±4.8 kg m−2) and 12 normal-weight females (age: 36±12 years, BMI: 22.7±1.8 kg m−2), both before and 30 min after consumption of a standardized meal (~260 kcal). Results: Compared with normal-weight controls, obese females had increased low-frequency activity in clusters located in the putamen, claustrum and insula (P<0.05). This group difference was not altered by food intake. Self-reported hunger dropped and plasma glucose concentrations increased after food intake (P<0.05); however, these changes did not differ between the BMI groups. Conclusion: Reward-related brain regions are more active under resting-state conditions in obese than in normal-weight females. This difference was independent of food intake under the experimental settings applied in the current study. Future studies involving males and females, as well as utilizing repeated post-prandial resting-state fMRI scans and various types of meals are needed to further investigate how food intake alters resting-state brain activity in obese humans. PMID:27349694

  13. 5-HT receptors and reward-related behaviour: a review.

    PubMed

    Hayes, Dave J; Greenshaw, Andrew J

    2011-05-01

    The brain's serotonin (5-HT) system is key in the regulation of reward-related behaviours, from eating and drinking to sexual activity. The complexity of studying this system is due, in part, to the fact that 5-HT acts at many receptor subtypes throughout the brain. The recent development of drugs with greater selectivity for individual receptor subtypes has allowed for rapid advancements in our understanding of this system. Use of these drugs in combination with animal models entailing selective reward measures (i.e. intracranial self-stimulation, drug self-administration, conditioned place preference) have resulted in a greater understanding of the pharmacology of reward-related processing and behaviour (particularly regarding drugs of abuse). The putative roles of each 5-HT receptor subtype in the pharmacology of reward are outlined and discussed here. It is concluded that the actions of 5-HT in reward are receptor subtype-dependent (and thus should not be generalized) and that all studied subtypes appear to have a unique profile which is determined by content (e.g. receptor function, localization - both throughout the brain and within the synapse) and context (e.g. type of behavioural paradigm, type of drug). Given evidence of altered reward-related processing and serotonergic function in numerous neuropsychiatric disorders, such as depression, schizophrenia, and addiction, a clearer understanding of the role of 5-HT receptor subtypes in this context may lead to improved drug development and therapeutic approaches.

  14. Chronic nicotine activates stress/reward-related brain regions and facilitates the transition to compulsive alcohol drinking.

    PubMed

    Leão, Rodrigo M; Cruz, Fábio C; Vendruscolo, Leandro F; de Guglielmo, Giordano; Logrip, Marian L; Planeta, Cleopatra S; Hope, Bruce T; Koob, George F; George, Olivier

    2015-04-15

    Alcohol and nicotine are the two most co-abused drugs in the world. Previous studies have shown that nicotine can increase alcohol drinking in nondependent rats, yet it is unknown whether nicotine facilitates the transition to alcohol dependence. We tested the hypothesis that chronic nicotine will speed up the escalation of alcohol drinking in rats and that this effect will be accompanied by activation of sparsely distributed neurons (neuronal ensembles) throughout the brain that are specifically recruited by the combination of nicotine and alcohol. Rats were trained to respond for alcohol and made dependent using chronic, intermittent exposure to alcohol vapor, while receiving daily nicotine (0.8 mg/kg) injections. Identification of neuronal ensembles was performed after the last operant session, using immunohistochemistry. Nicotine produced an early escalation of alcohol drinking associated with compulsive alcohol drinking in dependent, but not in nondependent rats (air exposed), as measured by increased progressive-ratio responding and increased responding despite adverse consequences. The combination of nicotine and alcohol produced the recruitment of discrete and phenotype-specific neuronal ensembles (∼4-13% of total neuronal population) in the nucleus accumbens core, dorsomedial prefrontal cortex, central nucleus of the amygdala, bed nucleus of stria terminalis, and posterior ventral tegmental area. Blockade of nicotinic receptors using mecamylamine (1 mg/kg) prevented both the behavioral and neuronal effects of nicotine in dependent rats. These results demonstrate that nicotine and activation of nicotinic receptors are critical factors in the development of alcohol dependence through the dysregulation of a set of interconnected neuronal ensembles throughout the brain.

  15. Menthol Enhances Nicotine Reward-Related Behavior by Potentiating Nicotine-Induced Changes in nAChR Function, nAChR Upregulation, and DA Neuron Excitability.

    PubMed

    Henderson, Brandon J; Wall, Teagan R; Henley, Beverley M; Kim, Charlene H; McKinney, Sheri; Lester, Henry A

    2017-04-12

    Understanding why the quit rate among smokers of menthol cigarettes is lower than non-menthol smokers requires identifying the neurons that are altered by nicotine, menthol, and acetylcholine. Dopaminergic (DA) neurons in the ventral tegmental area (VTA) mediate the positive reinforcing effects of nicotine. Using mouse models, we show that menthol enhances nicotine-induced changes in nicotinic acetylcholine receptors (nAChRs) expressed on midbrain DA neurons. Menthol plus nicotine upregulates nAChR number and function on midbrain DA neurons more than nicotine alone. Menthol also enhances nicotine-induced changes in DA neuron excitability. In a conditioned place preference (CPP) assay, we observed that menthol plus nicotine produces greater reward-related behavior than nicotine alone. Our results connect changes in midbrain DA neurons to menthol-induced enhancements of nicotine reward-related behavior and may help explain how smokers of menthol cigarettes exhibit reduced cessation rates.Neuropsychopharmacology accepted article preview online, 12 April 2017. doi:10.1038/npp.2017.72.

  16. Neural mechanisms underlying the reward-related enhancement of motivation when remembering episodic memories with high difficulty.

    PubMed

    Shigemune, Yayoi; Tsukiura, Takashi; Nouchi, Rui; Kambara, Toshimune; Kawashima, Ryuta

    2017-04-04

    The motivation to receive rewards enhances episodic memories, and the motivation is modulated by task difficulty. In episodic retrieval, however, functional neuroimaging evidence regarding the motivation that mediates interactions between reward and task difficulty is scarce. The present fMRI study investigated this issue. During encoding performed without fMRI, participants encoded Japanese words using either deep or shallow strategies, which led to variation in difficulty level during subsequent retrieval. During retrieval with fMRI, participants recognized the target words in either high or low monetary reward conditions. In the behavioral results, a reward-related enhancement of memory was found only when the memory retrieval was difficult, and the rewarding effect on subjective motivation was greater in the retrieval of memories with high difficulty than those with low difficulty. The fMRI data showed that reward-related increases in the activation of the substantia nigra/ventral tegmental area (SN/VTA), medial temporal lobe (MTL), dorsomedial prefrontal cortex (dmPFC), and dorsolateral prefrontal cortex (dlPFC) were greater during the retrieval of memories with high difficulty than those with low difficulty. Furthermore, reward-related enhancement of functional connectivity between the SN/VTA and MTL and between the SN/VTA and dmPFC during the retrieval of memories with high difficulty was significantly correlated with reward-related increases of retrieval accuracy and subjective motivation. The reward-related enhancement of episodic retrieval and retrieval-related motivation could be most effective when the level of retrieval difficulty is optimized. Such reward-related enhancement of memory and motivation could be modulated by a network including the reward-related SN/VTA, motivation-related dmPFC, and memory-related MTL. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.

  17. Cocaine- and amphetamine-regulated transcript (CART) peptide immunoreactivity in feeding- and reward-related brain areas of young OLETF rats.

    PubMed

    Armbruszt, Simon; Abraham, Hajnalka; Figler, Maria; Kozicz, Tamas; Hajnal, Andras

    2013-05-01

    Cocaine- and amphetamine-regulated transcript (CART) peptide is expressed in brain areas involved in the control of appetite, drug reward and homeostatic regulation and it has an overall anorexigenic effect. Recently, we have shown that CART peptide immunoreactivity was significantly reduced in the rostral part of the nucleus accumbens and in the rostro-medial part of the nucleus of the solitary tract in adult CCK-1 receptor deficient obese diabetic Otsuka Long Evans Tokushima Fatty (OLETF) rats compared to Long Evans Tokushima Otsuka (LETO) lean controls. It is not clear, however, whether altered CART expression is caused primarily by the deficiency in CCK-1 signaling or whether is related to the obese and diabetic phenotype of the OLETF strain which develops at a later age. Therefore, in the present study, CART-immunoreaction in feeding-related areas of the brain was compared in young, age-matched (6-7 weeks old) non-obese, non-diabetic OLETF rats and in LETO controls. We found that, young, non-diabetic OLETF rats revealed unaltered distribution of CART-peptide expressing neurons and axons throughout the brain when compared to age-matched LETO rats. In contrast to previous results observed in the obese diabetic adult rats, intensity of CART immunoreaction did not differ in the areas related to control of food-intake and reward in the young OLETFs compared to young LETO rats. Our findings suggest that factors secondary to obesity and/or diabetes rather than impaired CCK-1 receptor signaling may contribute to altered CART expression in the OLETF strain.

  18. Reward-Related Decision-Making in Pediatric Major Depressive Disorder: An fMRI Study

    ERIC Educational Resources Information Center

    Forbes, Erika E.; Christopher May, J.; Siegle, Greg J.; Ladouceur, Cecile D.; Ryan, Neal D.; Carter, Cameron S.; Birmaher, Boris; Axelson, David A.; Dahl, Ronald E.

    2006-01-01

    Background: Although reward processing is considered an important part of affective functioning, few studies have investigated reward-related decisions or responses in young people with affective disorders. Depression is postulated to involve decreased activity in reward-related affective systems. Methods: Using functional magnetic resonance…

  19. Operant ethanol self-administration increases extracellular-signal regulated protein kinase (ERK) phosphorylation in reward-related brain regions: selective regulation of positive reinforcement in the prefrontal cortex of C57BL/6J mice

    PubMed Central

    Faccidomo, Sara; Salling, Michael C; Galunas, Christina; Hodge, Clyde W

    2015-01-01

    Rationale Extracellular-signal regulated protein kinase (ERK1/2) is activated by ethanol in reward-related brain regions. Accordingly, systemic inhibition of ERK1/2 potentiates ethanol reinforcement. However, the brain region(s) that mediate this effect are unknown. Objective To pharmacologically inhibit ERK1/2 in the medial prefrontal cortex (PFC), nucleus accumbens (NAC) and amygdala (AMY) prior to ethanol or sucrose self-administration, and evaluate effects of operant ethanol self-administration on ERK1/2 phosphorylation (pERK1/2). Methods Male C57BL/6J mice were trained to lever press on a fixed-ratio-4 schedule of 9% ethanol+2% sucrose (ethanol) or 2% sucrose (sucrose) reinforcement. Mice were sacrificed immediately after the 30th self-administration session and pERK1/2 immunoreactivity was quantified in targeted brain regions. Additional groups of mice were injected with SL 327 (0–1.7 μg/side) in PFC, NAC or AMY prior to self-administration. Results pERK1/2 immunoreactivity was significantly increased by operant ethanol (g/kg=1.21 g/kg; BAC=54.9 mg/dl) in the PFC, NAC (core and shell), and AMY (central nucleus) as compared to sucrose. Microinjection of SL 327 (1.7 μg) into the PFC selectively increased ethanol self-administration. Intra-NAC injection of SL 327 had no effect on ethanol- but suppressed sucrose-reinforced responding. Intra-AMY microinjection of SL 327 had no effect on either ethanol- or sucrose-reinforced responding. Locomotor activity was unaffected under all conditions. Conclusions Operant ethanol self-administration increases pERK1/2 activation in the PFC, NAC and AMY. However, ERK1/2 activity only in the PFC mechanistically regulates ethanol self-administration. These data suggest that ethanol-induced activation of ERK1/2 in the PFC is a critical pharmacological effect that mediates the reinforcing properties of the drug. PMID:26123321

  20. 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.

  1. FNDC5/irisin, a molecular target for boosting reward-related learning and motivation.

    PubMed

    Zsuga, Judit; Tajti, Gabor; Papp, Csaba; Juhasz, Bela; Gesztelyi, Rudolf

    2016-05-01

    Interventions focusing on the prevention and treatment of chronic non-communicable diseases are on rise. In the current article, we propose that dysfunction of the mesocortico-limbic reward system contributes to the emergence of the WHO-identified risk behaviors (tobacco use, unhealthy diet, physical inactivity and harmful use of alcohol), behaviors that underlie the evolution of major non-communicable diseases (e.g. cardiovascular diseases, cancer, diabetes and chronic respiratory diseases). Given that dopaminergic neurons of the mesocortico-limbic system are tightly associated with reward-related processes and motivation, their dysfunction may fundamentally influence behavior. While nicotine and alcohol alter dopamine neuron function by influencing some receptors, mesocortico-limbic system dysfunction was associated with elevation of metabolic set-point leading to hedonic over-eating. Although there is some empirical evidence, precise molecular mechanism for linking physical inactivity and mesocortico-limbic dysfunction per se seems to be missing; identification of which may contribute to higher success rates for interventions targeting lifestyle changes pertaining to physical activity. In the current article, we compile evidence in support of a link between exercise and the mesocortico-limbic system by elucidating interactions on the axis of muscle - irisin - brain derived neurotrophic factor (BDNF) - and dopaminergic function of the midbrain. Irisin is a contraction-regulated myokine formed primarily in skeletal muscle but also in the brain. Irisin stirred considerable interest, when its ability to induce browning of white adipose tissue parallel to increasing thermogenesis was discovered. Furthermore, it may also play a role in the regulation of behavior given it readily enters the central nervous system, where it induces BDNF expression in several brain areas linked to reward processing, e.g. the ventral tegmental area and the hippocampus. BDNF is a

  2. Association between reward-related activation in the ventral striatum and trait reward sensitivity is moderated by dopamine transporter genotype.

    PubMed

    Hahn, Tim; Heinzel, Sebastian; Dresler, Thomas; Plichta, Michael M; Renner, Tobias J; Markulin, Falko; Jakob, Peter M; Lesch, Klaus-Peter; Fallgatter, Andreas J

    2011-10-01

    The impact of individual differences on human reward processing has been a focus of research in recent years, particularly, as they are associated with a variety of neuropsychiatric diseases including addiction and attention-deficit/hyperactivity disorder. Studies exploring the neural basis of individual differences in reward sensitivity have consistently implicated the ventral striatum (VS) as a core component of the human reward system. However, the mechanisms of dopaminergic neurotransmission underlying ventral striatal activation as well as trait reward sensitivity remain speculative. We addressed this issue by investigating the triadic interplay between VS reactivity during reward anticipation using functional magnetic resonance imaging, trait reward sensitivity, and dopamine (DA) transporter genotype (40-bp 3'VNTR of DAT, SLC6A3) affecting synaptic DA neurotransmission. Our results show that DAT variation moderates the association between VS-reactivity and trait reward sensitivity. Specifically, homozygote carriers of the DAT 10-repeat allele exhibit a strong positive correlation between reward sensitivity and reward-related VS activity whereas this relationship is absent in the DAT 9-repeat allele carriers. We discuss the possibility that this moderation of VS-trait relation might arise from DAT-dependent differences in DA availability affecting synaptic plasticity within the VS. Generally, studying the impact of dopaminergic gene variations on the relation between reward-related brain activity and trait reward sensitivity might facilitate the investigation of complex mechanisms underlying disorders linked to dysregulation of DA neurotransmission.

  3. Dopamine Modulates Reward-Related Vigor

    PubMed Central

    Beierholm, Ulrik; Guitart-Masip, Marc; Economides, Marcos; Chowdhury, Rumana; Düzel, Emrah; Dolan, Ray; Dayan, Peter

    2013-01-01

    Subjects routinely control the vigor with which they emit motoric responses. However, the bulk of formal treatments of decision-making ignores this dimension of choice. A recent theoretical study suggested that action vigor should be influenced by experienced average reward rate and that this rate is encoded by tonic dopamine in the brain. We previously examined how average reward rate modulates vigor as exemplified by response times and found a measure of agreement with the first suggestion. In the current study, we examined the second suggestion, namely the potential influence of dopamine signaling on vigor. Ninety healthy subjects participated in a double-blind experiment in which they received one of the following: placebo, L-DOPA (which increases dopamine levels in the brain), or citalopram (which has a selective, if complex, effect on serotonin levels). Subjects performed multiple trials of a rewarded odd-ball discrimination task in which we varied the potential reward over time in order to exercise the putative link between vigor and average reward rate. Replicating our previous findings, we found that a significant fraction of the variance in subjects' responses could be explained by our experimentally manipulated changes in average reward rate. Crucially, this relationship was significantly stronger under L-Dopa than under Placebo, suggesting that the impact of average reward levels on action vigor is indeed subject to a dopaminergic influence. PMID:23419875

  4. Split Brain Functioning.

    ERIC Educational Resources Information Center

    Cassel, Russell N.

    1978-01-01

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

  5. 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

  6. Cellular signal mechanisms of reward-related plasticity in the hippocampus.

    PubMed

    Isokawa, Masako

    2012-01-01

    The hippocampus has the extraordinary capacity to process and store information. Consequently, there is an intense interest in the mechanisms that underline learning and memory. Synaptic plasticity has been hypothesized to be the neuronal substrate for learning. Ca(2+) and Ca(2+)-activated kinases control cellular processes of most forms of hippocampal synapse plasticity. In this paper, I aim to integrate our current understanding of Ca(2+)-mediated synaptic plasticity and metaplasticity in motivational and reward-related learning in the hippocampus. I will introduce two representative neuromodulators that are widely studied in reward-related learning (e.g., ghrelin and endocannabinoids) and show how they might contribute to hippocampal neuron activities and Ca(2+)-mediated signaling processes in synaptic plasticity. Additionally, I will discuss functional significance of these two systems and their signaling pathways for its relevance to maladaptive reward learning leading to addiction.

  7. Task-specific functional brain geometry from model maps.

    PubMed

    Langs, Georg; Samaras, Dimitris; Paragios, Nikos; Honorio, Jean; Alia-Klein, Nelly; Tomasi, Dardo; Volkow, Nora D; Goldstein, Rita Z

    2008-01-01

    In this paper we propose model maps to derive and represent the intrinsic functional geometry of a brain from functional magnetic resonance imaging (fMRI) data for a specific task. Model maps represent the coherence of behavior of individual fMRI-measurements for a set of observations, or a time sequence. The maps establish a relation between individual positions in the brain by encoding the blood oxygen level dependent (BOLD) signal over a time period in a Markov chain. They represent this relation by mapping spatial positions to a new metric space, the model map. In this map the Euclidean distance between two points relates to the joint modeling behavior of their signals and thus the co-dependencies of the corresponding signals. The map reflects the functional as opposed to the anatomical geometry of the brain. It provides a quantitative tool to explore and study global and local patterns of resource allocation in the brain. To demonstrate the merit of this representation, we report quantitative experimental results on 29 fMRI time sequences, each with sub-sequences corresponding to 4 different conditions for two groups of individuals. We demonstrate that drug abusers exhibit lower differentiation in brain interactivity between baseline and reward related tasks, which could not be quantified until now.

  8. Increased Reward-Related Behaviors during Sleep and Wakefulness in Sleepwalking and Idiopathic Nightmares

    PubMed Central

    Perogamvros, Lampros; Aberg, Kristoffer; Gex-Fabry, Marianne; Perrig, Stephen; Cloninger, C. Robert; Schwartz, Sophie

    2015-01-01

    to reward-related brain functions. They also provide further support to the notion that reward-seeking networks are active during human sleep. PMID:26287974

  9. Modulating brain oscillations to drive brain function.

    PubMed

    Thut, Gregor

    2014-12-01

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

  10. 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

  11. Linking variability in brain chemistry and circuit function through multimodal human neuroimaging.

    PubMed

    Fisher, P M; Hariri, A R

    2012-08-01

    Identifying neurobiological mechanisms mediating the emergence of individual differences in behavior is critical for advancing our understanding of relative risk for psychopathology. Neuroreceptor positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) can be used to assay in vivo regional brain chemistry and function, respectively. Typically, these neuroimaging modalities are implemented independently despite the capacity for integrated data sets to offer unique insight into molecular mechanisms associated with brain function. Through examples from the serotonin and dopamine system and its effects on threat- and reward-related brain function, we review evidence for how such a multimodal neuroimaging strategy can be successfully implemented. Furthermore, we discuss how multimodal PET-fMRI can be integrated with techniques such as imaging genetics, pharmacological challenge paradigms and gene-environment interaction models to more completely map biological pathways mediating individual differences in behavior and related risk for psychopathology and inform the development of novel therapeutic targets.

  12. Reduced reward-related probability learning in schizophrenia patients.

    PubMed

    Yılmaz, Alpaslan; Simsek, Fatma; Gonul, Ali Saffet

    2012-01-01

    Although it is known that individuals with schizophrenia demonstrate marked impairment in reinforcement learning, the details of this impairment are not known. The aim of this study was to test the hypothesis that reward-related probability learning is altered in schizophrenia patients. Twenty-five clinically stable schizophrenia patients and 25 age- and gender-matched controls participated in the study. A simple gambling paradigm was used in which five different cues were associated with different reward probabilities (50%, 67%, and 100%). Participants were asked to make their best guess about the reward probability of each cue. Compared with controls, patients had significant impairment in learning contingencies on the basis of reward-related feedback. The correlation analyses revealed that the impairment of patients partially correlated with the severity of negative symptoms as measured on the Positive and Negative Syndrome Scale but that it was not related to antipsychotic dose. In conclusion, the present study showed that the schizophrenia patients had impaired reward-based learning and that this was independent from their medication status.

  13. Cognitive Control, Reward Related Decision Making and Outcomes of Late-Life Depression Treated with an Antidepressant

    PubMed Central

    Alexopoulos, George S.; Manning, Kevin; Kanellopoulos, Dora; McGovern, Amanda; Seirup, Joanna K.; Banerjee, Samprit; Gunning, Faith

    2015-01-01

    Background Executive processes consist of at least two sets of functions: one concerned with cognitive control and the other with reward-related decision making. Abnormal performance in both sets occurs in late-life depression. This study tested the hypothesis that only abnormal performance in cognitive control tasks predicts poor outcomes of late-life depression treated with escitalopram. Methods We studied older subjects with major depression (N=53) and non-depressed subjects (N=30). Executive functions were tested with the Iowa Gambling Test (IGT), Stroop Color/Word test, Tower of London, and Dementia Rating Scale-Initiation/Perseveration Domain (DRS-IP). After a 2-week placebo washout, depressed subjects received escitalopram (target daily dose: 20 mg) for 12 weeks. Results There were no significant differences between depressed and non-depressed subjects on executive function tests. Hierarchical cluster analysis of depressed subjects identified a Cognitive Control Cluster (abnormal Stroop, Tower, DRS-IP), a Reward-Related Cluster (IGT), and an Executively Unimpaired Cluster. Decline in depression was greater in the Executively Unimpaired (t=−2.09, df=331, p=0.0375) and the Reward-Related Cluster (t=−2.33, df=331,p=0.0202) than the Cognitive Control Cluster. The Executively Unimpaired Cluster (t=2.17, df=331, p=0.03) and the Reward-Related Cluster (t=2.03, df=331, p=0.0433) had a higher probability of remission than the Cognitive Control Cluster. Conclusions Dysfunction of cognitive control functions, but not reward-related decision making, may influence the decline of symptoms and the probability of remission of late-life depression treated with escitalopram. If replicated, simple to administer cognitive control tests may be used to select depressed older patients at risk for poor outcomes to SSRIs who may require structured psychotherapy. PMID:26169527

  14. Structure of brain functional networks.

    PubMed

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

    2009-01-01

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

  15. Brain Functioning Models for Learning.

    ERIC Educational Resources Information Center

    Tipps, Steve; And Others

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

  16. Two views of brain function.

    PubMed

    Raichle, Marcus E

    2010-04-01

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

  17. Emerging concepts of brain function.

    PubMed

    Bach-Y-Rita, Paul

    2005-06-01

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

  18. [Physical activity and brain function].

    PubMed

    Kempermann, G

    2012-06-01

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

  19. Higher Brain Function.

    ERIC Educational Resources Information Center

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

    1983-01-01

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

  20. Brain function, disease and dementia.

    PubMed

    Sandilyan, Malarvizhi Babu; Dening, Tom

    2015-05-27

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

  1. Vitamin K and brain function.

    PubMed

    Ferland, Guylaine

    2013-11-01

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

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

    MedlinePlus

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

  3. The effects of poor quality sleep on brain function and risk taking in adolescence.

    PubMed

    Telzer, Eva H; Fuligni, Andrew J; Lieberman, Matthew D; Galván, Adriana

    2013-05-01

    Insufficient sleep and poor quality sleep are pervasive during adolescence and relate to impairments in cognitive control and increased risk taking. However, the neurobiology underlying the association between sleep and adolescent behavior remains elusive. In the current study, we examine how poor sleep quality relates to cognitive control and reward related brain function during risk taking. Forty-six adolescents participated in a functional magnetic imaging (fMRI) scan during which they completed a cognitive control and risk taking task. Behaviorally, adolescents who reported poorer sleep also exhibited greater risk-taking. This association was paralleled by less recruitment of the dorsolateral prefrontal cortex (DLPFC) during cognitive control, greater insula activation during reward processing, and reduced functional coupling between the DLPFC and affective regions including the insula and ventral striatum during reward processing. Collectively, these results suggest that poor sleep may exaggerate the normative imbalance between affective and cognitive control systems, leading to greater risk-taking in adolescents.

  4. Behavioral and neural evidence of incentive bias for immediate rewards relative to preference-matched delayed rewards

    PubMed Central

    Luo, Shan; Ainslie, George; Giragosian, Lisa; Monterosso, John R.

    2010-01-01

    Several theories of self-control (including intertemporal bargaining Ainslie (1992) and self-signaling Bodner and Prelec (2001)) imply that intertemporal decisions can be more farsighted than would be predicted by the incentive associated with rewards outside a decision context. We examined this hypothesis using behavior and functional neuroimaging. First, subjects expressed preferences between amounts of money delayed by four months and smaller amounts available that day. This allowed us to establish “indifference pairs” individualized to each participant -- immediate and delayed amounts that were equally preferred. Participants subsequently performed a reaction time fMRI task (Knutson et al, 2001a) that provided them with distinct opportunities to win each of the rewards that comprised the indifference pairs. Anatomical Region of Interest analysis as well as whole-brain analysis indicated greater response recruited by the immediate rewards (relative to the preference matched delayed rewards) in regions previously implicated as sensitive to incentive value using the same task (including bilateral putamen, bilateral anterior insula and midbrain). RT to the target was also faster during the immediate relative to delayed reward trials (p < .01), and individual differences in RT between immediate versus delayed reward trials correlated with variance in MR signal in those clusters that responded preferentially to immediate rewards (r = .33, p < .05). These findings indicate a discrepancy in incentive associated with the immediate versus the preference-matched delayed rewards. This discrepancy may mark the contribution of self-control processes that are recruited during decision-making, but that are absent when rewards are individually anticipated. PMID:19940177

  5. Reactivation of Reward-Related Patterns from Single Past Episodes Supports Memory-Based Decision Making.

    PubMed

    Wimmer, G Elliott; Büchel, Christian

    2016-03-09

    Rewarding experiences exert a strong influence on later decision making. While decades of neuroscience research have shown how reinforcement gradually shapes preferences, decisions are often influenced by single past experiences. Surprisingly, relatively little is known about the influence of single learning episodes. Although recent work has proposed a role for episodes in decision making, it is largely unknown whether and how episodic experiences contribute to value-based decision making and how the values of single episodes are represented in the brain. In multiple behavioral experiments and an fMRI experiment, we tested whether and how rewarding episodes could support later decision making. Participants experienced episodes of high reward or low reward in conjunction with incidental, trial-unique neutral pictures. In a surprise test phase, we found that participants could indeed remember the associated level of reward, as evidenced by accurate source memory for value and preferences to re-engage with rewarded objects. Further, in a separate experiment, we found that high-reward objects shown as primes before a gambling task increased financial risk taking. Neurally, re-exposure to objects in the test phase led to significant reactivation of reward-related patterns. Importantly, individual variability in the strength of reactivation predicted value memory performance. Our results provide a novel demonstration that affect-related neural patterns are reactivated during later experience. Reactivation of value information represents a mechanism by which memory can guide decision making.

  6. Subanesthetic ketamine decreases the incentive-motivational value of reward-related cues.

    PubMed

    Fitzpatrick, Christopher J; Morrow, Jonathan D

    2017-01-01

    The attribution of incentive-motivational value to reward-related cues contributes to cue-induced craving and relapse in addicted patients. Recently, it was demonstrated that subanesthetic ketamine increases motivation to quit and decreases cue-induced craving in cocaine-dependent individuals. Although the underlying mechanism of this effect is currently unknown, one possibility is that subanesthetic ketamine decreases the incentive-motivational value of reward-related cues. In the present study, we used a Pavlovian conditioned approach procedure to identify sign-trackers, rats that attribute incentive-motivational value to reward-related cues, and goal-trackers, rats that assign only predictive value to reward-related cues. This model is of interest because sign-trackers are more vulnerable to cue-induced reinstatement of drug-seeking behavior and will persist in this drug-seeking behavior despite adverse consequences. We tested the effect of subanesthetic ketamine on the expression of Pavlovian conditioned approach behavior and the conditioned reinforcing properties of a reward-related cue in sign- and goal-trackers. We found that subanesthetic ketamine decreased sign-tracking and increased goal-tracking behavior in sign-trackers, though it had no effect on conditioned reinforcement. These results suggest that subanesthetic ketamine may be a promising pharmacotherapy for addiction that acts by decreasing the incentive-motivational value of reward-related cues.

  7. [Brain function and white matter].

    PubMed

    Wake, Hiroaki; Kato, Daisuke

    2015-04-01

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

  8. Thermodynamic laws apply to brain function.

    PubMed

    Salerian, Alen J

    2010-02-01

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

  9. Functional brain imaging across development.

    PubMed

    Rubia, Katya

    2013-12-01

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

  10. Superbinding in Integrative Brain Function and Memory

    DTIC Science & Technology

    2007-11-02

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

  11. 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.

  12. Hippocampal place cells construct reward related sequences through unexplored space

    PubMed Central

    Saleem, Aman B

    2015-01-01

    Dominant theories of hippocampal function propose that place cell representations are formed during an animal's first encounter with a novel environment and are subsequently replayed during off-line states to support consolidation and future behaviour. Here we report that viewing the delivery of food to an unvisited portion of an environment leads to off-line pre-activation of place cells sequences corresponding to that space. Such ‘preplay’ was not observed for an unrewarded but otherwise similar portion of the environment. These results suggest that a hippocampal representation of a visible, yet unexplored environment can be formed if the environment is of motivational relevance to the animal. We hypothesise such goal-biased preplay may support preparation for future experiences in novel environments. DOI: http://dx.doi.org/10.7554/eLife.06063.001 PMID:26112828

  13. Lateralized reward-related visual discrimination in the avian entopallium.

    PubMed

    Verhaal, Josine; Kirsch, Janina A; Vlachos, Ioannis; Manns, Martina; Güntürkün, Onur

    2012-04-01

    In humans and many other animals, the two cerebral hemispheres are partly specialized for different functions. However, knowledge about the neuronal basis of lateralization is mostly lacking. The visual system of birds is an excellent model in which to investigate hemispheric asymmetries as birds show a pronounced left hemispheric advantage in the discrimination of various visual objects. In addition, visual input crosses at the optic chiasm and thus testing of each hemisphere is easily accomplished. We aimed to find a neuronal correlate for three hallmarks of visual lateralization in pigeons: first, the animals learn faster with the right eye-left hemisphere; second, they reach higher performance levels under this condition; third, visually guided behavior is mostly under left hemisphere control. To this end, we recorded from the left and right forebrain entopallium while the animals performed a colour discrimination task. We found that, even before learning, left entopallial neurons were more responsive to visual stimulation. Subsequent discrimination acquisition recruited more neuronal responses in the left entopallium and these cells showed a higher degree of differentiation between the rewarded and the unrewarded stimulus. Thus, differential left-right responses are already present, albeit to a modest degree, before learning. As soon as some cues are associated with reward, however, this asymmetry increases substantially and the higher discrimination ratio of the left hemispheric tectofugal pathway would not only contribute to a higher performance of this hemisphere but could thereby also result in a left hemispheric dominance over downstream motor structures via reward-associated feedback systems.

  14. 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.

  15. Functional Prions in the Brain.

    PubMed

    Rayman, Joseph B; Kandel, Eric R

    2017-01-03

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

  16. Genetic Versus Pharmacological Assessment of the Role of Cannabinoid Type 2 Receptors in Alcohol Reward-Related Behaviors

    PubMed Central

    Powers, Matthew S.; Breit, Kristen R.; Chester, Julia A.

    2016-01-01

    Background Emerging evidence suggests that the endocannabinoid system (ECS) is involved in modulating the rewarding effects of abused drugs. Recently, the cannabinoid receptor 2 (CB2R) was shown to be expressed in brain reward circuitry and is implicated in modulating the rewarding effects of alcohol. Methods CB2 ligands and CB2R knockout (KO) mice were used to assess CB2R involvement in alcohol reward-related behavior in 2 well-established behavioral models: limited-access 2-bottle choice drinking and conditioned place preference (CPP). For the pharmacological studies, mice received pre-treatments of either vehicle, the CB2R agonist JWH-133 (10 and 20 mg/kg) or the CB2R antagonist AM630 (10 and 20 mg/kg) 30 minutes before behavioral testing. For the genetic studies, CB2R KO mice were compared to wild-type (WT) littermate controls. Results CB2R KO mice displayed increased magnitude of alcohol-induced CPP compared to WT mice. Neither agonism nor antagonism of CB2R affected alcohol intake or the expression of CPP, and antagonism of CB2R during CPP acquisition trials also did not affect CPP. Conclusions The CB2R KO CPP data provide partial support for the hypothesis that CB2Rs are involved in the modulation of alcohol reward-related behaviors. However, pharmacological manipulation of CB2Rs did not alter alcohol’s rewarding effects in the alcohol-seeking models used here. These results highlight the importance of pharmacological validation of effects seen with lifetime KO models. Given the ongoing efforts toward medications development, future studies should continue to explore the role of the CB2R as a potential neurobiological target for the treatment of alcohol use disorders. PMID:26756798

  17. 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.

  18. 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

  19. Functional data analysis in brain imaging studies.

    PubMed

    Tian, Tian Siva

    2010-01-01

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

  20. 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

  1. 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

  2. Interaction between DRD2 C957T polymorphism and an acute psychosocial stressor on reward-related behavioral impulsivity.

    PubMed

    White, Melanie J; Lawford, Bruce R; Morris, C Phillip; Young, Ross McD

    2009-05-01

    The dopamine D2 receptor (DRD2) C957T polymorphism CC genotype is associated with decreased striatal binding of DRD2 and executive function and working memory impairments in healthy adults. We investigated the relationships between C957T and acute stress with behavioral phenotypes of impulsivity in 72 young adults randomly allocated to either an acute psychosocial stress or relaxation induction condition. Homozygotes for 957C showed increased reward responsiveness after stress induction. They were also quicker when making immediate choices on the delay discounting task when stressed, compared with homozygotes who were not stressed. No effects were found for response inhibition, a dimension of impulsivity not related to extrinsic rewards. These data suggest that C957T is associated with a reward-related impulsivity endophenotype in response to acute psychosocial stress. Future studies should examine whether the greater sensitivity of 957C homozygotes to the effects of stress is mediated through dopamine release.

  3. 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

  4. 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.

  5. 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

  6. Reward-Related Decision Making in Older Adults: Relationship to Clinical Presentation of Depression

    PubMed Central

    McGovern, Amanda R.; Alexopoulos, George S.; Yuen, Genevieve S.; Morimoto, Sarah Shizuko; Gunning, Faith M.

    2015-01-01

    Objective Impairment in reward processes has been found in individuals with depression and in the aging population. The purpose of this study was twofold: 1. To use an affective neuroscience probe to identify abnormalities in reward-related decision making in late-life depression. 2. To examine the relationship of reward-related decision making abnormalities in depressed, older adults to the clinical expression of apathy in depression. We hypothesized that relative to elderly, healthy subjects, depressed, elderly patients would exhibit impaired decision making and that apathetic, depressed patients would show greater impairment in decision making than non-apathetic, depressed patients. Methods We used the Iowa Gambling Task to examine reward-related decision making in 60 non-demented, elderly patients with non-psychotic major depression and 36 elderly, psychiatrically healthy participants. Apathy was quantified using the Apathy Evaluation Scale. Of those with major depression, 18 individuals reported clinically significant apathy whereas 42 participants did not have apathy. Results Older adults with depression and healthy comparison participants did not differ in their performance on the IGT. However, apathetic, depressed older adults adopted an advantageous strategy and selected cards from the conservative decks compared to non-apathetic, depressed older adults. Non-apathetic, depressed patients showed a failure to adopt a conservative strategy and persisted in making risky decisions throughout the task. Conclusions This study indicates that apathy in older, depressed adults is associated with a conservative response style on a behavioral probe of the systems involved in reward-related decision making. This conservative response style may be the result of reduced sensitivity to rewards in apathetic individuals. PMID:25306937

  7. Effects of the chronic restraint stress induced depression on reward-related learning in rats.

    PubMed

    Xu, Pan; Wang, Kezhu; Lu, Cong; Dong, Liming; Chen, Yixi; Wang, Qiong; Shi, Zhe; Yang, Yanyan; Chen, Shanguang; Liu, Xinmin

    2017-03-15

    Chronic mild or unpredictability stress produces a persistent depressive-like state. The main symptoms of depression include weight loss, despair, anhedonia, diminished motivation and mild cognition impairment, which could influence the ability of reward-related learning. In the present study, we aimed to evaluate the effects of chronic restraint stress on the performance of reward-related learning of rats. We used the exposure of repeated restraint stress (6h/day, for 28days) to induce depression-like behavior in rats. Then designed tasks including Pavlovian conditioning (magazine head entries), acquisition and maintenance of instrumental conditioning (lever pressing) and goal directed learning (higher fixed ratio schedule of reinforcement) to study the effects of chronic restraint stress. The results indicated that chronic restraint stress influenced rats in those aspects including the acquisition of a Pavlovian stimulus-outcome (S-O) association, the formation and maintenance of action-outcome (A-O) causal relation and the ability of learning in higher fixed ratio schedule. In conclusion, depression could influence the performances in reward-related learning obviously and the series of instrumental learning tasks may have potential as a method to evaluate cognitive changes in depression.

  8. 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)

  9. Reward-related decision making in eating and weight disorders: A systematic review and meta-analysis of the evidence from neuropsychological studies.

    PubMed

    Wu, Mudan; Brockmeyer, Timo; Hartmann, Mechthild; Skunde, Mandy; Herzog, Wolfgang; Friederich, Hans-Christoph

    2016-02-01

    Eating disorders (EDs) and overweight/obesity (OW/OB) are serious public health concerns that share common neuropsychological features and patterns of disturbed eating. Reward-related decision making as a basic neurocognitive function may trans-diagnostically underlie both pathological overeating and restricted eating. The present meta-analysis synthesizes the evidence from N=82 neuropsychological studies for altered reward-related decision making in all ED subtypes, OW and OB. The overall effect sizes for the differences between currently-ill ED patients and OW/OB people and controls were Hedge's g=-0.49 [CI: -0.63; -0.35], and Hedge's g=-0.39 [CI: -0.53; -0.25], respectively. Decision making was found to be altered to similar degrees in all ED subtypes and OB. Effect sizes, however, diverged for the different measures of decision making. Adolescents appear to be less affected than adults. When foods were used as rewarding stimuli, decision making was found to be intact in OB. The findings support that altered general reward-related decision making is a salient neuropsychological factor across eating and weight disorders in adulthood.

  10. The gravitational field and brain function

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed

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

    2013-01-01

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

  12. Brain, Mind and Language Functional Architectures

    PubMed Central

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

    2010-01-01

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

  13. Sex Differences in Functional Brain Asymmetry.

    DTIC Science & Technology

    1976-07-01

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

  14. Functional connectivity hubs of the mouse brain.

    PubMed

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

    2015-07-15

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

  15. Dopamine Agonist Increases Risk Taking but Blunts Reward-Related Brain Activity

    PubMed Central

    Riba, Jordi; Krämer, Ulrike M.; Heldmann, Marcus; Richter, Sylvia; Münte, Thomas F.

    2008-01-01

    The use of D2/D3 dopaminergic agonists in Parkinson's disease (PD) may lead to pathological gambling. In a placebo-controlled double-blind study in healthy volunteers, we observed riskier choices in a lottery task after administration of the D3 receptor-preferring agonist pramipexole thus mimicking risk-taking behavior in PD. Moreover, we demonstrate decreased activation in the rostral basal ganglia and midbrain, key structures of the reward system, following unexpected high gains and therefore propose that pathological gambling in PD results from the need to seek higher rewards to overcome the blunted response in this system. PMID:18575579

  16. 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.

  17. Elevated reward-related neural activation as a unique biological marker of bipolar disorder: assessment and treatment implications.

    PubMed

    Nusslock, Robin; Young, Christina B; Damme, Katherine S F

    2014-11-01

    Growing evidence indicates that risk for bipolar disorder is characterized by elevated activation in a fronto-striatal reward neural circuit involving the ventral striatum and orbitofrontal cortex, among other regions. It is proposed that individuals with abnormally elevated reward-related neural activation are at risk for experiencing an excessive increase in approach-related motivation during life events involving rewards or goal striving and attainment. In the extreme, this increase in motivation is reflected in hypomanic/manic symptoms. By contrast, unipolar depression (without a history of hypomania/mania) is characterized by decreased reward responsivity and decreased reward-related neural activation. Collectively, this suggests that risk for bipolar disorder and unipolar depression are characterized by distinct and opposite profiles of reward processing and reward-related neural activation. The objective of the present paper is threefold. First, we review the literature on reward processing and reward-related neural activation in bipolar disorder, and in particular risk for hypomania/mania. Second, we propose that reward-related neural activation reflects a biological marker of differential risk for bipolar disorder versus unipolar depression that may help facilitate psychiatric assessment and differential diagnosis. We also discuss, however, the challenges to using neuroscience techniques and biological markers in a clinical setting for assessment and diagnostic purposes. Lastly, we address the pharmacological and psychosocial treatment implications of research on reward-related neural activation in bipolar disorder.

