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Sample records for altered brain activity

  1. Intrinsic Brain Activity in Altered States of Consciousness

    PubMed Central

    Boly, M.; Phillips, C.; Tshibanda, L.; Vanhaudenhuyse, A.; Schabus, M.; Dang-Vu, T.T.; Moonen, G.; Hustinx, R.; Maquet, P.; Laureys, S.

    2010-01-01

    Spontaneous brain activity has recently received increasing interest in the neuroimaging community. However, the value of resting-state studies to a better understanding of brain–behavior relationships has been challenged. That altered states of consciousness are a privileged way to study the relationships between spontaneous brain activity and behavior is proposed, and common resting-state brain activity features observed in various states of altered consciousness are reviewed. Early positron emission tomography studies showed that states of extremely low or high brain activity are often associated with unconsciousness. However, this relationship is not absolute, and the precise link between global brain metabolism and awareness remains yet difficult to assert. In contrast, voxel-based analyses identified a systematic impairment of associative frontoparieto–cingulate areas in altered states of consciousness, such as sleep, anesthesia, coma, vegetative state, epileptic loss of consciousness, and somnambulism. In parallel, recent functional magnetic resonance imaging studies have identified structured patterns of slow neuronal oscillations in the resting human brain. Similar coherent blood oxygen level–dependent (BOLD) systemwide patterns can also be found, in particular in the default-mode network, in several states of unconsciousness, such as coma, anesthesia, and slow-wave sleep. The latter results suggest that slow coherent spontaneous BOLD fluctuations cannot be exclusively a reflection of conscious mental activity, but may reflect default brain connectivity shaping brain areas of most likely interactions in a way that transcends levels of consciousness, and whose functional significance remains largely in the dark. PMID:18591474

  2. Altered brain activity for phonological manipulation in dyslexic Japanese children.

    PubMed

    Kita, Yosuke; Yamamoto, Hisako; Oba, Kentaro; Terasawa, Yuri; Moriguchi, Yoshiya; Uchiyama, Hitoshi; Seki, Ayumi; Koeda, Tatsuya; Inagaki, Masumi

    2013-12-01

    Because of unique linguistic characteristics, the prevalence rate of developmental dyslexia is relatively low in the Japanese language. Paradoxically, Japanese children have serious difficulty analysing phonological processes when they have dyslexia. Neurobiological deficits in Japanese dyslexia remain unclear and need to be identified, and may lead to better understanding of the commonality and diversity in the disorder among different linguistic systems. The present study investigated brain activity that underlies deficits in phonological awareness in Japanese dyslexic children using functional magnetic resonance imaging. We developed and conducted a phonological manipulation task to extract phonological processing skills and to minimize the influence of auditory working memory on healthy adults, typically developing children, and dyslexic children. Current experiments revealed that several brain regions participated in manipulating the phonological information including left inferior and middle frontal gyrus, left superior temporal gyrus, and bilateral basal ganglia. Moreover, dyslexic children showed altered activity in two brain regions. They showed hyperactivity in the basal ganglia compared with the two other groups, which reflects inefficient phonological processing. Hypoactivity in the left superior temporal gyrus was also found, suggesting difficulty in composing and processing phonological information. The altered brain activity shares similarity with those of dyslexic children in countries speaking alphabetical languages, but disparity also occurs between these two populations. These are initial findings concerning the neurobiological impairments in dyslexic Japanese children.

  3. Altered Spontaneous Brain Activity in Betel Quid Dependence

    PubMed Central

    Liu, Tao; Li, Jian-jun; Zhao, Zhong-yan; Yang, Guo-shuai; Pan, Meng-jie; Li, Chang-qing; Pan, Su-yue; Chen, Feng

    2016-01-01

    Abstract It has been suggested by the first voxel-based morphometry investigation that betel quid dependence (BQD) individuals are presented with brain structural changes in previous reports, and there may be a neurobiological basis for BQD individuals related to an increased risk of executive dysfunction and disinhibition, subjected to the reward system, cognitive system, and emotion system. However, the effects of BQD on neural activity remain largely unknown. Individuals with impaired cognitive control of behavior often reveal altered spontaneous cerebral activity in resting-state functional magnetic resonance imaging and those changes are usually earlier than structural alteration. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy control participants (n = 32) in an resting-state functional magnetic resonance imaging study to observe brain function alterations associated with the severity of BQD. Amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) values were both evaluated to stand for spontaneous cerebral activity. Gray matter volumes of these participants were also calculated for covariate. In comparison with healthy controls, BQD individuals demonstrated dramatically decreased ALFF and ReHo values in the prefrontal gurus along with left fusiform, and increased ALFF and ReHo values in the primary motor cortex area, temporal lobe as well as some regions of occipital lobe. The betel quid dependence scores (BQDS) were negatively related to decreased activity in the right anterior cingulate. The abnormal spontaneous cerebral activity revealed by ALFF and ReHo calculation excluding the structural differences in patients with BQD may help us probe into the neurological pathophysiology underlying BQD-related executive dysfunction and disinhibition. Diminished spontaneous brain activity in the right anterior cingulate cortex may, therefore, represent a biomarker of BQD individuals. PMID

  4. Alteration of spontaneous brain activity in COPD patients

    PubMed Central

    Zhang, Jiaxing; Chen, Ji; Yu, Qian; Fan, Cunxiu; Zhang, Ran; Lin, Jianzhong; Yang, Tianhe; Fan, Ming