  18. [Brain mechanisms of male sexual function].

    PubMed

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

    2011-08-01

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

  19. 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.

  20. Toward discovery science of human brain function.

    PubMed

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

    2010-03-09

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

  1. 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?

  2. 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

  3. 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.

  4. Functional brain network efficiency predicts intelligence.

    PubMed

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

    2012-06-01

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

  5. Advantages in functional imaging of the brain

    PubMed Central

    Mier, Walter; Mier, Daniela

    2015-01-01

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

  6. Reward-related behavioral paradigms for addiction research in the mouse: performance of common inbred strains.

    PubMed

    Lederle, Lauren; Weber, Susanna; Wright, Tara; Feyder, Michael; Brigman, Jonathan L; Crombag, Hans S; Saksida, Lisa M; Bussey, Timothy J; Holmes, Andrew

    2011-01-10

    The mouse has emerged as a uniquely valuable species for studying the molecular and genetic basis of complex behaviors and modeling neuropsychiatric disease states. While valid and reliable preclinical assays for reward-related behaviors are critical to understanding addiction-related processes, and various behavioral procedures have been developed and characterized in rats and primates, there have been relatively few studies using operant-based addiction-relevant behavioral paradigms in the mouse. Here we describe the performance of the C57BL/6J inbred mouse strain on three major reward-related paradigms, and replicate the same procedures in two other commonly used inbred strains (DBA/2J, BALB/cJ). We examined Pavlovian-instrumental transfer (PIT) by measuring the ability of an auditory cue associated with food reward to promote an instrumental (lever press) response. In a separate experiment, we assessed the acquisition and extinction of a simple stimulus-reward instrumental behavior on a touch screen based task. Reinstatement of this behavior was then examined following either continuous exposure to cues (conditioned reinforcers, CRs) associated with reward, brief reward and CR exposure, or brief reward exposure followed by continuous CR exposure. The third paradigm examined sensitivity of an instrumental (lever press) response to devaluation of food reward (a probe for outcome insensitive, habitual behavior) by repeated pairing with malaise. Results showed that C57BL/6J mice displayed robust PIT, as well as clear extinction and reinstatement, but were insensitive to reinforcer devaluation. DBA/2J mice showed good PIT and (rewarded) reinstatement, but were slow to extinguish and did not show reinforcer devaluation or significant CR-reinstatement. BALB/cJ mice also displayed good PIT, extinction and reinstatement, and retained instrumental responding following devaluation, but, unlike the other strains, demonstrated reduced Pavlovian approach behavior (food

  7. Reward-Related Attentional Bias and Adolescent Substance Use: A Prognostic Relationship?

    PubMed Central

    van Hemel-Ruiter, Madelon E.; de Jong, Peter J.; Ostafin, Brian D.; Oldehinkel, Albertine J.

    2015-01-01

    Current cognitive-motivational addiction theories propose that prioritizing appetitive, reward-related information (attentional bias) plays a vital role in substance abuse behavior. Previous cross-sectional research has shown that adolescent substance use is related to reward-related attentional biases. The present study was designed to extend these findings by testing whether these reward biases have predictive value for adolescent substance use at three-year follow-up. Participants (N = 657, mean age = 16.2 yrs at baseline) were a sub-sample of Tracking Adolescents’ Individual Lives Survey (TRAILS), a large longitudinal community cohort study. We used a spatial orienting task as a behavioral index of appetitive-related attentional processes at baseline and a substance use questionnaire at both baseline and three years follow-up. Bivariate correlational analyses showed that enhanced attentional engagement with cues that predicted potential reward and nonpunishment was positively associated with substance use (alcohol, tobacco, and cannabis) three years later. However, reward bias was not predictive of changes in substance use. A post-hoc analysis in a selection of adolescents who started using illicit drugs (other than cannabis) in the follow-up period demonstrated that stronger baseline attentional engagement toward cues of nonpunishment was related to a higher level of illicit drug use three years later. The finding that reward bias was not predictive for the increase in substance use in adolescents who already started using substances at baseline, but did show prognostic value in adolescents who initiated drug use in between baseline and follow-up suggests that appetitive bias might be especially important in the initiation stages of adolescent substance use. PMID:25816295

  8. Classroom Seating and Functional Brain Asymmetry

    ERIC Educational Resources Information Center

    Gur, Raquel E.; And Others

    1975-01-01

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

  9. 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…

  10. 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.

  11. 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

  12. Structure and function of complex brain networks

    PubMed Central

    Sporns, Olaf

    2013-01-01

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

  13. 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

  14. Reward-related cortical inputs define a large striatal region in primates that interface with associative cortical connections, providing a substrate for incentive-based learning.

    PubMed

    Haber, Suzanne N; Kim, Ki-Sok; Mailly, Philippe; Calzavara, Roberta

    2006-08-09

    The anterior cingulate and orbital cortices and the ventral striatum process different aspects of reward evaluation, whereas the dorsolateral prefrontal cortex and the dorsal striatum are involved in cognitive function. Collectively, these areas are critical to decision making. We mapped the striatal area that receives information about reward evaluation. We also explored the extent to which terminals from reward-related cortical areas converge in the striatum with those from cognitive regions. Using three-dimensional-rendered reconstructions of corticostriatal projection fields along with two-dimensional chartings, we demonstrate the reward and cognitive territories in the primate striatum and show the convergence between these cortical inputs. The results show two labeling patterns: a focal projection field that consists of densely distributed terminal patches, and a diffuse projection consisting of clusters of fibers, extending throughout a wide area of the striatum. Together, these projection fields demonstrate a remarkably large, rostral, reward-related striatal territory that reaches into the dorsal striatum. Fibers from different reward-processing and cognitive cortical areas occupy both separate and converging territories. Furthermore, the diffuse projection may serve a separate integrative function by broadly disseminating general cortical activity. These findings show that the rostral striatum is in a unique position to mediate different aspects of incentive learning. Furthermore, areas of convergence may be particularly sensitive to dopamine modulation during decision making and habit formation.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. Robust Transient Dynamics and Brain Functions

    PubMed Central

    Rabinovich, Mikhail I.; Varona, Pablo

    2011-01-01

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

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

    PubMed

    Roy, Sisir; Llinás, Rodolfo

    2008-01-01

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

  1. Functional brain imaging in respiratory medicine.

    PubMed

    Pattinson, Kyle

    2015-06-01

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

  2. Default brain functionality in blind people.

    PubMed

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

    2004-10-26

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

  3. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

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

  4. Circadian clocks, brain function, and development.

    PubMed

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

    2013-12-01

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

  5. Chemogenetic tools to interrogate brain functions.

    PubMed

    Sternson, Scott M; Roth, Bryan L

    2014-01-01

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

  6. 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.

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

    ERIC Educational Resources Information Center

    Omarzu, Julia

    2004-01-01

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

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

    PubMed

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

    2014-01-01

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

  9. Fast Optical Imaging of Human Brain Function

    PubMed Central

    Gratton, Gabriele; Fabiani, Monica

    2010-01-01

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

  10. Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens

    PubMed Central

    Zhao, Changjiu; Eisinger, Brian Earl; Driessen, Terri M.; Gammie, Stephen C.

    2014-01-01

    Motherhood involves a switch in natural rewards, whereby offspring become highly rewarding. Nucleus accumbens (NAC) is a key CNS region for natural rewards and addictions, but to date no study has evaluated on a large scale the events in NAC that underlie the maternal change in natural rewards. In this study we utilized microarray and bioinformatics approaches to evaluate postpartum NAC gene expression changes in mice. Modular Single-set Enrichment Test (MSET) indicated that postpartum (relative to virgin) NAC gene expression profile was significantly enriched for genes related to addiction and reward in five of five independently curated databases (e.g., Malacards, Phenopedia). Over 100 addiction/reward related genes were identified and these included: Per1, Per2, Arc, Homer2, Creb1, Grm3, Fosb, Gabrb3, Adra2a, Ntrk2, Cry1, Penk, Cartpt, Adcy1, Npy1r, Htr1a, Drd1a, Gria1, and Pdyn. ToppCluster analysis found maternal NAC expression profile to be significantly enriched for genes related to the drug action of nicotine, ketamine, and dronabinol. Pathway analysis indicated postpartum NAC as enriched for RNA processing, CNS development/differentiation, and transcriptional regulation. Weighted Gene Coexpression Network Analysis (WGCNA) identified possible networks for transcription factors, including Nr1d1, Per2, Fosb, Egr1, and Nr4a1. The postpartum state involves increased risk for mental health disorders and MSET analysis indicated postpartum NAC to be enriched for genes related to depression, bipolar disorder (BPD), and schizophrenia. Mental health related genes included: Fabp7, Grm3, Penk, and Nr1d1. We confirmed via quantitative PCR Nr1d1, Per2, Grm3, Penk, Drd1a, and Pdyn. This study indicates for the first time that postpartum NAC involves large scale gene expression alterations linked to addiction and reward. Because the postpartum state also involves decreased response to drugs, the findings could provide insights into how to mitigate addictions. PMID:25414651

  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. Early Brain Stimulation May Help Stroke Survivors Recover Language Function

    MedlinePlus

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

  14. 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

  15. Order and disorder in the brain function.

    PubMed

    Quadens, Olga

    2003-01-01

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

  16. PER1 rs3027172 Genotype Interacts with Early Life Stress to Predict Problematic Alcohol Use, but Not Reward-Related Ventral Striatum Activity

    PubMed Central

    Baranger, David A. A.; Ifrah, Chloé; Prather, Aric A.; Carey, Caitlin E.; Corral-Frías, Nadia S.; Drabant Conley, Emily; Hariri, Ahmad R.; Bogdan, Ryan

    2016-01-01

    Increasing evidence suggests that the circadian and stress regulatory systems contribute to alcohol use disorder (AUD) risk, which may partially arise through effects on reward-related neural function. The C allele of the PER1 rs3027172 single nucleotide polymorphism (SNP) reduces PER1 expression in cells incubated with cortisol and has been associated with increased risk for adult AUD and problematic drinking among adolescents exposed to high levels of familial psychosocial adversity. Using data from undergraduate students who completed the ongoing Duke Neurogenetics Study (DNS) (n = 665), we tested whether exposure to early life stress (ELS; Childhood Trauma Questionnaire) moderates the association between rs3027172 genotype and later problematic alcohol use (Alcohol Use Disorders Identification Test) as well as ventral striatum (VS) reactivity to reward (card-guessing task while functional magnetic resonance imaging data were acquired). Initial analyses found that PER1 rs3027172 genotype interacted with ELS to predict both problematic drinking and VS reactivity; minor C allele carriers, who were also exposed to elevated ELS reported greater problematic drinking and exhibited greater ventral striatum reactivity to reward-related stimuli. When gene × covariate and environment × covariate interactions were controlled for, the interaction predicting problematic alcohol use remained significant (p < 0.05, corrected) while the interaction predicting VS reactivity was no longer significant. These results extend our understanding of relationships between PER1 genotype, ELS, and problematic alcohol use, and serve as a cautionary tale on the importance of controlling for potential confounders in studies of moderation including gene × environment interactions. PMID:27065929

  17. 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.

  18. Brain surface conformal parameterization with algebraic functions.

    PubMed

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

    2006-01-01

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

  19. Mapping Functional Connectivity in Patients with Brain Lesions

    PubMed Central

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

    2013-01-01

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

  20. 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.

  1. 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.

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

    PubMed

    Braun, S M G; Jessberger, S

    2014-02-01

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

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

    PubMed

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

    2015-11-01

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

  4. 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…

  5. 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.

  6. 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

  7. 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.

  8. Gut microbial communities modulating brain development and function.

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2013-02-01

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

  10. Estimating functional brain networks by incorporating a modularity prior

    PubMed Central

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

    2017-01-01

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

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

    PubMed

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

    2015-08-01

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

  12. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

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

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

    PubMed

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

    2015-01-01

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

  14. 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…

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

    PubMed

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

    2013-10-01

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

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

    PubMed Central

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

    2013-01-01

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

  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. Manifold learning on brain functional networks in aging.

    PubMed

    Qiu, Anqi; Lee, Annie; Tan, Mingzhen; Chung, Moo K

    2015-02-01

    We propose a new analysis framework to utilize the full information of brain functional networks for computing the mean of a set of brain functional networks and embedding brain functional networks into a low-dimensional space in which traditional regression and classification analyses can be easily employed. For this, we first represent the brain functional network by a symmetric positive matrix computed using sparse inverse covariance estimation. We then impose a Log-Euclidean Riemannian manifold structure on brain functional networks whose norm gives a convenient and practical way to define a mean. Finally, based on the fact that the computation of linear operations can be done in the tangent space of this Riemannian manifold, we adopt Locally Linear Embedding (LLE) to the Log-Euclidean Riemannian manifold space in order to embed the brain functional networks into a low-dimensional space. We show that the integration of the Log-Euclidean manifold with LLE provides more efficient and succinct representation of the functional network and facilitates regression analysis, such as ridge regression, on the brain functional network to more accurately predict age when compared to that of the Euclidean space of functional networks with LLE. Interestingly, using the Log-Euclidean analysis framework, we demonstrate the integration and segregation of cortical-subcortical networks as well as among the salience, executive, and emotional networks across lifespan.

  20. Centrality of Social Interaction in Human Brain Function.

    PubMed

    Hari, Riitta; Henriksson, Linda; Malinen, Sanna; Parkkonen, Lauri

    2015-10-07

    People are embedded in social interaction that shapes their brains throughout lifetime. Instead of emerging from lower-level cognitive functions, social interaction could be the default mode via which humans communicate with their environment. Should this hypothesis be true, it would have profound implications on how we think about brain functions and how we dissect and simulate them. We suggest that the research on the brain basis of social cognition and interaction should move from passive spectator science to studies including engaged participants and simultaneous recordings from the brains of the interacting persons.

  1. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs

    PubMed Central

    Ochoa, Melissa; Malbert, Charles-Henri; Meurice, Paul; Val-Laillet, David

    2016-01-01

    Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy) was provided by starch, glucose or fructose (n = 8 per diet). Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001), regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg). Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral correlates of these

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

    PubMed Central

    Supekar, Kaustubh; Musen, Mark; Menon, Vinod

    2009-01-01

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

  3. 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.

  4. 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].

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

    PubMed

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

    2011-12-05

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

  6. Connectivity and functional profiling of abnormal brain structures in pedophilia.

    PubMed

    Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

    2015-06-01

    Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia.

  7. Hierarchical organization of brain functional networks during visual tasks.

    PubMed

    Zhuo, Zhao; Cai, Shi-Min; Fu, Zhong-Qian; Zhang, Jie

    2011-09-01

    The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.

  8. Hierarchical organization of brain functional networks during visual tasks

    NASA Astrophysics Data System (ADS)

    Zhuo, Zhao; Cai, Shi-Min; Fu, Zhong-Qian; Zhang, Jie

    2011-09-01

    The functional network of the brain is known to demonstrate modular structure over different hierarchical scales. In this paper, we systematically investigated the hierarchical modular organizations of the brain functional networks that are derived from the extent of phase synchronization among high-resolution EEG time series during a visual task. In particular, we compare the modular structure of the functional network from EEG channels with that of the anatomical parcellation of the brain cortex. Our results show that the modular architectures of brain functional networks correspond well to those from the anatomical structures over different levels of hierarchy. Most importantly, we find that the consistency between the modular structures of the functional network and the anatomical network becomes more pronounced in terms of vision, sensory, vision-temporal, motor cortices during the visual task, which implies that the strong modularity in these areas forms the functional basis for the visual task. The structure-function relationship further reveals that the phase synchronization of EEG time series in the same anatomical group is much stronger than that of EEG time series from different anatomical groups during the task and that the hierarchical organization of functional brain network may be a consequence of functional segmentation of the brain cortex.

  9. Let thy left brain know what thy right brain doeth: Inter-hemispheric compensation of functional deficits after brain damage.

    PubMed

    Bartolomeo, Paolo; Thiebaut de Schotten, Michel

    2016-12-01

    Recent evidence revealed the importance of inter-hemispheric communication for the compensation of functional deficits after brain damage. This review summarises the biological consequences observed using histology as well as the longitudinal findings measured with magnetic resonance imaging methods in brain damaged animals and patients. In particular, we discuss the impact of post-stroke brain hyperactivity on functional recovery in relation to time. The reviewed evidence also suggests that the proportion of the preserved functional network both in the lesioned and in the intact hemispheres, rather than the simple lesion location, determines the extent of functional recovery. Hence, future research exploring longitudinal changes in patients with brain damage may unveil potential biomarkers underlying functional recovery.

  10. Can we observe epigenetic effects on human brain function?

    PubMed

    Nikolova, Yuliya S; Hariri, Ahmad R

    2015-07-01

    Imaging genetics has identified many contributions of DNA sequence variation to individual differences in brain function, behavior, and risk for psychopathology. Recent studies have extended this work beyond the genome by mapping epigenetic differences, specifically gene methylation in peripherally assessed DNA, onto variability in behaviorally and clinically relevant brain function. These data have generated understandable enthusiasm for the potential of such research to illuminate biological mechanisms of risk. We use our research on the effects of genetic and epigenetic variation in the human serotonin transporter on brain function to generate a guardedly optimistic opinion that the available data encourage continued research in this direction, and suggest strategies to promote faster progress.

  11. Transcriptomic analysis of instinctive and learned reward-related behaviors in honey bees.

    PubMed

    Naeger, Nicholas L; Robinson, Gene E

    2016-11-15

    We used transcriptomics to compare instinctive and learned, reward-based honey bee behaviors with similar spatio-temporal components: mating flights by males (drones) and time-trained foraging flights by females (workers), respectively. Genome-wide gene expression profiling via RNA sequencing was performed on the mushroom bodies, a region of the brain known for multi-modal sensory integration and responsive to various types of reward. Differentially expressed genes (DEGs) associated with the onset of mating (623 genes) were enriched for the gene ontology (GO) categories of Transcription, Unfolded Protein Binding, Post-embryonic Development, and Neuron Differentiation. DEGs associated with the onset of foraging (473) were enriched for Lipid Transport, Regulation of Programmed Cell Death, and Actin Cytoskeleton Organization. These results demonstrate that there are fundamental molecular differences between similar instinctive and learned behaviors. In addition, there were 166 genes with strong similarities in expression across the two behaviors - a statistically significant overlap in gene expression, also seen in Weighted Gene Co-Expression Network Analysis. This finding indicates that similar instinctive and learned behaviors also share common molecular architecture. This common set of DEGs was enriched for Regulation of RNA Metabolic Process, Transcription Factor Activity, and Response to Ecdysone. These findings provide a starting point for better understanding the relationship between instincts and learned behaviors. In addition, because bees collect food for their colony rather than for themselves, these results also support the idea that altruistic behavior relies, in part, on elements of brain reward systems associated with selfish behavior.

  12. Optogenetic probing of functional brain circuitry.

    PubMed

    Mancuso, James J; Kim, Jinsook; Lee, Soojung; Tsuda, Sachiko; Chow, Nicholas B H; Augustine, George J

    2011-01-01

    Recently developed optogenetic technologies offer the promise of high-speed mapping of brain circuitry. Genetically targeted light-gated channels and pumps, such as channelrhodopsins and halorhodopsin, allow optical control of neuronal activity with high spatial and temporal resolution. Optogenetic probes of neuronal activity, such as Clomeleon and Mermaid, allow light to be used to monitor the activity of a genetically defined population of neurons. Combining these two complementary sets of optogenetic probes will make it possible to perform all-optical circuit mapping. Owing to the improved efficiency and higher speed of data acquisition, this hybrid approach should enable high-throughput mapping of brain circuitry.

  13. Mapping functional brain development: Building a social brain through interactive specialization.

    PubMed

    Johnson, Mark H; Grossmann, Tobias; Cohen Kadosh, Kathrin

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the social brain. They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social cognition and mentalizing computations in the brain. Second, they extend the implications of the IS view from the emergence of specialized functions within a cortical region to a focus on how different cortical regions with complementary functions become orchestrated into networks during human postnatal development.

  14. Complex Networks - A Key to Understanding Brain Function

    SciTech Connect

    Olaf Sporns

    2008-01-23

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  15. Complex Networks - A Key to Understanding Brain Function

    SciTech Connect

    Sporns, Olaf

    2008-01-23

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life. How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood. In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  16. Complex Networks - A Key to Understanding Brain Function

    ScienceCinema

    Olaf Sporns

    2016-07-12

    The brain is a complex network of neurons, engaging in spontaneous and evoked activity that is thought to be the main substrate of mental life.  How this complex system works together to process information and generate coherent cognitive states, even consciousness, is not yet well understood.  In my talk I will review recent studies that have revealed characteristic structural and functional attributes of brain networks, and discuss efforts to build computational models of the brain that are informed by our growing knowledge of brain anatomy and physiology.

  17. Mapping Functional Brain Development: Building a Social Brain through Interactive Specialization

    ERIC Educational Resources Information Center

    Johnson, Mark H.; Grossmann, Tobias; Kadosh, Kathrin Cohen

    2009-01-01

    The authors review a viewpoint on human functional brain development, interactive specialization (IS), and its application to the emerging network of cortical regions referred to as the "social brain." They advance the IS view in 2 new ways. First, they extend IS into a domain to which it has not previously been applied--the emergence of social…

  18. Neural Substrate Expansion for the Restoration of Brain Function

    PubMed Central

    Chen, H. Isaac; Jgamadze, Dennis; Serruya, Mijail D.; Cullen, D. Kacy; Wolf, John A.; Smith, Douglas H.

    2016-01-01

    Restoring neurological and cognitive function in individuals who have suffered brain damage is one of the principal objectives of modern translational neuroscience. Electrical stimulation approaches, such as deep-brain stimulation, have achieved the most clinical success, but they ultimately may be limited by the computational capacity of the residual cerebral circuitry. An alternative strategy is brain substrate expansion, in which the computational capacity of the brain is augmented through the addition of new processing units and the reconstitution of network connectivity. This latter approach has been explored to some degree using both biological and electronic means but thus far has not demonstrated the ability to reestablish the function of large-scale neuronal networks. In this review, we contend that fulfilling the potential of brain substrate expansion will require a significant shift from current methods that emphasize direct manipulations of the brain (e.g., injections of cellular suspensions and the implantation of multi-electrode arrays) to the generation of more sophisticated neural tissues and neural-electric hybrids in vitro that are subsequently transplanted into the brain. Drawing from neural tissue engineering, stem cell biology, and neural interface technologies, this strategy makes greater use of the manifold techniques available in the laboratory to create biocompatible constructs that recapitulate brain architecture and thus are more easily recognized and utilized by brain networks. PMID:26834579

  19. Generating Text from Functional Brain Images

    PubMed Central

    Pereira, Francisco; Detre, Greg; Botvinick, Matthew

    2011-01-01

    Recent work has shown that it is possible to take brain images acquired during viewing of a scene and reconstruct an approximation of the scene from those images. Here we show that it is also possible to generate text about the mental content reflected in brain images. We began with images collected as participants read names of concrete items (e.g., “Apartment’’) while also seeing line drawings of the item named. We built a model of the mental semantic representation of concrete concepts from text data and learned to map aspects of such representation to patterns of activation in the corresponding brain image. In order to validate this mapping, without accessing information about the items viewed for left-out individual brain images, we were able to generate from each one a collection of semantically pertinent words (e.g., “door,” “window” for “Apartment’’). Furthermore, we show that the ability to generate such words allows us to perform a classification task and thus validate our method quantitatively. PMID:21927602

  20. Brain Hemispheric Functions and the Native American.

    ERIC Educational Resources Information Center

    Ross, Allen Chuck

    1982-01-01

    Uses brain research conducted by Dr. Roger Sperry to show that traditional Native Americans are more dominant in right hemisphere thinking, setting them apart from a modern left hemisphere-oriented society (especially emphasized in schools). Describes some characteristics of Native American thinking that illustrate a right hemisphere orientation…

  1. Hyper-connectivity of functional networks for brain disease diagnosis

    PubMed Central

    Jie, Biao; Wee, Chong-Yaw

    2017-01-01

    Exploring structural and functional interactions among various brain regions enables better understanding of pathological underpinnings of neurological disorders. Brain connectivity network, as a simplified representation of those structural and functional interactions, has been widely used for diagnosis and classification of neurodegenerative diseases, especially for Alzheimer’s disease (AD) and its early stage - mild cognitive impairment (MCI). However, the conventional functional connectivity network is usually constructed based on the pairwise correlation among different brain regions and thus ignores their higher-order relationships. Such loss of high-order information could be important for disease diagnosis, since neurologically a brain region predominantly interacts with more than one other brain regions. Accordingly, in this paper, we propose a novel framework for estimating the hyper-connectivity network of brain functions and then use this hyper-network for brain disease diagnosis. Here, the functional connectivity hyper-network denotes a network where each of its edges representing the interactions among multiple brain regions (i.e., an edge can connect with more than two brain regions), which can be naturally represented by a hyper-graph. Specifically, we first construct connectivity hyper-networks from the resting-state fMRI (R-fMRI) time series by using sparse representation. Then, we extract three sets of brain-region specific features from the connectivity hyper-networks, and further exploit a manifold regularized multi-task feature selection method to jointly select the most discriminative features. Finally, we use multi-kernel support vector machine (SVM) for classification. The experimental results on both MCI dataset and attention deficit hyperactivity disorder (ADHD) dataset demonstrate that, compared with the conventional connectivity network-based methods, the proposed method can not only improve the classification performance, but also

  2. Network Analysis of Intrinsic Functional Brain Connectivity in Alzheimer's Disease

    PubMed Central

    Supekar, Kaustubh; Menon, Vinod; Rubin, Daniel; Musen, Mark; Greicius, Michael D.

    2008-01-01

    Functional brain networks detected in task-free (“resting-state”) functional magnetic resonance imaging (fMRI) have a small-world architecture that reflects a robust functional organization of the brain. Here, we examined whether this functional organization is disrupted in Alzheimer's disease (AD). Task-free fMRI data from 21 AD subjects and 18 age-matched controls were obtained. Wavelet analysis was applied to the fMRI data to compute frequency-dependent correlation matrices. Correlation matrices were thresholded to create 90-node undirected-graphs of functional brain networks. Small-world metrics (characteristic path length and clustering coefficient) were computed using graph analytical methods. In the low frequency interval 0.01 to 0.05 Hz, functional brain networks in controls showed small-world organization of brain activity, characterized by a high clustering coefficient and a low characteristic path length. In contrast, functional brain networks in AD showed loss of small-world properties, characterized by a significantly lower clustering coefficient (p<0.01), indicative of disrupted local connectivity. Clustering coefficients for the left and right hippocampus were significantly lower (p<0.01) in the AD group compared to the control group. Furthermore, the clustering coefficient distinguished AD participants from the controls with a sensitivity of 72% and specificity of 78%. Our study provides new evidence that there is disrupted organization of functional brain networks in AD. Small-world metrics can characterize the functional organization of the brain in AD, and our findings further suggest that these network measures may be useful as an imaging-based biomarker to distinguish AD from healthy aging. PMID:18584043

  3. [The advantages and limitations of brain function analyses by PET].

    PubMed

    Kato, M; Taniwaki, T; Kuwabara, Y

    2000-12-01

    PET has been proved to be a powerful tool for exploring the brain function. We discussed the advantages and limitations of PET for analyzing the brain function on the basis of our clinical and experimental experiences of functional imaging. A multimodality PET study measuring cerebral energy metabolism (CMRO2 and CMRglc), cerebral blood flow (CBF), oxygen extraction fraction (OEF) and neurotransmitter function (presynaptic and postsynaptic) opens up a closer insight into a precise pathophysiology of the brain dysfunction: In cerebral infarction, it reveals a state of "misery perfusion" in the acute stage, "luxury perfusion" in the intermediate stage, and proportionately decreased CBF and CMRO2 in the chronic stage. Neurotransmitter function may identify specifically a neuronal subgroup of dysfunction. Owing to the low temporal resolution of PET, a neuronal activity may propagate transsynaptically to remote areas during the period of scanning, resulting in an obscured primary site of the neuronal activity. Uncoupling between neuronal activities and cerebral energy metabolism/CBF may occur under a certain state of brain pathology, particularly after an acute destructive lesion, according to our experimental studies. Neurotransmitter function may reveal the effect of drugs on the brain function, and may be useful for developing a new method of drug therapy for brain diseases in the future.

  4. Breakdown of the brain's functional network modularity with awareness.

    PubMed

    Godwin, Douglass; Barry, Robert L; Marois, René

    2015-03-24

    Neurobiological theories of awareness propose divergent accounts of the spatial extent of brain changes that support conscious perception. Whereas focal theories posit mostly local regional changes, global theories propose that awareness emerges from the propagation of neural signals across a broad extent of sensory and association cortex. Here we tested the scalar extent of brain changes associated with awareness using graph theoretical analysis applied to functional connectivity data acquired at ultra-high field while subjects performed a simple masked target detection task. We found that awareness of a visual target is associated with a degradation of the modularity of the brain's functional networks brought about by an increase in intermodular functional connectivity. These results provide compelling evidence that awareness is associated with truly global changes in the brain's functional connectivity.

  5. Functional brain imaging in schizophrenia: selected results and methods.

    PubMed

    Brown, Gregory G; Thompson, Wesley K

    2010-01-01

    Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although

  6. Functional brain network modularity predicts response to cognitive training after brain injury

    PubMed Central

    Chen, Anthony J.-W.; Novakovic-Agopian, Tatjana; Gratton, Caterina; Nomura, Emi M.; D'Esposito, Mark

    2015-01-01

    Objective: We tested the value of measuring modularity, a graph theory metric indexing the relative extent of integration and segregation of distributed functional brain networks, for predicting individual differences in response to cognitive training in patients with brain injury. Methods: Patients with acquired brain injury (n = 11) participated in 5 weeks of cognitive training and a comparison condition (brief education) in a crossover intervention study design. We quantified the measure of functional brain network organization, modularity, from functional connectivity networks during a state of tonic attention regulation measured during fMRI scanning before the intervention conditions. We examined the relationship of baseline modularity with pre- to posttraining changes in neuropsychological measures of attention and executive control. Results: The modularity of brain network organization at baseline predicted improvement in attention and executive function after cognitive training, but not after the comparison intervention. Individuals with higher baseline modularity exhibited greater improvements with cognitive training, suggesting that a more modular baseline network state may contribute to greater adaptation in response to cognitive training. Conclusions: Brain network properties such as modularity provide valuable information for understanding mechanisms that influence rehabilitation of cognitive function after brain injury, and may contribute to the discovery of clinically relevant biomarkers that could guide rehabilitation efforts. PMID:25788557

  7. Telemedicine for evaluation of brain function by a metacomputer.

    PubMed

    Mizuno-Matsumoto, Y; Date, S; Tabuchi, Y; Tamura, S; Sato, Y; Zoroofi, R A; Shimojo, S; Kadobayashi, Y; Tatsumi, H; Nogawa, H; Shinosaki, K; Takeda, M; Inouye, T; Miyahara, H

    2000-06-01

    A method of evaluating brain function using the metacomputer concept of the Globus system combined with a message-passing interface is described. The proposed method has the ability to exploit various geographically distributed resources and parallel computing linked to a high-technology medical instrumentation system, magnetoencephalography, to analyze the functional state of the brain. It is envisaged that the method will lead to the realization of an efficient telemedicine system for health care.

  8. [Functions of microglia in the healthy brain: focus on neuroplasticity].

    PubMed

    Tishkina, A O; Stepanichev, M Iu; Aniol, V A; Guliaeva, N V

    2014-01-01

    Microglia is in the center of modern research because it is involved in neuroinflammation processes, which is considered as an important part of pathogenesis of many brain pathologies. On the contrary, normal physiological functions of microglia are less studied. Here we review modern data on functioning of microglia in the healthy brain. We consider involvement of microglia in angiogenesis, neurogenesis, synaptogenesis, long-term potentiation, and the mechanisms of microglia-neuron interaction. We further consider modern concept on active interaction of microglia with neurons in developing and healthy mature brain and the essential role of microglia in neuroplasticity mechanisms at various levels.

  9. Human brain activity with functional NIR optical imager

    NASA Astrophysics Data System (ADS)

    Luo, Qingming

    2001-08-01

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

  10. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation

    PubMed Central

    Webber, Emily S.; Mankin, David E.

    2016-01-01

    Abstract The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility. PMID:27822506

  11. Striatal Activity and Reward Relativity: Neural Signals Encoding Dynamic Outcome Valuation.

    PubMed

    Webber, Emily S; Mankin, David E; Cromwell, Howard C

    2016-01-01

    The striatum is a key brain region involved in reward processing. Striatal activity has been linked to encoding reward magnitude and integrating diverse reward outcome information. Recent work has supported the involvement of striatum in the valuation of outcomes. The present work extends this idea by examining striatal activity during dynamic shifts in value that include different levels and directions of magnitude disparity. A novel task was used to produce diverse relative reward effects on a chain of instrumental action. Rats (Rattus norvegicus) were trained to respond to cues associated with specific outcomes varying by food pellet magnitude. Animals were exposed to single-outcome sessions followed by mixed-outcome sessions, and neural activity was compared among identical outcome trials from the different behavioral contexts. Results recording striatal activity show that neural responses to different task elements reflect incentive contrast as well as other relative effects that involve generalization between outcomes or possible influences of outcome variety. The activity that was most prevalent was linked to food consumption and post-food consumption periods. Relative encoding was sensitive to magnitude disparity. A within-session analysis showed strong contrast effects that were dependent upon the outcome received in the immediately preceding trial. Significantly higher numbers of responses were found in ventral striatum linked to relative outcome effects. Our results support the idea that relative value can incorporate diverse relationships, including comparisons from specific individual outcomes to general behavioral contexts. The striatum contains these diverse relative processes, possibly enabling both a higher information yield concerning value shifts and a greater behavioral flexibility.

  12. Special surgical considerations for functional brain mapping.

    PubMed

    Kekhia, Hussein; Rigolo, Laura; Norton, Isaiah; Golby, Alexandra J

    2011-04-01

    The development of functional mapping techniques gives neurosurgeons many options for preoperative planning. Integrating functional and anatomic data can inform patient selection and surgical planning and makes functional mapping more accessible than when only invasive studies were available. However, the applications of functional mapping to neurosurgical patients are still evolving. Functional imaging remains complex and requires an understanding of the underlying physiologic and imaging characteristics. Neurosurgeons must be accustomed to interpreting highly processed data. Successful implementation of functional image-guided procedures requires efficient interactions between neurosurgeon, neurologist, radiologist, neuropsychologist, and others, but promises to enhance the care of patients.

  13. EEG-based research on brain functional networks in cognition.

    PubMed

    Wang, Niannian; Zhang, Li; Liu, Guozhong

    2015-01-01

    Recently, exploring the cognitive functions of the brain by establishing a network model to understand the working mechanism of the brain has become a popular research topic in the field of neuroscience. In this study, electroencephalography (EEG) was used to collect data from subjects given four different mathematical cognitive tasks: recite numbers clockwise and counter-clockwise, and letters clockwise and counter-clockwise to build a complex brain function network (BFN). By studying the connectivity features and parameters of those brain functional networks, it was found that the average clustering coefficient is much larger than its corresponding random network and the average shortest path length is similar to the corresponding random networks, which clearly shows the characteristics of the small-world network. The brain regions stimulated during the experiment are consistent with traditional cognitive science regarding learning, memory, comprehension, and other rational judgment results. The new method of complex networking involves studying the mathematical cognitive process of reciting, providing an effective research foundation for exploring the relationship between brain cognition and human learning skills and memory. This could help detect memory deficits early in young and mentally handicapped children, and help scientists understand the causes of cognitive brain disorders.

  14. 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

  15. Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior

    PubMed Central

    Grosenick, Logan; Warden, Melissa R.; Amatya, Debha; Katovich, Kiefer; Mehta, Hershel; Patenaude, Brian; Ramakrishnan, Charu; Kalanithi, Paul; Etkin, Amit; Knutson, Brian; Glover, Gary H.; Deisseroth, Karl

    2016-01-01

    Motivation for reward drives adaptive behaviors, whereas impairment of reward perception and experience (anhedonia) can contribute to psychiatric diseases, including depression and schizophrenia. We sought to test the hypothesis that the medial prefrontal cortex (mPFC) controls interactions among specific subcortical regions that govern hedonic responses. By using optogenetic functional magnetic resonance imaging to locally manipulate but globally visualize neural activity in rats, we found that dopamine neuron stimulation drives striatal activity, whereas locally increased mPFC excitability reduces this striatal response and inhibits the behavioral drive for dopaminergic stimulation. This chronic mPFC overactivity also stably suppresses natural reward-motivated behaviors and induces specific new brainwide functional interactions, which predict the degree of anhedonia in individuals. These findings describe a mechanism by which mPFC modulates expression of reward-seeking behavior, by regulating the dynamical interactions between specific distant subcortical regions. PMID:26722001

  16. Branched-chain amino acids and brain function.

    PubMed

    Fernstrom, John D

    2005-06-01

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

  17. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain.

    PubMed

    Li, Guangye; Zhang, Dingguo

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain.

  18. Brain-Computer Interface Controlled Cyborg: Establishing a Functional Information Transfer Pathway from Human Brain to Cockroach Brain

    PubMed Central

    2016-01-01

    An all-chain-wireless brain-to-brain system (BTBS), which enabled motion control of a cyborg cockroach via human brain, was developed in this work. Steady-state visual evoked potential (SSVEP) based brain-computer interface (BCI) was used in this system for recognizing human motion intention and an optimization algorithm was proposed in SSVEP to improve online performance of the BCI. The cyborg cockroach was developed by surgically integrating a portable microstimulator that could generate invasive electrical nerve stimulation. Through Bluetooth communication, specific electrical pulse trains could be triggered from the microstimulator by BCI commands and were sent through the antenna nerve to stimulate the brain of cockroach. Serial experiments were designed and conducted to test overall performance of the BTBS with six human subjects and three cockroaches. The experimental results showed that the online classification accuracy of three-mode BCI increased from 72.86% to 78.56% by 5.70% using the optimization algorithm and the mean response accuracy of the cyborgs using this system reached 89.5%. Moreover, the results also showed that the cyborg could be navigated by the human brain to complete walking along an S-shape track with the success rate of about 20%, suggesting the proposed BTBS established a feasible functional information transfer pathway from the human brain to the cockroach brain. PMID:26982717

  19. Characterizing dynamic local functional connectivity in the human brain

    PubMed Central

    Deng, Lifu; Sun, Junfeng; Cheng, Lin; Tong, Shanbao

    2016-01-01

    Functional connectivity (FC), obtained from functional magnetic resonance imaging (fMRI), brings insights into the functional organization of the brain. Recently, rich and complex behaviour of brain has been revealed by the dynamic fluctuation of FC, which had previously been regarded as confounding ‘noise’. While the dynamics of long-distance, inter-regional FC has been extensively studied, the dynamics of local FC within a few millimetres in space remains largely unexplored. In this study, the local FC was depicted by regional homogeneity (ReHo), and the dynamics of local FC was obtained using sliding windows method. We observed a robust positive correlation between ReHo and its temporal variability, which was shown to be an intrinsic feature of the brain rather than a pure stochastic effect. Furthermore, fluctuation of ReHo was associated with global functional organization: (i) brain regions with higher centrality of inter-regional FC tended to possess higher ReHo variability; (ii) coherence of ReHo fluctuation was higher within brain’s functional modules. Finally, we observed alteration of ReHo variability during a motor task compared with resting-state. Our findings associated the temporal fluctuation of ReHo with brain function, opening up the possibility of dynamic local FC study in the future. PMID:27231194

  20. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  1. Brain Reward Circuits in Morphine Addiction

    PubMed Central

    Kim, Juhwan; Ham, Suji; Hong, Heeok; Moon, Changjong; Im, Heh-In

    2016-01-01

    Morphine is the most potent analgesic for chronic pain, but its clinical use has been limited by the opiate’s innate tendency to produce tolerance, severe withdrawal symptoms and rewarding properties with a high risk of relapse. To understand the addictive properties of morphine, past studies have focused on relevant molecular and cellular changes in the brain, highlighting the functional roles of reward-related brain regions. Given the accumulated findings, a recent, emerging trend in morphine research is that of examining the dynamics of neuronal interactions in brain reward circuits under the influence of morphine action. In this review, we highlight recent findings on the roles of several reward circuits involved in morphine addiction based on pharmacological, molecular and physiological evidences. PMID:27506251

  2. Self-portraits of the brain: cognitive science, data visualization, and communicating brain structure and function.

    PubMed

    Goldstone, Robert L; Pestilli, Franco; Börner, Katy

    2015-08-01

    With several large-scale human brain projects currently underway and a range of neuroimaging techniques growing in availability to researchers, the amount and diversity of data relevant for understanding the human brain is increasing rapidly. A complete understanding of the brain must incorporate information about 3D neural location, activity, timing, and task. Data mining, high-performance computing, and visualization can serve as tools that augment human intellect; however, the resulting visualizations must take into account human abilities and limitations to be effective tools for exploration and communication. In this feature review, we discuss key challenges and opportunities that arise when leveraging the sophisticated perceptual and conceptual processing of the human brain to help researchers understand brain structure, function, and behavior.

  3. [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].

    PubMed

    Hilker, R

    2010-10-01

    Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

  4. Effect of glycolysis inhibition on mitochondrial function in rat brain.

    PubMed

    Cano-Ramírez, D; Torres-Vargas, C E; Guerrero-Castillo, S; Uribe-Carvajal, S; Hernández-Pando, R; Pedraza-Chaverri, J; Orozco-Ibarra, M

    2012-05-01

    Inhibition of the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase enhances the neural vulnerability to excitotoxicity both in vivo and in vitro through an unknown mechanism possibly related to mitochondrial failure. However, as the effect of glycolysis inhibition on mitochondrial function in brain has not been studied, the aim of the present work was to evaluate the effect of glycolysis inhibition induced by iodoacetate on mitochondrial function and oxidative stress in brain. Mitochondria were isolated from brain cortex, striatum and cerebellum of rats treated systemically with iodoacetate (25 mg/kg/day for 3 days). Oxygen consumption, ATP synthesis, transmembrane potential, reactive oxygen species production, lipoperoxidation, glutathione levels, and aconitase activity were assessed. Oxygen consumption and aconitase activity decreased in the brain cortex and striatum, showing that glycolysis inhibition did not trigger severe mitochondrial impairment, but a slight mitochondrial malfunction and oxidative stress were present.