    2016-01-01

    Background and objective Airflow limitation in chronic obstructive pulmonary disease (COPD) results in a decrease in oxygen transport to the brain. The aim of the present study was to explore the alteration of spontaneous brain activity induced by hypoxia in patients with COPD. Patients and methods Twenty-five stable patients with COPD and 25 matching healthy volunteers were investigated. Amplitude of low-frequency fluctuation (ALFF) of blood oxygenation level-dependent signal at resting state in the brain was analyzed using functional magnetic resonance imaging. Results Whole-brain analysis using functional magnetic resonance imaging revealed significant decreases in ALFF in the bilateral posterior cingulate gyri and right lingual gyrus and an increase in ALFF in the left postcentral gyrus of patients with COPD. After controlling for SaO2, patients with COPD only showed an increase in ALFF in the left postcentral gyrus. Region of interest analysis showed a decrease in ALFF in the left precentral gyrus and an increase in ALFF in the left caudate nucleus of patients with COPD. In all subjects, ALFF in the bilateral posterior cingulate gyri and right lingual gyrus showed positive correlations with visual reproduction. Conclusion We demonstrated abnormal spontaneous brain activity of patients with COPD, which may have a pathophysiologic meaning. PMID:27555761

  5. Altered brain activity during pain processing in fibromyalgia.

    PubMed

    Burgmer, Markus; Pogatzki-Zahn, Esther; Gaubitz, Markus; Wessoleck, Erik; Heuft, Gereon; Pfleiderer, Bettina

    2009-01-15

    Fibromyalgia syndrome (FMS) is characterized by widespread pain. Studies with functional neuroimaging support the hypothesis of central pain augmentation in FMS. We tested this in our study with a novel paradigm of tonic pain induced by a single stimulus. Tonic pain, in contrast to phasic pain, seems to be a more appropriate experimental approach to study adaptive mechanisms of pain processing in FMS. We hypothesized that brain areas related to the "medial" pain system and the amygdalae will present different activation in patients compared to healthy subjects. An fMRI-block design before, during and after an incision was made in patients with FMS and in healthy controls. Acute pain caused by the incision was measured during the course of the experiment. A 2 factorial model of BOLD-signal changes was designed to explore significant differences of brain activation between both groups during the pain stimulus. Additionally the first Eigenvariates in those areas which show an interaction between both factors were determined over the time course of pain stimulation. Differences of activation in the fronto-cingulate cortex, the supplemental motor areas, and the thalamus were found between both groups with distinct differences in BOLD-signals changes over the time course of pain stimulation, even during anticipation of pain. Our results support the hypothesis that central mechanisms of pain processing in the medial pain system, favourable cognitive/affective factors even during the anticipation of pain, may play an important role for pain processing in patients with FMS. PMID:18848998

  6. Sustained Treatment with Insulin Detemir in Mice Alters Brain Activity and Locomotion

    PubMed Central

    Sartorius, Tina; Hennige, Anita M.; Fritsche, Andreas; Häring, Hans-Ulrich

    2016-01-01

    Aims Recent studies have identified unique brain effects of insulin detemir (Levemir®). Due to its pharmacologic properties, insulin detemir may reach higher concentrations in the brain than regular insulin. This might explain the observed increased brain stimulation after acute insulin detemir application but it remained unclear whether chronic insulin detemir treatment causes alterations in brain activity as a consequence of overstimulation. Methods In mice, we examined insulin detemir’s prolonged brain exposure by continuous subcutaneous (s.c.) application using either micro-osmotic pumps or daily s.c. injections and performed continuous radiotelemetric electrocorticography and locomotion recordings. Results Acute intracerebroventricular injection of insulin detemir activated cortical and locomotor activity significantly more than regular insulin in equimolar doses (0.94 and 5.63 mU in total), suggesting an enhanced acute impact on brain networks. However, given continuously s.c., insulin detemir significantly reduced cortical activity (theta: 21.3±6.1% vs. 73.0±8.1%, P<0.001) and failed to maintain locomotion, while regular insulin resulted in an increase of both parameters. Conclusions The data suggest that permanently-increased insulin detemir levels in the brain convert its hyperstimulatory effects and finally mediate impairments in brain activity and locomotion. This observation might be considered when human studies with insulin detemir are designed to target the brain in order to optimize treatment regimens. PMID:27589235

  7. Altered host behaviour and brain serotonergic activity caused by acanthocephalans: evidence for specificity

    PubMed Central

    Tain, Luke; Perrot-Minnot, Marie-Jeanne; Cézilly, Frank

    2006-01-01

    Manipulative parasites can alter the phenotype of intermediate hosts in various ways. However, it is unclear whether such changes are just by-products of infection or adaptive and enhance transmission to the final host. Here, we show that the alteration of serotonergic activity is functionally linked to the alteration of specific behaviour in the amphipod Gammarus pulex infected with acanthocephalan parasites. Pomphorhynchus laevis and, to a lesser extent, Pomphorhynchus tereticollis altered phototactism, but not geotactism, in G. pulex, whereas the reverse was true for Polymorphus minutus. Serotonin (5-hydroxytryptamine, 5-HT) injected to uninfected G. pulex mimicked the altered phototactism, but had no effect on geotactism. Photophilic G. pulex infected with P. laevis or P. tereticollis showed a 40% increase in brain 5-HT immunoreactivity compared to photophobic, uninfected individuals. In contrast, brain 5-HT immunoreactivity did not differ between P. minutus-infected and uninfected G. pulex. Finally, brain 5-HT immunoreactivity differed significantly among P. tereticollis-infected individuals in accordance with their degree of manipulation. Our results demonstrate that altered 5-HT activity is not the mere consequence of infection by acanthocephalans but is specifically linked to the disruption of host photophobic behaviour, whereas the alteration of other behaviours such as geotactism may rely on distinct physiological routes. PMID:17015346

  8. Human ecstasy (MDMA) polydrug users have altered brain activation during semantic processing

    PubMed Central

    Watkins, Tristan J.; Raj, Vidya; Lee, Junghee; Dietrich, Mary S.; Cao, Aize; Blackford, Jennifer U.; Salomon, Ronald M.; Park, Sohee; Benningfield, Margaret M.; Di Iorio, Christina R.; Cowan, Ronald L.