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

    PubMed

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

    2016-01-01

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

  6. Resiliency of EEG-Based Brain Functional Networks.

    PubMed

    Jalili, Mahdi

    2015-01-01

    Applying tools available in network science and graph theory to study brain networks has opened a new era in understanding brain mechanisms. Brain functional networks extracted from EEG time series have been frequently studied in health and diseases. In this manuscript, we studied failure resiliency of EEG-based brain functional networks. The network structures were extracted by analysing EEG time series obtained from 30 healthy subjects in resting state eyes-closed conditions. As the network structure was extracted, we measured a number of metrics related to their resiliency. In general, the brain networks showed worse resilient behaviour as compared to corresponding random networks with the same degree sequences. Brain networks had higher vulnerability than the random ones (P < 0.05), indicating that their global efficiency (i.e., communicability between the regions) is more affected by removing the important nodes. Furthermore, the breakdown happened as a result of cascaded failures in brain networks was severer (i.e., less nodes survived) as compared to randomized versions (P < 0.05). These results suggest that real EEG-based networks have not been evolved to possess optimal resiliency against failures.

  7. Resiliency of EEG-Based Brain Functional Networks

    PubMed Central

    Jalili, Mahdi

    2015-01-01

    Applying tools available in network science and graph theory to study brain networks has opened a new era in understanding brain mechanisms. Brain functional networks extracted from EEG time series have been frequently studied in health and diseases. In this manuscript, we studied failure resiliency of EEG-based brain functional networks. The network structures were extracted by analysing EEG time series obtained from 30 healthy subjects in resting state eyes-closed conditions. As the network structure was extracted, we measured a number of metrics related to their resiliency. In general, the brain networks showed worse resilient behaviour as compared to corresponding random networks with the same degree sequences. Brain networks had higher vulnerability than the random ones (P < 0.05), indicating that their global efficiency (i.e., communicability between the regions) is more affected by removing the important nodes. Furthermore, the breakdown happened as a result of cascaded failures in brain networks was severer (i.e., less nodes survived) as compared to randomized versions (P < 0.05). These results suggest that real EEG-based networks have not been evolved to possess optimal resiliency against failures. PMID:26295341

  8. Joint brain connectivity estimation from diffusion and functional MRI data

    NASA Astrophysics Data System (ADS)

    Chu, Shu-Hsien; Lenglet, Christophe; Parhi, Keshab K.

    2015-03-01

    Estimating brain wiring patterns is critical to better understand the brain organization and function. Anatomical brain connectivity models axonal pathways, while the functional brain connectivity characterizes the statistical dependencies and correlation between the activities of various brain regions. The synchronization of brain activity can be inferred through the variation of blood-oxygen-level dependent (BOLD) signal from functional MRI (fMRI) and the neural connections can be estimated using tractography from diffusion MRI (dMRI). Functional connections between brain regions are supported by anatomical connections, and the synchronization of brain activities arises through sharing of information in the form of electro-chemical signals on axon pathways. Jointly modeling fMRI and dMRI data may improve the accuracy in constructing anatomical connectivity as well as functional connectivity. Such an approach may lead to novel multimodal biomarkers potentially able to better capture functional and anatomical connectivity variations. We present a novel brain network model which jointly models the dMRI and fMRI data to improve the anatomical connectivity estimation and extract the anatomical subnetworks associated with specific functional modes by constraining the anatomical connections as structural supports to the functional connections. The key idea is similar to a multi-commodity flow optimization problem that minimizes the cost or maximizes the efficiency for flow configuration and simultaneously fulfills the supply-demand constraint for each commodity. In the proposed network, the nodes represent the grey matter (GM) regions providing brain functionality, and the links represent white matter (WM) fiber bundles connecting those regions and delivering information. The commodities can be thought of as the information corresponding to brain activity patterns as obtained for instance by independent component analysis (ICA) of fMRI data. The concept of information

  9. Organization of Cognitive Functions in the Brain.

    ERIC Educational Resources Information Center

    Smith, Aaron

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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Mandonnet, Emmanuel; Duffau, Hugues

    2014-01-01

    Historically, cerebral processing has been conceptualized as a framework based on statically localized functions. However, a growing amount of evidence supports a hodotopical (delocalized) and flexible organization. A number of studies have reported absence of a permanent neurological deficit after massive surgical resections of eloquent brain tissue. These results highlight the tremendous plastic potential of the brain. Understanding anatomo-functional correlates underlying this cerebral reorganization is a prerequisite to restore brain functions through brain-computer interfaces (BCIs) in patients with cerebral diseases, or even to potentiate brain functions in healthy individuals. Here, we review current knowledge of neural networks that could be utilized in the BCIs that enable movements and language. To this end, intraoperative electrical stimulation in awake patients provides valuable information on the cerebral functional maps, their connectomics and plasticity. Overall, these studies indicate that the complex cerebral circuitry that underpins interactions between action, cognition and behavior should be throughly investigated before progress in BCI approaches can be achieved. PMID:24834030

  12. Stereotactic PET atlas of the human brain: Aid for visual interpretation of functional brain images

    SciTech Connect

    Minoshima, S.; Koeppe, R.A.; Frey, A.; Ishihara, M.; Kuhl, D.E.

    1994-06-01

    In the routine analysis of functional brain images obtained by PET, subjective visual interpretation is often used for anatomic localization. To enhance the accuracy and consistency of the anatomic interpretation, a PET stereotactic atlas and localization approach was designed for functional brain images. The PET atlas was constructed from a high-resolution [{sup 18}F]fluorodeoxyglucose (FDG) image set of a normal volunteer (a 41-yr-ld woman). The image set was reoriented stereotactically, according to the intercommissural (anterior and posterior commissures) line and transformed to the standard stereotactic atlas coordinates. Cerebral structures were annotated on the transaxial planes using a proportional grid system and surface-rendered images. The stereotactic localization technique was applied to image sets from patients with Alzheimer`s disease, and areas of functional alteration were localized visually by referring to the PET atlas. Major brain structures were identified on both transaxial planes and surface-rendered images. In the stereotactic system, anatomic correspondence between the PET atlas and stereotactically reoriented individual image sets of patients with Alzheimer`s disease facilitated both indirect and direct localization of the cerebral structures. Because rapid stereotactic alignment methods for PET images are now available for routine use, the PET atlas will serve as an aid for visual interpretation of functional brain images in the stereotactic system. Widespread application of stereotactic localization may be used in functional brain images, not only in the research setting, but also in routine clinical situations. 41 refs., 3 figs.

  13. An Adaptive Complex Network Model for Brain Functional Networks

    PubMed Central

    Gomez Portillo, Ignacio J.; Gleiser, Pablo M.

    2009-01-01

    Brain functional networks are graph representations of activity in the brain, where the vertices represent anatomical regions and the edges their functional connectivity. These networks present a robust small world topological structure, characterized by highly integrated modules connected sparsely by long range links. Recent studies showed that other topological properties such as the degree distribution and the presence (or absence) of a hierarchical structure are not robust, and show different intriguing behaviors. In order to understand the basic ingredients necessary for the emergence of these complex network structures we present an adaptive complex network model for human brain functional networks. The microscopic units of the model are dynamical nodes that represent active regions of the brain, whose interaction gives rise to complex network structures. The links between the nodes are chosen following an adaptive algorithm that establishes connections between dynamical elements with similar internal states. We show that the model is able to describe topological characteristics of human brain networks obtained from functional magnetic resonance imaging studies. In particular, when the dynamical rules of the model allow for integrated processing over the entire network scale-free non-hierarchical networks with well defined communities emerge. On the other hand, when the dynamical rules restrict the information to a local neighborhood, communities cluster together into larger ones, giving rise to a hierarchical structure, with a truncated power law degree distribution. PMID:19738902

  14. The development of social brain functions in infancy.

    PubMed

    Grossmann, Tobias

    2015-11-01

    One fundamental question in psychology is what makes humans such intensely social beings. Probing the developmental and neural origins of our social capacities is a way of addressing this question. In the last 10 years the field of social-cognitive development has witnessed a surge in studies using neuroscience methods to elucidate the development of social information processing during infancy. While the use of electroencephalography (EEG)/event-related brain potentials (ERPs) and functional near-infrared spectroscopy (fNIRS) has revealed a great deal about the timing and localization of the cortical processes involved in early social cognition, the principles underpinning the early development of social brain functioning remain largely unexplored. Here I provide a framework that delineates the essential processes implicated in the early development of the social brain. In particular, I argue that the development of social brain functions in infancy is characterized by the following key principles: (a) self-relevance, (b) joint engagement, (c) predictability, (d) categorization, (e) discrimination, and (f) integration. For all of the proposed principles, I provide empirical examples to illustrate when in infancy they emerge. Moreover, I discuss to what extent they are in fact specifically social in nature or share properties with more domain-general developmental principles. Taken together, this article provides a conceptual integration of the existing EEG/ERPs and fNIRS work on infant social brain function and thereby offers the basis for a principle-based approach to studying the neural correlates of early social cognition.

  15. Can we observe epigenetic effects on human brain function?

    PubMed Central

    Nikolova, Yuliya S.; Hariri, Ahmad R.

    2015-01-01

    Imaging genetics has identified many contributions of DNA sequence variation to individual differences in brain function, behavior, and risk for psychopathology. Recent studies have extended this work beyond the genome by mapping epigenetic differences, specifically gene methylation in peripherally assessed DNA, onto variability in behaviorally and clinically relevant brain function. These data have generated understandable enthusiasm for the potential of such research to illuminate biological mechanisms of risk. Here, we use our research on effects of genetic and epigenetic variation in the human serotonin transporter on brain function to generate a guardedly optimistic opinion that available data encourages continued research in this direction, and suggest strategies to promote faster progress moving forward. PMID:26051383

  16. Assortative mixing in functional brain networks during epileptic seizures

    NASA Astrophysics Data System (ADS)

    Bialonski, Stephan; Lehnertz, Klaus

    2013-09-01

    We investigate assortativity of functional brain networks before, during, and after one-hundred epileptic seizures with different anatomical onset locations. We construct binary functional networks from multi-channel electroencephalographic data recorded from 60 epilepsy patients; and from time-resolved estimates of the assortativity coefficient, we conclude that positive degree-degree correlations are inherent to seizure dynamics. While seizures evolve, an increasing assortativity indicates a segregation of the underlying functional network into groups of brain regions that are only sparsely interconnected, if at all. Interestingly, assortativity decreases already prior to seizure end. Together with previous observations of characteristic temporal evolutions of global statistical properties and synchronizability of epileptic brain networks, our findings may help to gain deeper insights into the complicated dynamics underlying generation, propagation, and termination of seizures.

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

    PubMed

    Gaines, K Drorit; Soper, Henry V

    2016-09-27

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

  18. Functional brain regeneration in the acoel worm Symsagittifera roscoffensis

    PubMed Central

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

    2015-01-01

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

  19. Reduction of brain kynurenic acid improves cognitive function.

    PubMed

    Kozak, Rouba; Campbell, Brian M; Strick, Christine A; Horner, Weldon; Hoffmann, William E; Kiss, Tamas; Chapin, Douglas S; McGinnis, Dina; Abbott, Amanda L; Roberts, Brooke M; Fonseca, Kari; Guanowsky, Victor; Young, Damon A; Seymour, Patricia A; Dounay, Amy; Hajos, Mihaly; Williams, Graham V; Castner, Stacy A

    2014-08-06

    The elevation of kynurenic acid (KYNA) observed in schizophrenic patients may contribute to core symptoms arising from glutamate hypofunction, including cognitive impairments. Although increased KYNA levels reduce excitatory neurotransmission, KYNA has been proposed to act as an endogenous antagonist at the glycine site of the glutamate NMDA receptor (NMDAR) and as a negative allosteric modulator at the α7 nicotinic acetylcholine receptor. Levels of KYNA are elevated in CSF and the postmortem brain of schizophrenia patients, and these elevated levels of KYNA could contribute to NMDAR hypofunction and the cognitive deficits and negative symptoms associated with this disease. However, the impact of endogenously produced KYNA on brain function and behavior is less well understood due to a paucity of pharmacological tools. To address this issue, we identified PF-04859989, a brain-penetrable inhibitor of kynurenine aminotransferase II (KAT II), the enzyme responsible for most brain KYNA synthesis. In rats, systemic administration of PF-04859989 dose-dependently reduced brain KYNA to as little as 28% of basal levels, and prevented amphetamine- and ketamine-induced disruption of auditory gating and improved performance in a sustained attention task. It also prevented ketamine-induced disruption of performance in a working memory task and a spatial memory task in rodents and nonhuman primates, respectively. Together, these findings support the hypotheses that endogenous KYNA impacts cognitive function and that inhibition of KAT II, and consequent lowering of endogenous brain KYNA levels, improves cognitive performance under conditions considered relevant for schizophrenia.

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

    PubMed Central

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

    2016-01-01

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

  1. Hemispheric asymmetry of electroencephalography-based functional brain networks.

    PubMed

    Jalili, Mahdi

    2014-11-12

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

  2. Estimating brain's functional graph from the structural graph's Laplacian

    NASA Astrophysics Data System (ADS)

    Abdelnour, F.; Dayan, M.; Devinsky, O.; Thesen, T.; Raj, A.

    2015-09-01

    The interplay between the brain's function and structure has been of immense interest to the neuroscience and connectomics communities. In this work we develop a simple linear model relating the structural network and the functional network. We propose that the two networks are related by the structural network's Laplacian up to a shift. The model is simple to implement and gives accurate prediction of function's eigenvalues at the subject level and its eigenvectors at group level.

  3. Human brain networks function in connectome-specific harmonic waves.

    PubMed

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-21

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

  4. Human brain networks function in connectome-specific harmonic waves

    PubMed Central

    Atasoy, Selen; Donnelly, Isaac; Pearson, Joel

    2016-01-01

    A key characteristic of human brain activity is coherent, spatially distributed oscillations forming behaviour-dependent brain networks. However, a fundamental principle underlying these networks remains unknown. Here we report that functional networks of the human brain are predicted by harmonic patterns, ubiquitous throughout nature, steered by the anatomy of the human cerebral cortex, the human connectome. We introduce a new technique extending the Fourier basis to the human connectome. In this new frequency-specific representation of cortical activity, that we call ‘connectome harmonics', oscillatory networks of the human brain at rest match harmonic wave patterns of certain frequencies. We demonstrate a neural mechanism behind the self-organization of connectome harmonics with a continuous neural field model of excitatory–inhibitory interactions on the connectome. Remarkably, the critical relation between the neural field patterns and the delicate excitation–inhibition balance fits the neurophysiological changes observed during the loss and recovery of consciousness. PMID:26792267

  5. The microbiota-gut-brain axis in functional gastrointestinal disorders.

    PubMed

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.

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

    PubMed

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

    2003-11-01

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

  7. 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.

  8. Hierarchical organization unveiled by functional connectivity in complex brain networks.

    PubMed

    Zhou, Changsong; Zemanová, Lucia; Zamora, Gorka; Hilgetag, Claus C; Kurths, Jürgen

    2006-12-08

    How do diverse dynamical patterns arise from the topology of complex networks? We study synchronization dynamics in the cortical brain network of the cat, which displays a hierarchically clustered organization, by modeling each node (cortical area) with a subnetwork of interacting excitable neurons. We find that in the biologically plausible regime the dynamics exhibits a hierarchical modular organization, in particular, revealing functional clusters coinciding with the anatomical communities at different scales. Our results provide insights into the relationship between network topology and functional organization of complex brain networks.

  9. Expectation modulates neural representations of valence throughout the human brain

    PubMed Central

    Ramayya, Ashwin G.; Pedisich, Isaac; Kahana, Michael J.

    2015-01-01

    The brain's sensitivity to unexpected gains or losses plays an important role in our ability to learn new behaviors (Rescorla and Wagner, 1972; Sutton and Barto, 1990). Recent work suggests that gains and losses are ubiquitously encoded throughout the human brain (Vickery et al., 2011), however, the extent to which reward expectation modulates these valence representations is not known. To address this question we analyzed recordings from 4,306 intracranially implanted electrodes in 39 neurosurgical patients as they performed a two-alternative probability learning task. Using high-frequency activity (HFA, 70-200 Hz) as an indicator of local firing rates, we found that expectation modulated reward-related neural activity in widespread brain regions, including regions that receive sparse inputs from midbrain dopaminergic neurons. The strength of unexpected gain signals predicted subjects’ abilities to encode stimulus-reward associations. Thus, neural signals that are functionally related to learning are widely distributed throughout the human brain. PMID:25937489

  10. Loss of functional GABAA receptors in the Alzheimer diseased brain

    PubMed Central

    Limon, Agenor; Reyes-Ruiz, Jorge Mauricio; Miledi, Ricardo

    2012-01-01

    The cholinergic and glutamatergic neurotransmission systems are known to be severely disrupted in Alzheimer's disease (AD). GABAergic neurotransmission, in contrast, is generally thought to be well preserved. Evidence from animal models and human postmortem tissue suggest GABAergic remodeling in the AD brain. Nevertheless, there is no information on changes, if any, in the electrophysiological properties of human native GABA receptors as a consequence of AD. To gain such information, we have microtransplanted cell membranes, isolated from temporal cortices of control and AD brains, into Xenopus oocytes, and recorded the electrophysiological activity of the transplanted GABA receptors. We found an age-dependent reduction of GABA currents in the AD brain. This reduction was larger when the AD membranes were obtained from younger subjects. We also found that GABA currents from AD brains have a faster rate of desensitization than those from non-AD brains. Furthermore, GABA receptors from AD brains were slightly, but significantly, less sensitive to GABA than receptors from non-AD brains. The reduction of GABA currents in AD was associated with reductions of mRNA and protein of the principal GABA receptor subunits normally present in the temporal cortex. Pairwise analysis of the transcripts within control and AD groups and analyses of the proportion of GABA receptor subunits revealed down-regulation of α1 and γ2 subunits in AD. In contrast, the proportions of α2, β1, and γ1 transcripts were up-regulated in the AD brains. Our data support a functional remodeling of GABAergic neurotransmission in the human AD brain. PMID:22691495

  11. Interactions between occlusion and human brain function activities.

    PubMed

    Ohkubo, C; Morokuma, M; Yoneyama, Y; Matsuda, R; Lee, J S

    2013-02-01

    There are few review articles in the area of human research that focus on the interactions between occlusion and brain function. This systematic review discusses the effect of occlusion on the health of the entire body with a focus on brain function. Available relevant articles in English from 1999 to 2011 were assessed in an online database and as hard copies in libraries. The selected 19 articles were classified into the following five categories: chewing and tongue movements, clenching and grinding, occlusal splints and occlusal interference, prosthetic rehabilitation, and pain and stimulation. The relationships between the brain activity observed in the motor and sensory cortices and movements of the oral and maxillofacial area, such as those produced by gum chewing, tapping and clenching, were investigated. It was found that the sensorimotor cortex was also affected by the placement of the occlusal interference devices, splints and implant prostheses. Brain activity may change depending on the strength of the movements in the oral and maxillofacial area. Therefore, mastication and other movements stimulate the activity in the cerebral cortex and may be helpful in preventing degradation of a brain function. However, these findings must be verified by evidence gathered from more subjects.

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

    PubMed

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

    2001-05-01

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

  13. Hyperbaric oxygen therapy improves cognitive functioning after brain injury.

    PubMed

    Liu, Su; Shen, Guangyu; Deng, Shukun; Wang, Xiubin; Wu, Qinfeng; Guo, Aisong

    2013-12-15

    Hyperbaric oxygen therapy has been widely applied and recognized in the treatment of brain injury; however, the correlation between the protective effect of hyperbaric oxygen therapy and changes of metabolites in the brain remains unclear. To investigate the effect and potential mechanism of hyperbaric oxygen therapy on cognitive functioning in rats, we established traumatic brain injury models using Feeney's free falling method. We treated rat models with hyperbaric oxygen therapy at 0.2 MPa for 60 minutes per day. The Morris water maze test for spatial navigation showed that the average escape latency was significantly prolonged and cognitive function decreased in rats with brain injury. After treatment with hyperbaric oxygen therapy for 1 and 2 weeks, the rats' spatial learning and memory abilities were improved. Hydrogen proton magnetic resonance spectroscopy analysis showed that the N-acetylaspartate/creatine ratio in the hippocampal CA3 region was significantly increased at 1 week, and the N-acetylaspartate/choline ratio was significantly increased at 2 weeks after hyperbaric oxygen therapy. Nissl staining and immunohistochemical staining showed that the number of nerve cells and Nissl bodies in the hippocampal CA3 region was significantly increased, and glial fibrillary acidic protein positive cells were decreased after a 2-week hyperbaric oxygen therapy treatment. Our findings indicate that hyperbaric oxygen therapy significantly improves cognitive functioning in rats with traumatic brain injury, and the potential mechanism is mediated by metabolic changes and nerve cell restoration in the hippocampal CA3 region.

  14. Effects of Soccer Heading on Brain Structure and Function

    PubMed Central

    Rodrigues, Ana Carolina; Lasmar, Rodrigo Pace; Caramelli, Paulo

    2016-01-01

    Soccer is the most popular sport in the world, with more than 265 million players worldwide, including professional and amateur ones. Soccer is unique in comparison to other sports, as it is the only sport in which participants purposely use their head to hit the ball. Heading is considered as an offensive or defensive move whereby the player’s unprotected head is used to deliberately impact the ball and direct it during play. A soccer player can be subjected to an average of 6–12 incidents of heading the ball per competitive game, where the ball reaches high velocities. Moreover, in practice sessions, heading training, which involves heading the ball repeatedly at low velocities, is common. Although the scientific community, as well as the media, has focused on the effects of concussions in contact sports, the role of subconcussive impacts, as it can occur during heading, has recently gained attention, considering that it may represent an additional mechanism of cumulative brain injury. The purpose of this study is to review the existing literature regarding the effects of soccer heading on brain structure and function. Only in the last years, some investigations have addressed the impact of heading on brain structure, by using neuroimaging techniques. Similarly, there have been some recent studies investigating biochemical markers of brain injury in soccer players. There is evidence of association between heading and abnormal brain structure, but the data are still preliminary. Also, some studies have suggested that subconcussive head impacts, as heading, could cause cognitive impairment, whereas others have not corroborated this finding. Questions persist as to whether or not heading is deleterious to cognitive functioning. Further studies, especially with longitudinal designs, are needed to clarify the clinical significance of heading as a cause of brain injury and to identify risk factors. Such investigations might contribute to the establishment of safety

  15. Functional constraints in the evolution of brain circuits

    PubMed Central

    Bosman, Conrado A.; Aboitiz, Francisco

    2015-01-01

    Regardless of major anatomical and neurodevelopmental differences, the vertebrate isocortex shows a remarkably well-conserved organization. In the isocortex, reciprocal connections between excitatory and inhibitory neurons are distributed across multiple layers, encompassing modular, dynamical and recurrent functional networks during information processing. These dynamical brain networks are often organized in neuronal assemblies interacting through rhythmic phase relationships. Accordingly, these oscillatory interactions are observed across multiple brain scale levels, and they are associated with several sensory, motor, and cognitive processes. Most notably, oscillatory interactions are also found in the complete spectrum of vertebrates. Yet, it is unknown why this functional organization is so well conserved in evolution. In this perspective, we propose some ideas about how functional requirements of the isocortex can account for the evolutionary stability observed in microcircuits across vertebrates. We argue that isocortex architectures represent canonical microcircuits resulting from: (i) the early selection of neuronal architectures based on the oscillatory excitatory-inhibitory balance, which lead to the implementation of compartmentalized oscillations and (ii) the subsequent emergence of inferential coding strategies (predictive coding), which are able to expand computational capacities. We also argue that these functional constraints may be the result of several advantages that oscillatory activity contributes to brain network processes, such as information transmission and code reliability. In this manner, similarities in mesoscale brain circuitry and input-output organization between different vertebrate groups may reflect evolutionary constraints imposed by these functional requirements, which may or may not be traceable to a common ancestor. PMID:26388716

  16. Continuous theta burst transcranial magnetic stimulation affects brain functional connectivity.

    PubMed

    Dan Cao; Yingjie Li; Ling Wei; Yingying Tang

    2016-08-01

    Prefrontal cortex (PFC) plays an important role in the emotional processing as well as in the functional brain network. Hyperactivity in the right dorsolateral prefrontal cortex (DLPFC) would be found in anxious participants. However, it is still unclear what the role of PFC played in a resting functional network. Continuous theta burst transcranial magnetic stimulation (cTBS) is an effective tool to create virtual lesions on brain regions. In this paper, we applied cTBS over right prefrontal area, and investigated the effects of cTBS on the brain activity for functional connectivity by the method of graph theory. We recorded 64-channels EEG on thirteen healthy participants in the resting condition and emotional tasks before and after 40 s of cTBS. This work focused on the effect of cTBS on cortical activities in the resting condition by calculating the coherence between EEG channels and building functional networks before and after cTBS in the delta, theta, alpha and beta bands. Results revealed that 1) The functional connectivity after cTBS was significantly increased compared with that before cTBS in delta, theta, alpha and beta bands in the resting condition; 2) The efficiency-cost reached the maximum before and after cTBS both with the cost about 0.3 in the bands above, which meant that the information transmission of functional brain network with this cost was highly efficient; 3) the clustering coefficient and path length after cTBS was significantly increased in delta, theta and beta bands. In conclusion, cTBS over PFC indeed enhanced the functional connectivity in the resting condition. In addition, the information transmission in the resting brain network was highly efficient with the cost about 0.3.

  17. Diverse Functions of Retinoic Acid in Brain Vascular Development

    PubMed Central

    Bonney, Stephanie; Harrison-Uy, Susan; Mishra, Swati; MacPherson, Amber M.; Choe, Youngshik; Li, Dan; Jaminet, Shou-Ching; Fruttiger, Marcus; Pleasure, Samuel J.

    2016-01-01

    As neural structures grow in size and increase metabolic demand, the CNS vasculature undergoes extensive growth, remodeling, and maturation. Signals from neural tissue act on endothelial cells to stimulate blood vessel ingression, vessel patterning, and acquisition of mature brain vascular traits, most notably the blood–brain barrier. Using mouse genetic and in vitro approaches, we identified retinoic acid (RA) as an important regulator of brain vascular development via non-cell-autonomous and cell-autonomous regulation of endothelial WNT signaling. Our analysis of globally RA-deficient embryos (Rdh10 mutants) points to an important, non-cell-autonomous function for RA in the development of the vasculature in the neocortex. We demonstrate that Rdh10 mutants have severe defects in cerebrovascular development and that this phenotype correlates with near absence of endothelial WNT signaling, specifically in the cerebrovasculature, and substantially elevated expression of WNT inhibitors in the neocortex. We show that RA can suppress the expression of WNT inhibitors in neocortical progenitors. Analysis of vasculature in non-neocortical brain regions suggested that RA may have a separate, cell-autonomous function in brain endothelial cells to inhibit WNT signaling. Using both gain and loss of RA signaling approaches, we show that RA signaling in brain endothelial cells can inhibit WNT-β-catenin transcriptional activity and that this is required to moderate the expression of WNT target Sox17. From this, a model emerges in which RA acts upstream of the WNT pathway via non-cell-autonomous and cell-autonomous mechanisms to ensure the formation of an adequate and stable brain vascular plexus. SIGNIFICANCE STATEMENT Work presented here provides novel insight into important yet little understood aspects of brain vascular development, implicating for the first time a factor upstream of endothelial WNT signaling. We show that RA is permissive for cerebrovascular growth via

  18. The role of sleep in emotional brain function.

    PubMed

    Goldstein, Andrea N; Walker, Matthew P

    2014-01-01

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

  19. A cellular perspective on brain energy metabolism and functional imaging.

    PubMed

    Magistretti, Pierre J; Allaman, Igor

    2015-05-20

    The energy demands of the brain are high: they account for at least 20% of the body's energy consumption. Evolutionary studies indicate that the emergence of higher cognitive functions in humans is associated with an increased glucose utilization and expression of energy metabolism genes. Functional brain imaging techniques such as fMRI and PET, which are widely used in human neuroscience studies, detect signals that monitor energy delivery and use in register with neuronal activity. Recent technological advances in metabolic studies with cellular resolution have afforded decisive insights into the understanding of the cellular and molecular bases of the coupling between neuronal activity and energy metabolism and point at a key role of neuron-astrocyte metabolic interactions. This article reviews some of the most salient features emerging from recent studies and aims at providing an integration of brain energy metabolism across resolution scales.

  20. The Role of Sleep in Emotional Brain Function

    PubMed Central

    Goldstein, Andrea N.; Walker, Matthew P.

    2014-01-01

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

  1. Structural and functional clusters of complex brain networks

    NASA Astrophysics Data System (ADS)

    Zemanová, Lucia; Zhou, Changsong; Kurths, Jürgen

    2006-12-01

    Recent research using the complex network approach has revealed a rich and complicated network topology in the cortical connectivity of mammalian brains. It is of importance to understand the implications of such complex network structures in the functional organization of the brain activities. Here we study this problem from the viewpoint of dynamical complex networks. We investigate synchronization dynamics on the corticocortical network of the cat by modeling each node (cortical area) of the network with a sub-network of interacting excitable neurons. We find that the network displays clustered synchronization behavior, and the dynamical clusters coincide with the topological community structures observed in the anatomical network. Our results provide insights into the relationship between the global organization and the functional specialization of the brain cortex.

  2. Evaluation of traumatic brain injury: brain potentials in diagnosis, function, and prognosis.

    PubMed

    Duncan, Connie C; Summers, Angela C; Perla, Elizabeth J; Coburn, Kerry L; Mirsky, Allan F

    2011-10-01

    The focus of this review is an analysis of the use of event-related brain potential (ERP) abnormalities as indices of functional pathophysiology in survivors of traumatic brain injury (TBI). TBI may be the most prevalent but least understood neurological disorder in both civilian and military populations. In the military, thousands of new brain injuries occur yearly; this lends considerable urgency to the use of highly sensitive ERP tools to illuminate brain changes and to address remediation issues. We review the processes thought to be indexed by the cognitive components of the ERP and outline the rationale for applying ERPs to evaluate deficits after TBI. Studies in which ERPs were used to clarify the nature of cognitive complaints of TBI survivors are reviewed, emphasizing impairment in attention, information processing, and cognitive control. Also highlighted is research on the application of ERPs to predict emergence from coma and eventual outcome. We describe primary blast injury, the leading cause of TBI for active duty military personnel in present day warfare. The review concludes with a description of an ongoing investigation of mild TBI, aimed at using indices of brain structure and function to predict the course of posttraumatic stress disorder. An additional goal of this ongoing investigation is to characterize the structural and functional sequelae of blast injury.

  3. Netrin 1 regulates blood-brain barrier function and neuroinflammation.

    PubMed

    Podjaski, Cornelia; Alvarez, Jorge I; Bourbonniere, Lyne; Larouche, Sandra; Terouz, Simone; Bin, Jenea M; Lécuyer, Marc-André; Saint-Laurent, Olivia; Larochelle, Catherine; Darlington, Peter J; Arbour, Nathalie; Antel, Jack P; Kennedy, Timothy E; Prat, Alexandre

    2015-06-01

    Blood-brain barrier function is driven by the influence of astrocyte-secreted factors. During neuroinflammatory responses the blood-brain barrier is compromised resulting in central nervous system damage and exacerbated pathology. Here, we identified endothelial netrin 1 induction as a vascular response to astrocyte-derived sonic hedgehog that promotes autocrine barrier properties during homeostasis and increases with inflammation. Netrin 1 supports blood-brain barrier integrity by upregulating endothelial junctional protein expression, while netrin 1 knockout mice display disorganized tight junction protein expression and barrier breakdown. Upon inflammatory conditions, blood-brain barrier endothelial cells significantly upregulated netrin 1 levels in vitro and in situ, which prevented junctional breach and endothelial cell activation. Finally, netrin 1 treatment during experimental autoimmune encephalomyelitis significantly reduced blood-brain barrier disruption and decreased clinical and pathological indices of disease severity. Our results demonstrate that netrin 1 is an important regulator of blood-brain barrier maintenance that protects the central nervous system against inflammatory conditions such as multiple sclerosis and experimental autoimmune encephalomyelitis.

  4. Disrupted functional brain connectome in unilateral sudden sensorineural hearing loss.

    PubMed

    Xu, Haibo; Fan, Wenliang; Zhao, Xueyan; Li, Jing; Zhang, Wenjuan; Lei, Ping; Liu, Yuan; Wang, Haha; Cheng, Huamao; Shi, Hong

    2016-05-01

    Sudden sensorineural hearing loss (SSNHL) is generally defined as sensorineural hearing loss of 30 dB or greater over at least three contiguous audiometric frequencies and within a three-day period. This hearing loss is usually unilateral and can be associated with tinnitus and vertigo. The pathogenesis of unilateral sudden sensorineural hearing loss is still unknown, and the alterations in the functional connectivity are suspected to involve one possible pathogenesis. Despite scarce findings with respect to alterations in brain functional networks in unilateral sudden sensorineural hearing loss, the alterations of the whole brain functional connectome and whether these alterations were already in existence in the acute period remains unknown. The aim of this study was to investigate the alterations of brain functional connectome in two large samples of unilateral sudden sensorineural hearing loss patients and to investigate the correlation between unilateral sudden sensorineural hearing loss characteristics and changes in the functional network properties. Pure tone audiometry was performed to assess hearing ability. Abnormal changes in the peripheral auditory system were examined using conventional magnetic resonance imaging. The graph theoretical network analysis method was used to detect brain connectome alterations in unilateral sudden sensorineural hearing loss. Compared with the control groups, both groups of unilateral SSNHL patients exhibited a significantly increased clustering coefficient, global efficiency, and local efficiency but a significantly decreased characteristic path length. In addition, the primary increased nodal strength (e.g., nodal betweenness, hubs) was observed in several regions primarily, including the limbic and paralimbic systems, and in the auditory network brain areas. These findings suggest that the alteration of network organization already exists in unilateral sudden sensorineural hearing loss patients within the acute period

  5. Does sleep restore the topology of functional brain networks?

    PubMed

    Koenis, Maria M G; Romeijn, Nico; Piantoni, Giovanni; Verweij, Ilse; Van der Werf, Ysbrand D; Van Someren, Eus J W; Stam, Cornelis J

    2013-02-01

    Previous studies have shown that healthy anatomical as well as functional brain networks have small-world properties and become less optimal with brain disease. During sleep, the functional brain network becomes more small-world-like. Here we test the hypothesis that the functional brain network during wakefulness becomes less optimal after sleep deprivation (SD). Electroencephalography (EEG) was recorded five times a day after a night of SD and after a night of normal sleep in eight young healthy subjects, both during eyes-closed and eyes-open resting state. Overall synchronization was determined with the synchronization likelihood (SL) and the phase lag index (PLI). From these coupling strength matrices the normalized clustering coefficient C (a measurement of local clustering) and path length L (a measurement of global integration) were computed. Both measures were normalized by dividing them by their corresponding C-s and L-s values of random control networks. SD reduced alpha band C/C-s and L/L-s and theta band C/C-s during eyes-closed resting state. In contrast, SD increased gamma-band C/C-s and L/L-s during eyes-open resting state. Functional relevance of these changes in network properties was suggested by their association with sleep deprivation-induced performance deficits on a sustained attention simple reaction time task. The findings indicate that SD results in a more random network of alpha-coupling and a more ordered network of gamma-coupling. The present study shows that SD induces frequency-specific changes in the functional network topology of the brain, supporting the idea that sleep plays a role in the maintenance of an optimal functional network.

  6. Altered resting brain function and structure in professional badminton players.

    PubMed

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

    2012-01-01

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

  7. Aberrant functional brain connectome in people with antisocial personality disorder

    PubMed Central

    Tang, Yan; Long, Jun; Wang, Wei; Liao, Jian; Xie, Hua; Zhao, Guihu; Zhang, Hao

    2016-01-01

    Antisocial personality disorder (ASPD) is characterised by a disregard for social obligations and callous unconcern for the feelings of others. Studies have demonstrated that ASPD is associated with abnormalities in brain regions and aberrant functional connectivity. In this paper, topological organisation was examined in resting-state fMRI data obtained from 32 ASPD patients and 32 non-ASPD controls. The frequency-dependent functional networks were constructed using wavelet-based correlations over 90 brain regions. The topology of the functional networks of ASPD subjects was analysed via graph theoretical analysis. Furthermore, the abnormal functional connectivity was determined with a network-based statistic (NBS) approach. Our results revealed that, compared with the controls, the ASPD patients exhibited altered topological configuration of the functional connectome in the frequency interval of 0.016–0.031 Hz, as indicated by the increased clustering coefficient and decreased betweenness centrality in the medial superior frontal gyrus, precentral gyrus, Rolandic operculum, superior parietal gyrus, angular gyrus, and middle temporal pole. In addition, the ASPD patients showed increased functional connectivity mainly located in the default-mode network. The present study reveals an aberrant topological organisation of the functional brain network in individuals with ASPD. Our findings provide novel insight into the neuropathological mechanisms of ASPD. PMID:27257047

  8. Variability in functional brain networks predicts expertise during action observation.

    PubMed

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

    2017-02-01

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

  9. Brain structure and function correlates of cognitive subtypes in schizophrenia.

    PubMed

    Geisler, Daniel; Walton, Esther; Naylor, Melissa; Roessner, Veit; Lim, Kelvin O; Charles Schulz, S; Gollub, Randy L; Calhoun, Vince D; Sponheim, Scott R; Ehrlich, Stefan

    2015-10-30

    Stable neuropsychological deficits may provide a reliable basis for identifying etiological subtypes of schizophrenia. The aim of this study was to identify clusters of individuals with schizophrenia based on dimensions of neuropsychological performance, and to characterize their neural correlates. We acquired neuropsychological data as well as structural and functional magnetic resonance imaging from 129 patients with schizophrenia and 165 healthy controls. We derived eight cognitive dimensions and subsequently applied a cluster analysis to identify possible schizophrenia subtypes. Analyses suggested the following four cognitive clusters of schizophrenia: (1) Diminished Verbal Fluency, (2) Diminished Verbal Memory and Poor Motor Control, (3) Diminished Face Memory and Slowed Processing, and (4) Diminished Intellectual Function. The clusters were characterized by a specific pattern of structural brain changes in areas such as Wernicke's area, lingual gyrus and occipital face area, and hippocampus as well as differences in working memory-elicited neural activity in several fronto-parietal brain regions. Separable measures of cognitive function appear to provide a method for deriving cognitive subtypes meaningfully related to brain structure and function. Because the present study identified brain-based neural correlates of the cognitive clusters, the proposed groups of individuals with schizophrenia have some external validity.

  10. The nicotinic cholinergic system function in the human brain.

    PubMed

    Nees, Frauke

    2015-09-01

    Research on the nicotinic cholinergic system function in the brain was previously mainly derived from animal studies, yet, research in humans is growing. Up to date, findings allow significant advances on the understanding of nicotinic cholinergic effects on human cognition, emotion and behavior using a range of functional brain imaging approaches such as pharmacological functional magnetic resonance imaging or positron emission tomography. Studies provided insights across various mechanistic psychological domains using different tasks as well as at rest in both healthy individuals and patient populations, with so far partly mixed results reporting both enhancements and decrements of neural activity related to the nicotinic cholinergic system. Moreover, studies on the relation between brain structure and the nicotinic cholinergic system add important information in this context. The present review summarizes the current status of human brain imaging studies and presents the findings within a theoretical and clinical perspective as they may be useful not only for an advancement of the understanding of basic nicotinic cholinergic-related mechanisms, but also for the development and integration of psychological and pharmacological treatment approaches. Patterns of functional neuroanatomy and neural circuitry across various cognitive and emotional domains may be used as neuropsychological markers of mental disorders such as addiction, Alzheimer's disease, Parkinson disease or schizophrenia, where nicotinic cholinergic system changes are characteristic. This article is part of the Special Issue entitled 'The Nicotinic Acetylcholine Receptor: From Molecular Biology to Cognition'.

  11. "Hotheaded": the role OF TRPV1 in brain functions.

    PubMed

    Martins, D; Tavares, I; Morgado, C

    2014-10-01

    The TRPV1 (vanilloid 1) channel is best known for its role in sensory transmission in the nociceptive neurons of the peripheral nervous system. Although first studied in the dorsal root ganglia as the receptor for capsaicin, TRPV1 has been recently recognized to have a broader distribution in the central nervous system, where it is likely to constitute an atypical neurotransmission system involved in several functions through modulation of both neuronal and glial activities. The endovanilloid-activated brain TRPV1 channels seem to be involved in somatosensory, motor and visceral functions. Recent studies suggested that TRPV1 channels also account for more complex functions, as addiction, anxiety, mood and cognition/learning. However, more studies are needed before the relevance of TRPV1 in brain activity can be clearly stated. This review highlights the increasing importance of TRPV1 as a regulator of brain function and discusses possible bases for the future development of new therapeutic approaches that by targeting brain TRPV1 receptors might be used for the treatment of several neurological disorders.

  12. Assessment of Emotional Functioning in Brain-Impaired Individuals.

    ERIC Educational Resources Information Center

    Nelson, Linda D.; Cicchetti, Domenic V.

    1995-01-01

    Two basic models are presented of emotional functioning as it is commonly considered relative to brain damage. Methodological concerns in the literature are reviewed, and issues of measurement are highlighted to demonstrate the importance of empirically defining the prevalence of emotional effects. (SLD)

  13. Structural and Functional Plasticity in the Maternal Brain Circuitry

    ERIC Educational Resources Information Center

    Pereira, Mariana

    2016-01-01

    Parenting recruits a distributed network of brain structures (and neuromodulators) that coordinates caregiving responses attuned to the young's affect, needs, and developmental stage. Many of these structures and connections undergo significant structural and functional plasticity, mediated by the interplay between maternal hormones and social…

  14. Functional craniology and brain evolution: from paleontology to biomedicine

    PubMed Central

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

    2014-01-01

    Anatomical systems are organized through a network of structural and functional relationships among their elements. This network of relationships is the result of evolution, it represents the actual target of selection, and it generates the set of rules orienting and constraining the morphogenetic processes. Understanding the relationship among cranial and cerebral components is necessary to investigate the factors that have influenced and characterized our neuroanatomy, and possible drawbacks associated with the evolution of large brains. The study of the spatial relationships between skull and brain in the human genus has direct relevance in cranial surgery. Geometrical modeling can provide functional perspectives in evolution and brain physiology, like in simulations to investigate metabolic heat production and dissipation in the endocranial form. Analysis of the evolutionary constraints between facial and neural blocks can provide new information on visual impairment. The study of brain form variation in fossil humans can supply a different perspective for interpreting the processes behind neurodegeneration and Alzheimer’s disease. Following these examples, it is apparent that paleontology and biomedicine can exchange relevant information and contribute at the same time to the development of robust evolutionary hypotheses on brain evolution, while offering more comprehensive biological perspectives with regard to the interpretation of pathological processes. PMID:24765064

  15. Astrocyte functions in the copper homeostasis of the brain.

    PubMed

    Scheiber, Ivo F; Dringen, Ralf

    2013-04-01

    Copper is an essential element that is required for a variety of important cellular functions. Since not only copper deficiency but also excess of copper can seriously affect cellular functions, the cellular copper metabolism is tightly regulated. In brain, astrocytes appear to play a pivotal role in the copper metabolism. With their strategically important localization between capillary endothelial cells and neuronal structures they are ideally positioned to transport copper from the blood-brain barrier to parenchymal brain cells. Accordingly, astrocytes have the capacity to efficiently take up, store and to export copper. Cultured astrocytes appear to be remarkably resistant against copper-induced toxicity. However, copper exposure can lead to profound alterations in the metabolism of these cells. This article will summarize the current knowledge on the copper metabolism of astrocytes, will describe copper-induced alterations in the glucose and glutathione metabolism of astrocytes and will address the potential role of astrocytes in the copper metabolism of the brain in diseases that have been connected with disturbances in brain copper homeostasis.

  16. Functional craniology and brain evolution: from paleontology to biomedicine.

    PubMed

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

    2014-01-01

    Anatomical systems are organized through a network of structural and functional relationships among their elements. This network of relationships is the result of evolution, it represents the actual target of selection, and it generates the set of rules orienting and constraining the morphogenetic processes. Understanding the relationship among cranial and cerebral components is necessary to investigate the factors that have influenced and characterized our neuroanatomy, and possible drawbacks associated with the evolution of large brains. The study of the spatial relationships between skull and brain in the human genus has direct relevance in cranial surgery. Geometrical modeling can provide functional perspectives in evolution and brain physiology, like in simulations to investigate metabolic heat production and dissipation in the endocranial form. Analysis of the evolutionary constraints between facial and neural blocks can provide new information on visual impairment. The study of brain form variation in fossil humans can supply a different perspective for interpreting the processes behind neurodegeneration and Alzheimer's disease. Following these examples, it is apparent that paleontology and biomedicine can exchange relevant information and contribute at the same time to the development of robust evolutionary hypotheses on brain evolution, while offering more comprehensive biological perspectives with regard to the interpretation of pathological processes.

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

    SciTech Connect

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

    2008-12-01

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

  18. Beyond genotype: serotonin transporter epigenetic modification predicts human brain function.

    PubMed

    Nikolova, Yuliya S; Koenen, Karestan C; Galea, Sandro; Wang, Chiou-Miin; Seney, Marianne L; Sibille, Etienne; Williamson, Douglas E; Hariri, Ahmad R

    2014-09-01

    We examined epigenetic regulation in regards to behaviorally and clinically relevant human brain function. Specifically, we found that increased promoter methylation of the serotonin transporter gene predicted increased threat-related amygdala reactivity and decreased mRNA expression in postmortem amygdala tissue. These patterns were independent of functional genetic variation in the same region. Furthermore, the association with amygdala reactivity was replicated in a second cohort and was robust to both sampling methods and age.

  19. Left Brain vs. Right Brain: Findings on Visual Spatial Capacities and the Functional Neurology of Giftedness

    ERIC Educational Resources Information Center

    Kalbfleisch, M. Layne; Gillmarten, Charles

    2013-01-01

    As neuroimaging technologies increase their sensitivity to assess the function of the human brain and results from these studies draw the attention of educators, it becomes paramount to identify misconceptions about what these data illustrate and how these findings might be applied to educational contexts. Some of these "neuromyths" have…

  20. Functional recovery after surgical resection of low grade gliomas in eloquent brain: hypothesis of brain compensation

    PubMed Central

    Duffau, H; Capelle, L; Denvil, D; Sichez, N; Gatignol, P; Lopes, M; Mitchell, M; Sichez, J; Van Effenterre, R

    2003-01-01

    Objectives: To describe functional recovery after surgical resection of low grade gliomas (LGG) in eloquent brain areas, and discuss the mechanisms of compensation. Methods: Seventy-seven right-handed patients without deficit were operated on for a LGG invading primary and/or secondary sensorimotor and/or language areas, as shown anatomically by pre-operative MRI and intraoperatively by electrical brain stimulation and cortico-subcortical mapping. Results: Tumours involved 31 supplementary motor areas, 28 insulas, 8 primary somatosensory areas, 4 primary motor areas, 4 Broca's areas, and 2 left temporal language areas. All patients had immediate post-operative deficits. Recovery occurred within 3 months in all except four cases (definitive morbidity: 5%). Ninety-two percent of the lesions were either totally or extensively resected on post-operative MRI. Conclusions: These findings suggest that spatio-temporal functional re-organisation is possible in peritumoural brain, and that the process is dynamic. The recruitment of compensatory areas with long term perilesional functional reshaping would explain why: before surgery, there is no clinical deficit despite the tumour growth in eloquent regions; immediately after surgery, the occurrence of a deficit, which could be due to the resection of invaded areas participating (but not essential) to the function; and why three months after surgery, almost complete recovery had occurred. This brain plasticity, which decreases the long term risk of surgical morbidity, may be used to extend the limits of surgery in eloquent areas. PMID:12810776

  1. Effects of exercise on brain functions in diabetic animal models.

    PubMed

    Yi, Sun Shin

    2015-05-15

    Human life span has dramatically increased over several decades, and the quality of life has been considered to be equally important. However, diabetes mellitus (DM) characterized by problems related to insulin secretion and recognition has become a serious health problem in recent years that threatens human health by causing decline in brain functions and finally leading to neurodegenerative diseases. Exercise is recognized as an effective therapy for DM without medication administration. Exercise studies using experimental animals are a suitable option to overcome this drawback, and animal studies have improved continuously according to the needs of the experimenters. Since brain health is the most significant factor in human life, it is very important to assess brain functions according to the different exercise conditions using experimental animal models. Generally, there are two types of DM; insulin-dependent type 1 DM and an insulin-independent type 2 DM (T2DM); however, the author will mostly discuss brain functions in T2DM animal models in this review. Additionally, many physiopathologic alterations are caused in the brain by DM such as increased adiposity, inflammation, hormonal dysregulation, uncontrolled hyperphagia, insulin and leptin resistance, and dysregulation of neurotransmitters and declined neurogenesis in the hippocampus and we describe how exercise corrects these alterations in animal models. The results of changes in the brain environment differ according to voluntary, involuntary running exercises and resistance exercise, and gender in the animal studies. These factors have been mentioned in this review, and this review will be a good reference for studying how exercise can be used with therapy for treating DM.

  2. Correspondence between evoked and intrinsic functional brain network configurations.

    PubMed

    Bolt, Taylor; Nomi, Jason S; Rubinov, Mikail; Uddin, Lucina Q

    2017-04-01

    Much of the literature exploring differences between intrinsic and task-evoked brain architectures has examined changes in functional connectivity patterns between specific brain regions. While informative, this approach overlooks important overall functional changes in hub organization and network topology that may provide insights about differences in integration between intrinsic and task-evoked states. Examination of changes in overall network organization, such as a change in the concentration of hub nodes or a quantitative change in network organization, is important for understanding the underlying processes that differ between intrinsic and task-evoked brain architectures. The present study used graph-theoretical techniques applied to publicly available neuroimaging data collected from a large sample of individuals (N = 202), and a within-subject design where resting-state and several task scans were collected from each participant as part of the Human Connectome Project. We demonstrate that differences between intrinsic and task-evoked brain networks are characterized by a task-general shift in high-connectivity hubs from primarily sensorimotor/auditory processing areas during the intrinsic state to executive control/salience network areas during task performance. In addition, we demonstrate that differences between intrinsic and task-evoked architectures are associated with changes in overall network organization, such as increases in network clustering, global efficiency and integration between modules. These findings offer a new perspective on the principles guiding functional brain organization by identifying unique and divergent properties of overall network organization between the resting-state and task performance. Hum Brain Mapp 38:1992-2007, 2017. © 2017 Wiley Periodicals, Inc.

  3. Complex function in the dynamic brain. Comment on “Understanding brain networks and brain organization” by Luiz Pessoa

    NASA Astrophysics Data System (ADS)

    Anderson, Michael L.

    2014-09-01

    There is much to commend in this excellent overview of the progress we've made toward-and the challenges that remain for-developing an empirical framework for neuroscience that is adequate to the dynamic complexity of the brain [17]. Here I will limit myself first to highlighting the concept of dynamic affiliation, which I take to be the central feature of the functional architecture of the brain, and second to clarifying Pessoa's brief discussion of the ontology of cognition, to be sure readers appreciate this crucial issue.

  4. Tesmilifene modifies brain endothelial functions and opens the blood-brain/blood-glioma barrier.

    PubMed

    Walter, Fruzsina R; Veszelka, Szilvia; Pásztói, Mária; Péterfi, Zoltán A; Tóth, András; Rákhely, Gábor; Cervenak, László; Ábrahám, Csongor S; Deli, Mária A

    2015-09-01

    Tesmilifene, a tamoxifen analog with antihistamine action, has chemopotentiating properties in experimental and clinical cancer studies. In our previous works, tesmilifene increased the permeability of the blood-brain barrier (BBB) in animal and culture models. Our aim was to investigate the effects of tesmilifene on brain microvessel permeability in the rat RG2 glioma model and to reveal its mode of action in brain endothelial cells. Tesmilifene significantly increased fluorescein extravasation in the glioma. Short-term treatment with tesmilifene reduced the resistance and increased the permeability for marker molecules in a rat triple co-culture BBB model. Tesmilifene also affected the barrier integrity in brain endothelial cells co-cultured with RG2 glioblastoma cells. Tesmilifene inhibited the activity of P-glycoprotein and multidrug resistance-associated protein-1 efflux pumps and down-regulated the mRNA expression of tight junction proteins, efflux pumps, solute carriers, and metabolic enzymes important for BBB functions. Among the possible signaling pathways that regulate BBB permeability, tesmilifene activated the early nuclear translocation of NFκB. The MAPK/ERK and PI3K/Akt kinase pathways were also involved. We demonstrate for the first time that tesmilifene increases permeability marker molecule extravasation in glioma and inhibits efflux pump activity in brain endothelial cells, which may have therapeutic relevance. Tesmilifene, a chemopotentiator in experimental and clinical cancer studies increases vascular permeability in RG2 glioma in rats and permeability for marker molecules in a culture model of the blood-brain barrier. Tesmilifene inhibits the activity of efflux pumps and down-regulates the mRNA expression of tight junction proteins, transporters, and metabolic enzymes important for the blood-brain barrier functions, which may have therapeutic relevance.

  5. Functional MRI during Hippocampal Deep Brain Stimulation in the Healthy Rat Brain

    PubMed Central

    Van Den Berge, Nathalie; Vanhove, Christian; Descamps, Benedicte; Dauwe, Ine; van Mierlo, Pieter; Vonck, Kristl; Keereman, Vincent; Raedt, Robrecht; Boon, Paul; Van Holen, Roel

    2015-01-01

    Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were <0.05 after correction for multiple comparisons. Our data indicate that real-time hippocampal DBS evokes a bilateral BOLD response in hippocampal and other mesolimbic structures, depending on the applied stimulation intensity. We conclude that simultaneous DBS and fMRI can be used to detect local and whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploration of cerebral changes in response to DBS for both preclinical and clinical DBS. PMID:26193653

  6. 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.

  7. Cross-hemispheric functional connectivity in the human fetal brain.

    PubMed

    Thomason, Moriah E; Dassanayake, Maya T; Shen, Stephen; Katkuri, Yashwanth; Alexis, Mitchell; Anderson, Amy L; Yeo, Lami; Mody, Swati; Hernandez-Andrade, Edgar; Hassan, Sonia S; Studholme, Colin; Jeong, Jeong-Won; Romero, Roberto

    2013-02-20

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

  8. Cross-hemispheric functional connectivity in the human fetal brain

    PubMed Central

    Thomason, ME; Dassanayake, MT; Shen, S; Katkuri, Y; Alexis, M; Anderson, AL; Yeo, L; Mody, S; Hernandez-Andrade, E; Hassan, SS; Studholme, C; Jeong, JW; Romero, R

    2013-01-01

    Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC. PMID:23427244

  9. 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.

  10. 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.

  11. Mapping Multiplex Hubs in Human Functional Brain Networks

    PubMed Central

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

    2016-01-01

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

  12. 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

  13. Functional MRI and intraoperative brain mapping to evaluate brain plasticity in patients with brain tumours and hemiparesis

    PubMed Central

    Roux, F; Boulanouar, K; Ibarrola, D; Tremoulet, M; Chollet, F; Berry, I

    2000-01-01

    OBJECTIVE—To support the hypothesis about the potential compensatory role of ipsilateral corticofugal pathways when the contralateral pathways are impaired by brain tumours.
METHODS—Retrospective analysis was carried out on the results of functional MRI (fMRI) of a selected group of five paretic patients with Rolandic brain tumours who exhibited an abnormally high ipsilateral/contralateral ratio of activation—that is, movements of the paretic hand activated predominately the ipsilateral cortex. Brain activation was achieved with a flexion extension of the fingers. Statistical parametric activation was obtained using a t test and a threshold of p<0.001. These patients, candidates for tumour resection, also underwent cortical intraoperative stimulation that was correlated to the fMRI spatial data using three dimensional reconstructions of the brain. Three patients also had postoperative control fMRI.
RESULTS—The absence of fMRI activation of the primary sensorimotor cortex normally innervating the paretic hand for the threshold chosen, was correlated with completely negative cortical responses of the cortical hand area during the operation. The preoperative fMRI activation of these patients predominantly found in the ipsilateral frontal and primary sensorimotor cortices could be related to the residual ipsilateral hand function. Postoperatively, the fMRI activation returned to more classic patterns of activation, reflecting the consequences of therapy.
CONCLUSION—In paretic patients with brain tumours, ipsilateral control could be implicated in the residual hand function, when the normal primary pathways are impaired. The possibility that functional tissue still remains in the peritumorous sensorimotor cortex even when the preoperative fMRI and the cortical intraoperative stimulations are negative, should be taken into account when planning the tumour resection and during the operation.

 PMID:10990503

  14. Partial sleep in the context of augmentation of brain function.

    PubMed

    Pigarev, Ivan N; Pigareva, Marina L

    2014-01-01

    Inability to solve complex problems or errors in decision making is often attributed to poor brain processing, and raises the issue of brain augmentation. Investigation of neuronal activity in the cerebral cortex in the sleep-wake cycle offers insights into the mechanisms underlying the reduction in mental abilities for complex problem solving. Some cortical areas may transit into a sleep state while an organism is still awake. Such local sleep would reduce behavioral ability in the tasks for which the sleeping areas are crucial. The studies of this phenomenon have indicated that local sleep develops in high order cortical areas. This is why complex problem solving is mostly affected by local sleep, and prevention of local sleep might be a potential way of augmentation of brain function. For this approach to brain augmentation not to entail negative consequences for the organism, it is necessary to understand the functional role of sleep. Our studies have given an unexpected answer to this question. It was shown that cortical areas that process signals from extero- and proprioreceptors during wakefulness, switch to the processing of interoceptive information during sleep. It became clear that during sleep all "computational power" of the brain is directed to the restoration of the vital functions of internal organs. These results explain the logic behind the initiation of total and local sleep. Indeed, a mismatch between the current parameters of any visceral system and the genetically determined normal range would provide the feeling of tiredness, or sleep pressure. If an environmental situation allows falling asleep, the organism would transit to a normal total sleep in all cortical areas. However, if it is impossible to go to sleep immediately, partial sleep may develop in some cortical areas in the still behaviorally awake organism. This local sleep may reduce both the "intellectual power" and the restorative function of sleep for visceral organs.

  15. Partial sleep in the context of augmentation of brain function

    PubMed Central

    Pigarev, Ivan N.; Pigareva, Marina L.

    2014-01-01

    Inability to solve complex problems or errors in decision making is often attributed to poor brain processing, and raises the issue of brain augmentation. Investigation of neuronal activity in the cerebral cortex in the sleep-wake cycle offers insights into the mechanisms underlying the reduction in mental abilities for complex problem solving. Some cortical areas may transit into a sleep state while an organism is still awake. Such local sleep would reduce behavioral ability in the tasks for which the sleeping areas are crucial. The studies of this phenomenon have indicated that local sleep develops in high order cortical areas. This is why complex problem solving is mostly affected by local sleep, and prevention of local sleep might be a potential way of augmentation of brain function. For this approach to brain augmentation not to entail negative consequences for the organism, it is necessary to understand the functional role of sleep. Our studies have given an unexpected answer to this question. It was shown that cortical areas that process signals from extero- and proprioreceptors during wakefulness, switch to the processing of interoceptive information during sleep. It became clear that during sleep all “computational power” of the brain is directed to the restoration of the vital functions of internal organs. These results explain the logic behind the initiation of total and local sleep. Indeed, a mismatch between the current parameters of any visceral system and the genetically determined normal range would provide the feeling of tiredness, or sleep pressure. If an environmental situation allows falling asleep, the organism would transit to a normal total sleep in all cortical areas. However, if it is impossible to go to sleep immediately, partial sleep may develop in some cortical areas in the still behaviorally awake organism. This local sleep may reduce both the “intellectual power” and the restorative function of sleep for visceral organs. PMID

  16. Acetyl-L-carnitine improves aged brain function.

    PubMed

    Kobayashi, Satoru; Iwamoto, Machiko; Kon, Kazuo; Waki, Hatsue; Ando, Susumu; Tanaka, Yasukazu

    2010-07-01

    The effects of acetyl-L-carnitine (ALCAR), an acetyl derivative of L-carnitine, on memory and learning capacity and on brain synaptic functions of aged rats were examined. Male Fischer 344 rats were given ALCAR (100 mg/kg bodyweight) per os for 3 months and were subjected to the Hebb-Williams tasks and AKON-1 task to assess their learning capacity. Cholinergic activities were determined with synaptosomes isolated from brain cortices of the rats. Choline parameters, the high-affinity choline uptake, acetylcholine (ACh) synthesis and depolarization-evoked ACh release were all enhanced in the ALCAR group. An increment of depolarization-induced calcium ion influx into synaptosomes was also evident in rats given ALCAR. Electrophysiological studies using hippocampus slices indicated that the excitatory postsynaptic potential slope and population spike size were both increased in ALCAR-treated rats. These results indicate that ALCAR increases synaptic neurotransmission in the brain and consequently improves learning capacity in aging rats.

  17. [Effects of anesthetics on the higher brain function].

    PubMed

    Sobue, Kazuya; Note, Hideaki; So, MinHye

    2014-11-01

    Number of surgeries for the elderly is increasing year by year. Postoperative cognitive dysfunction, POCD, and delirium are typical failure's of higher brain function after surgery. The mechanism of POCD and delirium has been suggested to be associated with inflammation, but its details are unknown. Alzheimer's disease leads to derangement in cognitive function. The number of patients with Alzheimer's disease is expected to increase rapidly. There is a possibility that inhalation anesthesia exacerbates the pathology of patients with impaired higher brain function such as Alzheimer's disease. On the other hand, the another suspect, that propofol is safe. However, it should be recognized that these results became clear by basic research. Further clinical study is required.

  18. Two distinct forms of functional lateralization in the human brain

    PubMed Central

    Gotts, Stephen J.; Jo, Hang Joon; Wallace, Gregory L.; Saad, Ziad S.; Cox, Robert W.; Martin, Alex

    2013-01-01

    The hemispheric lateralization of certain faculties in the human brain has long been held to be beneficial for functioning. However, quantitative relationships between the degree of lateralization in particular brain regions and the level of functioning have yet to be established. Here we demonstrate that two distinct forms of functional lateralization are present in the left vs. the right cerebral hemisphere, with the left hemisphere showing a preference to interact more exclusively with itself, particularly for cortical regions involved in language and fine motor coordination. In contrast, right-hemisphere cortical regions involved in visuospatial and attentional processing interact in a more integrative fashion with both hemispheres. The degree of lateralization present in these distinct systems selectively predicted behavioral measures of verbal and visuospatial ability, providing direct evidence that lateralization is associated with enhanced cognitive ability. PMID:23959883

  19. Dynamic reorganization of intrinsic functional networks in the mouse brain.

    PubMed

    Grandjean, Joanes; Preti, Maria Giulia; Bolton, Thomas A W; Buerge, Michaela; Seifritz, Erich; Pryce, Christopher R; Van De Ville, Dimitri; Rudin, Markus

    2017-03-14

    Functional connectivity (FC) derived from resting-state functional magnetic resonance imaging (rs-fMRI) allows for the integrative study of neuronal processes at a macroscopic level. The majority of studies to date have assumed stationary interactions between brain regions, without considering the dynamic aspects of network organization. Only recently has the latter received increased attention, predominantly in human studies. Applying dynamic FC (dFC) analysis to mice is attractive given the relative simplicity of the mouse brain and the possibility to explore mechanisms underlying network dynamics using pharmacological, environmental or genetic interventions. Therefore, we have evaluated the feasibility and research potential of mouse dFC using the interventions of social stress or anesthesia duration as two case-study examples. By combining a sliding-window correlation approach with dictionary learning, several dynamic functional states (dFS) with a complex organization were identified, exhibiting highly dynamic inter- and intra-modular interactions. Each dFS displayed a high degree of reproducibility upon changes in analytical parameters and across datasets. They fluctuated at different degrees as a function of anesthetic depth, and were sensitive indicators of pathology as shown for the chronic psychosocial stress mouse model of depression. Dynamic functional states are proposed to make a major contribution to information integration and processing in the healthy and diseased brain.

  20. Exercise-mimetic AICAR transiently benefits brain function.

    PubMed

    Guerrieri, Davide; van Praag, Henriette

    2015-07-30

    Exercise enhances learning and memory in animals and humans. The role of peripheral factors that may trigger the beneficial effects of running on brain function has been sparsely examined. In particular, it is unknown whether AMP-kinase (AMPK) activation in muscle can predict enhancement of brain plasticity. Here we compare the effects of running and administration of AMPK agonist 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR, 500 mg/kg), for 3, 7 or 14 days in one-month-old male C57BL/6J mice, on muscle AMPK signaling. At the time-points where we observed equivalent running- and AICAR-induced muscle pAMPK levels (7 and 14 days), cell proliferation, synaptic plasticity and gene expression, as well as markers of oxidative stress and inflammation in the dentate gyrus (DG) of the hippocampus and lateral entorhinal cortex (LEC) were evaluated. At the 7-day time-point, both regimens increased new DG cell number and brain-derived neurotrophic factor (BDNF) protein levels. Furthermore, microarray analysis of DG and LEC tissue showed a remarkable overlap between running and AICAR in the regulation of neuronal, mitochondrial and metabolism related gene classes. Interestingly, while similar outcomes for both treatments were stable over time in muscle, in the brain an inversion occurred at fourteen days. The compound no longer increased DG cell proliferation or neurotrophin levels, and upregulated expression of apoptotic genes and inflammatory cytokine interleukin-1β. Thus, an exercise mimetic that produces changes in muscle consistent with those of exercise does not have the same sustainable positive effects on the brain, indicating that only running consistently benefits brain function.

  1. Thyroid hormone receptors in brain development and function.

    PubMed

    Bernal, Juan

    2007-03-01

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

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

    PubMed Central

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

    2016-01-01

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

  3. Functional brain networks associated with eating behaviors in obesity.

    PubMed

    Park, Bo-Yong; Seo, Jongbum; Park, Hyunjin

    2016-03-31

    Obesity causes critical health problems including diabetes and hypertension that affect billions of people worldwide. Obesity and eating behaviors are believed to be closely linked but their relationship through brain networks has not been fully explored. We identified functional brain networks associated with obesity and examined how the networks were related to eating behaviors. Resting state functional magnetic resonance imaging (MRI) scans were obtained for 82 participants. Data were from an equal number of people of healthy weight (HW) and non-healthy weight (non-HW). Connectivity matrices were computed with spatial maps derived using a group independent component analysis approach. Brain networks and associated connectivity parameters with significant group-wise differences were identified and correlated with scores on a three-factor eating questionnaire (TFEQ) describing restraint, disinhibition, and hunger eating behaviors. Frontoparietal and cerebellum networks showed group-wise differences between HW and non-HW groups. Frontoparietal network showed a high correlation with TFEQ disinhibition scores. Both frontoparietal and cerebellum networks showed a high correlation with body mass index (BMI) scores. Brain networks with significant group-wise differences between HW and non-HW groups were identified. Parts of the identified networks showed a high correlation with eating behavior scores.

  4. Meta-analysis of functional brain imaging in specific phobia.

    PubMed

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

    2013-07-01

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

  5. Sleep restriction impairs blood-brain barrier function.

    PubMed

    He, Junyun; Hsuchou, Hung; He, Yi; Kastin, Abba J; Wang, Yuping; Pan, Weihong

    2014-10-29

    The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice.

  6. Functional brain networks associated with eating behaviors in obesity

    PubMed Central

    Park, Bo-yong; Seo, Jongbum; Park, Hyunjin

    2016-01-01

    Obesity causes critical health problems including diabetes and hypertension that affect billions of people worldwide. Obesity and eating behaviors are believed to be closely linked but their relationship through brain networks has not been fully explored. We identified functional brain networks associated with obesity and examined how the networks were related to eating behaviors. Resting state functional magnetic resonance imaging (MRI) scans were obtained for 82 participants. Data were from an equal number of people of healthy weight (HW) and non-healthy weight (non-HW). Connectivity matrices were computed with spatial maps derived using a group independent component analysis approach. Brain networks and associated connectivity parameters with significant group-wise differences were identified and correlated with scores on a three-factor eating questionnaire (TFEQ) describing restraint, disinhibition, and hunger eating behaviors. Frontoparietal and cerebellum networks showed group-wise differences between HW and non-HW groups. Frontoparietal network showed a high correlation with TFEQ disinhibition scores. Both frontoparietal and cerebellum networks showed a high correlation with body mass index (BMI) scores. Brain networks with significant group-wise differences between HW and non-HW groups were identified. Parts of the identified networks showed a high correlation with eating behavior scores. PMID:27030024

  7. Network functional connectivity and whole-brain functional connectomics to investigate cognitive decline in neurodegenerative conditions.

    PubMed

    Dipasquale, O; Cercignani, Mara

    Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain's intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC. In this paper we provide an overview of these two techniques and some examples of their clinical applications in the most common neurodegenerative disorders associated with cognitive decline, including mild cognitive impairment, Alzheimer's disease, Parkinson's disease, dementia with Lewy Bodies and behavioral variant frontotemporal dementia.

  8. Functional magnetic resonance imaging of mild traumatic brain injury.

    PubMed

    Mayer, Andrew R; Bellgowan, Patrick S F; Hanlon, Faith M

    2015-02-01

    Functional magnetic resonance imaging (fMRI) offers great promise for elucidating the neuropathology associated with a single or repetitive mild traumatic brain injury (mTBI). The current review discusses the physiological underpinnings of the blood-oxygen level dependent response and how trauma affects the signal. Methodological challenges associated with fMRI data analyses are considered next, followed by a review of current mTBI findings. The majority of evoked studies have examined working memory and attentional functioning, with results suggesting a complex relationship between cognitive load/attentional demand and neuronal activation. Researchers have more recently investigated how brain trauma affects functional connectivity, and the benefits/drawbacks of evoked and functional connectivity studies are also discussed. The review concludes by discussing the major clinical challenges associated with fMRI studies of brain-injured patients, including patient heterogeneity and variations in scan-time post-injury. We conclude that the fMRI signal represents a complex filter through which researchers can measure the physiological correlates of concussive symptoms, an important goal for the burgeoning field of mTBI research.

  9. Large-scale brain networks in affective and social neuroscience: towards an integrative functional architecture of the brain.

    PubMed

    Barrett, Lisa Feldman; Satpute, Ajay Bhaskar

    2013-06-01

    Understanding how a human brain creates a human mind ultimately depends on mapping psychological categories and concepts to physical measurements of neural response. Although it has long been assumed that emotional, social, and cognitive phenomena are realized in the operations of separate brain regions or brain networks, we demonstrate that it is possible to understand the body of neuroimaging evidence using a framework that relies on domain general, distributed structure-function mappings. We review current research in affective and social neuroscience and argue that the emerging science of large-scale intrinsic brain networks provides a coherent framework for a domain-general functional architecture of the human brain.

  10. Resting-state functional brain connectivity: lessons from functional near-infrared spectroscopy.

    PubMed

    Niu, Haijing; He, Yong

    2014-04-01

    Resting-state functional near-infrared spectroscopy (R-fNIRS) is an active area of interest and is currently attracting considerable attention as a new imaging tool for the study of resting-state brain function. Using variations in hemodynamic concentration signals, R-fNIRS measures the brain's low-frequency spontaneous neural activity, combining the advantages of portability, low-cost, high temporal sampling rate and less physical burden to participants. The temporal synchronization of spontaneous neuronal activity in anatomically separated regions is referred to as resting-state functional connectivity (RSFC). In the past several years, an increasing body of R-fNIRS RSFC studies has led to many important findings about functional integration among local or whole-brain regions by measuring inter-regional temporal synchronization. Here, we summarize recent advances made in the R-fNIRS RSFC methodologies, from the detection of RSFC (e.g., seed-based correlation analysis, independent component analysis, whole-brain correlation analysis, and graph-theoretical topological analysis), to the assessment of RSFC performance (e.g., reliability, repeatability, and validity), to the application of RSFC in studying normal development and brain disorders. The literature reviewed here suggests that RSFC analyses based on R-fNIRS data are valid and reliable for the study of brain function in healthy and diseased populations, thus providing a promising imaging tool for cognitive science and clinics.

  11. Functional connectivity networks for preoperative brain mapping in neurosurgery.

    PubMed

    Hart, Michael G; Price, Stephen J; Suckling, John

    2016-08-26

    OBJECTIVE Resection of focal brain lesions involves maximizing the resection while preserving brain function. Mapping brain function has entered a new era focusing on distributed connectivity networks at "rest," that is, in the absence of a specific task or stimulus, requiring minimal participant engagement. Central to this frame shift has been the development of methods for the rapid assessment of whole-brain connectivity with functional MRI (fMRI) involving blood oxygenation level-dependent imaging. The authors appraised the feasibility of fMRI-based mapping of a repertoire of functional connectivity networks in neurosurgical patients with focal lesions and the potential benefits of resting-state connectivity mapping for surgical planning. METHODS Resting-state fMRI sequences with a 3-T scanner and multiecho echo-planar imaging coupled to independent component analysis were acquired preoperatively from 5 study participants who had a right temporoparietooccipital glioblastoma. Seed-based functional connectivity analysis was performed with InstaCorr. Network identification focused on 7 major functional connectivity networks described in the literature and a putative language network centered on Broca's area. RESULTS All 8 functional connectivity networks were identified in each participant. Tumor-related topological changes to the default mode network were observed in all participants. In addition, each participant had at least 1 other abnormal network, and each network was abnormal in at least 1 participant. Individual patterns of network irregularities were identified with a qualitative approach and included local displacement due to mass effect, loss of a functional network component, and recruitment of new regions. CONCLUSIONS Resting-state fMRI can reliably and rapidly detect common functional connectivity networks in patients with glioblastoma and also has sufficient sensitivity for identifying patterns of network alterations. Mapping of functional

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  13. Executive control- and reward-related neural processes associated with the opportunity to engage in voluntary dishonest moral decision making.

    PubMed

    Hu, Xiaoqing; Pornpattananangkul, Narun; Nusslock, Robin

    2015-06-01

    Research has begun to examine the neurocognitive processes underlying voluntary moral decision making, which involves engaging in honest or dishonest behavior in a setting in which the individual is free to make his or her own moral decisions. Employing event-related potentials, we measured executive control-related and reward-related neural processes during an incentivized coin-guessing task in which participants had the opportunity to voluntarily engage in dishonest behavior, by overreporting their wins to maximize earnings. We report four primary findings: First, the opportunity to deceive recruited executive control processes involving conflict monitoring and conflict resolution, as evidenced by a higher N2 and a smaller P3. Second, processing the outcome of the coin flips engaged reward-related processes, as evidenced by a larger medial feedback negativity (MFN) for incorrect (loss) than for correct (win) guesses, reflecting a reward prediction error signal. Third, elevated executive control-related neural activity reflecting conflict resolution (i.e., an attenuated executive control P3) predicted a greater likelihood of engaging in overall deceptive behavior. Finally, whereas elevated reward-related neural activity (the reward P3) was associated with a greater likelihood of engaging in overall deceptive behavior, an elevated reward prediction error signal (MFN difference score) predicted increased trial-by-trial moral behavioral adjustment (i.e., a greater likelihood to overreport wins following a previous honest loss than following a previous honest win trial). Collectively, these findings suggest that both executive control- and reward-related neural processes are implicated in moral decision making.

  14. Control of Brain Development, Function, and Behavior by the Microbiome

    PubMed Central

    Sampson, Timothy R.; Mazmanian, Sarkis K.

    2015-01-01

    Animals share an intimate and life-long partnership with a myriad of resident microbial species, collectively referred to as the microbiota. Symbiotic microbes have been shown to regulate nutrition and metabolism, and are critical for the development and function of the immune system. More recently, studies have suggested that gut bacteria can impact neurological outcomes – altering behavior and potentially affecting the onset and/or severity of nervous system disorders. In this review, we highlight emerging evidence that the microbiome extends its influence to the brain via various pathways connecting the gut to the central nervous system. While understanding and appreciation of a gut microbial impact on neurological function is nascent, unraveling gut-microbiome-brain connections holds the promise of transforming the neurosciences and revealing potentially novel etiologies for psychiatric and neurodegenerative disorders. PMID:25974299

  15. Electrophysiological assessment of brain function in severe malnutrition.

    PubMed

    Robinson, S; Young, R E; Golden, M H

    1995-11-01

    Brain function in 10 severely malnourished children and matched controls was assessed using spectral analysis of electroencephalographic responses to photic driving during slow-wave sleep. The percentage power in the classical EEG broad-band domains was derived from temporo-occipital records. The malnourished group (5-23 months old; z-score height-for-age -3.2 +/- 0.3, weight-for-height -2.5 +/- 0.3) were tested on admission and on discharge from hospital. No significant differences were found between admission and discharge. Significant differences were found between malnourished and control groups, in the alpha 1 band in the undriven EEG, and in the alpha/beta 1 power ratio while driving at 8 Hz. These electrophysiological abnormalities, persisting despite somatic rehabilitation, must be associated with the chronic rather than the acute aspects of malnutrition, and can index the deviation of brain function from normality.

  16. Empirical Network Model of Human Higher Cognitive Brain Functions

    DTIC Science & Technology

    1990-03-31

    forms as val. and to 8 lags ( -,-/- 62 msec) for the 4-7 potentials, in keeping with common usage. Hz-filtered intervals. The ERC was defined as the...Functional topography of the graded. Further refinement of the techniques used human brain. In: G. Pfurtscheller and F.H. Lopes da Silva (Eds...sufficiently dense spatial sampling and techniques of spatial enhancement such as Laplacian Transform. Classical neurological and neurolinguistic thinking

  17. Global features of functional brain networks change with contextual disorder

    PubMed Central

    Andric, Michael; Hasson, Uri

    2015-01-01

    It is known that features of stimuli in the environment affect the strength of functional connectivity in the human brain. However, investigations to date have not converged in determining whether these also impact functional networks' global features, such as modularity strength, number of modules, partition structure, or degree distributions. We hypothesized that one environmental attribute that may strongly impact global features is the temporal regularity of the environment, as prior work indicates that differences in regularity impact regions involved in sensory, attentional and memory processes. We examined this with an fMRI study, in which participants passively listened to tonal series that had identical physical features and differed only in their regularity, as defined by the strength of transition structure between tones. We found that series-regularity induced systematic changes to global features of functional networks, including modularity strength, number of modules, partition structure, and degree distributions. In tandem, we used a novel node-level analysis to determine the extent to which brain regions maintained their within-module connectivity across experimental conditions. This analysis showed that primary sensory regions and those associated with default-mode processes are most likely to maintain their within-module connectivity across conditions, whereas prefrontal regions are least likely to do so. Our work documents a significant capacity for global-level brain network reorganization as a function of context. These findings suggest that modularity and other core, global features, while likely constrained by white-matter structural brain connections, are not completely determined by them. PMID:25988223

  18. 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.

  19. Imaging emotional brain functions: conceptual and methodological issues.

    PubMed

    Peper, Martin

    2006-06-01

    This article reviews the psychophysiological and brain imaging literature on emotional brain function from a methodological point of view. The difficulties in defining, operationalising and measuring emotional activation and, in particular, aversive learning will be considered. Emotion is a response of the organism during an episode of major significance and involves physiological activation, motivational, perceptual, evaluative and learning processes, motor expression, action tendencies and monitoring/subjective feelings. Despite the advances in assessing the physiological correlates of emotional perception and learning processes, a critical appraisal shows that functional neuroimaging approaches encounter methodological difficulties regarding measurement precision (e.g., response scaling and reproducibility) and validity (e.g., response specificity, generalisation to other paradigms, subjects or settings). Since emotional processes are not only the result of localised but also of widely distributed activation, a more representative model of assessment is needed that systematically relates the hierarchy of high- and low-level emotion constructs with the corresponding patterns of activity and functional connectivity of the brain.

  20. Characterizing Resting-State Brain Function Using Arterial Spin Labeling.

    PubMed

    Chen, J Jean; Jann, Kay; Wang, Danny J J

    2015-11-01

    Arterial spin labeling (ASL) is an increasingly established magnetic resonance imaging (MRI) technique that is finding broader applications in studying the healthy and diseased brain. This review addresses the use of ASL to assess brain function in the resting state. Following a brief technical description, we discuss the use of ASL in the following main categories: (1) resting-state functional connectivity (FC) measurement: the use of ASL-based cerebral blood flow (CBF) measurements as an alternative to the blood oxygen level-dependent (BOLD) technique to assess resting-state FC; (2) the link between network CBF and FC measurements: the use of network CBF as a surrogate of the metabolic activity within corresponding networks; and (3) the study of resting-state dynamic CBF-BOLD coupling and cerebral metabolism: the use of dynamic CBF information obtained using ASL to assess dynamic CBF-BOLD coupling and oxidative metabolism in the resting state. In addition, we summarize some future challenges and interesting research directions for ASL, including slice-accelerated (multiband) imaging as well as the effects of motion and other physiological confounds on perfusion-based FC measurement. In summary, this work reviews the state-of-the-art of ASL and establishes it as an increasingly viable MRI technique with high translational value in studying resting-state brain function.

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

    PubMed

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

    2017-03-01

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

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

    PubMed Central

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

    2017-01-01

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

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

    MedlinePlus

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

  4. A Mapping Between Structural and Functional Brain Networks.

    PubMed

    Meier, Jil; Tewarie, Prejaas; Hillebrand, Arjan; Douw, Linda; van Dijk, Bob W; Stufflebeam, Steven M; Van Mieghem, Piet

    2016-05-01

    The relationship between structural and functional brain networks is still highly debated. Most previous studies have used a single functional imaging modality to analyze this relationship. In this work, we use multimodal data, from functional MRI, magnetoencephalography, and diffusion tensor imaging, and assume that there exists a mapping between the connectivity matrices of the resting-state functional and structural networks. We investigate this mapping employing group averaged as well as individual data. We indeed find a significantly high goodness of fit level for this structure-function mapping. Our analysis suggests that a functional connection is shaped by all walks up to the diameter in the structural network in both modality cases. When analyzing the inverse mapping, from function to structure, longer walks in the functional network also seem to possess minor influence on the structural connection strengths. Even though similar overall properties for the structure-function mapping are found for different functional modalities, our results indicate that the structure-function relationship is modality dependent.

  5. Functional magnetic resonance imaging of the brain: a quick review.

    PubMed

    Vaghela, Viratsinh; Kesavadas, Chandrasekharan; Thomas, Bejoy

    2010-01-01

    Ability to non-invasively map the hemodynamic changes occurring focally in areas of brain involved in various motor, sensory and cognitive functions by functional magnetic resonance imaging (fMRI) has revolutionized research in neuroscience in the last two decades. This technique has already gained clinical use especially in pre-surgical evaluation of epilepsy and neurosurgical planning of resection of mass lesions adjacent to eloquent cortex. In this review we attempt to illustrate basic principles and techniques of fMRI, its applications, practical points to consider while performing and evaluating clinical fMRI and its limitations.

  6. Differential Effects of Brain Disorders on Structural and Functional Connectivity

    PubMed Central

    Vega-Pons, Sandro; Olivetti, Emanuele; Avesani, Paolo; Dodero, Luca; Gozzi, Alessandro; Bifone, Angelo

    2017-01-01

    Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate. PMID:28119556

  7. Synchronization-based approach for detecting functional activation of brain

    NASA Astrophysics Data System (ADS)

    Hong, Lei; Cai, Shi-Min; Zhang, Jie; Zhuo, Zhao; Fu, Zhong-Qian; Zhou, Pei-Ling

    2012-09-01

    In this paper, we investigate a synchronization-based, data-driven clustering approach for the analysis of functional magnetic resonance imaging (fMRI) data, and specifically for detecting functional activation from fMRI data. We first define a new measure of similarity between all pairs of data points (i.e., time series of voxels) integrating both complete phase synchronization and amplitude correlation. These pairwise similarities are taken as the coupling between a set of Kuramoto oscillators, which in turn evolve according to a nearest-neighbor rule. As the network evolves, similar data points naturally synchronize with each other, and distinct clusters will emerge. The clustering behavior of the interaction network of the coupled oscillators, therefore, mirrors the clustering property of the original multiple time series. The clustered regions whose cross-correlation coefficients are much greater than other regions are considered as the functionally activated brain regions. The analysis of fMRI data in auditory and visual areas shows that the recognized brain functional activations are in complete correspondence with those from the general linear model of statistical parametric mapping, but with a significantly lower time complexity. We further compare our results with those from traditional K-means approach, and find that our new clustering approach can distinguish between different response patterns more accurately and efficiently than the K-means approach, and therefore more suitable in detecting functional activation from event-related experimental fMRI data.