    2012-01-01

    Rationale Ecstasy (MDMA) polydrug users have verbal memory performance that is statistically significantly lower than comparison control subjects. Studies have correlated long-term MDMA use with altered brain activation in regions that play a role in verbal memory. Objectives The aim of our study was to examine the association of lifetime ecstasy use with semantic memory performance and brain activation in ecstasy polydrug users. Methods 23 abstinent ecstasy polydrug users (age=24.57) and 11 controls (age=22.36) performed a two-part fMRI semantic encoding and recognition task. To isolate brain regions activated during each semantic task, we created statistical activation maps in which brain activation was greater for word stimuli than for non-word stimuli (corrected p<0.05). Results During the encoding phase, ecstasy polydrug users had greater activation during semantic encoding bilaterally in language processing regions, including Brodmann Areas 7, 39, and 40. Of this bilateral activation, signal intensity with a peak T in the right superior parietal lobe was correlated with lifetime ecstasy use (rs=0.43, p=0.042). Behavioral performance did not differ between groups. Conclusions These findings demonstrate that ecstasy polydrug users have increased brain activation during semantic processing. This increase in brain activation in the absence of behavioral deficits suggests that ecstasy polydrug users have reduced cortical efficiency during semantic encoding, possibly secondary to MDMA-induced 5-HT neurotoxicity. Although pre-existing differences cannot be ruled out, this suggests the possibility of a compensatory mechanism allowing ecstasy polydrug users to perform equivalently to controls, providing additional support for an association of altered cerebral neurophysiology with MDMA exposure. PMID:23241648

  9. The hyperactive syndrome: metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity.

    PubMed

    Viggiano, Davide

    2008-12-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal models. To further understand the resulting data set, we have organized a second database of the alterations (genetic, pharmacological or brain lesions) that reduce locomotor activity. Using this approach, we estimated that 1.56% of the genes in the genome yield to hyperactivity and 0.75% of genes produce hypoactivity when altered. These genes have been classified into genes for neurotransmitter systems, hormonal, metabolic systems, ion channels, structural proteins, transcription factors, second messengers and growth factors. Finally, two additional classes included animals with neurodegeneration and inner ear abnormalities. The analysis of the database revealed several unexpected findings. First, the genes that, when mutated, induce hyperactive behaviour do not pertain to a single neurotransmitter system. In fact, alterations in most neurotransmitter systems can give rise to a hyperactive phenotype. In contrast, fewer changes can decrease locomotor activity. Specifically, genetic and pharmacological alterations that enhance the dopamine, orexin, histamine, cannabinoids systems or that antagonize the cholinergic system induce an increase in locomotor activity. Similarly, imbalances in the two main neurotransmitters of the nervous system, GABA and glutamate usually result in hyperactive behaviour. It is remarkable that no genetic alterations pertaining to the GABA system have been reported to reduce locomotor behaviour. Other neurotransmitters, such as norepinephrine and serotonin, have a more complex influence. For instance, a decrease in norepinephrine

  10. Alterations of Regional Spontaneous Brain Activity and Gray Matter Volume in the Blind

    PubMed Central

    Jiang, Aili; Tian, Jing; Li, Rui; Liu, Yong; Jiang, Tianzi; Qin, Wen; Yu, Chunshui

    2015-01-01

    Visual deprivation can induce alterations of regional spontaneous brain activity (RSBA). However, the effects of onset age of blindness on the RSBA and the association between the alterations of RSBA and brain structure are still unclear in the blind. In this study, we performed resting-state functional and structural magnetic resonance imaging on 50 sighted controls and 91 blind subjects (20 congenitally blind, 27 early blind, and 44 late blind individuals). Compared with the sighted control, we identified increased RSBA in the blind in primary and high-level visual areas and decreased RSBA in brain regions which are ascribed to sensorimotor and salience networks. In contrast, blind subjects exhibited significantly decreased gray matter volume (GMV) in the visual areas, while they exhibited significantly increased GMV in the sensorimotor areas. Moreover, the onset age of blindness was negatively correlated with the GMV of visual areas in blind subjects, whereas it exerted complex influences on the RSBA. Finally, significant negative correlations were shown between RSBA and GMV values. Our results demonstrated system-dependent, inverse alterations in RSBA and GMV after visual deprivation. Furthermore, the onset age of blindness has different effects on the reorganizations in RSBA and GMV. PMID:26568891

  11. Alterations of Regional Spontaneous Brain Activity and Gray Matter Volume in the Blind.

    PubMed

    Jiang, Aili; Tian, Jing; Li, Rui; Liu, Yong; Jiang, Tianzi; Qin, Wen; Yu, Chunshui

    2015-01-01

    Visual deprivation can induce alterations of regional spontaneous brain activity (RSBA). However, the effects of onset age of blindness on the RSBA and the association between the alterations of RSBA and brain structure are still unclear in the blind. In this study, we performed resting-state functional and structural magnetic resonance imaging on 50 sighted controls and 91 blind subjects (20 congenitally blind, 27 early blind, and 44 late blind individuals). Compared with the sighted control, we identified increased RSBA in the blind in primary and high-level visual areas and decreased RSBA in brain regions which are ascribed to sensorimotor and salience networks. In contrast, blind subjects exhibited significantly decreased gray matter volume (GMV) in the visual areas, while they exhibited significantly increased GMV in the sensorimotor areas. Moreover, the onset age of blindness was negatively correlated with the GMV of visual areas in blind subjects, whereas it exerted complex influences on the RSBA. Finally, significant negative correlations were shown between RSBA and GMV values. Our results demonstrated system-dependent, inverse alterations in RSBA and GMV after visual deprivation. Furthermore, the onset age of blindness has different effects on the reorganizations in RSBA and GMV. PMID:26568891

  12. Brain Injury Alters Volatile Metabolome.

    PubMed

    Kimball, Bruce A; Cohen, Akiva S; Gordon, Amy R; Opiekun, Maryanne; Martin, Talia; Elkind, Jaclynn; Lundström, Johan N; Beauchamp, Gary K