  8. Differential Effects of Brain Disorders on Structural and Functional Connectivity.

    PubMed

    Vega-Pons, Sandro; Olivetti, Emanuele; Avesani, Paolo; Dodero, Luca; Gozzi, Alessandro; Bifone, Angelo

    2016-01-01

    Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate.

  9. Hypothalamic-Pituitary Function in Brain Death: A Review.

    PubMed

    Nair-Collins, Michael; Northrup, Jesse; Olcese, James

    2016-01-01

    The Uniform Determination of Death Act (UDDA) states that an individual is dead when "all functions of the entire brain" have ceased irreversibly. However, it has been questioned whether some functions of the hypothalamus, particularly osmoregulation, can continue after the clinical diagnosis of brain death (BD). In order to learn whether parts of the hypothalamus can continue to function after the diagnosis of BD, we performed 2 separate systematic searches of the MEDLINE database, corresponding to the functions of the posterior and anterior pituitary. No meta-analysis is possible due to nonuniformity in the clinical literature. However, some modest generalizations can reasonably be drawn from a narrative review and from anatomic considerations that explain why these findings should be expected. We found evidence suggesting the preservation of hypothalamic function, including secretion of hypophysiotropic hormones, responsiveness to anterior pituitary stimulation, and osmoregulation, in a substantial proportion of patients declared dead by neurological criteria. We discuss several possible explanations for these findings. We conclude by suggesting that additional clinical research with strict inclusion criteria is necessary and further that a more nuanced and forthright public dialogue is needed, particularly since standard diagnostic practices and the UDDA may not be entirely in accord.

  10. A Multivariate Granger Causality Concept towards Full Brain Functional Connectivity.

    PubMed

    Schmidt, Christoph; Pester, Britta; Schmid-Hertel, Nicole; Witte, Herbert; Wismüller, Axel; Leistritz, Lutz

    2016-01-01

    Detecting changes of spatially high-resolution functional connectivity patterns in the brain is crucial for improving the fundamental understanding of brain function in both health and disease, yet still poses one of the biggest challenges in computational neuroscience. Currently, classical multivariate Granger Causality analyses of directed interactions between single process components in coupled systems are commonly restricted to spatially low- dimensional data, which requires a pre-selection or aggregation of time series as a preprocessing step. In this paper we propose a new fully multivariate Granger Causality approach with embedded dimension reduction that makes it possible to obtain a representation of functional connectivity for spatially high-dimensional data. The resulting functional connectivity networks may consist of several thousand vertices and thus contain more detailed information compared to connectivity networks obtained from approaches based on particular regions of interest. Our large scale Granger Causality approach is applied to synthetic and resting state fMRI data with a focus on how well network community structure, which represents a functional segmentation of the network, is preserved. It is demonstrated that a number of different community detection algorithms, which utilize a variety of algorithmic strategies and exploit topological features differently, reveal meaningful information on the underlying network module structure.

  11. Abdominal Pain, the Adolescent and Altered Brain Structure and Function

    PubMed Central

    Becerra, Lino; Heinz, Nicole; Ludwick, Allison; Rasooly, Tali; Wu, Rina; Johnson, Adriana; Schechter, Neil L.; Borsook, David; Nurko, Samuel

    2016-01-01

    Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder of unknown etiology. Although relatively common in children, how this condition affects brain structure and function in a pediatric population remains unclear. Here, we investigate brain changes in adolescents with IBS and healthy controls. Imaging was performed with a Siemens 3 Tesla Trio Tim MRI scanner equipped with a 32-channel head coil. A high-resolution T1-weighted anatomical scan was acquired followed by a T2-weighted functional scan. We used a surface-based morphometric approach along with a seed-based resting-state functional connectivity (RS-FC) analysis to determine if groups differed in cortical thickness and whether areas showing structural differences also showed abnormal RS-FC patterns. Patients completed the Abdominal Pain Index and the GI Module of the Pediatric Quality of Life Inventory to assess abdominal pain severity and impact of GI symptoms on health-related quality of life (HRQOL). Disease duration and pain intensity were also assessed. Pediatric IBS patients, relative to controls, showed cortical thickening in the posterior cingulate (PCC), whereas cortical thinning in posterior parietal and prefrontal areas were found, including the dorsolateral prefrontal cortex (DLPFC). In patients, abdominal pain severity was related to cortical thickening in the intra-abdominal area of the primary somatosensory cortex (SI), whereas HRQOL was associated with insular cortical thinning. Disease severity measures correlated with cortical thickness in bilateral DLPFC and orbitofrontal cortex. Patients also showed reduced anti-correlations between PCC and DLPFC compared to controls, a finding that may reflect aberrant connectivity between default mode and cognitive control networks. We are the first to demonstrate concomitant structural and functional brain changes associated with abdominal pain severity, HRQOL related to GI-specific symptoms, and disease-specific measures in

  12. 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.

  13. Automated Talairach atlas labels for functional brain mapping.

    PubMed

    Lancaster, J L; Woldorff, M G; Parsons, L M; Liotti, M; Freitas, C S; Rainey, L; Kochunov, P V; Nickerson, D; Mikiten, S A; Fox, P T

    2000-07-01

    An automated coordinate-based system to retrieve brain labels from the 1988 Talairach Atlas, called the Talairach Daemon (TD), was previously introduced [Lancaster et al., 1997]. In the present study, the TD system and its 3-D database of labels for the 1988 Talairach atlas were tested for labeling of functional activation foci. TD system labels were compared with author-designated labels of activation coordinates from over 250 published functional brain-mapping studies and with manual atlas-derived labels from an expert group using a subset of these activation coordinates. Automated labeling by the TD system compared well with authors' labels, with a 70% or greater label match averaged over all locations. Author-label matching improved to greater than 90% within a search range of +/-5 mm for most sites. An adaptive grey matter (GM) range-search utility was evaluated using individual activations from the M1 mouth region (30 subjects, 52 sites). It provided an 87% label match to Brodmann area labels (BA 4 & BA 6) within a search range of +/-5 mm. Using the adaptive GM range search, the TD system's overall match with authors' labels (90%) was better than that of the expert group (80%). When used in concert with authors' deeper knowledge of an experiment, the TD system provides consistent and comprehensive labels for brain activation foci. Additional suggested applications of the TD system include interactive labeling, anatomical grouping of activation foci, lesion-deficit analysis, and neuroanatomy education.

  14. Socioeconomic status and functional brain development - associations in early infancy.

    PubMed

    Tomalski, Przemyslaw; Moore, Derek G; Ribeiro, Helena; Axelsson, Emma L; Murphy, Elizabeth; Karmiloff-Smith, Annette; Johnson, Mark H; Kushnerenko, Elena

    2013-09-01

    Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subject comparisons of infants from low- and high-income families revealed significantly lower frontal gamma power in infants from low-income homes. Similar power differences were found when comparing infants according to maternal occupation, with lower occupational status groups yielding lower power. Infant sleep, maternal education, length of gestation, and birth weight, as well as smoke exposure and bilingualism, did not explain these differences. Our results show that the effects of socioeconomic disparities on brain activity can already be detected in early infancy, potentially pointing to very early risk for language and attention difficulties. This is the first study to reveal region-selective differences in functional brain development associated with early infancy in low-income families.

  15. Kappa-opioid receptor signaling and brain reward function

    PubMed Central

    Bruijnzeel, Adrie W.

    2009-01-01

    The dynorphin-like peptides have profound effects on the state of the brain reward system and human and animal behavior. The dynorphin-like peptides affect locomotor activity, food intake, sexual behavior, anxiety-like behavior, and drug intake. Stimulation of kappa-opioid receptors, the endogenous receptor for the dynorphin-like peptides, inhibits dopamine release in the striatum (nucleus accumbens and caudate putamen) and induces a negative mood state in humans and animals. The administration of drugs of abuse increases the release of dopamine in the striatum and mediates the concomitant release of dynorphin-like peptides in this brain region. The reviewed studies suggest that chronic drug intake leads to an upregulation of the brain dynorphin system in the striatum and in particular in the dorsal part of the striatum/caudate putamen. This might inhibit drug-induced dopamine release and provide protection against the neurotoxic effects of high dopamine levels. After the discontinuation of chronic drug intake these neuroadaptations remain unopposed which has been suggested to contribute to the negative emotional state associated with drug withdrawal and increased drug intake. Kappa-opioid receptor agonists have also been shown to inhibit calcium channels. Calcium channel inhibitors have antidepressant-like effects and inhibit the release of norepinephrine. This might explain that in some studies kappa-opioid receptor agonists attenuate nicotine and opioid withdrawal symptomatology. A better understanding of the role of dynorphins in the regulation of brain reward function might contribute to the development of novel treatments for mood disorders and other disorders that stem from a dysregulation of the brain reward system. PMID:19804796

  16. The study of brain functional connectivity in Parkinson's disease.

    PubMed

    Gao, Lin-Lin; Wu, Tao

    2016-01-01

    Parkinson's disease (PD) is a neurodegenerative disorder primarily affecting the aging population. The neurophysiological mechanisms underlying parkinsonian symptoms remain unclear. PD affects extensive neural networks and a more thorough understanding of network disruption will help bridge the gap between known pathological changes and observed clinical presentations in PD. Development of neuroimaging techniques, especially functional magnetic resonance imaging, allows for detection of the functional connectivity of neural networks in patients with PD. This review aims to provide an overview of current research involving functional network disruption in PD relating to motor and non-motor symptoms. Investigations into functional network connectivity will further our understanding of the mechanisms underlying the effectiveness of clinical interventions, such as levodopa and deep brain stimulation treatment. In addition, identification of PD-specific neural network patterns has the potential to aid in the development of a definitive diagnosis of PD.

  17. Effects of Deep Brain Stimulation on Autonomic Function

    PubMed Central

    Basiago, Adam; Binder, Devin K.

    2016-01-01

    Over the course of the development of deep brain stimulation (DBS) into a well-established therapy for Parkinson’s disease, essential tremor, and dystonia, its utility as a potential treatment for autonomic dysfunction has emerged. Dysfunction of autonomic processes is common in neurological diseases. Depending on the specific target in the brain, DBS has been shown to raise or lower blood pressure, normalize the baroreflex, to alter the caliber of bronchioles, and eliminate hyperhidrosis, all through modulation of the sympathetic nervous system. It has also been shown to improve cortical control of the bladder, directly induce or inhibit the micturition reflex, and to improve deglutition and gastric emptying. In this review, we will attempt to summarize the relevant available studies describing these effects of DBS on autonomic function, which vary greatly in character and magnitude with respect to stimulation target. PMID:27537920

  18. Microstructural and functional connectivity in the developing preterm brain.

    PubMed

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

    2011-02-01

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

  19. A propositional representation model of anatomical and functional brain data.

    PubMed

    Maturana, Pablo; Batrancourt, Bénédicte

    2011-01-01

    Networks can represent a large number of systems. Recent advances in the domain of networks have been transferred to the field of neuroscience. For example, the graph model has been used in neuroscience research as a methodological tool to examine brain networks organization, topology and complex dynamics, as well as a framework to test the structure-function hypothesis using neuroimaging data. In the current work we propose a graph-theoretical framework to represent anatomical, functional and neuropsychological assessment instruments information. On the one hand, interrelationships between anatomic elements constitute an anatomical graph. On the other hand, a functional graph contains several cognitive functions and their more elementary cognitive processes. Finally, the neuropsychological assessment instruments graph includes several neuropsychological tests and scales linked with their different sub-tests and variables. The two last graphs are connected by relations of type "explore" linking a particular instrument with the cognitive function it explores. We applied this framework to a sample of patients with focal brain damage. Each patient was related to: (i) the cerebral entities injured (assessed with structural neuroimaging data) and (ii) the neusopsychological assessment tests carried out (weight by performance). Our model offers a suitable platform to visualize patients' relevant information, facilitating the representation, standardization and sharing of clinical data. At the same time, the integration of a large number of patients in this framework will make possible to explore relations between anatomy (injured entities) and function (performance in different tests assessing different cognitive functions) and the use of neurocomputational tools for graph analysis may help diagnostic and contribute to the comprehension of neural bases of cognitive functions.

  20. 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

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

    PubMed

    Lowery, Laura Anne; Sive, Hazel

    2009-04-01

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

  2. Imaging structural and functional brain networks in temporal lobe epilepsy

    PubMed Central

    Bernhardt, Boris C.; Hong, SeokJun; Bernasconi, Andrea; Bernasconi, Neda

    2013-01-01

    Early imaging studies in temporal lobe epilepsy (TLE) focused on the search for mesial temporal sclerosis, as its surgical removal results in clinically meaningful improvement in about 70% of patients. Nevertheless, a considerable subgroup of patients continues to suffer from post-operative seizures. Although the reasons for surgical failure are not fully understood, electrophysiological and imaging data suggest that anomalies extending beyond the temporal lobe may have negative impact on outcome. This hypothesis has revived the concept of human epilepsy as a disorder of distributed brain networks. Recent methodological advances in non-invasive neuroimaging have led to quantify structural and functional networks in vivo. While structural networks can be inferred from diffusion MRI tractography and inter-regional covariance patterns of structural measures such as cortical thickness, functional connectivity is generally computed based on statistical dependencies of neurophysiological time-series, measured through functional MRI or electroencephalographic techniques. This review considers the application of advanced analytical methods in structural and functional connectivity analyses in TLE. We will specifically highlight findings from graph-theoretical analysis that allow assessing the topological organization of brain networks. These studies have provided compelling evidence that TLE is a system disorder with profound alterations in local and distributed networks. In addition, there is emerging evidence for the utility of network properties as clinical diagnostic markers. Nowadays, a network perspective is considered to be essential to the understanding of the development, progression, and management of epilepsy. PMID:24098281

  3. Network functional connectivity and whole-brain functional connectomics to investigate cognitive decline in neurodegenerative conditions

    PubMed Central

    Dipasquale, Ottavia; Cercignani, Mara

    2016-01-01

    Summary Non-invasive mapping of brain functional connectivity (FC) has played a fundamental role in neuroscience, and numerous scientists have been fascinated by its ability to reveal the brain’s intricate morphology and functional properties. In recent years, two different techniques have been developed that are able to explore FC in pathophysiological conditions and to provide simple and non-invasive biomarkers for the detection of disease onset, severity and progression. These techniques are independent component analysis, which allows a network-based functional exploration of the brain, and graph theory, which provides a quantitative characterization of the whole-brain FC. In this paper we provide an overview of these two techniques and some examples of their clinical applications in the most common neurodegenerative disorders associated with cognitive decline, including mild cognitive impairment, Alzheimer’s disease, Parkinson’s disease, dementia with Lewy Bodies and behavioral variant frontotemporal dementia. PMID:28072380

  4. Reorganization of Functional Connectivity as a Correlate of Cognitive Recovery in Acquired Brain Injury

    ERIC Educational Resources Information Center

    Castellanos, Nazareth P.; Paul, Nuria; Ordonez, Victoria E.; Demuynck, Olivier; Bajo, Ricardo; Campo, Pablo; Bilbao, Alvaro; Ortiz, Tomas; del-Pozo, Francisco; Maestu, Fernando

    2010-01-01

    Cognitive processes require a functional interaction between specialized multiple, local and remote brain regions. Although these interactions can be strongly altered by an acquired brain injury, brain plasticity allows network reorganization to be principally responsible for recovery. The present work evaluates the impact of brain injury on…

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

    NASA Astrophysics Data System (ADS)

    Bressler, Steven L.

    2014-09-01

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

  6. Tau and Beta-Amyloid Deposition, Microhemorrhage and Brain Function after Traumatic Brain Injury in War Veterans

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0418 TITLE: Tau and Beta-Amyloid Deposition, Microhemorrhage and Brain Function after Traumatic Brain Injury in War...COVERED 25 Sep 2014 - 24 Sep 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Tau and Beta-Amyloid Deposition, Microhemorrhage and Brain Function after...Traumatic Brain Injury in War Veterans 5b. GRANT NUMBER W81XWH-14-1-0418 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Christopher Rowe 5d. PROJECT

  7. Dynamic reconfiguration of human brain functional networks through neurofeedback.

    PubMed

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

    2013-11-01

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

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

    PubMed

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

    2009-05-01

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

  9. Predicting individual brain functional connectivity using a Bayesian hierarchical model.

    PubMed

    Dai, Tian; Guo, Ying

    2017-02-15

    Network-oriented analysis of functional magnetic resonance imaging (fMRI), especially resting-state fMRI, has revealed important association between abnormal connectivity and brain disorders such as schizophrenia, major depression and Alzheimer's disease. Imaging-based brain connectivity measures have become a useful tool for investigating the pathophysiology, progression and treatment response of psychiatric disorders and neurodegenerative diseases. Recent studies have started to explore the possibility of using functional neuroimaging to help predict disease progression and guide treatment selection for individual patients. These studies provide the impetus to develop statistical methodology that would help provide predictive information on disease progression-related or treatment-related changes in neural connectivity. To this end, we propose a prediction method based on Bayesian hierarchical model that uses individual's baseline fMRI scans, coupled with relevant subject characteristics, to predict the individual's future functional connectivity. A key advantage of the proposed method is that it can improve the accuracy of individualized prediction of connectivity by combining information from both group-level connectivity patterns that are common to subjects with similar characteristics as well as individual-level connectivity features that are particular to the specific subject. Furthermore, our method also offers statistical inference tools such as predictive intervals that help quantify the uncertainty or variability of the predicted outcomes. The proposed prediction method could be a useful approach to predict the changes in individual patient's brain connectivity with the progression of a disease. It can also be used to predict a patient's post-treatment brain connectivity after a specified treatment regimen. Another utility of the proposed method is that it can be applied to test-retest imaging data to develop a more reliable estimator for individual

  10. Structure-function clustering in multiplex brain networks

    NASA Astrophysics Data System (ADS)

    Crofts, J. J.; Forrester, M.; O'Dea, R. D.

    2016-10-01

    A key question in neuroscience is to understand how a rich functional repertoire of brain activity arises within relatively static networks of structurally connected neural populations: elucidating the subtle interactions between evoked “functional connectivity” and the underlying “structural connectivity” has the potential to address this. These structural-functional networks (and neural networks more generally) are more naturally described using a multilayer or multiplex network approach, in favour of standard single-layer network analyses that are more typically applied to such systems. In this letter, we address such issues by exploring important structure-function relations in the Macaque cortical network by modelling it as a duplex network that comprises an anatomical layer, describing the known (macro-scale) network topology of the Macaque monkey, and a functional layer derived from simulated neural activity. We investigate and characterize correlations between structural and functional layers, as system parameters controlling simulated neural activity are varied, by employing recently described multiplex network measures. Moreover, we propose a novel measure of multiplex structure-function clustering which allows us to investigate the emergence of functional connections that are distinct from the underlying cortical structure, and to highlight the dependence of multiplex structure on the neural dynamical regime.

  11. What are the functions of fish brain pallium?

    PubMed

    Vargas, Juan Pedro; López, Juan Carlos; Portavella, Manuel

    2009-08-14

    There is some experimental evidence that the pallial areas of a fish's brain are involved in distincted learning functions. Recently published data suggest that the medial pallium is essential for avoidance learning and the lateral pallium is crucial for spatial learning and is also involved in temporal aspects of the learning processes. This data joined to the proposal of homologies between medial and lateral fish pallia and pallial amygdala and hippocampus respectively, suggest that the pallial areas could have preserved their functions throughout vertebrates' evolution. However, the functional implication of dorsal pallium that has been proposed as homologous to mammalian isocortex and transition cortex is largely unknown. In this study we analyze the role of dorsal pallium in trace and non-trace avoidance learning. Our results show the implication of this area in trace conditioning, but not in non-trace conditioning. This result allows discussion of homology proposals among lateral, dorsal, and medial pallia and hippocampus, isocortex, and pallial amygdala respectively.

  12. The heme oxygenase system and its functions in the brain.

    PubMed

    Maines, M D

    2000-05-01

    The heme oxygenase (HO) system was identified in the early 1970s as a distinct microsomal enzyme system that catalyzes formation of bile pigments (Maines and Kappas, 1974). Up to the early 1990s the system was considered only as a "molecular wrecking ball" (Lane, 1998) for degradation of the heme molecule and production of toxic waste products, CO and bile pigments. For those years, the HO system remained relatively unknown to the research community. In a rather short span of the past 10 years following the discovery of high levels of a second form of the enzyme, HO-2, in the brain, suggesting that "heme oxygenase in the brain has functions aside from heme degradation" (Sun et al., 1990); concomitant with finding that another toxic gas, NO, is a signal molecule for generation of cGMP (Ignarro et al., 1982), the system was propelled into main stream research. This propulsion was fueled by the realization of the multiple and diverse functions of heme degradation products. Heme oxygenase has now found relevance in all kinds of human pathophysiology ranging from stroke, cancer, multiple sclerosis, and malaria to transplantation and immune response. As it turns out, its potential benefits are mesmerizing investigators in diverse fields (Lane, 1998). The most recent findings with HO-2 being a hemoprotein and potentially an intracellular "sink" for NO (McCoubrey et al., 1997a; Ding et al., 1999), together with the discovery of the third form of the enzyme, HO-3 (McCoubrey et al., 1997b), are likely to insure the widespread interest in the enzyme system in the coming years. The present review is intended to highlight molecular properties of HO isozymes and their likely functions in the brain. Extended reviews of the system are found in Maines (1992, 1997).

  13. Critical periods of brain growth and cognitive function in children.

    PubMed

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

    2004-02-01

    There is evidence that IQ tends to be higher in those who were heavier at birth or who grew taller in childhood and adolescence. Although these findings imply that growth in both foetal and postnatal life influences cognitive performance, little is known about the relative importance of brain growth during different periods of development. We investigated the relationship between brain growth in different periods of pre- and postnatal life and cognitive function in 221 9-year-old children whose mothers had taken part in a study of nutrition in pregnancy and whose head circumference had been measured at 18 weeks gestation, birth and 9 months of age. Cognitive function of the children and their mothers was assessed with the Wechsler Abbreviated Scale of Intelligence. Full-scale IQ at age 9 years rose by 1.98 points [95% confidence interval (CI) 0.34 to 3.62] for each SD increase in head circumference at 9 months and by 2.87 points (95% CI 1.05 to 4.69) for each SD increase in head circumference at 9 years of age, after adjustment for sex, number of older siblings, maternal IQ, age, education, social class, duration of breastfeeding and history of low mood in the post-partum period. Postnatal head growth was significantly greater in children whose mothers were educated to degree level or of higher socio-economic status. There was no relation between IQ and measurements of head size at 18 weeks gestation or at birth. These results suggest that brain growth during infancy and early childhood is more important than growth during foetal life in determining cognitive function.

  14. Large-Scale Functional Brain Network Reorganization During Taoist Meditation.

    PubMed

    Jao, Tun; Li, Chia-Wei; Vértes, Petra E; Wu, Changwei Wesley; Achard, Sophie; Hsieh, Chao-Hsien; Liou, Chien-Hui; Chen, Jyh-Horng; Bullmore, Edward T

    2016-02-01

    Meditation induces a distinct and reversible mental state that provides insights into brain correlates of consciousness. We explored brain network changes related to meditation by graph theoretical analysis of resting-state functional magnetic resonance imaging data. Eighteen Taoist meditators with varying levels of expertise were scanned using a within-subjects counterbalanced design during resting and meditation states. State-related differences in network topology were measured globally and at the level of individual nodes and edges. Although measures of global network topology, such as small-worldness, were unchanged, meditation was characterized by an extensive and expertise-dependent reorganization of the hubs (highly connected nodes) and edges (functional connections). Areas of sensory cortex, especially the bilateral primary visual and auditory cortices, and the bilateral temporopolar areas, which had the highest degree (or connectivity) during the resting state, showed the biggest decrease during meditation. Conversely, bilateral thalamus and components of the default mode network, mainly the bilateral precuneus and posterior cingulate cortex, had low degree in the resting state but increased degree during meditation. Additionally, these changes in nodal degree were accompanied by reorganization of anatomical orientation of the edges. During meditation, long-distance longitudinal (antero-posterior) edges increased proportionally, whereas orthogonal long-distance transverse (right-left) edges connecting bilaterally homologous cortices decreased. Our findings suggest that transient changes in consciousness associated with meditation introduce convergent changes in the topological and spatial properties of brain functional networks, and the anatomical pattern of integration might be as important as the global level of integration when considering the network basis for human consciousness.

  15. Behavioral Relevance of the Dynamics of the Functional Brain Connectome

    PubMed Central

    Jia, Hao

    2014-01-01

    Abstract While many previous studies assumed the functional connectivity (FC) between brain regions to be stationary, recent studies have demonstrated that FC dynamically varies across time. However, two challenges have limited the interpretability of dynamic FC information. First, a principled framework for selecting the temporal extent of the window used to examine the dynamics is lacking and this has resulted in ad-hoc selections of window lengths and subsequent divergent results. Second, it is unclear whether there is any behavioral relevance to the dynamics of the functional connectome in addition to that obtained from conventional static FC (SFC). In this work, we address these challenges by first proposing a principled framework for selecting the extent of the temporal windows in a dynamic and data-driven fashion based on statistical tests of the stationarity of time series. Further, we propose a method involving three levels of clustering—across space, time, and subjects—which allow for group-level inferences of the dynamics. Next, using a large resting-state functional magnetic resonance imaging and behavioral dataset from the Human Connectome Project, we demonstrate that metrics derived from dynamic FC can explain more than twice the variance in 75 behaviors across different domains (alertness, cognition, emotion, and personality traits) as compared with SFC in healthy individuals. Further, we found that individuals with brain networks exhibiting greater dynamics performed more favorably in behavioral tasks. This indicates that the ease with which brain regions engage or disengage may provide potential biomarkers for disorders involving altered neural circuitry. PMID:25163490

  16. Functional magnetic resonance imaging and the brain: A brief review

    PubMed Central

    Chow, Maggie S M; Wu, Sharon L; Webb, Sarah E; Gluskin, Katie; Yew, D T

    2017-01-01

    Functional magnetic resonance imaging (fMRI) is employed in many behavior analysis studies, with blood oxygen level dependent- (BOLD-) contrast imaging being the main method used to generate images. The use of BOLD-contrast imaging in fMRI has been refined over the years, for example, the inclusion of a spin echo pulse and increased magnetic strength were shown to produce better recorded images. Taking careful precautions to control variables during measurement, comparisons between different specimen groups can be illustrated by fMRI imaging using both quantitative and qualitative methods. Differences have been observed in comparisons of active and resting, developing and aging, and defective and damaged brains in various studies. However, cognitive studies using fMRI still face a number of challenges in interpretation that can only be overcome by imaging large numbers of samples. Furthermore, fMRI studies of brain cancer, lesions and other brain pathologies of both humans and animals are still to be explored. PMID:28144401

  17. Mitochondrial activity and brain functions during cortical depolarization

    NASA Astrophysics Data System (ADS)

    Mayevsky, Avraham; Sonn, Judith

    2008-12-01

    Cortical depolarization (CD) of the cerebral cortex could be developed under various pathophysiological conditions. In animal models, CD was recorded under partial or complete ischemia as well as when cortical spreading depression (SD) was induced externally or by internal stimulus. The development of CD in patients and the changes in various metabolic parameters, during CD, was rarely reported. Brain metabolic, hemodynamic, ionic and electrical responses to the CD event are dependent upon the O2 balance in the tissue. When the O2 balance is negative (i.e. ischemia), the CD process will be developed due to mitochondrial dysfunction, lack of energy and the inhibition of Na+-K+-ATPase. In contradiction, when oxygen is available (i.e. normoxia) the development of CD after induction of SD will accelerate mitochondrial respiration for retaining ionic homeostasis and normal brain functions. We used the multiparametric monitoring approach that enable real time monitoring of mitochondrial NADH redox state, microcirculatory blood flow and oxygenation, extracellular K+, Ca2+, H+ levels, DC steady potential and electrocorticogram (ECoG). This monitoring approach, provide a unique tool that has a significant value in analyzing the pathophysiology of the brain when SD developed under normoxia, ischemia, or hypoxia. We applied the same monitoring approach to patients suffered from severe head injury or exposed to neurosurgical procedures.

  18. Diverse functions of 24(S)-hydroxycholesterol in the brain.

    PubMed

    Noguchi, Noriko; Saito, Yoshiro; Urano, Yasuomi

    2014-04-11

    24(S)-hydroxycholesterol (24S-OHC) which is enzymatically produced in the brain plays important physiological roles in maintaining brain cholesterol homeostasis. We found that 24S-OHC at sub-lethal concentrations down-regulated amyloid precursor protein (APP) trafficking via enhancement of the complex formation of APP with up-regulated glucose-regulated protein 78, an endoplasmic reticulum chaperone. In accordance with this mechanism, 24S-OHC suppressed amyloid-β production in human neuroblastoma SH-SY5Y cells. Furthermore, 24S-OHC at sub-lethal concentrations induced adaptive responses via transcriptional activation of the liver X receptor signaling pathway, thereby protecting neuronal cells against the forthcoming oxidative stress induced by 7-ketocholesterol. On the other hand, we found that high concentrations of 24S-OHC induced apoptosis in T-lymphoma Jurkat cells which endogenously expressed caspase-8, and induced necroptosis - a form of programmed necrosis - in neuronal SH-SY5Y cells which expressed no caspase-8. In this Article, we show the diverse functions of 24S-OHC and consider the possible importance of controlling 24S-OHC levels in the brain for preventing neurodegenerative diseases.

  19. Bisphenol A Interaction With Brain Development and Functions

    PubMed Central

    2015-01-01

    Brain development is an organized, but constantly adaptive, process in which genetic and epigenetic signals allow neurons to differentiate, to migrate, and to develop correct connections. Gender specific prenatal sex hormone milieu participates in the dimorphic development of many neuronal networks. Environmental cues may interfere with these developmental programs, producing adverse outcomes. Bisphenol A (BPA), an estrogenic/antiandrogenic endocrine disruptor widely diffused in the environment, produces adverse effects at levels below the acceptable daily intake. This review analyzes the recent literature on the consequences of perinatal exposure to BPA environmental doses on the development of a dimorphic brain. The BPA interference with the development and function of the neuroendocrine hypothalamus and of the nuclei controlling energy balance, and with the hippocampal memory processing is also discussed. The detrimental action of BPA appears complex, involving different hormonal and epigenetic pathways activated, often in a dimorphic way, within clearcut susceptibility windows. To date, discrepancies in experimental approaches and in related outcomes make unfeasible to translate the available information into clear dose–response models for human risk assessment. Evaluation of BPA brain levels in relation to the appearance of adverse effects in future basic studies will certainly give better definition of the warning threshold for human health. PMID:26672480

  20. Chronic Methamphetamine Effects on Brain Structure and Function in Rats

    PubMed Central

    Thanos, Panayotis K.; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J.; Masad, Ihssan; Muniz, Jose A.; Grant, Samuel C.; Gold, Mark S.; Cadet, Jean Lud; Volkow, Nora D.

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  1. Chronic Methamphetamine Effects on Brain Structure and Function in Rats.

    PubMed

    Thanos, Panayotis K; Kim, Ronald; Delis, Foteini; Ananth, Mala; Chachati, George; Rocco, Mark J; Masad, Ihssan; Muniz, Jose A; Grant, Samuel C; Gold, Mark S; Cadet, Jean Lud; Volkow, Nora D

    2016-01-01

    Methamphetamine (MA) addiction is a growing epidemic worldwide. Chronic MA use has been shown to lead to neurotoxicity in rodents and humans. Magnetic resonance imaging (MRI) studies in MA users have shown enlarged striatal volumes and positron emission tomography (PET) studies have shown decreased brain glucose metabolism (BGluM) in the striatum of detoxified MA users. The present study examines structural changes of the brain, observes microglial activation, and assesses changes in brain function, in response to chronic MA treatment. Rats were randomly split into three distinct treatment groups and treated daily for four months, via i.p. injection, with saline (controls), or low dose (LD) MA (4 mg/kg), or high dose (HD) MA (8 mg/kg). Sixteen weeks into the treatment period, rats were injected with a glucose analog, [18F] fluorodeoxyglucose (FDG), and their brains were scanned with micro-PET to assess regional BGluM. At the end of MA treatment, magnetic resonance imaging at 21T was performed on perfused rats to determine regional brain volume and in vitro [3H]PK 11195 autoradiography was performed on fresh-frozen brain tissue to measure microglia activation. When compared with controls, chronic HD MA-treated rats had enlarged striatal volumes and increases in [3H]PK 11195 binding in striatum, the nucleus accumbens, frontal cortical areas, the rhinal cortices, and the cerebellar nuclei. FDG microPET imaging showed that LD MA-treated rats had higher BGluM in insular and somatosensory cortices, face sensory nucleus of the thalamus, and brainstem reticular formation, while HD MA-treated rats had higher BGluM in primary and higher order somatosensory and the retrosplenial cortices, compared with controls. HD and LD MA-treated rats had lower BGluM in the tail of the striatum, rhinal cortex, and subiculum and HD MA also had lower BGluM in hippocampus than controls. These results corroborate clinical findings and help further examine the mechanisms behind MA

  2. Delta opioid receptors in brain function and diseases

    PubMed Central

    Chung, Paul Chu Sin; Kieffer, Brigitte L.

    2013-01-01

    Evidence that the delta opioid receptor (DOR) is an attractive target for the treatment of brain disorders has strengthened in recent years. This receptor is broadly expressed in the brain, binds endogenous opioid peptides, and shows as functional profile highly distinct from those of mu and kappa opioid receptors. Our knowledge of DOR function has enormously progressed from in vivo studies using pharmacological tools and genetic approaches. The important role of this receptor in reducing chronic pain has been extensively overviewed; therefore this review focuses on facets of delta receptor activity relevant to psychiatric and other neurological disorders. Beneficial effects of DOR agonists are now well established in the context of emotional responses and mood disorders. DOR activation also regulates drug reward, inhibitory controls and learning processes, but whether delta compounds may represent useful drugs in the treatment of drug abuse remains open. Epileptogenic and locomotor-stimulating effects of delta agonists appear drug-dependent, and the possibility of biased agonism at DOR for these effects is worthwhile further investigations to increase benefit/risk ratio of delta therapies. Neuroprotective effects of DOR activity represent a forthcoming research area. Future developments in DOR research will benefit from in-depth investigations of DOR function at cellular and circuit levels. PMID:23764370

  3. Functionally Driven Brain Networks Using Multi-layer Graph Clustering

    PubMed Central

    Ghanbari, Yasser; Bloy, Luke; Shankar, Varsha; Edgar, J. Christopher; Roberts, Timothy P.L.; Schultz, Robert T.; Verma, Ragini

    2016-01-01

    Connectivity analysis of resting state brain has provided a novel means of investigating brain networks in the study of neurodevelopmental disorders. The study of functional networks, often represented by high dimensional graphs, predicates on the ability of methods in succinctly extracting meaningful representative connectivity information at the subject and population level. This need motivates the development of techniques that can extract underlying network modules that characterize the connectivity in a population, while capturing variations of these modules at the individual level. In this paper, we propose a multi-layer graph clustering technique that fuses the information from a collection of connectivity networks of a population to extract the underlying common network modules that serve as network hubs for the population. These hubs form a functional network atlas. In addition, our technique provides subject-specific factors designed to characterize and quantify the degree of intra- and inter- connectivity between hubs, thereby providing a representation that is amenable to group level statistical analyses. We demonstrate the utility of the technique by creating a population network atlas of connectivity by examining MEG based functional connectivity in typically developing children, and using this to describe the individualized variation in those diagnosed with autism spectrum disorder. PMID:25320789

  4. A Statistical Method to Distinguish Functional Brain Networks

    PubMed Central

    Fujita, André; Vidal, Maciel C.; Takahashi, Daniel Y.

    2017-01-01

    One major problem in neuroscience is the comparison of functional brain networks of different populations, e.g., distinguishing the networks of controls and patients. Traditional algorithms are based on search for isomorphism between networks, assuming that they are deterministic. However, biological networks present randomness that cannot be well modeled by those algorithms. For instance, functional brain networks of distinct subjects of the same population can be different due to individual characteristics. Moreover, networks of subjects from different populations can be generated through the same stochastic process. Thus, a better hypothesis is that networks are generated by random processes. In this case, subjects from the same group are samples from the same random process, whereas subjects from different groups are generated by distinct processes. Using this idea, we developed a statistical test called ANOGVA to test whether two or more populations of graphs are generated by the same random graph model. Our simulations' results demonstrate that we can precisely control the rate of false positives and that the test is powerful to discriminate random graphs generated by different models and parameters. The method also showed to be robust for unbalanced data. As an example, we applied ANOGVA to an fMRI dataset composed of controls and patients diagnosed with autism or Asperger. ANOGVA identified the cerebellar functional sub-network as statistically different between controls and autism (p < 0.001). PMID:28261045

  5. A Statistical Method to Distinguish Functional Brain Networks.

    PubMed

    Fujita, André; Vidal, Maciel C; Takahashi, Daniel Y

    2017-01-01

    One major problem in neuroscience is the comparison of functional brain networks of different populations, e.g., distinguishing the networks of controls and patients. Traditional algorithms are based on search for isomorphism between networks, assuming that they are deterministic. However, biological networks present randomness that cannot be well modeled by those algorithms. For instance, functional brain networks of distinct subjects of the same population can be different due to individual characteristics. Moreover, networks of subjects from different populations can be generated through the same stochastic process. Thus, a better hypothesis is that networks are generated by random processes. In this case, subjects from the same group are samples from the same random process, whereas subjects from different groups are generated by distinct processes. Using this idea, we developed a statistical test called ANOGVA to test whether two or more populations of graphs are generated by the same random graph model. Our simulations' results demonstrate that we can precisely control the rate of false positives and that the test is powerful to discriminate random graphs generated by different models and parameters. The method also showed to be robust for unbalanced data. As an example, we applied ANOGVA to an fMRI dataset composed of controls and patients diagnosed with autism or Asperger. ANOGVA identified the cerebellar functional sub-network as statistically different between controls and autism (p < 0.001).

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

    PubMed

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

    2016-03-10

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

  7. Bayesian network models in brain functional connectivity analysis

    PubMed Central

    Zhang, Sheng; Li, Chiang-shan R.

    2013-01-01

    Much effort has been made to better understand the complex integration of distinct parts of the human brain using functional magnetic resonance imaging (fMRI). Altered functional connectivity between brain regions is associated with many neurological and mental illnesses, such as Alzheimer and Parkinson diseases, addiction, and depression. In computational science, Bayesian networks (BN) have been used in a broad range of studies to model complex data set in the presence of uncertainty and when expert prior knowledge is needed. However, little is done to explore the use of BN in connectivity analysis of fMRI data. In this paper, we present an up-to-date literature review and methodological details of connectivity analyses using BN, while highlighting caveats in a real-world application. We present a BN model of fMRI dataset obtained from sixty healthy subjects performing the stop-signal task (SST), a paradigm widely used to investigate response inhibition. Connectivity results are validated with the extant literature including our previous studies. By exploring the link strength of the learned BN’s and correlating them to behavioral performance measures, this novel use of BN in connectivity analysis provides new insights to the functional neural pathways underlying response inhibition. PMID:24319317

  8. Mitochondrial function in the brain links anxiety with social subordination.

    PubMed

    Hollis, Fiona; van der Kooij, Michael A; Zanoletti, Olivia; Lozano, Laura; Cantó, Carles; Sandi, Carmen

    2015-12-15

    Dominance hierarchies are integral aspects of social groups, yet whether personality traits may predispose individuals to a particular rank remains unclear. Here we show that trait anxiety directly influences social dominance in male outbred rats and identify an important mediating role for mitochondrial function in the nucleus accumbens. High-anxious animals that are prone to become subordinate during a social encounter with a low-anxious rat exhibit reduced mitochondrial complex I and II proteins and respiratory capacity as well as decreased ATP and increased ROS production in the nucleus accumbens. A causal link for these findings is indicated by pharmacological approaches. In a dyadic contest between anxiety-matched animals, microinfusion of specific mitochondrial complex I or II inhibitors into the nucleus accumbens reduced social rank, mimicking the low probability to become dominant observed in high-anxious animals. Conversely, intraaccumbal infusion of nicotinamide, an amide form of vitamin B3 known to enhance brain energy metabolism, prevented the development of a subordinate status in high-anxious individuals. We conclude that mitochondrial function in the nucleus accumbens is crucial for social hierarchy establishment and is critically involved in the low social competitiveness associated with high anxiety. Our findings highlight a key role for brain energy metabolism in social behavior and point to mitochondrial function in the nucleus accumbens as a potential marker and avenue of treatment for anxiety-related social disorders.

  9. Functional connectivity of the rodent brain using optical imaging

    NASA Astrophysics Data System (ADS)

    Guevara Codina, Edgar

    The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis

  10. Brain functional connectivity and the pathophysiology of schizophrenia.

    PubMed

    Angelopoulos, E

    2014-01-01

    In the last decade there is extensive evidence to suggest that cognitive functions depending on coordination of distributed neuronal responses are associated with synchronized oscillatory activity in various frequency ranges suggesting a functional mechanism of neural oscillations in cortical networks. In addition to their role in normal brain functioning, there is increasing evidence that altered oscillatory activity may be associated with certain neuropsychiatric disorders, such as schizophrenia. Consequently, disturbances in neural synchronization may represent the functional relationship of disordered connectivity of cortical networks underlying the characteristic fragmentation of mind and behavior in schizophrenia. In recent studies the synchronization of oscillatory activity in the experience of characteristic symptoms such as auditory verbal hallucinations and thought blocks have been studied in patients with schizophrenia. Studies involving analysis of EEG activity obtained from individuals in resting state (in cage Faraday, isolated from external influences and with eyes closed). In patients with schizophrenia and persistent auditory verbal hallucinations (AVHs) observed a temporary increase in the synchronization phase of α and high θ oscillations of the electroencephalogram (EEG) compared with those of healthy controls and patients without AVHs . This functional hyper-connection manifested in time windows corresponding to experience AVHs, as noted by the patients during the recording of EEG and observed in speech related cortical areas. In another study an interaction of theta and gamma oscillations engages in the production and experience of AVHs. The results showed increased phase coupling between theta and gamma EEG rhythms in the left temporal cortex during AVHs experiences. A more recent study, approaches the thought blocking experience in terms of functional brain connectivity. Thought blocks (TBs) are characterized by regular interruptions of

  11. Crossed-Brain Representation of Verbal and Nonverbal Functions

    PubMed Central

    Matute, Esmeralda; Ardila, Alfredo; Rosselli, Monica; Molina Del Rio, Jahaziel; López Elizalde, Ramiro; López, Manuel; Ontiveros, Angel

    2015-01-01

    A 74-year-old, left-handed man presented with a rapidly evolving loss of strength in his right leg associated with difficulty in walking. MR images disclosed an extensive left hemisphere tumor. A neuropsychological examination revealed that language was broadly normal but that the patient presented with severe nonlinguistic abnormalities, including hemineglect (both somatic and spatial), constructional defects, and general spatial disturbances; symptoms were usually associated with right hemisphere pathologies. No ideomotor apraxia was found. The implications of crossed-brain representations of verbal and nonverbal functions are analyzed. PMID:25802778

  12. Functional interactions as big data in the human brain.

    PubMed

    Turk-Browne, Nicholas B

    2013-11-01

    Noninvasive studies of human brain function hold great potential to unlock mysteries of the human mind. The complexity of data generated by such studies, however, has prompted various simplifying assumptions during analysis. Although this has enabled considerable progress, our current understanding is partly contingent upon these assumptions. An emerging approach embraces the complexity, accounting for the fact that neural representations are widely distributed, neural processes involve interactions between regions, interactions vary by cognitive state, and the space of interactions is massive. Because what you see depends on how you look, such unbiased approaches provide the greatest flexibility for discovery.

  13. Highly adaptive tests for group differences in brain functional connectivity.

    PubMed

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that "there is currently no unique solution, but a spectrum of related methods and analytical strategies" to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not only

  14. Highly adaptive tests for group differences in brain functional connectivity

    PubMed Central

    Kim, Junghi; Pan, Wei

    2015-01-01

    Resting-state functional magnetic resonance imaging (rs-fMRI) and other technologies have been offering evidence and insights showing that altered brain functional networks are associated with neurological illnesses such as Alzheimer's disease. Exploring brain networks of clinical populations compared to those of controls would be a key inquiry to reveal underlying neurological processes related to such illnesses. For such a purpose, group-level inference is a necessary first step in order to establish whether there are any genuinely disrupted brain subnetworks. Such an analysis is also challenging due to the high dimensionality of the parameters in a network model and high noise levels in neuroimaging data. We are still in the early stage of method development as highlighted by Varoquaux and Craddock (2013) that “there is currently no unique solution, but a spectrum of related methods and analytical strategies” to learn and compare brain connectivity. In practice the important issue of how to choose several critical parameters in estimating a network, such as what association measure to use and what is the sparsity of the estimated network, has not been carefully addressed, largely because the answers are unknown yet. For example, even though the choice of tuning parameters in model estimation has been extensively discussed in the literature, as to be shown here, an optimal choice of a parameter for network estimation may not be optimal in the current context of hypothesis testing. Arbitrarily choosing or mis-specifying such parameters may lead to extremely low-powered tests. Here we develop highly adaptive tests to detect group differences in brain connectivity while accounting for unknown optimal choices of some tuning parameters. The proposed tests combine statistical evidence against a null hypothesis from multiple sources across a range of plausible tuning parameter values reflecting uncertainty with the unknown truth. These highly adaptive tests are not

  15. Changes in brain functional network connectivity after stroke

    PubMed Central

    Li, Wei; Li, Yapeng; Zhu, Wenzhen; Chen, Xi

    2014-01-01

    Studies have shown that functional network connection models can be used to study brain network changes in patients with schizophrenia. In this study, we inferred that these models could also be used to explore functional network connectivity changes in stroke patients. We used independent component analysis to find the motor areas of stroke patients, which is a novel way to determine these areas. In this study, we collected functional magnetic resonance imaging datasets from healthy controls and right-handed stroke patients following their first ever stroke. Using independent component analysis, six spatially independent components highly correlated to the experimental paradigm were extracted. Then, the functional network connectivity of both patients and controls was established to observe the differences between them. The results showed that there were 11 connections in the model in the stroke patients, while there were only four connections in the healthy controls. Further analysis found that some damaged connections may be compensated for by new indirect connections or circuits produced after stroke. These connections may have a direct correlation with the degree of stroke rehabilitation. Our findings suggest that functional network connectivity in stroke patients is more complex than that in hea-lthy controls, and that there is a compensation loop in the functional network following stroke. This implies that functional network reorganization plays a very important role in the process of rehabilitation after stroke. PMID:25206743

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

    PubMed

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

    2011-03-01

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

  17. Methamphetamine disrupts blood-brain barrier function by induction of oxidative stress in brain endothelial cells.

    PubMed

    Ramirez, Servio H; Potula, Raghava; Fan, Shongshan; Eidem, Tess; Papugani, Anil; Reichenbach, Nancy; Dykstra, Holly; Weksler, Babette B; Romero, Ignacio A; Couraud, Pierre O; Persidsky, Yuri

    2009-12-01

    Methamphetamine (METH), a potent stimulant with strong euphoric properties, has a high abuse liability and long-lasting neurotoxic effects. Recent studies in animal models have indicated that METH can induce impairment of the blood-brain barrier (BBB), thus suggesting that some of the neurotoxic effects resulting from METH abuse could be the outcome of barrier disruption. In this study, we provide evidence that METH alters BBB function through direct effects on endothelial cells and explore possible underlying mechanisms leading to endothelial injury. We report that METH increases BBB permeability in vivo, and exposure of primary human brain microvascular endothelial cells (BMVEC) to METH diminishes the tightness of BMVEC monolayers in a dose- and time-dependent manner by decreasing the expression of cell membrane-associated tight junction (TJ) proteins. These changes were accompanied by the enhanced production of reactive oxygen species, increased monocyte migration across METH-treated endothelial monolayers, and activation of myosin light chain kinase (MLCK) in BMVEC. Antioxidant treatment attenuated or completely reversed all tested aspects of METH-induced BBB dysfunction. Our data suggest that BBB injury is caused by METH-mediated oxidative stress, which activates MLCK and negatively affects the TJ complex. These observations provide a basis for antioxidant protection against brain endothelial injury caused by METH exposure.

  18. Cochlear implants: matching the prosthesis to the brain and facilitating desired plastic changes in brain function

    PubMed Central

    Wilson, Blake S.; Dorman, Michael F.; Woldorff, Marty G.; Tucci, Debara L.

    2013-01-01

    The cochlear implant (CI) is one of the great success stories of modern medicine. A high level of function is provided for most patients. However, some patients still do not achieve excellent or even good results using the present-day devices. Accumulating evidence is pointing to differences in the processing abilities of the “auditory brain” among patients as a principal contributor to this remaining and still large variability in outcomes. In this chapter, we describe a new approach to the design of CIs that takes these differences into account and thereby may improve outcomes for patients with compromised auditory brains. PMID:21867799

  19. Functional MR Imaging of Working Memory in the Human Brain

    PubMed Central

    Ryu, Jae Wook; Byun, Hong Sik; Choi, Dae Seob; Lee, Eun Jeong; Chung, Woo In; Cho, Jae Min; Han, Boo Kyung

    2000-01-01

    Objective In order to investigate the functional brain anatomy associated with verbal and visual working memory, functional magnetic resonance imaging was performed. Materials and Methods In ten normal right handed subjects, functional MR images were obtained using a 1.5-T MR scanner and the EPI BOLD technique. An item recognition task was used for stimulation, and during the activation period of the verbal working memory task, consonant letters were used. During the activation period of the visual working memory task, symbols or diagrams were employed instead of letters. For the post-processing of images, the SPM program was used, with the threshold of significance set at p < .001. We assessed activated brain areas during the two stimulation tasks and compared the activated regions between the two tasks. Results The prefrontal cortex and secondary visual cortex were activated bilaterally by both verbal and visual working memory tasks, and the patterns of activated signals were similar in both tasks. The superior parietal cortex was also activated by both tasks, with lateralization to the left in the verbal task, and bilaterally without lateralization in the visual task. The inferior frontal cortex, inferior parietal cortex and temporal gyrus were activated exclusively by the verbal working memory task, predominantly in the left hemisphere. Conclusion The prefrontal cortex is activated by two stimulation tasks, and this is related to the function of the central executive. The language areas activated by the verbal working memory task may be a function of the phonological loop. Bilateral prefrontal and superior parietal cortices activated by the visual working memory task may be related to the visual maintenance of objects, representing visual working memory. PMID:11752924

  20. Brain Structure and Executive Functions in Children with Cerebral Palsy: A Systematic Review

    ERIC Educational Resources Information Center

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

    2013-01-01

    This systematic review aimed to establish the current knowledge about brain structure and executive function (EF) in children with cerebral palsy (CP). Five databases were searched (up till July 2012). Six articles met the inclusion criteria, all included structural brain imaging though no functional brain imaging. Study quality was assessed using…

  1. Some Problems for Representations of Brain Organization Based on Activation in Functional Imaging

    ERIC Educational Resources Information Center

    Sidtis, John J.

    2007-01-01

    Functional brain imaging has overshadowed traditional lesion studies in becoming the dominant approach to the study of brain-behavior relationships. The proponents of functional imaging studies frequently argue that this approach provides an advantage over lesion studies by observing normal brain activity in vivo without the disruptive effects of…

  2. A Self-Study Tutorial using the Allen Brain Explorer and Brain Atlas to Teach Concepts of Mammalian Neuroanatomy and Brain Function.

    PubMed

    Jenks, Bruce G

    2009-01-01

    The Allen Brain Atlas is a repository of neuroanatomical data concerning the mouse brain. The core of the database is a Nissl-stained reference atlas of the brain accompanied by in situ hybridization data for essentially the entire mouse genome. This database is freely available at the Allen Institute for Brain Science website, as is an innovative tool to explore the database, the Brain Explorer. This tool is downloaded and installed on your own computer. I have developed a self-study tutorial, "Explorations with the Allen Brain Explorer", which uses the Brain Explorer and the Brain Atlas to teach fundamentals of mammalian neuroanatomy and brain function. In this tutorial background information and step-by-step exercises on the use of the Brain Explorer are given using PowerPoint as a platform. To do the tutorial both the PowerPoint and the Brain Explorer are opened on the computer and the students switch from one program to the other as they go, in a step-wise fashion, through the various exercises. There are two main groups of exercises, titled "The Basics" and "Explorations", with both groups accessed from a PowerPoint "Start Menu" by clicking on dynamic links to the appropriate exercises. Most exercises have a number of dynamic links to PowerPoint slides where background information for the exercises is given or the neuroanatomical data collected from the Brain Atlas is discussed.

  3. Traumatic Brain Injury and Neuronal Functionality Changes in Sensory Cortex

    PubMed Central

    Carron, Simone F.; Alwis, Dasuni S.; Rajan, Ramesh

    2016-01-01

    Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relative head-brain movement, can result in long-lasting cognitive and motor deficits which can be particularly consequential when they occur in young people with a long life ahead. Much is known of the molecular and anatomical changes produced in TBI but much less is known of the consequences of these changes to neuronal functionality, especially in the cortex. Given that much of our interior and exterior lives are dependent on responsiveness to information from and about the world around us, we have hypothesized that a significant contributor to the cognitive and motor deficits seen after TBI could be changes in sensory processing. To explore this hypothesis, and to develop a model test system of the changes in neuronal functionality caused by TBI, we have examined neuronal encoding of simple and complex sensory input in the rat’s exploratory and discriminative tactile system, the large face macrovibrissae, which feeds to the so-called “barrel cortex” of somatosensory cortex. In this review we describe the short-term and long-term changes in the barrel cortex encoding of whisker motion modeling naturalistic whisker movement undertaken by rats engaged in a variety of tasks. We demonstrate that the most common form of TBI results in persistent neuronal hyperexcitation specifically in the upper cortical layers, likely due to changes in inhibition. We describe the types of cortical inhibitory neurons and their roles and how selective effects on some of these could produce the particular forms of neuronal encoding changes described in TBI, and then generalize to compare the effects on inhibition seen in other forms of brain injury. From these findings we make specific predictions as to how non-invasive extra-cranial electrophysiology can be used to provide the high-precision information needed to monitor and understand the temporal evolution of changes in neuronal

  4. Traumatic Brain Injury and Neuronal Functionality Changes in Sensory Cortex.

    PubMed

    Carron, Simone F; Alwis, Dasuni S; Rajan, Ramesh

    2016-01-01

    Traumatic brain injury (TBI), caused by direct blows to the head or inertial forces during relative head-brain movement, can result in long-lasting cognitive and motor deficits which can be particularly consequential when they occur in young people with a long life ahead. Much is known of the molecular and anatomical changes produced in TBI but much less is known of the consequences of these changes to neuronal functionality, especially in the cortex. Given that much of our interior and exterior lives are dependent on responsiveness to information from and about the world around us, we have hypothesized that a significant contributor to the cognitive and motor deficits seen after TBI could be changes in sensory processing. To explore this hypothesis, and to develop a model test system of the changes in neuronal functionality caused by TBI, we have examined neuronal encoding of simple and complex sensory input in the rat's exploratory and discriminative tactile system, the large face macrovibrissae, which feeds to the so-called "barrel cortex" of somatosensory cortex. In this review we describe the short-term and long-term changes in the barrel cortex encoding of whisker motion modeling naturalistic whisker movement undertaken by rats engaged in a variety of tasks. We demonstrate that the most common form of TBI results in persistent neuronal hyperexcitation specifically in the upper cortical layers, likely due to changes in inhibition. We describe the types of cortical inhibitory neurons and their roles and how selective effects on some of these could produce the particular forms of neuronal encoding changes described in TBI, and then generalize to compare the effects on inhibition seen in other forms of brain injury. From these findings we make specific predictions as to how non-invasive extra-cranial electrophysiology can be used to provide the high-precision information needed to monitor and understand the temporal evolution of changes in neuronal functionality

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

    PubMed

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

    2012-01-01

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

  6. Abnormal regional brain function in Parkinson's disease: truth or fiction?

    PubMed

    Ma, Yilong; Tang, Chengke; Moeller, James R; Eidelberg, David

    2009-04-01

    Normalization of regional measurements by the global mean is commonly employed to minimize inter-subject variability in functional imaging studies. This practice is based on the assumption that global values do not substantially differ between patient and control groups. In this issue of NeuroImage, Borghammer and colleagues challenge the validity of this assumption. They focus on Parkinson's disease (PD) and use computer simulations to show that lower global values can produce spurious increases in subcortical brain regions. The authors speculate that the increased signal observed in these areas in PD is artefactual and unrelated to localized changes in brain function. In this commentary, we summarize what is currently known of the relationship between regional and global metabolic activity in PD and experimental parkinsonism. We found that early stage PD patients exhibit global values that are virtually identical to those of age-matched healthy subjects. SPM analysis revealed increased normalized metabolic activity in a discrete set of biologically relevant subcortical brain regions. Because of their higher variability, the corresponding absolute regional measures did not differ across the two groups. Longitudinal imaging studies in this population showed that the subcortical elevations in normalized metabolism appeared earlier and progressed faster than did focal cortical or global metabolic reductions. The observed increases in subcortical activity, but not the global changes, correlated with independent clinical measures of disease progression. Multivariate analysis with SSM/PCA further confirmed that the abnormal spatial covariance structure of early PD is dominated by these subcortical increases as opposed to network-related reductions in cortical metabolic activity or global changes. Thus, increased subcortical activity in PD cannot be regarded as a simple artefact of global normalization. Moreover, stability of the normalized measurements, particularly at

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

    PubMed

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

    2010-03-09

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

  8. Functional tissue pulsatility imaging of the brain during visual stimulation.

    PubMed

    Kucewicz, John C; Dunmire, Barbrina; Leotta, Daniel F; Panagiotides, Heracles; Paun, Marla; Beach, Kirk W

    2007-05-01

    Functional tissue pulsatility imaging is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility as a result of changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, nonultrasound technology for measuring expansion of a whole limb or body part as a result of perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow, and it relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate analysis of variance was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 of 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex.

  9. Brain images, babies, and bathwater: critiquing critiques of functional neuroimaging.

    PubMed

    Farah, Martha J

    2014-01-01

    Since the mid-1980s, psychologists and neuroscientists have used brain imaging to test hypotheses about human thought processes and their neural instantiation. In just three decades, functional neuroimaging has been transformed from a crude clinical tool to a widely used research method for understanding the human brain and mind. Such rapidly achieved success is bound to evoke skepticism. A degree of skepticism toward new methods and ideas is both inevitable and useful in any field. It is especially valuable in a science as young as cognitive neuroscience and its even younger siblings, social and affective neuroscience. Healthy skepticism encourages us to check our assumptions, recognize the limitations of our methods, and proceed thoughtfully. Skepticism itself, however, also must be examined. In this article, I review the most commonly voiced criticisms of functional neuroimaging. In the spirit of healthy skepticism, I will critically examine these criticisms themselves. Each contains at least a kernel of truth, although I will argue that in some cases the kernel has been over extended in ways that are inaccurate or misleading.

  10. Alteration and Reorganization of Functional Networks: A New Perspective in Brain Injury Study

    PubMed Central

    Castellanos, Nazareth P.; Bajo, Ricardo; Cuesta, Pablo; Villacorta-Atienza, José Antonio; Paúl, Nuria; Garcia-Prieto, Juan; del-Pozo, Francisco; Maestú, Fernando

    2011-01-01

    Plasticity is the mechanism underlying the brain’s potential capability to compensate injury. Recently several studies have shown how functional connections among the brain areas are severely altered by brain injury and plasticity leading to a reorganization of the networks. This new approach studies the impact of brain injury by means of alteration of functional interactions. The concept of functional connectivity refers to the statistical interdependencies between physiological time series simultaneously recorded in various areas of the brain and it could be an essential tool for brain functional studies, being its deviation from healthy reference an indicator for damage. In this article, we review studies investigating functional connectivity changes after brain injury and subsequent recovery, providing an accessible introduction to common mathematical methods to infer functional connectivity, exploring their capabilities, future perspectives, and clinical uses in brain injury studies. PMID:21960965

  11. Resting-state functional brain networks in Parkinson's disease.

    PubMed

    Baggio, Hugo C; Segura, Bàrbara; Junque, Carme

    2015-10-01

    The network approach is increasingly being applied to the investigation of normal brain function and its impairment. In the present review, we introduce the main methodological approaches employed for the analysis of resting-state neuroimaging data in Parkinson's disease studies. We then summarize the results of recent studies that used a functional network perspective to evaluate the changes underlying different manifestations of Parkinson's disease, with an emphasis on its cognitive symptoms. Despite the variability reported by many studies, these methods show promise as tools for shedding light on the pathophysiological substrates of different aspects of Parkinson's disease, as well as for differential diagnosis, treatment monitoring and establishment of imaging biomarkers for more severe clinical outcomes.

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

    PubMed

    Drummond, Sakina S; Boss, Michelle R

    2004-01-01

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

  13. Impact of Low-Level Thyroid Hormone Disruption Induced by Propylthiouracil on Brain Development and Function.*

    EPA Science Inventory

    The critical role of thyroid hormone (TH) in brain development is well established, severe deficiencies leading to significant neurological dysfunction. Much less information is available on more modest perturbations of TH on brain function. The present study induced varying degr...

  14. An Evolutionary Computation Approach to Examine Functional Brain Plasticity

    PubMed Central

    Roy, Arnab; Campbell, Colin; Bernier, Rachel A.; Hillary, Frank G.

    2016-01-01

    One common research goal in systems neurosciences is to understand how the functional relationship between a pair of regions of interest (ROIs) evolves over time. Examining neural connectivity in this way is well-suited for the study of developmental processes, learning, and even in recovery or treatment designs in response to injury. For most fMRI based studies, the strength of the functional relationship between two ROIs is defined as the correlation between the average signal representing each region. The drawback to this approach is that much information is lost due to averaging heterogeneous voxels, and therefore, the functional relationship between a ROI-pair that evolve at a spatial scale much finer than the ROIs remain undetected. To address this shortcoming, we introduce a novel evolutionary computation (EC) based voxel-level procedure to examine functional plasticity between an investigator defined ROI-pair by simultaneously using subject-specific BOLD-fMRI data collected from two sessions seperated by finite duration of time. This data-driven procedure detects a sub-region composed of spatially connected voxels from each ROI (a so-called sub-regional-pair) such that the pair shows a significant gain/loss of functional relationship strength across the two time points. The procedure is recursive and iteratively finds all statistically significant sub-regional-pairs within the ROIs. Using this approach, we examine functional plasticity between the default mode network (DMN) and the executive control network (ECN) during recovery from traumatic brain injury (TBI); the study includes 14 TBI and 12 healthy control subjects. We demonstrate that the EC based procedure is able to detect functional plasticity where a traditional averaging based approach fails. The subject-specific plasticity estimates obtained using the EC-procedure are highly consistent across multiple runs. Group-level analyses using these plasticity estimates showed an increase in the strength

  15. From brain topography to brain topology: relevance of graph theory to functional neuroscience.

    PubMed

    Minati, Ludovico; Varotto, Giulia; D'Incerti, Ludovico; Panzica, Ferruccio; Chan, Dennis

    2013-07-10

    Although several brain regions show significant specialization, higher functions such as cross-modal information integration, abstract reasoning and conscious awareness are viewed as emerging from interactions across distributed functional networks. Analytical approaches capable of capturing the properties of such networks can therefore enhance our ability to make inferences from functional MRI, electroencephalography and magnetoencephalography data. Graph theory is a branch of mathematics that focuses on the formal modelling of networks and offers a wide range of theoretical tools to quantify specific features of network architecture (topology) that can provide information complementing the anatomical localization of areas responding to given stimuli or tasks (topography). Explicit modelling of the architecture of axonal connections and interactions among areas can furthermore reveal peculiar topological properties that are conserved across diverse biological networks, and highly sensitive to disease states. The field is evolving rapidly, partly fuelled by computational developments that enable the study of connectivity at fine anatomical detail and the simultaneous interactions among multiple regions. Recent publications in this area have shown that graph-based modelling can enhance our ability to draw causal inferences from functional MRI experiments, and support the early detection of disconnection and the modelling of pathology spread in neurodegenerative disease, particularly Alzheimer's disease. Furthermore, neurophysiological studies have shown that network topology has a profound link to epileptogenesis and that connectivity indices derived from graph models aid in modelling the onset and spread of seizures. Graph-based analyses may therefore significantly help understand the bases of a range of neurological conditions. This review is designed to provide an overview of graph-based analyses of brain connectivity and their relevance to disease aimed

  16. Subliminal instrumental conditioning demonstrated in the human brain.

    PubMed

    Pessiglione, Mathias; Petrovic, Predrag; Daunizeau, Jean; Palminteri, Stefano; Dolan, Raymond J; Frith, Chris D

    2008-08-28

    How the brain uses success and failure to optimize future decisions is a long-standing question in neuroscience. One computational solution involves updating the values of context-action associations in proportion to a reward prediction error. Previous evidence suggests that such computations are expressed in the striatum and, as they are cognitively impenetrable, represent an unconscious learning mechanism. Here, we formally test this by studying instrumental conditioning in a situation where we masked contextual cues, such that they were not consciously perceived. Behavioral data showed that subjects nonetheless developed a significant propensity to choose cues associated with monetary rewards relative to punishments. Functional neuroimaging revealed that during conditioning cue values and prediction errors, generated from a computational model, both correlated with activity in ventral striatum. We conclude that, even without conscious processing of contextual cues, our brain can learn their reward value and use them to provide a bias on decision making.

  17. Functional and morphometric brain dissociation between dyslexia and reading ability.

    PubMed

    Hoeft, Fumiko; Meyler, Ann; Hernandez, Arvel; Juel, Connie; Taylor-Hill, Heather; Martindale, Jennifer L; McMillon, Glenn; Kolchugina, Galena; Black, Jessica M; Faizi, Afrooz; Deutsch, Gayle K; Siok, Wai Ting; Reiss, Allan L; Whitfield-Gabrieli, Susan; Gabrieli, John D E

    2007-03-06

    In functional neuroimaging studies, individuals with dyslexia frequently exhibit both hypoactivation, often in the left parietotemporal cortex, and hyperactivation, often in the left inferior frontal cortex, but there has been no evidence to suggest how to interpret the differential relations of hypoactivation and hyperactivation to dyslexia. To address this question, we measured brain activation by functional MRI during visual word rhyme judgment compared with visual cross-hair fixation rest, and we measured gray matter morphology by voxel-based morphometry in dyslexic adolescents in comparison with (i) an age-matched group, and (ii) a reading-matched group younger than the dyslexic group but equal to the dyslexic group in reading performance. Relative to the age-matched group (n = 19; mean 14.4 years), the dyslexic group (n = 19; mean 14.4 years) exhibited hypoactivation in left parietal and bilateral fusiform cortices and hyperactivation in left inferior and middle frontal gyri, caudate, and thalamus. Relative to the reading-matched group (n = 12; mean 9.8 years), the dyslexic group (n = 12; mean 14.5 years) also exhibited hypoactivation in left parietal and fusiform regions but equal activation in all four areas that had exhibited hyperactivation relative to age-matched controls as well. In regions that exhibited atypical activation in the dyslexic group, only the left parietal region exhibited reduced gray matter volume relative to both control groups. Thus, areas of hyperactivation in dyslexia reflected processes related to the level of current reading ability independent of dyslexia. In contrast, areas of hypoactivation in dyslexia reflected functional atypicalities related to dyslexia itself, independent of current reading ability, and related to atypical brain morphology in dyslexia.

  18. Quetiapine modulates functional connectivity in brain aggression networks.

    PubMed

    Klasen, Martin; Zvyagintsev, Mikhail; Schwenzer, Michael; Mathiak, Krystyna A; Sarkheil, Pegah; Weber, René; Mathiak, Klaus

    2013-07-15

    Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine.

  19. Efficient Computation of Functional Brain Networks: toward Real-Time Functional Connectivity

    PubMed Central

    García-Prieto, Juan; Bajo, Ricardo; Pereda, Ernesto

    2017-01-01

    Functional Connectivity has demonstrated to be a key concept for unraveling how the brain balances functional segregation and integration properties while processing information. This work presents a set of open-source tools that significantly increase computational efficiency of some well-known connectivity indices and Graph-Theory measures. PLV, PLI, ImC, and wPLI as Phase Synchronization measures, Mutual Information as an information theory based measure, and Generalized Synchronization indices are computed much more efficiently than prior open-source available implementations. Furthermore, network theory related measures like Strength, Shortest Path Length, Clustering Coefficient, and Betweenness Centrality are also implemented showing computational times up to thousands of times faster than most well-known implementations. Altogether, this work significantly expands what can be computed in feasible times, even enabling whole-head real-time network analysis of brain function. PMID:28220071

  20. Neuropsychological functioning and social functioning of survivors of pediatric brain tumors: evidence of nonverbal learning disability.

    PubMed

    Carey, M E; Barakat, L P; Foley, B; Gyato, K; Phillips, P C

    2001-12-01

    The purpose of the study was to examine if survivors of pediatric brain tumors exhibit a pattern of performance consistent with nonverbal learning disability (NVLD) and to explore the relationship between neuropsychological and social functioning in these children. A comprehensive neuropsychological battery and objective measures of psychosocial function designed to assess NVLD were administered to 15 survivors of brain tumors, ages 8-12 years. Despite the small sample size, a trend for better verbal skills compared to nonverbal skills was found using composite scores. Parents reported significant social deficits and a tendency for greater internalizing behavior problems as expected in NVLD. Additionally, there was a trend for a positive association between nonverbal scores and social function. Further research is needed to determine if the NVLD pattern observed is attributable to white matter damage of the right hemisphere. Routine neuropsychological and psychosocial assessment and intervention are indicated.

  1. Efficient Computation of Functional Brain Networks: toward Real-Time Functional Connectivity.

    PubMed

    García-Prieto, Juan; Bajo, Ricardo; Pereda, Ernesto

    2017-01-01

    Functional Connectivity has demonstrated to be a key concept for unraveling how the brain balances functional segregation and integration properties while processing information. This work presents a set of open-source tools that significantly increase computational efficiency of some well-known connectivity indices and Graph-Theory measures. PLV, PLI, ImC, and wPLI as Phase Synchronization measures, Mutual Information as an information theory based measure, and Generalized Synchronization indices are computed much more efficiently than prior open-source available implementations. Furthermore, network theory related measures like Strength, Shortest Path Length, Clustering Coefficient, and Betweenness Centrality are also implemented showing computational times up to thousands of times faster than most well-known implementations. Altogether, this work significantly expands what can be computed in feasible times, even enabling whole-head real-time network analysis of brain function.

  2. Prospective memory functioning in people with and without brain injury.

    PubMed

    Groot, Yvonne C T; Wilson, Barbara A; Evans, Jonathan; Watson, Peter

    2002-07-01

    Prospective remembering has been relatively underinvestigated in neurological patients. This paper describes a group study in which the prospective memory performance of 36 people with brain injury and 28 control participants is compared. We used a new instrument, the Cambridge Behaviour Prospective Memory Test (CBPMT) to assess prospective memory. This comprises 4 time-based and 4 event-based tasks. Participants were allowed to take notes to help them remember the tasks. The relationships between CBPMT scores, scores on formal tests and subjective reports on memory, attention and executive functioning were analyzed. The key findings were that (1) note-taking significantly benefited prospective memory performance, (2) significant relationships were found between scores on the prospective memory test and scores on tests of memory and executive functions, and (3) participants had more difficulty with the time-based than with the event-based prospective memory tasks. The results suggest that compensatory strategies improve prospective memory functioning; memory for content as well as attention and executive functioning processes are involved in prospective memory; and that time-based tasks are more difficult than event-based tasks because they place higher demands on inhibitory control mechanisms. Discussion focuses on the implications of these results for neuropsychological assessment and rehabilitation.

  3. Memory Networks in Tinnitus: A Functional Brain Image Study

    PubMed Central

    Laureano, Maura Regina; Onishi, Ektor Tsuneo; Bressan, Rodrigo Affonseca; Castiglioni, Mario Luiz Vieira; Batista, Ilza Rosa; Reis, Marilia Alves; Garcia, Michele Vargas; de Andrade, Adriana Neves; de Almeida, Roberta Ribeiro; Garrido, Griselda J.; Jackowski, Andrea Parolin

    2014-01-01

    Tinnitus is characterized by the perception of sound in the absence of an external auditory stimulus. The network connectivity of auditory and non-auditory brain structures associated with emotion, memory and attention are functionally altered in debilitating tinnitus. Current studies suggest that tinnitus results from neuroplastic changes in the frontal and limbic temporal regions. The objective of this study was to use Single-Photon Emission Computed Tomography (SPECT) to evaluate changes in the cerebral blood flow in tinnitus patients with normal hearing compared with healthy controls. Methods: Twenty tinnitus patients with normal hearing and 17 healthy controls, matched for sex, age and years of education, were subjected to Single Photon Emission Computed Tomography using the radiotracer ethylenedicysteine diethyl ester, labeled with Technetium 99 m (99 mTc-ECD SPECT). The severity of tinnitus was assessed using the “Tinnitus Handicap Inventory” (THI). The images were processed and analyzed using “Statistical Parametric Mapping” (SPM8). Results: A significant increase in cerebral perfusion in the left parahippocampal gyrus (pFWE <0.05) was observed in patients with tinnitus compared with healthy controls. The average total THI score was 50.8+18.24, classified as moderate tinnitus. Conclusion: It was possible to identify significant changes in the limbic system of the brain perfusion in tinnitus patients with normal hearing, suggesting that central mechanisms, not specific to the auditory pathway, are involved in the pathophysiology of symptoms, even in the absence of clinically diagnosed peripheral changes. PMID:24516567

  4. Predicting regional neurodegeneration from the healthy brain functional connectome.

    PubMed

    Zhou, Juan; Gennatas, Efstathios D; Kramer, Joel H; Miller, Bruce L; Seeley, William W

    2012-03-22

    Neurodegenerative diseases target large-scale neural networks. Four competing mechanistic hypotheses have been proposed to explain network-based disease patterning: nodal stress, transneuronal spread, trophic failure, and shared vulnerability. Here, we used task-free fMRI to derive the healthy intrinsic connectivity patterns seeded by brain regions vulnerable to any of five distinct neurodegenerative diseases. These data enabled us to investigate how intrinsic connectivity in health predicts region-by-region vulnerability to disease. For each illness, specific regions emerged as critical network "epicenters" whose normal connectivity profiles most resembled the disease-associated atrophy pattern. Graph theoretical analyses in healthy subjects revealed that regions with higher total connectional flow and, more consistently, shorter functional paths to the epicenters, showed greater disease-related vulnerability. These findings best fit a transneuronal spread model of network-based vulnerability. Molecular pathological approaches may help clarify what makes each epicenter vulnerable to its targeting disease and how toxic protein species travel between networked brain structures.

  5. Selectionist and Evolutionary Approaches to Brain Function: A Critical Appraisal

    PubMed Central

    Fernando, Chrisantha; Szathmáry, Eörs; Husbands, Phil

    2012-01-01

    We consider approaches to brain dynamics and function that have been claimed to be Darwinian. These include Edelman’s theory of neuronal group selection, Changeux’s theory of synaptic selection and selective stabilization of pre-representations, Seung’s Darwinian synapse, Loewenstein’s synaptic melioration, Adam’s selfish synapse, and Calvin’s replicating activity patterns. Except for the last two, the proposed mechanisms are selectionist but not truly Darwinian, because no replicators with information transfer to copies and hereditary variation can be identified in them. All of them fit, however, a generalized selectionist framework conforming to the picture of Price’s covariance formulation, which deliberately was not specific even to selection in biology, and therefore does not imply an algorithmic picture of biological evolution. Bayesian models and reinforcement learning are formally in agreement with selection dynamics. A classification of search algorithms is shown to include Darwinian replicators (evolutionary units with multiplication, heredity, and variability) as the most powerful mechanism for search in a sparsely occupied search space. Examples are given of cases where parallel competitive search with information transfer among the units is more efficient than search without information transfer between units. Finally, we review our recent attempts to construct and analyze simple models of true Darwinian evolutionary units in the brain in terms of connectivity and activity copying of neuronal groups. Although none of the proposed neuronal replicators include miraculous mechanisms, their identification remains a challenge but also a great promise. PMID:22557963

  6. Functional brain networks: random, "small world" or deterministic?

    PubMed

    Blinowska, Katarzyna J; Kaminski, Maciej

    2013-01-01

    Lately the problem of connectivity in brain networks is being approached frequently by graph theoretical analysis. In several publications based on bivariate estimators of relations between EEG channels authors reported random or "small world" structure of networks. The results of these works often have no relation to other evidence based on imaging, inverse solutions methods, physiological and anatomical data. Herein we try to find reasons for this discrepancy. We point out that EEG signals are very much interdependent, thus bivariate measures applied to them may produce many spurious connections. In fact, they may outnumber the true connections. Giving all connections equal weights, as it is usual in the framework of graph theoretical analysis, further enhances these spurious links. In effect, close to random and disorganized patterns of connections emerge. On the other hand, multivariate connectivity estimators, which are free of the artificial links, show specific, well determined patterns, which are in a very good agreement with other evidence. The modular structure of brain networks may be identified by multivariate estimators based on Granger causality and formalism of assortative mixing. In this way, the strength of coupling may be evaluated quantitatively. During working memory task, by means of multivariate Directed Transfer Function, it was demonstrated that the modules characterized by strong internal bonds exchange the information by weaker connections.

  7. Graph Analysis of Functional Brain Networks in Patients with Mild Traumatic Brain Injury

    PubMed Central

    van der Horn, Harm J.; Liemburg, Edith J.; Scheenen, Myrthe E.; de Koning, Myrthe E.; Spikman, Jacoba M.; van der Naalt, Joukje

    2017-01-01

    Mild traumatic brain injury (mTBI) is one of the most common neurological disorders worldwide. Posttraumatic complaints are frequently reported, interfering with outcome. However, a consistent neural substrate has not yet been found. We used graph analysis to further unravel the complex interactions between functional brain networks, complaints, anxiety and depression in the sub-acute stage after mTBI. This study included 54 patients with uncomplicated mTBI and 20 matched healthy controls. Posttraumatic complaints, anxiety and depression were measured at two weeks post-injury. Patients were selected based on presence (n = 34) or absence (n = 20) of complaints. Resting-state fMRI scans were made approximately four weeks post-injury. High order independent component analysis resulted in 89 neural components that were included in subsequent graph analyses. No differences in graph measures were found between patients with mTBI and healthy controls. Regarding the two patient subgroups, degree, strength, local efficiency and eigenvector centrality of the bilateral posterior cingulate/precuneus and bilateral parahippocampal gyrus were higher, and eigenvector centrality of the frontal pole/ bilateral middle & superior frontal gyrus was lower in patients with complaints compared to patients without complaints. In patients with mTBI, higher degree, strength and eigenvector centrality of default mode network components were related to higher depression scores, and higher degree and eigenvector centrality of executive network components were related to lower depression scores. In patients without complaints, one extra module was found compared to patients with complaints and healthy controls, consisting of the cingulate areas. In conclusion, this research extends the knowledge of functional network connectivity after mTBI. Specifically, our results suggest that an imbalance in the function of the default mode- and executive network plays a central role in the interaction

  8. Evolution of human brain functions: the functional structure of human consciousness.

    PubMed

    Cloninger, C Robert

    2009-11-01

    The functional structure of self-aware consciousness in human beings is described based on the evolution of human brain functions. Prior work on heritable temperament and character traits is extended to account for the quantum-like and holographic properties (i.e. parts elicit wholes) of self-aware consciousness. Cladistic analysis is used to identify the succession of ancestors leading to human beings. The functional capacities that emerge along this lineage of ancestors are described. The ecological context in which each cladogenesis occurred is described to illustrate the shifting balance of evolution as a complex adaptive system. Comparative neuroanatomy is reviewed to identify the brain structures and networks that emerged coincident with the emergent brain functions. Individual differences in human temperament traits were well developed in the common ancestor shared by reptiles and humans. Neocortical development in mammals proceeded in five major transitions: from early reptiles to early mammals, early primates, simians, early Homo, and modern Homo sapiens. These transitions provide the foundation for human self-awareness related to sexuality, materiality, emotionality, intellectuality, and spirituality, respectively. The functional structure of human self-aware consciousness is concerned with the regulation of five planes of being: sexuality, materiality, emotionality, intellectuality, and spirituality. Each plane elaborates neocortical functions organized around one of the five special senses. The interactions among these five planes gives rise to a 5 x 5 matrix of subplanes, which are functions that coarsely describe the focus of neocortical regulation. Each of these 25 neocortical functions regulates each of five basic motives or drives that can be measured as temperaments or basic emotions related to fear, anger, disgust, surprise, and happiness/sadness. The resulting 5 x 5 x 5 matrix of human characteristics provides a general and testable model of the

  9. Distributed representations in memory: insights from functional brain imaging.

    PubMed

    Rissman, Jesse; Wagner, Anthony D

    2012-01-01

    Forging new memories for facts and events, holding critical details in mind on a moment-to-moment basis, and retrieving knowledge in the service of current goals all depend on a complex interplay between neural ensembles throughout the brain. Over the past decade, researchers have increasingly utilized powerful analytical tools (e.g., multivoxel pattern analysis) to decode the information represented within distributed functional magnetic resonance imaging activity patterns. In this review, we discuss how these methods can sensitively index neural representations of perceptual and semantic content and how leverage on the engagement of distributed representations provides unique insights into distinct aspects of memory-guided behavior. We emphasize that, in addition to characterizing the contents of memories, analyses of distributed patterns shed light on the processes that influence how information is encoded, maintained, or retrieved, and thus inform memory theory. We conclude by highlighting open questions about memory that can be addressed through distributed pattern analyses.

  10. Can Cholesterol Metabolism Modulation Affect Brain Function and Behavior?

    PubMed

    Cartocci, Veronica; Servadio, Michela; Trezza, Viviana; Pallottini, Valentina

    2017-02-01

    Cholesterol is an important component for cell physiology. It regulates the fluidity of cell membranes and determines the physical and biochemical properties of proteins. In the central nervous system, cholesterol controls synapse formation and function and supports the saltatory conduction of action potential. In recent years, the role of cholesterol in the brain has caught the attention of several research groups since a breakdown of cholesterol metabolism has been associated with different neurodevelopmental and neurodegenerative diseases, and interestingly also with psychiatric conditions. The aim of this review is to summarize the current knowledge about the connection between cholesterol dysregulation and various neurologic and psychiatric disorders based on clinical and preclinical studies. J. Cell. Physiol. 232: 281-286, 2017. © 2016 Wiley Periodicals, Inc.

  11. 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.

  12. Reproducibility of graph metrics of human brain functional networks.

    PubMed

    Deuker, Lorena; Bullmore, Edward T; Smith, Marie; Christensen, Soren; Nathan, Pradeep J; Rockstroh, Brigitte; Bassett, Danielle S

    2009-10-01

    Graph theory provides many metrics of complex network organization that can be applied to analysis of brain networks derived from neuroimaging data. Here we investigated the test-retest reliability of graph metrics of functional networks derived from magnetoencephalography (MEG) data recorded in two sessions from 16 healthy volunteers who were studied at rest and during performance of the n-back working memory task in each session. For each subject's data at each session, we used a wavelet filter to estimate the mutual information (MI) between each pair of MEG sensors in each of the classical frequency intervals from gamma to low delta in the overall range 1-60 Hz. Undirected binary graphs were generated by thresholding the MI matrix and 8 global network metrics were estimated: the clustering coefficient, path length, small-worldness, efficiency, cost-efficiency, assortativity, hierarchy, and synchronizability. Reliability of each graph metric was assessed using the intraclass correlation (ICC). Good reliability was demonstrated for most metrics applied to the n-back data (mean ICC=0.62). Reliability was greater for metrics in lower frequency networks. Higher frequency gamma- and beta-band networks were less reliable at a global level but demonstrated high reliability of nodal metrics in frontal and parietal regions. Performance of the n-back task was associated with greater reliability than measurements on resting state data. Task practice was also associated with greater reliability. Collectively these results suggest that graph metrics are sufficiently reliable to be considered for future longitudinal studies of functional brain network changes.