    2016-06-01

    Chemical signals arising from body secretions and excretions communicate information about health status as have been reported in a range of animal models of disease. A potential common pathway for diseases to alter chemical signals is via activation of immune function-which is known to be intimately involved in modulation of chemical signals in several species. Based on our prior findings that both immunization and inflammation alter volatile body odors, we hypothesized that injury accompanied by inflammation might correspondingly modify the volatile metabolome to create a signature endophenotype. In particular, we investigated alteration of the volatile metabolome as a result of traumatic brain injury. Here, we demonstrate that mice could be trained in a behavioral assay to discriminate mouse models subjected to lateral fluid percussion injury from appropriate surgical sham controls on the basis of volatile urinary metabolites. Chemical analyses of the urine samples similarly demonstrated that brain injury altered urine volatile profiles. Behavioral and chemical analyses further indicated that alteration of the volatile metabolome induced by brain injury and alteration resulting from lipopolysaccharide-associated inflammation were not synonymous. Monitoring of alterations in the volatile metabolome may be a useful tool for rapid brain trauma diagnosis and for monitoring recovery. PMID:26926034

  13. Altered baseline brain activity differentiates regional mechanisms subserving biological and psychological alterations in obese men.

    PubMed

    Zhang, Bin; Tian, Derun; Yu, Chunshui; Li, Meng; Zang, Yufeng; Liu, Yijun; Walter, Martin

    2015-01-01

    Obesity as a chronic disease is a major factor for insulin resistance and Type 2 diabetes, which has become a global health problem. In the present study, we used resting state functional MRI to investigate the amplitude of low frequency fluctuations of spontaneous signal during both hunger and satiety states in 20 lean and 20 obese males. We found that, before food intake, obese men had significantly greater baseline activity in the precuneus and lesser activity in dorsal anterior cingulate cortex (dACC) relative to lean subjects. Furthermore, after food intake, obese males had significantly lesser activity in dACC than lean males. We further found a significant positive correlation between precuneus activation and hunger ratings before food intake, while dACC activity was negatively correlated with plasma insulin levels before and after food intake. These results indicated that both precuneus and dACC may play an important role in eating behavior. While precuneus rather seemed to mediate subjective satiety, dACC levels rather reflected indirect measures of glucose utilization. PMID:26099208

  14. Regulation of calpain activity in rat brain with altered Ca2+ homeostasis.

    PubMed

    Averna, Monica; Stifanese, Roberto; De Tullio, Roberta; Passalacqua, Mario; Defranchi, Enrico; Salamino, Franca; Melloni, Edon; Pontremoli, Sandro

    2007-01-26

    Activation of calpain occurs as an early event in correlation with an increase in [Ca2+]i induced in rat brain upon treatment with a high salt diet for a prolonged period of time. The resulting sequential events have been monitored in the brain of normal and hypertensive rats of the Milan strain, diverging for a constitutive alteration in the level of [Ca2+]i found to be present in nerve cells of hypertensive animals. After 2 weeks of treatment, the levels of the plasma membrane Ca2+-ATPase and of native calpastatin are profoundly decreased. These degradative processes, more pronounced in the brain of hypertensive rats, are progressively and efficiently compensated in the brain of both rat strains by different incoming mechanisms. Along with calpastatin degradation, 15-kDa still-active inhibitory fragments are accumulated, capable of efficiently replacing the loss of native inhibitor molecules. A partial return to a more efficient control of Ca2+ homeostasis occurs in parallel, assured by an early increase in the expression of Ca2+-ATPase and of calpastatin, both producing, after 12 weeks of a high salt (sodium) diet, the restoration of almost original levels of the Ca2+ pump and of significant amounts of native inhibitor molecules. Thus, conservative calpastatin fragmentation, associated with an increased expression of Ca2+-ATPase and of the calpain natural inhibitor, has been demonstrated to occur in vivo in rat brain. This represents a sequential adaptive response capable of overcoming the effects of calpain activation induced by a moderate long term elevation of [Ca2+]i.

  15. Alterations in Daytime and Nighttime Activity in Piglets after Focal and Diffuse Brain Injury.

    PubMed

    Olson, Emily; Badder, Carlie; Sullivan, Sarah; Smith, Colin; Propert, Kathleen; Margulies, Susan S

    2016-04-15

    We have developed and implemented a noninvasive, objective neurofunctional assessment for evaluating the sustained effects of traumatic brain injury (TBI) in piglets with both diffuse and focal injury types. Derived from commercial actigraphy methods in humans, this assessment continuously monitors the day/night activity of piglets using close-fitting jackets equipped with tri-axial accelerometers to monitor movements of the thorax. Acceleration metrics were correlated (N = 7 naïve piglets) with video images to define values associated with a range of activities, from recumbancy (rest) to running. Both focal (N = 8) and diffuse brain injury (N = 9) produced alterations in activity that were significant 4 days post-TBI. Compared to shams (N = 6) who acclimated to the animal facility 4 days after an anesthesia experience by blurring the distinction between day and night activity, post-TBI time-matched animals had larger fractions of inactive periods during the daytime than nighttime, and larger fractions of active time in the night were spent in high activity (e.g., constant walking, intermittent running) than during the day. These persistent disturbances in rest and activity are similar to those observed in human adults and children post-TBI, establishing actigraphy as a translational metric, used in both humans and large animals, for assessment of injury severity, progressions, and intervention. PMID:26414329

  16. An 8-Month Randomized Controlled Exercise Trial Alters Brain Activation During Cognitive Tasks in Overweight Children

    PubMed Central

    Krafft, Cynthia E.; Schwarz, Nicolette F.; Chi, Lingxi; Weinberger, Abby L.; Schaeffer, David J.; Pierce, Jordan E.; Rodrigue, Amanda L.; Yanasak, Nathan E.; Miller, Patricia H.; Tomporowski, Phillip D.; Davis, Catherine L.; McDowell, Jennifer E.

    2014-01-01

    Objective Children who are less fit reportedly have lower performance on tests of cognitive control and differences in brain function. This study examined the effect of an exercise intervention on brain function during two cognitive control tasks in overweight children. Design and Methods Participants included 43 unfit, overweight (BMI ≥ 85th percentile) children 8- to 11-years old (91% Black), who were randomly divided into either an aerobic exercise (n = 24) or attention control group (n = 19). Each group was offered a separate instructor-led after-school program every school day for 8 months. Before and after the program, all children performed two cognitive control tasks during functional magnetic resonance imaging (fMRI): antisaccade and flanker. Results Compared to the control group, the exercise group decreased activation in several regions supporting antisaccade performance, including precentral gyrus and posterior parietal cortex, and increased activation in several regions supporting flanker performance, including anterior cingulate and superior frontal gyrus. Conclusions Exercise may differentially impact these two task conditions, or the paradigms in which cognitive control tasks were presented may be sensitive to distinct types of brain activation that show different effects of exercise. In sum, exercise appears to alter efficiency or flexible modulation of neural circuitry supporting cognitive control in overweight children. PMID:23788510

  17. The time course of altered brain activity during 7-day simulated microgravity.

    PubMed

    Liao, Yang; Lei, Meiying; Huang, Haibo; Wang, Chuang; Duan, Jiaobo; Li, Hongzheng; Liu, Xufeng

    2015-01-01

    Microgravity causes multiple changes in physical and mental levels in humans, which can induce performance deficiency among astronauts. Studying the variations in brain activity that occur during microgravity would help astronauts to deal with these changes. In the current study, resting-state functional magnetic resonance imaging (rs-fMRI) was used to observe the variations in brain activity during a 7-day head down tilt (HDT) bed rest, which is a common and reliable model for simulated microgravity. The amplitudes of low frequency fluctuation (ALFF) of twenty subjects were recorded pre-head down tilt (pre-HDT), during a bed rest period (HDT0), and then each day in the HDT period (HDT1-HDT7). One-way analysis of variance (ANOVA) of the ALFF values over these 8 days was used to test the variation across time period (p < 0.05, corrected). Compared to HDT0, subjects presented lower ALFF values in the posterior cingulate cortex (PCC) and higher ALFF values in the anterior cingulate cortex (ACC) during the HDT period, which may partially account for the lack of cognitive flexibility and alterations in autonomic nervous system seen among astronauts in microgravity. Additionally, the observed improvement in function in CPL during the HDT period may play a compensatory role to the functional decline in the paracentral lobule to sustain normal levels of fine motor control for astronauts in a microgravity environment. Above all, those floating brain activities during 7 days of simulated microgravity may indicate that the brain self-adapts to help astronauts adjust to the multiple negative stressors encountered in a microgravity environment. PMID:26029071

  18. The time course of altered brain activity during 7-day simulated microgravity

    PubMed Central

    Liao, Yang; Lei, Meiying; Huang, Haibo; Wang, Chuang; Duan, Jiaobo; Li, Hongzheng; Liu, Xufeng

    2015-01-01

    Microgravity causes multiple changes in physical and mental levels in humans, which can induce performance deficiency among astronauts. Studying the variations in brain activity that occur during microgravity would help astronauts to deal with these changes. In the current study, resting-state functional magnetic resonance imaging (rs-fMRI) was used to observe the variations in brain activity during a 7-day head down tilt (HDT) bed rest, which is a common and reliable model for simulated microgravity. The amplitudes of low frequency fluctuation (ALFF) of twenty subjects were recorded pre-head down tilt (pre-HDT), during a bed rest period (HDT0), and then each day in the HDT period (HDT1–HDT7). One-way analysis of variance (ANOVA) of the ALFF values over these 8 days was used to test the variation across time period (p < 0.05, corrected). Compared to HDT0, subjects presented lower ALFF values in the posterior cingulate cortex (PCC) and higher ALFF values in the anterior cingulate cortex (ACC) during the HDT period, which may partially account for the lack of cognitive flexibility and alterations in autonomic nervous system seen among astronauts in microgravity. Additionally, the observed improvement in function in CPL during the HDT period may play a compensatory role to the functional decline in the paracentral lobule to sustain normal levels of fine motor control for astronauts in a microgravity environment. Above all, those floating brain activities during 7 days of simulated microgravity may indicate that the brain self-adapts to help astronauts adjust to the multiple negative stressors encountered in a microgravity environment. PMID:26029071

  19. Altered Spontaneous Brain Activity in Patients with Acute Spinal Cord Injury Revealed by Resting-State Functional MRI

    PubMed Central

    Zhu, Ling; Wu, Guangyao; Zhou, Xin; Li, Jielan; Wen, Zhi; Lin, Fuchun

    2015-01-01

    Background Previous neuroimaging studies have provided evidence of structural and functional reorganization of brain in patients with chronic spinal cord injury (SCI). However, it remains unknown whether the spontaneous brain activity changes in acute SCI. In this study, we investigated intrinsic brain activity in acute SCI patients using a regional homogeneity (ReHo) analysis based on resting-state functional magnetic resonance imaging. Methods A total of 15 patients with acute SCI and 16 healthy controls participated in the study. The ReHo value was used to evaluate spontaneous brain activity, and voxel-wise comparisons of ReHo were performed to identify brain regions with altered spontaneous brain activity between groups. We also assessed the associations between ReHo and the clinical scores in brain regions showing changed spontaneous brain activity. Results Compared with the controls, the acute SCI patients showed decreased ReHo in the bilateral primary motor cortex/primary somatosensory cortex, bilateral supplementary motor area/dorsal lateral prefrontal cortex, right inferior frontal gyrus, bilateral dorsal anterior cingulate cortex and bilateral caudate; and increased ReHo in bilateral precuneus, the left inferior parietal lobe, the left brainstem/hippocampus, the left cingulate motor area, bilateral insula, bilateral thalamus and bilateral cerebellum. The average ReHo values of the left thalamus and right insula were negatively correlated with the international standards for the neurological classification of spinal cord injury motor scores. Conclusion Our findings indicate that acute distant neuronal damage has an immediate impact on spontaneous brain activity. In acute SCI patients, the ReHo was prominently altered in brain regions involved in motor execution and cognitive control, default mode network, and which are associated with sensorimotor compensatory reorganization. Abnormal ReHo values in the left thalamus and right insula could serve as