  13. Functional Connectivity’s Degenerate View of Brain Computation

    PubMed Central

    Giron, Alain; Rudrauf, David

    2016-01-01

    Brain computation relies on effective interactions between ensembles of neurons. In neuroimaging, measures of functional connectivity (FC) aim at statistically quantifying such interactions, often to study normal or pathological cognition. Their capacity to reflect a meaningful variety of patterns as expected from neural computation in relation to cognitive processes remains debated. The relative weights of time-varying local neurophysiological dynamics versus static structural connectivity (SC) in the generation of FC as measured remains unsettled. Empirical evidence features mixed results: from little to significant FC variability and correlation with cognitive functions, within and between participants. We used a unified approach combining multivariate analysis, bootstrap and computational modeling to characterize the potential variety of patterns of FC and SC both qualitatively and quantitatively. Empirical data and simulations from generative models with different dynamical behaviors demonstrated, largely irrespective of FC metrics, that a linear subspace with dimension one or two could explain much of the variability across patterns of FC. On the contrary, the variability across BOLD time-courses could not be reduced to such a small subspace. FC appeared to strongly reflect SC and to be partly governed by a Gaussian process. The main differences between simulated and empirical data related to limitations of DWI-based SC estimation (and SC itself could then be estimated from FC). Above and beyond the limited dynamical range of the BOLD signal itself, measures of FC may offer a degenerate representation of brain interactions, with limited access to the underlying complexity. They feature an invariant common core, reflecting the channel capacity of the network as conditioned by SC, with a limited, though perhaps meaningful residual variability. PMID:27736900

  14. Brain function with complex decision making using electroencephalography.

    PubMed

    Davis, C Ervin; Hauf, Jessica D; Wu, D Qiang; Everhart, D Erik

    2011-02-01

    A computer-administered assessment for decision making relevant to daily-living decisions, using the technique of complex decision making (CDM), has been previously developed and tested in our laboratory. The present study sought to identify unique patterns of brain activity in the alpha band associated with CDM. We recorded electroencephalogram (EEG) from 30 scalp sites, during a series of baseline, eyes open fixation tasks, and CDM tasks, in different contexts, in a group of 9 male and 7 female young healthy adults, aged 18 to 34. The decision making contexts, designed to simulate real-world, daily-living decisions, were about taking a bus, choosing a friend, job, medication, and participating in research. Electroencephalograms (EEGs) were divided into the frequency bands, alpha, beta, delta, theta, and gamma, though the primary focus of this paper is the alpha band. Analysis of mean EEG power spectra across the alpha bands - alpha1 (8-10 Hz), alpha2 (10-12 Hz), and alpha 3 (12-14 Hz) - showed significant decreases from baseline to the CDM task. In addition, we observed significant increases in delta, theta, beta, and gamma. There were also significant bivariate correlations between EEG spectra, mostly in low and mid alpha bands, behavioral performance on the CDM task, and scores on standardized measures of executive functioning, including the Trail-making Test and the Wisconsin Card Sorting Task. These results demonstrate how brain activity in complex decision making is distributed across alpha frequency bands and electrode regions and this activity relates to executive functioning.

  15. Assessment of Ex Vivo Transport Function in Isolated Rodent Brain Capillaries.

    PubMed

    Chan, Gary N Y; Cannon, Ronald E

    2017-03-17

    The blood-brain barrier plays an important role in neuroprotection; however, it can be a major obstacle for drug delivery to the brain. This barrier primarily resides in the brain capillaries and functions as an interface between the brain and peripheral blood circulation. Several anatomical and biochemical elements of the blood-brain barrier are essential to regulate the permeability of nutrients, ions, hormones, toxic metabolites, and xenobiotics into and out of the brain. In particular, high expression of ATP-driven efflux transporters at the blood-brain barrier is a major obstacle in the delivery of CNS pharmacotherapeutics to the brain. The complete understanding of these elements can offer insights on how to modulate barrier functions for neuroprotection against CNS drug toxicity and to enhance drug delivery to the brain. In the literature, preclinical models of the blood-brain barrier are widely utilized to predict drug pharmacokinetics and pharmacodynamics properties in the brain. In addition, these models are essential tools to investigate cellular mechanisms and novel interventions that alter barrier function and permeability. This unit presents procedures to isolate fresh and viable rodent brain capillaries for the assessment of ex vivo transport activity at the blood-brain barrier. © 2017 by John Wiley & Sons, Inc.

  16. Neurovascular coupling: in vivo optical techniques for functional brain imaging

    PubMed Central

    2013-01-01

    Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology. PMID:23631798

  17. Inosine improves functional recovery after experimental traumatic brain injury.

    PubMed

    Dachir, Shlomit; Shabashov, Dalia; Trembovler, Victoria; Alexandrovich, Alexander G; Benowitz, Larry I; Shohami, Esther

    2014-03-25

    Despite years of research, no effective therapy is yet available for the treatment of traumatic brain injury (TBI). The most prevalent and debilitating features in survivors of TBI are cognitive deficits and motor dysfunction. A potential therapeutic method for improving the function of patients following TBI would be to restore, at least in part, plasticity to the CNS in a controlled way that would allow for the formation of compensatory circuits. Inosine, a naturally occurring purine nucleoside, has been shown to promote axon collateral growth in the corticospinal tract (CST) following stroke and focal TBI. In the present study, we investigated the effects of inosine on motor and cognitive deficits, CST sprouting, and expression of synaptic proteins in an experimental model of closed head injury (CHI). Treatment with inosine (100 mg/kg i.p. at 1, 24 and 48 h following CHI) improved outcome after TBI, significantly decreasing the neurological severity score (NSS, p<0.04 vs. saline), an aggregate measure of performance on several tasks. It improved non-spatial cognitive performance (object recognition, p<0.016 vs. saline) but had little effect on sensorimotor coordination (rotarod) and spatial cognitive functions (Y-maze). Inosine did not affect CST sprouting in the lumbar spinal cord but did restore levels of the growth-associated protein GAP-43 in the hippocampus, though not in the cerebral cortex. Our results suggest that inosine may improve functional outcome after TBI.

  18. Neurovascular coupling: in vivo optical techniques for functional brain imaging.

    PubMed

    Liao, Lun-De; Tsytsarev, Vassiliy; Delgado-Martínez, Ignacio; Li, Meng-Lin; Erzurumlu, Reha; Vipin, Ashwati; Orellana, Josue; Lin, Yan-Ren; Lai, Hsin-Yi; Chen, You-Yin; Thakor, Nitish V

    2013-04-30

    Optical imaging techniques reflect different biochemical processes in the brain, which is closely related with neural activity. Scientists and clinicians employ a variety of optical imaging technologies to visualize and study the relationship between neurons, glial cells and blood vessels. In this paper, we present an overview of the current optical approaches used for the in vivo imaging of neurovascular coupling events in small animal models. These techniques include 2-photon microscopy, laser speckle contrast imaging (LSCI), voltage-sensitive dye imaging (VSDi), functional photoacoustic microscopy (fPAM), functional near-infrared spectroscopy imaging (fNIRS) and multimodal imaging techniques. The basic principles of each technique are described in detail, followed by examples of current applications from cutting-edge studies of cerebral neurovascular coupling functions and metabolic. Moreover, we provide a glimpse of the possible ways in which these techniques might be translated to human studies for clinical investigations of pathophysiology and disease. In vivo optical imaging techniques continue to expand and evolve, allowing us to discover fundamental basis of neurovascular coupling roles in cerebral physiology and pathophysiology.

  19. Dynamic reorganization of brain functional networks during cognition.

    PubMed

    Bola, Michał; Sabel, Bernhard A

    2015-07-01

    How does cognition emerge from neural dynamics? The dominant hypothesis states that interactions among distributed brain regions through phase synchronization give basis for cognitive processing. Such phase-synchronized networks are transient and dynamic, established on the timescale of milliseconds in order to perform specific cognitive operations. But unlike resting-state networks, the complex organization of transient cognitive networks is typically not characterized within the graph theory framework. Thus, it is not known whether cognitive processing merely changes the strength of functional connections or, conversely, requires qualitatively new topological arrangements of functional networks. To address this question, we recorded high-density EEG while subjects performed a visual discrimination task. We conducted an event-related network analysis (ERNA) where source-space weighted functional networks were characterized with graph measures. ERNA revealed rapid, transient, and frequency-specific reorganization of the network's topology during cognition. Specifically, cognitive networks were characterized by strong clustering, low modularity, and strong interactions between hub-nodes. Our findings suggest that dense and clustered connectivity between the hub nodes belonging to different modules is the "network fingerprint" of cognition. Such reorganization patterns might facilitate global integration of information and provide a substrate for a "global workspace" necessary for cognition and consciousness to occur. Thus, characterizing topology of the event-related networks opens new vistas to interpret cognitive dynamics in the broader conceptual framework of graph theory.

  20. Disrupted Brain Functional Organization in Epilepsy Revealed by Graph Theory Analysis.

    PubMed

    Song, Jie; Nair, Veena A; Gaggl, Wolfgang; Prabhakaran, Vivek

    2015-06-01

    The human brain is a complex and dynamic system that can be modeled as a large-scale brain network to better understand the reorganizational changes secondary to epilepsy. In this study, we developed a brain functional network model using graph theory methods applied to resting-state fMRI data acquired from a group of epilepsy patients and age- and gender-matched healthy controls. A brain functional network model was constructed based on resting-state functional connectivity. A minimum spanning tree combined with proportional thresholding approach was used to obtain sparse connectivity matrices for each subject, which formed the basis of brain networks. We examined the brain reorganizational changes in epilepsy thoroughly at the level of the whole brain, the functional network, and individual brain regions. At the whole-brain level, local efficiency was significantly decreased in epilepsy patients compared with the healthy controls. However, global efficiency was significantly increased in epilepsy due to increased number of functional connections between networks (although weakly connected). At the functional network level, there were significant proportions of newly formed connections between the default mode network and other networks and between the subcortical network and other networks. There was a significant proportion of decreasing connections between the cingulo-opercular task control network and other networks. Individual brain regions from different functional networks, however, showed a distinct pattern of reorganizational changes in epilepsy. These findings suggest that epilepsy alters brain efficiency in a consistent pattern at the whole-brain level, yet alters brain functional networks and individual brain regions differently.

  1. Reorganization of functionally connected brain subnetworks in high-functioning autism.

    PubMed

    Glerean, Enrico; Pan, Raj K; Salmi, Juha; Kujala, Rainer; Lahnakoski, Juha M; Roine, Ulrika; Nummenmaa, Lauri; Leppämäki, Sami; Nieminen-von Wendt, Taina; Tani, Pekka; Saramäki, Jari; Sams, Mikko; Jääskeläinen, Iiro P

    2016-03-01

    Previous functional connectivity studies have found both hypo- and hyper-connectivity in brains of individuals having autism spectrum disorder (ASD). Here we studied abnormalities in functional brain subnetworks in high-functioning individuals with ASD during free viewing of a movie containing social cues and interactions. Twenty-six subjects (13 with ASD) watched a 68-min movie during functional magnetic resonance imaging. For each subject, we computed Pearson's correlation between haemodynamic time-courses of each pair of 6-mm isotropic voxels. From the whole-brain functional networks, we derived individual and group-level subnetworks using graph theory. Scaled inclusivity was then calculated between all subject pairs to estimate intersubject similarity of connectivity structure of each subnetwork. Additional 54 individuals (27 with ASD) from the ABIDE resting-state database were included to test the reproducibility of the results. Between-group differences were observed in the composition of default-mode and ventro-temporal-limbic (VTL) subnetworks. The VTL subnetwork included amygdala, striatum, thalamus, parahippocampal, fusiform, and inferior temporal gyri. Further, VTL subnetwork similarity between subject pairs correlated significantly with similarity of symptom gravity measured with autism quotient. This correlation was observed also within the controls, and in the reproducibility dataset with ADI-R and ADOS scores. Our results highlight how the reorganization of functional subnetworks in individuals with ASD clarifies the mixture of hypo- and hyper-connectivity findings. Importantly, only the functional organization of the VTL subnetwork emerges as a marker of inter-individual similarities that co-vary with behavioral measures across all participants. These findings suggest a pivotal role of ventro-temporal and limbic systems in autism.

  2. The connectomics of brain demyelination: Functional and structural patterns in the cuprizone mouse model.

    PubMed

    Hübner, Neele S; Mechling, Anna E; Lee, Hsu-Lei; Reisert, Marco; Bienert, Thomas; Hennig, Jürgen; von Elverfeldt, Dominik; Harsan, Laura-Adela

    2017-02-01

    Connectomics of brain disorders seeks to reveal how altered brain function emerges from the architecture of cerebral networks; however the causal impact of targeted cellular damage on the whole brain functional and structural connectivity remains unknown. In the central nervous system, demyelination is typically the consequence of an insult targeted at the oligodendrocytes, the cells forming and maintaining the myelin. This triggered perturbation generates cascades of pathological events that most likely alter the brain connectome. Here we induced oligodendrocyte death and subsequent demyelinating pathology via cuprizone treatment in mice and combining mouse brain resting state functional Magnetic Resonance Imaging and diffusion tractography we established functional and structural pathology-to-network signatures. We demonstrated that demyelinated brain fundamentally reorganizes its intrinsic functional connectivity paralleled by widespread damage of the structural scaffolding. We evidenced default mode-like network as core target of demyelination-induced connectivity modulations and hippocampus as the area with strongest connectional perturbations.

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

    PubMed Central

    Kanwisher, Nancy

    2010-01-01

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

  4. Functionally Enigmatic Genes: A Case Study of the Brain Ignorome

    PubMed Central

    Pandey, Ashutosh K.; Lu, Lu; Wang, Xusheng; Homayouni, Ramin; Williams, Robert W.

    2014-01-01

    What proportion of genes with intense and selective expression in specific tissues, cells, or systems are still almost completely uncharacterized with respect to biological function? In what ways do these functionally enigmatic genes differ from well-studied genes? To address these two questions, we devised a computational approach that defines so-called ignoromes. As proof of principle, we extracted and analyzed a large subset of genes with intense and selective expression in brain. We find that publications associated with this set are highly skewed—the top 5% of genes absorb 70% of the relevant literature. In contrast, approximately 20% of genes have essentially no neuroscience literature. Analysis of the ignorome over the past decade demonstrates that it is stubbornly persistent, and the rapid expansion of the neuroscience literature has not had the expected effect on numbers of these genes. Surprisingly, ignorome genes do not differ from well-studied genes in terms of connectivity in coexpression networks. Nor do they differ with respect to numbers of orthologs, paralogs, or protein domains. The major distinguishing characteristic between these sets of genes is date of discovery, early discovery being associated with greater research momentum—a genomic bandwagon effect. Finally we ask to what extent massive genomic, imaging, and phenotype data sets can be used to provide high-throughput functional annotation for an entire ignorome. In a majority of cases we have been able to extract and add significant information for these neglected genes. In several cases—ELMOD1, TMEM88B, and DZANK1—we have exploited sequence polymorphisms, large phenome data sets, and reverse genetic methods to evaluate the function of ignorome genes. PMID:24523945

  5. Alzheimer risk variant CLU and brain function during aging

    PubMed Central

    Thambisetty, Madhav; Beason-Held, Lori L.; An, Yang; Kraut, Michael; Nalls, Michael; Hernandez, Dena G.; Singleton, Andrew B.; Zonderman, Alan B.; Ferrucci, Luigi; Lovestone, Simon; Resnick, Susan M.

    2012-01-01

    Background We examined the effect of the novel Alzheimer's disease (AD) risk variant rs11136000 single nucleotide polymorphism (SNP) in the clusterin gene (CLU) on longitudinal changes in resting state regional cerebral blood flow (rCBF) during normal aging and investigated its influence on cognitive decline in pre-symptomatic stages of disease progression. Methods Subjects were participants in the Baltimore Longitudinal Study of Aging. A subset of 88 cognitively normal older individuals had longitudinal 15O-water PET measurements of rCBF at baseline and up to 8 annual follow-up visits. We also analyzed trajectories of cognitive decline among CLU risk carriers and non-carriers both in individuals who remained cognitively normal (N=599) as well as in those who subsequently converted to mild cognitive impairment (MCI) or AD (N=95). Results Cognitively normal carriers of the CLU risk allele show significant and dose-dependent longitudinal increases in resting state rCBF in brain regions intrinsic to memory processes. There were no differences in trajectories of memory performance between CLU risk carriers and non-carriers who remained cognitively normal. However, in cognitively normal individuals who eventually convert to MCI or AD, CLU risk carriers show faster rates of decline in memory performance relative to non-carriers in the pre-symptomatic stages of disease progression. Conclusions The AD risk variant CLU influences longitudinal changes in brain function in asymptomatic individuals and is associated with faster cognitive decline in pre-symptomatic stages of disease progression. These results suggest mechanisms underlying the role of CLU in AD and may be important in monitoring disease progression in at-risk elderly. PMID:22795969

  6. Methamphetamine effects on blood-brain barrier structure and function

    PubMed Central

    Northrop, Nicole A.; Yamamoto, Bryan K.

    2015-01-01

    Methamphetamine (Meth) is a widely abuse psychostimulant. Traditionally, studies have focused on the neurotoxic effects of Meth on monoaminergic neurotransmitter terminals. Recently, both in vitro and in vivo studies have investigated the effects of Meth on the BBB and found that Meth produces a decrease in BBB structural proteins and an increase in BBB permeability to various molecules. Moreover, preclinical studies are validated by clinical studies in which human Meth users have increased concentrations of toxins in the brain. Therefore, this review will focus on the structural and functional disruption of the BBB caused by Meth and the mechanisms that contribute to Meth-induced BBB disruption. The review will reveal that the mechanisms by which Meth damages dopamine and serotonin terminals are similar to the mechanisms by which the blood-brain barrier (BBB) is damaged. Furthermore, this review will cover the factors that are known to potentiate the effects of Meth (McCann et al., 1998) on the BBB, such as stress and HIV, both of which are co-morbid conditions associated with Meth abuse. Overall, the goal of this review is to demonstrate that the scope of damage produced by Meth goes beyond damage to monoaminergic neurotransmitter systems to include BBB disruption as well as provide a rationale for investigating therapeutics to treat Meth-induced BBB disruption. Since a breach of the BBB can have a multitude of consequences, therapies directed toward the treatment of BBB disruption may help to ameliorate the long-term neurodegeneration and cognitive deficits produced by Meth and possibly even Meth addiction. PMID:25788874

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

    PubMed

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

    2015-06-01

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

  8. Brain and Retinal Pericytes: Origin, Function and Role

    PubMed Central

    Trost, Andrea; Lange, Simona; Schroedl, Falk; Bruckner, Daniela; Motloch, Karolina A.; Bogner, Barbara; Kaser-Eichberger, Alexandra; Strohmaier, Clemens; Runge, Christian; Aigner, Ludwig; Rivera, Francisco J.; Reitsamer, Herbert A.

    2016-01-01

    Pericytes are specialized mural cells located at the abluminal surface of capillary blood vessels, embedded within the basement membrane. In the vascular network these multifunctional cells fulfil diverse functions, which are indispensable for proper homoeostasis. They serve as microvascular stabilizers, are potential regulators of microvascular blood flow and have a central role in angiogenesis, as they for example regulate endothelial cell proliferation. Furthermore, pericytes, as part of the neurovascular unit, are a major component of the blood-retina/brain barrier. CNS pericytes are a heterogenic cell population derived from mesodermal and neuro-ectodermal germ layers acting as modulators of stromal and niche environmental properties. In addition, they display multipotent differentiation potential making them an intriguing target for regenerative therapies. Pericyte-deficiencies can be cause or consequence of many kinds of diseases. In diabetes, for instance, pericyte-loss is a severe pathological process in diabetic retinopathy (DR) with detrimental consequences for eye sight in millions of patients. In this review, we provide an overview of our current understanding of CNS pericyte origin and function, with a special focus on the retina in the healthy and diseased. Finally, we highlight the role of pericytes in de- and regenerative processes. PMID:26869887

  9. Zinc: an underappreciated modulatory factor of brain function.

    PubMed

    Marger, L; Schubert, C R; Bertrand, D

    2014-10-15

    The divalent cation, zinc is the second most abundant metal in the human body and is indispensable for life. Zinc concentrations must however, be tightly regulated as deficiencies are associated with multiple pathological conditions while an excess can be toxic. Zinc plays an important role as a cofactor in protein folding and function, e.g. catalytic interactions, DNA recognition by zinc finger proteins and modulation ion channel activity. There are 24 mammalian proteins specific for zinc transport that are subdivided in two groups with opposing functions: ZnT proteins reduce cytosolic zinc concentration while ZIP proteins increase it. The mammalian brain contains a significant amount of zinc, with 5-15% concentrated in synaptic vesicles of glutamatergic neurons alone. Accumulated in these vesicles by the ZnT3 transporter, zinc is released into the synaptic cleft at concentrations from nanomolar at rest to high micromolar during active neurotransmission. Low concentrations of zinc modulate the activity of a multitude of voltage- or ligand-gated ion channels, indicating that this divalent cation must be taken into account in the analysis of the pathophysiology of CNS disorders including epilepsy, schizophrenia and Alzheimer's disease. In the context of the latest findings, we review the role of zinc in the central nervous system and discuss the relevance of the most recent association between the zinc transporter, ZIP8 and schizophrenia. An enhanced understanding of zinc transporters in the context of ion channel modulation may offer new avenues in identifying novel therapeutic entities that target neurological disorders.

  10. Oatp58Dc contributes to blood-brain barrier function by excluding organic anions from the Drosophila brain.

    PubMed

    Seabrooke, Sara; O'Donnell, Michael J

    2013-09-01

    The blood-brain barrier (BBB) physiologically isolates the brain from the blood and, thus, plays a vital role in brain homeostasis. Ion transporters play a critical role in this process by effectively regulating access of chemicals to the brain. Organic anion-transporting polypeptides (Oatps) transport a wide range of amphipathic substrates and are involved in efflux of chemicals across the vertebrate BBB. The anatomic complexity of the vascularized vertebrate BBB, however, creates challenges for experimental analysis of these processes. The less complex structure of the Drosophila BBB facilitates measurement of solute transport. Here we investigate a physiological function for Oatp58Dc in transporting small organic anions across the BBB. We used genetic manipulation, immunocytochemistry, and molecular techniques to supplement a whole animal approach to study the BBB. For this whole animal approach, the traceable small organic anion fluorescein was injected into the hemolymph. This research shows that Oatp58Dc is involved in maintaining a chemical barrier against fluorescein permeation into the brain. Oatp58Dc expression was found in the perineurial and subperineurial glia, as well as in postmitotic neurons. We specifically targeted knockdown of Oatp58Dc expression in the perineurial and subperineurial glia to reveal that Oatp58Dc expression in the perineurial glia is necessary to maintain the barrier against fluorescein influx into the brain. Our results show that Oatp58Dc contributes to maintenance of a functional barrier against fluorescein influx past the BBB into the brain.

  11. 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.

  12. Sustained deep-tissue pain alters functional brain connectivity.

    PubMed

    Kim, Jieun; Loggia, Marco L; Edwards, Robert R; Wasan, Ajay D; Gollub, Randy L; Napadow, Vitaly

    2013-08-01

    Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity.

  13. Graph analysis of functional brain networks: practical issues in translational neuroscience.

    PubMed

    De Vico Fallani, Fabrizio; Richiardi, Jonas; Chavez, Mario; Achard, Sophie

    2014-10-05

    The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes.

  14. Graph analysis of functional brain networks: practical issues in translational neuroscience

    PubMed Central

    De Vico Fallani, Fabrizio; Richiardi, Jonas; Chavez, Mario; Achard, Sophie

    2014-01-01

    The brain can be regarded as a network: a connected system where nodes, or units, represent different specialized regions and links, or connections, represent communication pathways. From a functional perspective, communication is coded by temporal dependence between the activities of different brain areas. In the last decade, the abstract representation of the brain as a graph has allowed to visualize functional brain networks and describe their non-trivial topological properties in a compact and objective way. Nowadays, the use of graph analysis in translational neuroscience has become essential to quantify brain dysfunctions in terms of aberrant reconfiguration of functional brain networks. Despite its evident impact, graph analysis of functional brain networks is not a simple toolbox that can be blindly applied to brain signals. On the one hand, it requires the know-how of all the methodological steps of the pipeline that manipulate the input brain signals and extract the functional network properties. On the other hand, knowledge of the neural phenomenon under study is required to perform physiologically relevant analysis. The aim of this review is to provide practical indications to make sense of brain network analysis and contrast counterproductive attitudes. PMID:25180301

  15. Measurement of brain function of car driver using functional near-infrared spectroscopy (fNIRS).

    PubMed

    Tsunashima, Hitoshi; Yanagisawa, Kazuki

    2009-01-01

    The aim of this study is to propose a method for analyzing measured signal obtained from functional Near-Infrared Spectroscopy (fNIRS), which is applicable for neuroimaging studies for car drivers. We developed a signal processing method by multiresolution analysis (MRA) based on discrete wavelet transform. Statistical group analysis using Z-score is conducted after the extraction of task-related signal using MRA. Brain activities of subjects with different level of mental calculation are measured by fNIRS and fMRI. Results of mental calculation with nine subjects by using fNIRS and fMRI showed that the proposed methods were effective for the evaluation of brain activities due to the task. Finally, the proposed method is applied for evaluating brain function of car driver with and without adaptive cruise control (ACC) system for demonstrating the effectiveness of the proposed method. The results showed that frontal lobe was less active when the subject drove with ACC.

  16. A novel pattern mining approach for identifying cognitive activity in EEG based functional brain networks.

    PubMed

    Thilaga, M; Vijayalakshmi, R; Nadarajan, R; Nandagopal, D

    2016-06-01

    The complex nature of neuronal interactions of the human brain has posed many challenges to the research community. To explore the underlying mechanisms of neuronal activity of cohesive brain regions during different cognitive activities, many innovative mathematical and computational models are required. This paper presents a novel Common Functional Pattern Mining approach to demonstrate the similar patterns of interactions due to common behavior of certain brain regions. The electrode sites of EEG-based functional brain network are modeled as a set of transactions and node-based complex network measures as itemsets. These itemsets are transformed into a graph data structure called Functional Pattern Graph. By mining this Functional Pattern Graph, the common functional patterns due to specific brain functioning can be identified. The empirical analyses show the efficiency of the proposed approach in identifying the extent to which the electrode sites (transactions) are similar during various cognitive load states.

  17. Aging. Aging-induced type I interferon response at the choroid plexus negatively affects brain function.

    PubMed

    Baruch, Kuti; Deczkowska, Aleksandra; David, Eyal; Castellano, Joseph M; Miller, Omer; Kertser, Alexander; Berkutzki, Tamara; Barnett-Itzhaki, Zohar; Bezalel, Dana; Wyss-Coray, Tony; Amit, Ido; Schwartz, Michal

    2014-10-03

    Aging-associated cognitive decline is affected by factors produced inside and outside the brain. By using multiorgan genome-wide analysis of aged mice, we found that the choroid plexus, an interface between the brain and the circulation, shows a type I interferon (IFN-I)-dependent gene expression profile that was also found in aged human brains. In aged mice, this response was induced by brain-derived signals, present in the cerebrospinal fluid. Blocking IFN-I signaling within the aged brain partially restored cognitive function and hippocampal neurogenesis and reestablished IFN-II-dependent choroid plexus activity, which is lost in aging. Our data identify a chronic aging-induced IFN-I signature, often associated with antiviral response, at the brain's choroid plexus and demonstrate its negative influence on brain function, thereby suggesting a target for ameliorating cognitive decline in aging.

  18. Beyond sex differences: new approaches for thinking about variation in brain structure and function.

    PubMed

    Joel, Daphna; Fausto-Sterling, Anne

    2016-02-19

    In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being.

  19. Beyond sex differences: new approaches for thinking about variation in brain structure and function

    PubMed Central

    Joel, Daphna; Fausto-Sterling, Anne

    2016-01-01

    In the study of variation in brain structure and function that might relate to sex and gender, language matters because it frames our research questions and methods. In this article, we offer an approach to thinking about variation in brain structure and function that pulls us outside the sex differences formulation. We argue that the existence of differences between the brains of males and females does not unravel the relations between sex and the brain nor is it sufficient to characterize a population of brains. Such characterization is necessary for studying sex effects on the brain as well as for studying brain structure and function in general. Animal studies show that sex interacts with environmental, developmental and genetic factors to affect the brain. Studies of humans further suggest that human brains are better described as belonging to a single heterogeneous population rather than two distinct populations. We discuss the implications of these observations for studies of brain and behaviour in humans and in laboratory animals. We believe that studying sex effects in context and developing or adopting analytical methods that take into account the heterogeneity of the brain are crucial for the advancement of human health and well-being. PMID:26833844

  20. Dynamic brain architectures in local brain activity and functional network efficiency associate with efficient reading in bilinguals.

    PubMed

    Feng, Gangyi; Chen, Hsuan-Chih; Zhu, Zude; He, Yong; Wang, Suiping

    2015-10-01

    The human brain is organized as a dynamic network, in which both regional brain activity and inter-regional connectivity support high-level cognitive processes, such as reading. However, it is still largely unknown how the functional brain network organizes to enable fast and effortless reading processing in the native language (L1) but not in a non-proficient second language (L2), and whether the mechanisms underlying local activity are associated with connectivity dynamics in large-scale brain networks. In the present study, we combined activation-based and multivariate graph-theory analysis with functional magnetic resonance imaging data to address these questions. Chinese-English unbalanced bilinguals read narratives for comprehension in Chinese (L1) and in English (L2). Compared with L2, reading in L1 evoked greater brain activation and recruited a more globally efficient but less clustered network organization. Regions with both increased network efficiency and enhanced brain activation in L1 reading were mostly located in the fronto-temporal reading-related network (RN), whereas regions with decreased global network efficiency, increased clustering, and more deactivation in L2 reading were identified in the default mode network (DMN). Moreover, functional network efficiency was closely associated with local brain activation, and such associations were also modulated by reading efficiency in the two languages. Our results demonstrate that an economical and integrative brain network topology is associated with efficient reading, and further reveal a dynamic association between network efficiency and local activation for both RN and DMN. These findings underscore the importance of considering interregional connectivity when interpreting local BOLD signal changes in bilingual reading.

  1. 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

  2. Complex network analysis of brain functional connectivity under a multi-step cognitive task

    NASA Astrophysics Data System (ADS)

    Cai, Shi-Min; Chen, Wei; Liu, Dong-Bai; Tang, Ming; Chen, Xun

    2017-01-01

    Functional brain network has been widely studied to understand the relationship between brain organization and behavior. In this paper, we aim to explore the functional connectivity of brain network under a multi-step cognitive task involving consecutive behaviors, and further understand the effect of behaviors on the brain organization. The functional brain networks are constructed based on a high spatial and temporal resolution fMRI dataset and analyzed via complex network based approach. We find that at voxel level the functional brain network shows robust small-worldness and scale-free characteristics, while its assortativity and rich-club organization are slightly restricted to the order of behaviors performed. More interestingly, the functional connectivity of brain network in activated ROIs strongly correlates with behaviors and is obviously restricted to the order of behaviors performed. These empirical results suggest that the brain organization has the generic properties of small-worldness and scale-free characteristics, and its diverse functional connectivity emerging from activated ROIs is strongly driven by these behavioral activities via the plasticity of brain.

  3. State-Dependent Changes of Connectivity Patterns and Functional Brain Network Topology in Autism Spectrum Disorder

    ERIC Educational Resources Information Center

    Barttfeld, Pablo; Wicker, Bruno; Cukier, Sebastian; Navarta, Silvana; Lew, Sergio; Leiguarda, Ramon; Sigman, Mariano

    2012-01-01

    Anatomical and functional brain studies have converged to the hypothesis that autism spectrum disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that…

  4. From the Left to the Right: How the Brain Compensates Progressive Loss of Language Function

    ERIC Educational Resources Information Center

    Thiel, Alexander; Habedank, Birgit; Herholz, Karl; Kessler, Josef; Winhuisen, Lutz; Haupt, Walter F.; Heiss, Wolf-Dieter

    2006-01-01

    In normal right-handed subjects language production usually is a function of the left brain hemisphere. Patients with aphasia following brain damage to the left hemisphere have a considerable potential to compensate for the loss of this function. Sometimes, but not always, areas of the right hemisphere which are homologous to language areas of the…

  5. Mapping Language Function in the Brain: A Review of the Recent Literature.

    ERIC Educational Resources Information Center

    Crafton, Robert E.; Kido, Elissa

    2000-01-01

    Considers the potential importance of brain study for composition instruction, briefly describes functional imaging techniques, and reviews the findings of recent brain-mapping studies investigating the neurocognitive systems involved in language function. Presents a review of the recent literature and considers the possible implications of this…

  6. Breathing as a Fundamental Rhythm of Brain Function

    PubMed Central

    Heck, Detlef H.; McAfee, Samuel S.; Liu, Yu; Babajani-Feremi, Abbas; Rezaie, Roozbeh; Freeman, Walter J.; Wheless, James W.; Papanicolaou, Andrew C.; Ruszinkó, Miklós; Sokolov, Yury; Kozma, Robert

    2017-01-01

    Ongoing fluctuations of neuronal activity have long been considered intrinsic noise that introduces unavoidable and unwanted variability into neuronal processing, which the brain eliminates by averaging across population activity (Georgopoulos et al., 1986; Lee et al., 1988; Shadlen and Newsome, 1994; Maynard et al., 1999). It is now understood, that the seemingly random fluctuations of cortical activity form highly structured patterns, including oscillations at various frequencies, that modulate evoked neuronal responses (Arieli et al., 1996; Poulet and Petersen, 2008; He, 2013) and affect sensory perception (Linkenkaer-Hansen et al., 2004; Boly et al., 2007; Sadaghiani et al., 2009; Vinnik et al., 2012; Palva et al., 2013). Ongoing cortical activity is driven by proprioceptive and interoceptive inputs. In addition, it is partially intrinsically generated in which case it may be related to mental processes (Fox and Raichle, 2007; Deco et al., 2011). Here we argue that respiration, via multiple sensory pathways, contributes a rhythmic component to the ongoing cortical activity. We suggest that this rhythmic activity modulates the temporal organization of cortical neurodynamics, thereby linking higher cortical functions to the process of breathing. PMID:28127277

  7. Astrocytes, Synapses and Brain Function: A Computational Approach

    NASA Astrophysics Data System (ADS)

    Nadkarni, Suhita

    2006-03-01

    Modulation of synaptic reliability is one of the leading mechanisms involved in long- term potentiation (LTP) and long-term depression (LTD) and therefore has implications in information processing in the brain. A recently discovered mechanism for modulating synaptic reliability critically involves recruitments of astrocytes - star- shaped cells that outnumber the neurons in most parts of the central nervous system. Astrocytes until recently were thought to be subordinate cells merely participating in supporting neuronal functions. New evidence, however, made available by advances in imaging technology has changed the way we envision the role of these cells in synaptic transmission and as modulator of neuronal excitability. We put forward a novel mathematical framework based on the biophysics of the bidirectional neuron-astrocyte interactions that quantitatively accounts for two distinct experimental manifestation of recruitment of astrocytes in synaptic transmission: a) transformation of a low fidelity synapse transforms into a high fidelity synapse and b) enhanced postsynaptic spontaneous currents when astrocytes are activated. Such a framework is not only useful for modeling neuronal dynamics in a realistic environment but also provides a conceptual basis for interpreting experiments. Based on this modeling framework, we explore the role of astrocytes for neuronal network behavior such as synchrony and correlations and compare with experimental data from cultured networks.

  8. Challenges for the functional diffusion map in pediatric brain tumors

    PubMed Central

    Grech-Sollars, Matthew; Saunders, Dawn E.; Phipps, Kim P.; Kaur, Ramneek; Paine, Simon M.L.; Jacques, Thomas S.; Clayden, Jonathan D.; Clark, Chris A.

    2014-01-01

    Background The functional diffusion map (fDM) has been suggested as a tool for early detection of tumor treatment efficacy. We aim to study 3 factors that could act as potential confounders in the fDM: areas of necrosis, tumor grade, and change in tumor size. Methods Thirty-four pediatric patients with brain tumors were enrolled in a retrospective study, approved by the local ethics committee, to examine the fDM. Tumors were selected to encompass a range of types and grades. A qualitative analysis was carried out to compare how fDM findings may be affected by each of the 3 confounders by comparing fDM findings to clinical image reports. Results Results show that the fDM in areas of necrosis do not discriminate between treatment response and tumor progression. Furthermore, tumor grade alters the behavior of the fDM: a decrease in apparent diffusion coefficient (ADC) is a sign of tumor progression in high-grade tumors and treatment response in low-grade tumors. Our results also suggest using only tumor area overlap between the 2 time points analyzed for the fDM in tumors of varying size. Conclusions Interpretation of fDM results needs to take into account the underlying biology of both tumor and healthy tissue. Careful interpretation of the results is required with due consideration to areas of necrosis, tumor grade, and change in tumor size. PMID:24305721

  9. Alterations of blood brain barrier function in hyperammonemia: an overview.

    PubMed

    Skowrońska, Marta; Albrecht, Jan

    2012-02-01

    Ammonia is a neurotoxin involved in the pathogenesis of neurological conditions associated with hyperammonemia, including hepatic encephalopathy, a condition associated with acute--(ALF) or chronic liver failure. This article reviews evidence that apart from directly affecting the metabolism and function of the central nervous system cells, ammonia influences the passage of different molecules across the blood brain barrier (BBB). A brief description is provided of the tight junctions, which couple adjacent cerebral capillary endothelial cells to each other to form the barrier. Ammonia modulates the transcellular passage of low-to medium-size molecules, by affecting their carriers located at the BBB. Ammonia induces interrelated aberrations of the transport of the large neutral amino acids and aromatic amino acids (AAA), whose influx is augmented by exchange with glutamine produced in the course of ammonia detoxification, and maybe also modulated by the extracellularly acting gamma-glutamyl moiety transferring enzyme, gamma-glutamyl-transpeptidase. Impaired AAA transport affects neurotransmission by altering intracerebral synthesis of catecholamines (serotonin and dopamine), and producing "false neurotransmitters" (octopamine and phenylethylamine). Ammonia also modulates BBB transport of the cationic amino acids: the nitric oxide precursor, arginine, and ornithine, which is an ammonia trap, and affects the transport of energy metabolites glucose and creatine. Moreover, ammonia acting either directly or in synergy with liver injury-derived inflammatory cytokines also evokes subtle increases of the transcellular passage of molecules of different size (BBB "leakage"), which appears to be responsible for the vasogenic component of cerebral edema associated with ALF.

  10. Functional brain network changes associated with clinical and biochemical measures of the severity of hepatic encephalopathy.

    PubMed

    Jao, Tun; Schröter, Manuel; Chen, Chao-Long; Cheng, Yu-Fan; Lo, Chun-Yi Zac; Chou, Kun-Hsien; Patel, Ameera X; Lin, Wei-Che; Lin, Ching-Po; Bullmore, Edward T

    2015-11-15

    Functional properties of the brain may be associated with changes in complex brain networks. However, little is known about how properties of large-scale functional brain networks may be altered stepwise in patients with disturbance of consciousness, e.g., an encephalopathy. We used resting-state fMRI data on patients suffering from various degrees of hepatic encephalopathy (HE) to explore how topological and spatial network properties of functional brain networks changed at different cognitive and consciousness states. Severity of HE was measured clinically and by neuropsychological tests. Fifty-eight non-alcoholic liver cirrhosis patients and 62 normal controls were studied. Patients were subdivided into liver cirrhosis with no outstanding HE (NoHE, n=23), minimal HE with cognitive impairment only detectable by neuropsychological tests (MHE, n=28), and clinically overt HE (OHE, n=7). From the earliest stage, the NoHE, functional brain networks were progressively more random, less clustered, and less modular. Since the intermediate stage (MHE), increased ammonia level was accompanied by concomitant exponential decay of mean connectivity strength, especially in the primary cortical areas and midline brain structures. Finally, at the OHE stage, there were radical reorganization of the topological centrality-i.e., the relative importance-of the hubs and reorientation of functional connections between nodes. In summary, this study illustrated progressively greater abnormalities in functional brain network organization in patients with clinical and biochemical evidence of more severe hepatic encephalopathy. The early-than-expected brain network dysfunction in cirrhotic patients suggests that brain functional connectivity and network analysis may provide useful and complementary biomarkers for more aggressive and earlier intervention of hepatic encephalopathy. Moreover, the stepwise deterioration of functional brain networks in HE patients may suggest that hierarchical

  11. Dynamic Functional Segregation and Integration in Human Brain Network During Complex Tasks.

    PubMed

    Ren, Shen; Li, Junhua; Taya, Fumihiko; deSouza, Joshua; Thakor, Nitish; Bezerianos, Anastasios

    2016-09-09

    The analysis of the topology and organisation of brain networks is known to greatly benefit from network measures in graph theory. However, to evaluate dynamic changes of brain functional connectivity, more sophisticated quantitative metrics characterising temporal evolution of brain topological features are required. To simplify conversion of time-varying brain connectivity to a static graph representation is straightforward but the procedure loses temporal information that could be critical in understanding the brain functions. To extend the understandings of functional segregation and integration to a dynamic fashion, we recommend dynamic graph metrics to characterise temporal changes of topological features of brain networks. This study investigated functional segregation and integration of brain networks over time by dynamic graph metrics derived from EEG signals during an experimental protocol: performance of complex flight simulation tasks with multiple levels of difficulty. We modelled time-varying brain functional connectivity as multilayer networks, in which each layer models brain connectivity at time window t + t. Dynamic graph metrics were calculated to quantify temporal and topological properties of the network. Results show that brain networks under the performance of complex tasks reveal a dynamic small-world architecture with a number of frequently connected nodes or hubs, which supports the balance of information segregation and integration in brain over time. The results also show that greater cognitive workloads caused by more difficult tasks induced a more globally efficient but less clustered dynamic small-world functional network. Our study illustrates that task-related changes of functional brain network segregation and integration can be characterised by dynamic graph metrics.

  12. The blind brain: how (lack of) vision shapes the morphological and functional architecture of the human brain.

    PubMed

    Ricciardi, Emiliano; Handjaras, Giacomo; Pietrini, Pietro

    2014-11-01

    Since the early days, how we represent the world around us has been a matter of philosophical speculation. Over the last few decades, modern neuroscience, and specifically the development of methodologies for the structural and the functional exploration of the brain have made it possible to investigate old questions with an innovative approach. In this brief review, we discuss the main findings from a series of brain anatomical and functional studies conducted in sighted and congenitally blind individuals by our's and others' laboratories. Historically, research on the 'blind brain' has focused mainly on the cross-modal plastic changes that follow sensory deprivation. More recently, a novel line of research has been developed to determine to what extent visual experience is truly required to achieve a representation of the surrounding environment. Overall, the results of these studies indicate that most of the brain fine morphological and functional architecture is programmed to develop and function independently from any visual experience. Distinct cortical areas are able to process information in a supramodal fashion, that is, independently from the sensory modality that carries that information to the brain. These observations strongly support the hypothesis of a modality-independent, i.e. more abstract, cortical organization, and may contribute to explain how congenitally blind individuals may interact efficiently with an external world that they have never seen.

  13. Mapping brain structure and function: cellular resolution, global perspective.

    PubMed

    Zupanc, Günther K H

    2017-04-01

    A comprehensive understanding of the brain requires analysis, although from a global perspective, with cellular, and even subcellular, resolution. An important step towards this goal involves the establishment of three-dimensional high-resolution brain maps, incorporating brain-wide information about the cells and their connections, as well as the chemical architecture. The progress made in such anatomical brain mapping in recent years has been paralleled by the development of physiological techniques that enable investigators to generate global neural activity maps, also with cellular resolution, while simultaneously recording the organism's behavioral activity. Combination of the high-resolution anatomical and physiological maps, followed by theoretical systems analysis of the deduced network, will offer unprecedented opportunities for a better understanding of how the brain, as a whole, processes sensory information and generates behavior.

  14. Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128.

    PubMed

    Adlakha, Yogita K; Saini, Neeru

    2014-02-21

    MicroRNAs, the non-coding single-stranded RNA of 19-25 nucleotides are emerging as robust players of gene regulation. Plethora of evidences support that the ability of microRNAs to regulate several genes of a pathway or even multiple cross talking pathways have significant impact on a complex regulatory network and ultimately the physiological processes and diseases. Brain being a complex organ with several cell types, expresses more distinct miRNAs than any other tissues. This review aims to discuss about the microRNAs in brain development, function and their dysfunction in brain tumors. We also provide a comprehensive summary of targets of brain specific and brain enriched miRNAs that contribute to the diversity and plasticity of the brain. In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers. This review describes the wide spectrum of targets of miRNA-128 that have been identified till date with potential roles in apoptosis, angiogenesis, proliferation, cholesterol metabolism, self renewal, invasion and cancer progression and how this knowledge might be exploited for the development of future miRNA-128 based therapies for the treatment of cancer as well as metabolic diseases.

  15. Brain microRNAs and insights into biological functions and therapeutic potential of brain enriched miRNA-128

    PubMed Central

    2014-01-01

    MicroRNAs, the non-coding single-stranded RNA of 19–25 nucleotides are emerging as robust players of gene regulation. Plethora of evidences support that the ability of microRNAs to regulate several genes of a pathway or even multiple cross talking pathways have significant impact on a complex regulatory network and ultimately the physiological processes and diseases. Brain being a complex organ with several cell types, expresses more distinct miRNAs than any other tissues. This review aims to discuss about the microRNAs in brain development, function and their dysfunction in brain tumors. We also provide a comprehensive summary of targets of brain specific and brain enriched miRNAs that contribute to the diversity and plasticity of the brain. In particular, we uncover recent findings on miRNA-128, a brain-enriched microRNA that is induced during neuronal differentiation and whose aberrant expression has been reported in several cancers. This review describes the wide spectrum of targets of miRNA-128 that have been identified till date with potential roles in apoptosis, angiogenesis, proliferation, cholesterol metabolism, self renewal, invasion and cancer progression and how this knowledge might be exploited for the development of future miRNA-128 based therapies for the treatment of cancer as well as metabolic diseases. PMID:24555688

  16. Phase synchronization in brain networks derived from correlation between probabilities of recurrences in functional MRI data.

    PubMed

    Rangaprakash, D; Hu, Xiaoping; Deshpande, Gopikrishna

    2013-04-01

    It is increasingly being recognized that resting state brain connectivity derived from functional magnetic resonance imaging (fMRI) data is an important marker of brain function both in healthy and clinical populations. Though linear correlation has been extensively used to characterize brain connectivity, it is limited to detecting first order dependencies. In this study, we propose a framework where in phase synchronization (PS) between brain regions is characterized using a new metric "correlation between probabilities of recurrence" (CPR) and subsequent graph-theoretic analysis of the ensuing networks. We applied this method to resting state fMRI data obtained from human subjects with and without administration of propofol anesthetic. Our results showed decreased PS during anesthesia and a biologically more plausible community structure using CPR rather than linear correlation. We conclude that CPR provides an attractive nonparametric method for modeling interactions in brain networks as compared to standard correlation for obtaining physiologically meaningful insights about brain function.

  17. The Developmental Trajectory of Brain-Scalp Distance from Birth through Childhood: Implications for Functional Neuroimaging

    PubMed Central

    Beauchamp, Michael S.; Beurlot, Michelle R.; Fava, Eswen; Nath, Audrey R.; Parikh, Nehal A.; Saad, Ziad S.; Bortfeld, Heather; Oghalai, John S.

    2011-01-01

    Measurements of human brain function in children are of increasing interest in cognitive neuroscience. Many techniques for brain mapping used in children, including functional near-infrared spectroscopy (fNIRS), electroencephalography (EEG), magnetoencephalography (MEG) and transcranial magnetic stimulation (TMS), use probes placed on or near the scalp. The distance between the scalp and the brain is a key variable for these techniques because optical, electrical and magnetic signals are attenuated by distance. However, little is known about how scalp-brain distance differs between different cortical regions in children or how it changes with development. We investigated scalp-brain distance in 71 children, from newborn to age 12 years, using structural T1-weighted MRI scans of the whole head. Three-dimensional reconstructions were created from the scalp surface to allow for accurate calculation of brain-scalp distance. Nine brain landmarks in different cortical regions were manually selected in each subject based on the published fNIRS literature. Significant effects were found for age, cortical region and hemisphere. Brain-scalp distances were lowest in young children, and increased with age to up to double the newborn distance. There were also dramatic differences between brain regions, with up to 50% differences between landmarks. In frontal and temporal regions, scalp-brain distances were significantly greater in the right hemisphere than in the left hemisphere. The largest contributors to developmental changes in brain-scalp distance were increases in the corticospinal fluid (CSF) and inner table of the cranium. These results have important implications for functional imaging studies of children: age and brain-region related differences in fNIRS signals could be due to the confounding factor of brain-scalp distance and not true differences in brain activity. PMID:21957470

  18. Exercise to enhance neurocognitive function after traumatic brain injury.

    PubMed

    Fogelman, David; Zafonte, Ross

    2012-11-01

    Vigorous exercise has long been associated with improved health in many domains. Results of clinical observation have suggested that neurocognitive performance also is improved by vigorous exercise. Data derived from animal model-based research have been emerging that show molecular and neuroanatomic mechanisms that may explain how exercise improves cognition, particularly after traumatic brain injury. This article will summarize the current state of the basic science and clinical literature regarding exercise as an intervention, both independently and in conjunction with other modalities, for brain injury rehabilitation. A key principle is the factor of timing of the initiation of exercise after mild traumatic brain injury, balancing potentially favorable and detrimental effects on recovery.

  19. Brain maps on the go: functional imaging during motor challenge in animals.

    PubMed

    Holschneider, D P; Maarek, J-M I

    2008-08-01

    Brain mapping in the freely moving animal is useful for studying motor circuits, not only because it avoids the potential confound of sedation or restraints, but because activated brain states may serve to accentuate differences that only manifest partially while a subject is in the resting state. Perfusion or metabolic mapping using autoradiography allows one to examine changes in brain function at the circuit level across the entire brain with a spatial resolution (approximately 100 micro) appropriate for the rat or mouse brain, and a temporal resolution (seconds-minutes) sufficient for capturing acute brain changes. Here we summarize the application of these methods to the functional brain mapping of behaviors involving locomotion of small animals, methods for the three-dimensional reconstruction of the brain from autoradiographic sections, voxel based analysis of the whole brain, and generation of maps of the flattened rat cortex. Application of these methods in animal models promises utility in improving our understanding of motor function in the normal brain, and of the effects of neuropathology and treatment interventions such as exercise have on the reorganization of motor circuits.

  20. Sodium nitrite protects against kidney injury induced by brain death and improves post-transplant function.

    PubMed

    Kelpke, Stacey S; Chen, Bo; Bradley, Kelley M; Teng, Xinjun; Chumley, Phillip; Brandon, Angela; Yancey, Brett; Moore, Brandon; Head, Hughston; Viera, Liliana; Thompson, John A; Crossman, David K; Bray, Molly S; Eckhoff, Devin E; Agarwal, Anupam; Patel, Rakesh P

    2012-08-01

    Renal injury induced by brain death is characterized by ischemia and inflammation, and limiting it is a therapeutic goal that could improve outcomes in kidney transplantation. Brain death resulted in decreased circulating nitrite levels and increased infiltrating inflammatory cell infiltration into the kidney. Since nitrite stimulates nitric oxide signaling in ischemic tissues, we tested whether nitrite therapy was beneficial in a rat model of brain death followed by kidney transplantation. Nitrite, administered over 2 h of brain death, blunted the increased inflammation without affecting brain death-induced alterations in hemodynamics. Kidneys were transplanted after 2 h of brain death and renal function followed over 7 days. Allografts collected from nitrite-treated brain-dead rats showed significant improvement in function over the first 2 to 4 days after transplantation compared with untreated brain-dead animals. Gene microarray analysis after 2 h of brain death without or with nitrite therapy showed that the latter significantly altered the expression of about 400 genes. Ingenuity Pathway Analysis indicated that multiple signaling pathways were affected by nitrite, including those related to hypoxia, transcription, and genes related to humoral immune responses. Thus, nitrite therapy attenuates brain death-induced renal injury by regulating responses to ischemia and inflammation, ultimately leading to better post-transplant kidney function.

  1. Contribution of Neuroimaging Studies to Understanding Development of Human Cognitive Brain Functions.

    PubMed

    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.

  2. Relationship Between Neurocognitive Function and Quality of Life After Whole-Brain Radiotherapy in Patients With Brain Metastasis

    SciTech Connect

    Li Jing; Bentzen, Soren M.; Li Jialiang; Renschler, Markus; Mehta, Minesh P.

    2008-05-01

    Purpose: To examine the relationship between neurocognitive function (NCF) and quality of life (QOL) in patients with brain metastases after whole-brain radiotherapy. Patients and Methods: A total of 208 patients from the whole-brain radiotherapy arm of a Phase III trial (PCI-P120-9801), who underwent regular NCF and QOL (ADL [activities of daily living] and FACT-Br [Functional Assessment of Cancer Therapy-Brain-specific]) testing, were analyzed. Spearman's rank correlation was calculated between NCF and QOL, using each patient's own data, at each time point. To test the hypothesis that NCF declines before QOL changes, the predictive effect of NCF from previous visits on QOL was studied with a linear mixed-effects model. Neurocognitive function or QOL deterioration was defined relative to each patient's own baseline. Lead or lag time, defined as NCF deterioration before or after the date of QOL decline, respectively, was computed. Results: At baseline, all NCF tests showed statistically significant correlations with ADL, which became stronger at 4 months. A similar observation was made with FACT-Br. Neurocognitive function scores from previous visits predicted ADL (p < 0.05 for seven of eight tests) or FACT-Br. Scores on all eight NCF tests deteriorated before ADL decline (net lead time 9-153 days); and scores on six of eight NCF tests deteriorated before FACT-Br (net lead time 9-82 days). Conclusions: Neurocognitive function and QOL are correlated. Neurocognitive function scores from previous visits are predictive of QOL. Neurocognitive function deterioration precedes QOL decline. The sequential association between NCF and QOL decline suggests that delaying NCF deterioration is a worthwhile treatment goal in brain metastases patients.

  3. Modeling dynamic functional information flows on large-scale brain networks.

    PubMed

    Lv, Peili; Guo, Lei; Hu, Xintao; Li, Xiang; Jin, Changfeng; Han, Junwei; Li, Lingjiang; Liu, Tianming

    2013-01-01

    Growing evidence from the functional neuroimaging field suggests that human brain functions are realized via dynamic functional interactions on large-scale structural networks. Even in resting state, functional brain networks exhibit remarkable temporal dynamics. However, it has been rarely explored to computationally model such dynamic functional information flows on large-scale brain networks. In this paper, we present a novel computational framework to explore this problem using multimodal resting state fMRI (R-fMRI) and diffusion tensor imaging (DTI) data. Basically, recent literature reports including our own studies have demonstrated that the resting state brain networks dynamically undergo a set of distinct brain states. Within each quasi-stable state, functional information flows from one set of structural brain nodes to other sets of nodes, which is analogous to the message package routing on the Internet from the source node to the destination. Therefore, based on the large-scale structural brain networks constructed from DTI data, we employ a dynamic programming strategy to infer functional information transition routines on structural networks, based on which hub routers that most frequently participate in these routines are identified. It is interesting that a majority of those hub routers are located within the default mode network (DMN), revealing a possible mechanism of the critical functional hub roles played by the DMN in resting state. Also, application of this framework on a post trauma stress disorder (PTSD) dataset demonstrated interesting difference in hub router distributions between PTSD patients and healthy controls.

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

    PubMed Central

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

    2015-01-01

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

  5. The Effects of Long Duration Bed Rest on Brain Functional Connectivity and Sensorimotor Functioning

    NASA Technical Reports Server (NTRS)

    Cassady, K.; Koppelmans, V.; De Dios, Y.; Stepanyan, V.; Szecsy, D.; Gadd, N.; Wood, S.; Reuter-Lorenz, P.; Castenada, R. Riascos; Kofman, I.; Bloomberg, J.; Mulavara, A; Seidler, R.

    2016-01-01

    Long duration spaceflight has been associated with detrimental alterations in human sensorimotor functioning. Prolonged exposure to a head-down tilt (HDT) position during long duration bed rest can resemble several effects of the microgravity environment such as reduced sensory inputs, body unloading and increased cephalic fluid distribution. The question of whether microgravity affects other central nervous system functions such as brain functional connectivity and its relationship with behavior is largely unknown, but of importance to the health and performance of astronauts both during and post-flight. In the present study, we investigate the effects of prolonged exposure to HDT bed rest on resting state brain functional connectivity and its association with behavioral changes in 17 male participants. To validate that our findings were not due to confounding factors such as time or task practice, we also acquired resting state functional magnetic resonance imaging (rs-fMRI) and behavioral measurements from 14 normative control participants at four time points. Bed rest participants remained in bed with their heads tilted down six degrees below their feet for 70 consecutive days. Rs-fMRI and behavioral data were obtained at seven time points averaging around: 12 and 8 days prior to bed rest; 7, 50, and 70 days during bed rest; and 8 and 12 days after bed rest. 70 days of HDT bed rest resulted in significant increases in functional connectivity during bed rest followed by a reversal of changes in the post bed rest recovery period between motor cortical and somatosensory areas of the brain. In contrast, decreases in connectivity were observed between temporoparietal regions. Furthermore, post-hoc correlation analyses revealed a significant relationship between motor-somatosensory network connectivity and standing balance performance changes; participants that exhibited the greatest increases in connectivity strength showed the least deterioration in postural

  6. Impact of prosocial neuropeptides on human brain function.

    PubMed

    Meyer-Lindenberg, Andreas

    2008-01-01

    Oxytocin and vasopressin are key effectors of social behaviour (Insel, T. R. and Fernald, R. D. (2004). Annu. Rev. Neurosci., 27: 697-722). Oxytocin effects in humans were recently demonstrated by a behavioural study showing selectively increased trust after hormone administration (Kosfeld, M., et al. (2005). Nature, 435: 673-676). Since this suggested involvement of the amygdala, which is linked to trust (Winston, J. S., et al. (2002). Nat. Neurosci., 5: 277-283) - presumably because of its role in danger monitoring - and highly expresses oxytocin receptors (Huber, D., et al. (2005). Science, 308: 245-248), we studied amygdala circuitry after double-blind crossover intranasal application of placebo or oxytocin (Kirsch, P., et al. (2005). J. Neurosci., 25: 11489-11493). Oxytocin potently reduced amygdala activation and decreased coupling to brainstem regions implicated in autonomic and behavioural manifestations of fear, indicating a neural mechanism for the effects of oxytocin in social cognition in humans and providing a potential therapeutic approach to social anxiety currently being tested in social phobia and autism. Furthermore, these data suggested a translational genetic approach. Preliminary findings (data not presented) from our laboratory using imaging genetics indeed implicate genetic variants for both AVPR1A, encoding the primary receptor of vasopressin in brain, and the oxytocin receptor, OXTR, in amygdala regulation and activation. Taken together, our results indicate neural mechanisms for human social behaviour mediating genetic risk for autism through an impact on amygdala signalling and provide a rationale for exploring therapeutic strategies aimed at abnormal amygdala function in this disorder and in social dysfunction in general.

  7. Localizing the site of magnetic brain stimulation by functional MRI.

    PubMed

    Terao, Y; Ugawa, Y; Sakai, K; Miyauchi, S; Fukuda, H; Sasaki, Y; Takino, R; Hanajima, R; Furubayashi, T; Pütz, B; Kanazawa, I

    1998-07-01

    In order to locate the site of action of transcranial magnetic stimulation (TMS) within the human motor cortices, we investigated how the optimal positions for evoking motor responses over the scalp corresponded to the hand and leg primary-motor areas. TMS was delivered with a figure-8 shaped coil over each point of a grid system constructed on the skull surface, each separated by 1 cm, to find the optimal site for obtaining motor-evoked potentials (MEPs) in the contralateral first dorsal interosseous (FDI) and tibialis anterior (TA) muscles. Magnetic resonance imaging scans of the brain were taken for each subject with markers placed over these sites, the positions of which were projected onto the cortical region just beneath. On the other hand, cortical areas where blood flow increased during finger tapping or leg movements were identified on functional magnetic resonance images (fMRI), which should include the hand and leg primary-motor areas. The optimal location for eliciting MEPs in FDI, regardless of their latency, lay just above the bank of the precentral gyrus, which coincided with the activated region during finger tapping in fMRI studies. The direction of induced current preferentially eliciting MEPs with the shortest latency in each subject was nearly perpendicular to the course of the precentral gyrus at this position. The optimal site for evoking motor responses in TA was also located just above the activated area during leg movements identified within the anterior portion of the paracentral lobule. The results suggest that, for magnetic stimulation, activation occurs in the primary hand and leg motor area (Brodmann area 4), which is closest in distance to the optimal scalp position for evoking motor responses.

  8. Functional Imaging of Dolphin Brain Metabolism and Blood Flow

    DTIC Science & Technology

    2006-05-25

    sinus abscess (Tristan et al., 2001). Prior to this study the animals were trained to slide out of Houser et al. (Houser et al., 2004) expanded the...2004). Origin and evolution ischemia. Brain Res. 22, 1-6. of large brains in toothed whales. Anat. Rec. A Discov. Mol. Cell Evol. Biol. Echlzenya, M...and Ewing, R. (2001). Computerized tomography of York: Springer-Verlag. a sinus abscess in a pygmy sperm whale (Kogia breviceps). IAAAM Proc. Rldgway, S

  9. Neurocognitive Function of Patients with Brain Metastasis Who Received Either Whole Brain Radiotherapy Plus Stereotactic Radiosurgery or Radiosurgery Alone

    SciTech Connect

    Aoyama, Hidefumi . E-mail: hao@radi.med.hokudai.ac.jp; Tago, Masao; Kato, Norio; Toyoda, Tatsuya; Kenjyo, Masahiro; Hirota, Saeko; Shioura, Hiroki; Inomata, Taisuke; Kunieda, Etsuo; Hayakawa, Kazushige; Nakagawa, Keiichi; Kobashi, Gen; Shirato, Hiroki

    2007-08-01

    Purpose: To determine how the omission of whole brain radiotherapy (WBRT) affects the neurocognitive function of patients with one to four brain metastases who have been treated with stereotactic radiosurgery (SRS). Methods and Materials: In a prospective randomized trial between WBRT+SRS and SRS alone for patients with one to four brain metastases, we assessed the neurocognitive function using the Mini-Mental State Examination (MMSE). Of the 132 enrolled patients, MMSE scores were available for 110. Results: In the baseline MMSE analyses, statistically significant differences were observed for total tumor volume, extent of tumor edema, age, and Karnofsky performance status. Of the 92 patients who underwent the follow-up MMSE, 39 had a baseline MMSE score of {<=}27 (17 in the WBRT+SRS group and 22 in the SRS-alone group). Improvements of {>=}3 points in the MMSEs of 9 WBRT+SRS patients and 11 SRS-alone patients (p = 0.85) were observed. Of the 82 patients with a baseline MMSE score of {>=}27 or whose baseline MMSE score was {<=}26 but had improved to {>=}27 after the initial brain treatment, the 12-, 24-, and 36-month actuarial free rate of the 3-point drop in the MMSE was 76.1%, 68.5%, and 14.7% in the WBRT+SRS group and 59.3%, 51.9%, and 51.9% in the SRS-alone group, respectively. The average duration until deterioration was 16.5 months in the WBRT+SRS group and 7.6 months in the SRS-alone group (p = 0.05). Conclusion: The results of the present study have revealed that, for most brain metastatic patients, control of the brain tumor is the most important factor for stabilizing neurocognitive function. However, the long-term adverse effects of WBRT on neurocognitive function might not be negligible.

  10. Mentalizing functions provide a conceptual link of brain function and social cognition in major mental disorders.

    PubMed

    Schnell, Knut

    2014-01-01

    The review presents a research perspective that defines mentalizing functions as a very promising topic to bridge psychopathology and neurobiological foundations of mental disorders. However, the high diversity of existing observations in mentalizing research calls for a structured assessment of functional mentalizing subdomains. A notable problem is the overlap of functional systems involved in mentalizing and emotion processing. A proposed solution is to conceptualize mentalizing functions due to their content (visuospatial vs. emotional) perspective and substrates (cognitive or explicit signals). This conceptual organization is mirrored in functional imaging experiments dissociating anteromedial and posterolateral brain regions, especially the involvement of the medial prefrontal cortex in mentalizing emotions and the temporoparietal cortex in visuospatial perspective taking. The present state and perspectives of mentalizing research are demonstrated in two major fields of mental disorders, depression and schizophrenia. In depression the existent contradictory findings demand a control of cognitive impairments, which are frequently associated with depressive disorders. In schizophrenia there is already consistent evidence that defines mentalizing functions as promising endophenotype, which can possibly link psychopathology to its neurobiological foundations.

  11. A novel brain partition highlights the modular skeleton shared by structure and function

    PubMed Central

    Diez, Ibai; Bonifazi, Paolo; Escudero, Iñaki; Mateos, Beatriz; Muñoz, Miguel A.; Stramaglia, Sebastiano; Cortes, Jesus M.

    2015-01-01

    Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain. PMID:26037235

  12. A novel brain partition highlights the modular skeleton shared by structure and function.

    PubMed

    Diez, Ibai; Bonifazi, Paolo; Escudero, Iñaki; Mateos, Beatriz; Muñoz, Miguel A; Stramaglia, Sebastiano; Cortes, Jesus M

    2015-06-03

    Elucidating the intricate relationship between brain structure and function, both in healthy and pathological conditions, is a key challenge for modern neuroscience. Recent progress in neuroimaging has helped advance our understanding of this important issue, with diffusion images providing information about structural connectivity (SC) and functional magnetic resonance imaging shedding light on resting state functional connectivity (rsFC). Here, we adopt a systems approach, relying on modular hierarchical clustering, to study together SC and rsFC datasets gathered independently from healthy human subjects. Our novel approach allows us to find a common skeleton shared by structure and function from which a new, optimal, brain partition can be extracted. We describe the emerging common structure-function modules (SFMs) in detail and compare them with commonly employed anatomical or functional parcellations. Our results underline the strong correspondence between brain structure and resting-state dynamics as well as the emerging coherent organization of the human brain.

  13. Brain Training Game Improves Executive Functions and Processing Speed in the Elderly: A Randomized Controlled Trial

    PubMed Central

    Nouchi, Rui; Taki, Yasuyuki; Takeuchi, Hikaru; Hashizume, Hiroshi; Akitsuki, Yuko; Shigemune, Yayoi; Sekiguchi, Atsushi; Kotozaki, Yuka; Tsukiura, Takashi; Yomogida, Yukihito; Kawashima, Ryuta

    2012-01-01

    Background The beneficial effects of brain training games are expected to transfer to other cognitive functions, but these beneficial effects are poorly understood. Here we investigate the impact of the brain training game (Brain Age) on cognitive functions in the elderly. Methods and Results Thirty-two elderly volunteers were recruited through an advertisement in the local newspaper and randomly assigned to either of two game groups (Brain Age, Tetris). This study was completed by 14 of the 16 members in the Brain Age group and 14 of the 16 members in the Tetris group. To maximize the benefit of the interventions, all participants were non-gamers who reported playing less than one hour of video games per week over the past 2 years. Participants in both the Brain Age and the Tetris groups played their game for about 15 minutes per day, at least 5 days per week, for 4 weeks. Each group played for a total of about 20 days. Measures of the cognitive functions were conducted before and after training. Measures of the cognitive functions fell into four categories (global cognitive status, executive functions, attention, and processing speed). Results showed that the effects of the brain training game were transferred to executive functions and to processing speed. However, the brain training game showed no transfer effect on any global cognitive status nor attention. Conclusions Our results showed that playing Brain Age for 4 weeks could lead to improve cognitive functions (executive functions and processing speed) in the elderly. This result indicated that there is a possibility which the elderly could improve executive functions and processing speed in short term training. The results need replication in large samples. Long-term effects and relevance for every-day functioning remain uncertain as yet. Trial Registration UMIN Clinical Trial Registry 000002825 PMID:22253758

  14. Chemotherapy Altered Brain Functional Connectivity in Women with Breast Cancer: A Pilot Study

    PubMed Central

    Dumas, Julie A.; Makarewicz, Jenna; Schaubhut, Geoffrey J.; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A.

    2013-01-01

    Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, one month after, and one year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity one month after chemotherapy that partially returned to baseline at one year in the dorsal attention network. Decreased connectivity was seen in the default mode network at one month and one year following chemotherapy. In addition, increased subjective memory complaints were noted at one month and one year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

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

    NASA Astrophysics Data System (ADS)

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

    1999-05-01

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

  16. 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

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

    PubMed Central

    Shi, Ran

    2016-01-01

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

  18. Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface.

    PubMed

    Young, Brittany M; Nigogosyan, Zack; Walton, Léo M; Song, Jie; Nair, Veena A; Grogan, Scott W; Tyler, Mitchell E; Edwards, Dorothy F; Caldera, Kristin; Sattin, Justin A; Williams, Justin C; Prabhakaran, Vivek

    2014-01-01

    This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions.

  19. Changes in functional brain organization and behavioral correlations after rehabilitative therapy using a brain-computer interface

    PubMed Central

    Young, Brittany M.; Nigogosyan, Zack; Walton, Léo M.; Song, Jie; Nair, Veena A.; Grogan, Scott W.; Tyler, Mitchell E.; Edwards, Dorothy F.; Caldera, Kristin; Sattin, Justin A.; Williams, Justin C.; Prabhakaran, Vivek

    2014-01-01

    This study aims to examine the changes in task-related brain activity induced by rehabilitative therapy using brain-computer interface (BCI) technologies and whether these changes are relevant to functional gains achieved through the use of these therapies. Stroke patients with persistent upper-extremity motor deficits received interventional rehabilitation therapy using a closed-loop neurofeedback BCI device (n = 8) or no therapy (n = 6). Behavioral assessments using the Stroke Impact Scale, the Action Research Arm Test (ARAT), and the Nine-Hole Peg Test (9-HPT) as well as task-based fMRI scans were conducted before, during, after, and 1 month after therapy administration or at analogous intervals in the absence of therapy. Laterality Index (LI) values during finger tapping of each hand were calculated for each time point and assessed for correlation with behavioral outcomes. Brain activity during finger tapping of each hand shifted over the course of BCI therapy, but not in the absence of therapy, to greater involvement of the non-lesioned hemisphere (and lesser involvement of the stroke-lesioned hemisphere) as measured by LI. Moreover, changes from baseline LI values during finger tapping of the impaired hand were correlated with gains in both objective and subjective behavioral measures. These findings suggest that the administration of interventional BCI therapy can induce differential changes in brain activity patterns between the lesioned and non-lesioned hemispheres and that these brain changes are associated with changes in specific motor functions. PMID:25076886

  20. Functional Connectivity of Multiple Brain Regions Required for the Consolidation of Social Recognition Memory.

    PubMed

    Tanimizu, Toshiyuki; Kenney, Justin W; Okano, Emiko; Kadoma, Kazune; Frankland, Paul W; Kida, Satoshi

    2017-04-12

    Social recognition memory is an essential and basic component of social behavior that is used to discriminate familiar and novel animals/humans. Previous studies have shown the importance of several brain regions for social recognition memories; however, the mechanisms underlying the consolidation of social recognition memory at the molecular and anatomic levels remain unknown. Here, we show a brain network necessary for the generation of social recognition memory in mice. A mouse genetic study showed that cAMP-responsive element-binding protein (CREB)-mediated transcription is required for the formation of social recognition memory. Importantly, significant inductions of the CREB target immediate-early genes c-fos and Arc were observed in the hippocampus (CA1 and CA3 regions), medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and amygdala (basolateral region) when social recognition memory was generated. Pharmacological experiments using a microinfusion of the protein synthesis inhibitor anisomycin showed that protein synthesis in these brain regions is required for the consolidation of social recognition memory. These findings suggested that social recognition memory is consolidated through the activation of CREB-mediated gene expression in the hippocampus/mPFC/ACC/amygdala. Network analyses suggested that these four brain regions show functional connectivity with other brain regions and, more importantly, that the hippocampus functions as a hub to integrate brain networks and generate social recognition memory, whereas the ACC and amygdala are important for coordinating brain activity when social interaction is initiated by connecting with other brain regions. We have found that a brain network composed of the hippocampus/mPFC/ACC/amygdala is required for the consolidation of social recognition memory.SIGNIFICANCE STATEMENT Here, we identify brain networks composed of multiple brain regions for the consolidation of social recognition memory. We

  1. Intrinsic functional connectivity pattern-based brain parcellation using normalized cut

    NASA Astrophysics Data System (ADS)

    Cheng, Hewei; Song, Dandan; Wu, Hong; Fan, Yong

    2012-02-01

    In imaging data based brain network analysis, a necessary precursor for constructing meaningful brain networks is to identify functionally homogeneous regions of interest (ROIs) for defining network nodes. For parcellating the brain based on resting state fMRI data, normalized cut is one widely used clustering algorithm which groups voxels according to the similarity of functional signals. Due to low signal to noise ratio (SNR) of resting state fMRI signals, spatial constraint is often applied to functional similarity measures to generate smooth parcellation. However, improper spatial constraint might alter the intrinsic functional connectivity pattern, thus yielding biased parcellation results. To achieve reliable and least biased parcellation of the brain, we propose an optimization method for the spatial constraint to functional similarity measures in normalized cut based brain parcellation. Particularly, we first identify the space of all possible spatial constraints that are able to generate smooth parcellation, then find the spatial constraint that leads to the brain parcellation least biased from the intrinsic function pattern based parcellation, measured by the minimal Ncut value calculated based on the functional similarity measure of original functional signals. The proposed method has been applied to the parcellation of medial superior frontal cortex for 20 subjects based on their resting state fMRI data. The experiment results indicate that our method can generate meaningful parcellation results, consistent with existing functional anatomy knowledge.

  2. Brain temperature fluctuation: a reflection of functional neural activation.

    PubMed

    Kiyatkin, Eugene A; Brown, P Leon; Wise, Roy A

    2002-07-01

    Although it is known that relatively large increases in local brain temperature can occur during behaviour and in response to various novel, stressful and emotionally arousing environmental stimuli, the source of this heat is not clearly established. To clarify this issue, we monitored the temperature in three brain structures (dorsal and ventral striatum, cerebellum) and in arterial blood at the level of the abdominal aorta in freely moving rats exposed to several environmental challenges ranging from traditional stressors to simple sensory stimuli (cage change, tail pinch, exposure to another male rat, a female rat, a mouse or an unexpected sound). We found that brain temperature was consistently higher than arterial blood temperature, and that brain temperature increased prior to, and to a greater extent than, the increase in blood temperature evoked by each test challenge. Thus, the local metabolic consequences of widely correlated neural activity appear to be the primary source of increases in brain temperature and a driving force behind the associated changes in body temperature.

  3. Blood-brain barrier P-glycoprotein function in neurodegenerative disease.

    PubMed

    Bartels, A L

    2011-01-01

    Protection of the brain is strengthened by active transport and ABC transporters. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a substrate from the brain, which is important for maintaining loco-regional homeostasis in the brain and protection against toxic compounds. Importantly, dysfunctional BBB P-gp transport is postulated as an important factor contributing to accumulation of aggregated protein in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, P-gp is a major factor in mediating resistance to brain entry of numerous exogenous compounds, including toxins that can be involved in PD pathogenesis. This review highlights the role of altered P-gp function in the pathogenesis and progression of neurodegenerative disease. Also the implications of alterations in P-gp function for the treatment of these diseases are discussed.

  4. Integration of visual and motor functional streams in the human brain.

    PubMed

    Sepulcre, Jorge

    2014-05-01

    A long-standing difficulty in brain research has been to disentangle how information flows across circuits composed by multiple local and distant cerebral areas. At the large-scale level, several brain imaging methods have contributed to the understanding of those circuits by capturing the covariance or coupling patterns of blood oxygen level-dependent (BOLD) activity between distributed brain regions. The hypothesis is that underlying information processes are closely associated to synchronized brain activity, and therefore to the functional connectivity structure of the human brain. In this study, we have used a recently developed method called stepwise functional connectivity analysis. Our results show that motor and visual connectivity merge in a multimodal integration network that links together perception, action and cognition in the human functional connectome.

  5. Random matrix theory for analyzing the brain functional network in attention deficit hyperactivity disorder

    NASA Astrophysics Data System (ADS)

    Wang, Rong; Wang, Li; Yang, Yong; Li, Jiajia; Wu, Ying; Lin, Pan

    2016-11-01

    Attention deficit hyperactivity disorder (ADHD) is the most common childhood neuropsychiatric disorder and affects approximately 6 -7 % of children worldwide. Here, we investigate the statistical properties of undirected and directed brain functional networks in ADHD patients based on random matrix theory (RMT), in which the undirected functional connectivity is constructed based on correlation coefficient and the directed functional connectivity is measured based on cross-correlation coefficient and mutual information. We first analyze the functional connectivity and the eigenvalues of the brain functional network. We find that ADHD patients have increased undirected functional connectivity, reflecting a higher degree of linear dependence between regions, and increased directed functional connectivity, indicating stronger causality and more transmission of information among brain regions. More importantly, we explore the randomness of the undirected and directed functional networks using RMT. We find that for ADHD patients, the undirected functional network is more orderly than that for normal subjects, which indicates an abnormal increase in undirected functional connectivity. In addition, we find that the directed functional networks are more random, which reveals greater disorder in causality and more chaotic information flow among brain regions in ADHD patients. Our results not only further confirm the efficacy of RMT in characterizing the intrinsic properties of brain functional networks but also provide insights into the possibilities RMT offers for improving clinical diagnoses and treatment evaluations for ADHD patients.

  6. Random matrix theory for analyzing the brain functional network in attention deficit hyperactivity disorder.

    PubMed

    Wang, Rong; Wang, Li; Yang, Yong; Li, Jiajia; Wu, Ying; Lin, Pan

    2016-11-01

    Attention deficit hyperactivity disorder (ADHD) is the most common childhood neuropsychiatric disorder and affects approximately 6-7% of children worldwide. Here, we investigate the statistical properties of undirected and directed brain functional networks in ADHD patients based on random matrix theory (RMT), in which the undirected functional connectivity is constructed based on correlation coefficient and the directed functional connectivity is measured based on cross-correlation coefficient and mutual information. We first analyze the functional connectivity and the eigenvalues of the brain functional network. We find that ADHD patients have increased undirected functional connectivity, reflecting a higher degree of linear dependence between regions, and increased directed functional connectivity, indicating stronger causality and more transmission of information among brain regions. More importantly, we explore the randomness of the undirected and directed functional networks using RMT. We find that for ADHD patients, the undirected functional network is more orderly than that for normal subjects, which indicates an abnormal increase in undirected functional connectivity. In addition, we find that the directed functional networks are more random, which reveals greater disorder in causality and more chaotic information flow among brain regions in ADHD patients. Our results not only further confirm the efficacy of RMT in characterizing the intrinsic properties of brain functional networks but also provide insights into the possibilities RMT offers for improving clinical diagnoses and treatment evaluations for ADHD patients.

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

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

    2010-11-01

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

  9. Distinct disruptions of resting-state functional brain networks in familial and sporadic schizophrenia

    PubMed Central

    Zhu, Jiajia; Zhuo, Chuanjun; Liu, Feng; Qin, Wen; Xu, Lixue; Yu, Chunshui

    2016-01-01

    Clinical and brain structural differences have been reported between patients with familial and sporadic schizophrenia; however, little is known about the brain functional differences between the two subtypes of schizophrenia. Twenty-six patients with familial schizophrenia (PFS), 26 patients with sporadic schizophrenia (PSS) and 26 healthy controls (HC) underwent a resting-state functional magnetic resonance imaging. The whole-brain functional network was constructed and analyzed using graph theoretical approaches. Topological properties (including global, nodal and edge measures) were compared among the three groups. We found that PFS, PSS and HC exhibited common small-world architecture of the functional brain networks. However, at a global level, only PFS showed significantly lower normalized clustering coefficient, small-worldness, and local efficiency, indicating a randomization shift of their brain networks. At a regional level, PFS and PSS disrupted different neural circuits, consisting of abnormal nodes (increased or decreased nodal centrality) and edges (decreased functional connectivity strength), which were widely distributed throughout the entire brain. Furthermore, some of these altered network measures were significantly correlated with severity of psychotic symptoms. These results suggest that familial and sporadic schizophrenia had segregated disruptions in the topological organization of the intrinsic functional brain network, which may be due to different etiological contributions. PMID:27032817

  10. 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…

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

    ERIC Educational Resources Information Center

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

    2010-01-01

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

  12. Using Structural Equation Modeling to Assess Functional Connectivity in the Brain: Power and Sample Size Considerations

    ERIC Educational Resources Information Center

    Sideridis, Georgios; Simos, Panagiotis; Papanicolaou, Andrew; Fletcher, Jack

    2014-01-01

    The present study assessed the impact of sample size on the power and fit of structural equation modeling applied to functional brain connectivity hypotheses. The data consisted of time-constrained minimum norm estimates of regional brain activity during performance of a reading task obtained with magnetoencephalography. Power analysis was first…

  13. Integrating Functional Brain Neuroimaging and Developmental Cognitive Neuroscience in Child Psychiatry Research

    ERIC Educational Resources Information Center

    Pavuluri, Mani N.; Sweeney, John A.

    2008-01-01

    The use of cognitive neuroscience and functional brain neuroimaging to understand brain dysfunction in pediatric psychiatric disorders is discussed. Results show that bipolar youths demonstrate impairment in affective and cognitive neural systems and in these two circuits' interface. Implications for the diagnosis and treatment of psychiatric…

  14. Family-Based Training Program Improves Brain Function, Cognition, and Behavior in Lower Socioeconomic Status Preschoolers

    ERIC Educational Resources Information Center

    Pakulak, Eric; Stevens, Courtney; Bell, Theodore A.; Fanning, Jessica; Klein, Scott; Isbell, Elif; Neville, Helen

    2013-01-01

    Over the course of several years of research, the authors have employed psychophysics, electrophysiological (ERP) and magnetic resonance imaging (MRI) techniques to study the development and neuroplasticity of the human brain. During this time, they observed that different brain systems and related functions display markedly different degrees or…

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

    ERIC Educational Resources Information Center

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

    2003-01-01

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

  16. Changes in Connectivity after Visual Cortical Brain Damage Underlie Altered Visual Function

    ERIC Educational Resources Information Center

    Bridge, Holly; Thomas, Owen; Jbabdi, Saad; Cowey, Alan

    2008-01-01

    The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional…

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

    PubMed

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

    2016-11-09

    Human visual performance has been observed to show superiority in localized regions of the visual field across many classes of stimuli. However, the underlying neural mechanisms remain unclear. This study aims to determine whether the visual information processing in the human brain is dependent on the location of stimuli in the visual field and the corresponding neuroarchitecture using blood-oxygenation-level-dependent functional MRI (fMRI) and diffusion kurtosis MRI, respectively, in 15 healthy individuals at 3 T. In fMRI, visual stimulation to the lower hemifield showed stronger brain responses and larger brain activation volumes than the upper hemifield, indicative of the differential sensitivity of the human brain across the visual field. In diffusion kurtosis MRI, the brain regions mapping to the lower visual field showed higher mean kurtosis, but not fractional anisotropy or mean diffusivity compared with the upper visual field. These results suggested the different distributions of microstructural organization across visual field brain representations. There was also a strong positive relationship between diffusion kurtosis and fMRI responses in the lower field brain representations. In summary, this study suggested the structural and functional brain involvements in the asymmetry of visual field responses in humans, and is important to the neurophysiological and psychological understanding of human visual information processing.

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

    PubMed

    Licht, Tamar; Keshet, Eli

    2013-05-01

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

  19. 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.

  20. Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus.

    PubMed

    Zhang, Jiyong; Sadowska, Grazyna B; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G; Gaitanis, John; Banks, William A; Stonestreet, Barbara S

    2015-05-01

    Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti-IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.