  20. PRENATAL ALCOHOL EXPOSURE ALTERS STEADY-STATE AND ACTIVATED GENE EXPRESSION IN THE ADULT RAT BRAIN

    PubMed Central

    Stepien, Katarzyna A.; Lussier, Alexandre A.; Neumann, Sarah M.; Pavlidis, Paul; Kobor, Michael S.; Weinberg, Joanne

    2016-01-01

    Background Prenatal alcohol exposure (PAE) is associated with alterations in numerous physiological systems, including the stress and immune systems . We have previously shown that PAE increases the course and severity of arthritis in an adjuvant-induced arthritis (AA) model. While the molecular mechanisms underlying these effects are not fully known, changes in neural gene expression are emerging as important factors in the etiology of PAE effects. As the prefrontal cortex (PFC) and hippocampus (HPC) play key roles in neuroimmune function, PAE-induced alterations to their transcriptome may underlie abnormal steady-state functions and responses to immune challenge. The current study examined brains from adult PAE and control females from our recent AA study to determine whether PAE causes long-term alterations in gene expression and whether these mediate the altered severity and course of arthritis in PAE females Methods Adult females from PAE, pair-fed [PF], and ad libitum-fed control [C]) groups were injected with either saline or complete Freund’s adjuvant. Animals were terminated at the peak of inflammation or during resolution (days 16 and 39 post-injection, respectively); cohorts of saline-injected PAE, PF and C females were terminated in parallel. Gene expression was analyzed in the PFC and HPC using whole genome mRNA expression microarrays. Results Significant changes in gene expression in both the PFC and HPC were found in PAE compared to controls in response to ethanol exposure alone (saline-injected females), including genes involved in neurodevelopment, apoptosis, and energy metabolism. Moreover, in response to inflammation (adjuvant-injected females), PAE animals showed unique expression patterns, while failing to exhibit the activation of genes and regulators involved in the immune response observed in control and pair-fed animals. Conclusions These results support the hypothesis that PAE affects neuroimmune function at the level of gene expression

  1. Relationships between locomotor activation and alterations in brain temperature during selective blockade and stimulation of dopamine transmission.

    PubMed

    Brown, P L; Bae, D; Kiyatkin, E A

    2007-03-01

    It is well known that the dopamine (DA) system plays an essential role in the organization and regulation of brain activational processes. Various environmental stimuli that induce locomotor activation also increase DA transmission, while DA antagonists decrease spontaneous locomotion. Our previous work supports close relationships between locomotor activation and brain and body temperature increases induced by salient environmental challenges or occurring during motivated behavior. While this correlation was also true for psychomotor stimulant drugs such as methamphetamine and MDMA, more complex relationships or even inverted correlations were found for other drugs that are known to increase DA transmission (i.e. heroin and cocaine). In the present study we examined brain, muscle and skin temperatures together with conventional locomotion during selective interruption of DA transmission induced by a mixture of D1 and D2 antagonists (SCH-23390 and eticlopride at 0.2 mg/kg, s.c.) and its selective activation by apomorphine (APO; 0.05 and 0.25 mg/kg, i.v.) in rats. While full DA receptor blockade decreased spontaneous locomotion, it significantly increased brain, muscle and skin temperatures, suggesting metabolic brain activation under conditions of vasodilatation (or weakening of normal vascular tone). In contrast, APO strongly decreased skin temperature but tended to decrease brain and muscle temperatures despite strong hyperlocomotion and stereotypy. The brain temperature response to APO was strongly dependent on basal brain temperature, with hypothermia at high basal temperatures and weak hyperthermia at low temperatures. While supporting the role of DA in locomotor activation, these data suggest more complex relationships between drug-induced alterations in DA transmission, behavioral activation and metabolic brain activation.

  2. From Nose to Brain: Un-Sensed Electrical Currents Applied in the Nose Alter Activity in Deep Brain Structures

    PubMed Central

    Weiss, Tali; Shushan, Sagit; Ravia, Aharon; Hahamy, Avital; Secundo, Lavi; Weissbrod, Aharon; Ben-Yakov, Aya; Holtzman, Yael; Cohen-Atsmoni, Smadar; Roth, Yehudah; Sobel, Noam

    2016-01-01

    Rules linking patterns of olfactory receptor neuron activation in the nose to activity patterns in the brain and ensuing odor perception remain poorly understood. Artificially stimulating olfactory neurons with electrical currents and measuring ensuing perception may uncover these rules. We therefore inserted an electrode into the nose of 50 human volunteers and applied various currents for about an hour in each case. This induced assorted non-olfactory sensations but never once the perception of odor. To validate contact with the olfactory path, we used functional magnetic resonance imaging to measure resting-state brain activity in 18 subjects before and after un-sensed stimulation. We observed stimulation-induced neural decorrelation specifically in primary olfactory cortex, implying contact with the olfactory path. These results suggest that indiscriminate olfactory activation does not equate with odor perception. Moreover, this effort serendipitously uncovered a novel path for minimally invasive brain stimulation through the nose. PMID:27591145

  3. Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia

    PubMed Central

    Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

    2015-01-01

    The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN. PMID:26508861

  4. Methionine-choline deprivation alters liver and brain acetylcholinesterase activity in C57BL6 mice.

    PubMed

    Vučević, Danijela B; Cerović, Ivana B; Mladenović, Dušan R; Vesković, Milena N; Stevanović, Ivana; Jorgačević, Bojan Z; Ješić Vukićević, Rada; Radosavljević, Tatjana S

    2016-07-01

    Choline and methionine are precursors of acetylcholine, whose hydrolysis is catalyzed by acetylcholinesterase (AChE). Considering the possibility of their common deficiency, we investigated the influence of methionine-choline deprivation on AChE activity in liver and various brain regions (hypothalamus, hippocampus, cerebral cortex and striatum) in mice fed with methionine-choline deficient (MCD) diet. Male C57BL/6 mice (n = 28) were randomly and equally divided into following groups: control group fed with standard diet for 6 weeks (C) and groups fed with MCD diet for 2 weeks (MCD2), 4 weeks (MCD4) and for 6 weeks (MCD6). After the diet, mice were sacrificied and AChE activity in liver and brain was determined spectrophotometrically. Hepatic AChE activity was higher in MCD2, MCD4 and MCD6 compared to control (p < 0.01), with most prominent increase in MCD6. AChE activity in hypothalamus was higher in MCD4 and MCD6 vs. control (p < 0.05 and p < 0.01, respectively), as well as in MCD6 compared to MCD4 (p < 0.01). In hippocampus, increase in AChE activity was shown in MCD6 compared to control (p < 0.01). In cortex and striatum, increase in AChE activity was noted in MCD6 compared to control (p < 0.05). Our findings indicate the increase of hepatic and brain AChE activity in mice caused by methionine-choline deprivation.

  5. Alzheimer Disease Alters the Relationship of Cardiorespiratory Fitness With Brain Activity During the Stroop Task

    PubMed Central

    Gayed, Matthew R.; Honea, Robyn A.; Savage, Cary R.; Hobbs, Derek; Burns, Jeffrey M.

    2013-01-01

    Background Despite mounting evidence that physical activity has positive benefits for brain and cognitive health, there has been little characterization of the relationship between cardiorespiratory (CR) fitness and cognition-associated brain activity as measured by functional magnetic resonance imaging (fMRI). The lack of evidence is particularly glaring for diseases such as Alzheimer disease (AD) that degrade cognitive and functional performance. Objective The aim of this study was to describe the relationship between regional brain activity during cognitive tasks and CR fitness level in people with and without AD. Design A case-control, single-observation study design was used. Methods Thirty-four individuals (18 without dementia and 16 in the earliest stages of AD) completed maximal exercise testing and performed a Stroop task during fMRI. Results Cardiorespiratory fitness was inversely associated with anterior cingulate activity in the participants without dementia (r=−.48, P=.05) and unassociated with activation in those with AD (P>.7). Weak associations of CR fitness and middle frontal cortex were noted. Limitations The wide age range and the use of a single task in fMRI rather than multiple tasks challenging different cognitive capacities were limitations of the study. Conclusions The results offer further support of the relationship between CR fitness and regional brain activity. However, this relationship may be attenuated by disease. Future work in this area may provide clinicians and researchers with interpretable and dependable regional fMRI biomarker signatures responsive to exercise intervention. It also may shed light on mechanisms by which exercise can support cognitive function. PMID:23559521

  6. Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior.

    PubMed

    McCoy, C R; Golf, S R; Melendez-Ferro, M; Perez-Costas, E; Glover, M E; Jackson, N L; Stringfellow, S A; Pugh, P C; Fant, A D; Clinton, S M

    2016-06-01

    Individual differences in human temperament can increase the risk of psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of cytochrome C oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in the HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes. PMID:26979051

  7. Expression of p21-activated kinases 1 and 3 is altered in the brain of subjects with depression.

    PubMed

    Fuchsova, Beata; Alvarez Juliá, Anabel; Rizavi, Hooriyah S; Frasch, Alberto Carlos; Pandey, Ghanshyam N

    2016-10-01

    The p21-activated kinases (PAKs) of group I are the main effectors for the small Rho GTPases, critically involved in neurodevelopment, plasticity and maturation of the nervous system. Moreover, the neuronal complexity controlled by PAK1/PAK3 signaling determines the postnatal brain size and synaptic properties. Stress induces alterations at the level of structural and functional synaptic plasticity accompanied by reductions in size and activity of the hippocampus and the prefrontal cortex (PFC). These abnormalities are likely to contribute to the pathology of depression and, in part, reflect impaired cytoskeleton remodeling pointing to the role of Rho GTPase signaling. Thus, the present study assessed the expression of the group I PAKs and their activators in the brain of depressed subjects. Using quantitative polymerase chain reaction (qPCR), mRNA levels and coexpression of the group I PAKs: PAK1, PAK2, and PAK3 as well as of their activators: RAC1, CDC42 and ARHGEF7 were examined in postmortem samples from the PFC (n=25) and the hippocampus (n=23) of subjects with depression and compared to control subjects (PFC n=24; hippocampus n=21). Results demonstrated that mRNA levels of PAK1 and PAK3, are significantly reduced in the brain of depressed subjects, with PAK1 being reduced in the PFC and PAK3 in the hippocampus. No differences were observed for the ubiquitously expressed PAK2. Following analysis of gene coexpression demonstrated disruption of coordinated gene expression in the brain of subjects with depression. Abnormalities in mRNA expression of PAK1 and PAK3 as well as their altered coexpression patterns were detected in the brain of subjects with depression. PMID:27474226

  8. Brain injury induces specific changes in the caecal microbiota of mice via altered autonomic activity and mucoprotein production.

    PubMed

    Houlden, A; Goldrick, M; Brough, D; Vizi, E S; Lénárt, N; Martinecz, B; Roberts, I S; Denes, A

    2016-10-01

    Intestinal microbiota are critical for health with changes associated with diverse human diseases. Research suggests that altered intestinal microbiota can profoundly affect brain function. However, whether altering brain function directly affects the microbiota is unknown. Since it is currently unclear how brain injury induces clinical complications such as infections or paralytic ileus, key contributors to prolonged hospitalization and death post-stroke, we tested in mice the hypothesis that brain damage induced changes in the intestinal microbiota. Experimental stroke altered the composition of caecal microbiota, with specific changes in Peptococcaceae and Prevotellaceae correlating with the extent of injury. These effects are mediated by noradrenaline release from the autonomic nervous system with altered caecal mucoprotein production and goblet cell numbers. Traumatic brain injury also caused changes in the gut microbiota, confirming brain injury effects gut microbiota. Changes in intestinal microbiota after brain injury may affect recovery and treatment of patients should appreciate such changes.

  9. Methamphetamine Alters Brain Structures, Impairs Mental Flexibility

    MedlinePlus

    ... Alters Brain Structures, Impairs Mental Flexibility Methamphetamine Alters Brain Structures, Impairs Mental Flexibility Email Facebook Twitter March ... methamphetamine use, such as tobacco smoking. Can the Brain Recover? The UCLA study’s findings underscore the importance ...

  10. What's Special about the Ethical Challenges of Studying Disorders with Altered Brain Activity?

    PubMed

    Cassaday, Helen J

    2015-01-01

    Where there is no viable alternative, studies of neuronal activity are conducted on animals. The use of animals, particularly for invasive studies of the brain, raises a number of ethical issues. Practical or normative ethics are enforced by legislation, in relation to the dominant welfare guidelines developed in the United Kingdom and elsewhere. Guidelines have typically been devised to cover all areas of biomedical research using animals in general, and thus lack any specific focus on neuroscience studies at the level of the ethics, although details of the specific welfare recommendations are different for invasive studies of the brain. Ethically, there is no necessary distinction between neuroscience and other biomedical research in that the brain is a final common path for suffering, irrespective of whether this involves any direct experience of pain. One exception arises in the case of in vitro studies, which are normally considered as an acceptable replacement for in vivo studies. However, to the extent sentience is possible, maintaining central nervous system tissue outside the body naturally raises ethical questions. Perhaps the most intractable challenge to the ethical use of animals in order to model neuronal disorder is presented by the logical impasse in the argument that the animal is similar enough to justify the validity of the experimental model, but sufficiently different in sentience and capacity for suffering, for the necessary experimental procedures to be permissible.

  11. It still hurts: altered endogenous opioid activity in the brain during social rejection and acceptance in major depressive disorder.

    PubMed

    Hsu, D T; Sanford, B J; Meyers, K K; Love, T M; Hazlett, K E; Walker, S J; Mickey, B J; Koeppe, R A; Langenecker, S A; Zubieta, J-K

    2015-02-01

    The μ-opioid receptor (MOR) system, well known for dampening physical pain, is also hypothesized to dampen 'social pain.' We used positron emission tomography scanning with the selective MOR radioligand [(11)C]carfentanil to test the hypothesis that MOR system activation (reflecting endogenous opioid release) in response to social rejection and acceptance is altered in medication-free patients diagnosed with current major depressive disorder (MDD, n=17) compared with healthy controls (HCs, n=18). During rejection, MDD patients showed reduced endogenous opioid release in brain regions regulating stress, mood and motivation, and slower emotional recovery compared with HCs. During acceptance, only HCs showed increased social motivation, which was positively correlated with endogenous opioid release in the nucleus accumbens, a reward structure. Altered endogenous opioid activity in MDD may hinder emotional recovery from negative social interactions and decrease pleasure derived from positive interactions. Both effects may reinforce depression, trigger relapse and contribute to poor treatment outcomes.

  12. Altered cognition-related brain activity and interactions with acute pain in migraine

    PubMed Central

    Mathur, Vani A.; Khan, Shariq A.; Keaser, Michael L.; Hubbard, Catherine S.; Goyal, Madhav; Seminowicz, David A.

    2015-01-01

    Little is known about the effect of migraine on neural cognitive networks. However, cognitive dysfunction is increasingly being recognized as a comorbidity of chronic pain. Pain appears to affect cognitive ability and the function of cognitive networks over time, and decrements in cognitive function can exacerbate affective and sensory components of pain. We investigated differences in cognitive processing and pain–cognition interactions between 14 migraine patients and 14 matched healthy controls using an fMRI block-design with two levels of task difficulty and concurrent heat (painful and not painful) stimuli. Across groups, cognitive networks were recruited in response to a difficult cognitive task, and a pain–task interaction was found in the right (contralateral to pain stimulus) posterior insula (pINS), such that activity was modulated by decreasing the thermal pain stimulus or by engaging the difficult cognitive task. Migraine patients had less task-related deactivation within the left dorsolateral prefrontal cortex (DLPFC) and left dorsal anterior midcingulate cortex (aMCC) compared to controls. These regions have been reported to have decreased cortical thickness and cognitive-related deactivation within other pain populations, and are also associated with pain regulation, suggesting that the current findings may reflect altered cognitive function and top-down regulation of pain. During pain conditions, patients had decreased task-related activity, but more widespread task-related reductions in pain-related activity, compared to controls, suggesting cognitive resources may be diverted from task-related to pain-reduction-related processes in migraine. Overall, these findings suggest that migraine is associated with altered cognitive-related neural activity, which may reflect altered pain regulatory processes as well as broader functional restructuring. PMID:25610798

  13. Frequency Dependent Alterations in Regional Homogeneity of Baseline Brain Activity in Schizophrenia

    PubMed Central

    Wang, Hsiao-Lan Sharon; Liu, Chih-Min; Liu, Chen-Chung; Hwang, Tzung-Jeng; Chien, Yi-Ling; Hwu, Hai-Gwo; Tseng, Wen-Yih Isaac

    2013-01-01

    Low frequency oscillations are essential in cognitive function impairment in schizophrenia. While functional connectivity can reveal the synchronization between distant brain regions, the regional abnormalities in task-independent baseline brain activity are less clear, especially in specific frequency bands. Here, we used a regional homogeneity (ReHo) method combined with resting-state functional magnetic resonance imaging to investigate low frequency spontaneous neural activity in the three different frequency bands (slow-5∶0.01–0.027 Hz; slow-4∶0.027–0.08 Hz; and typical band: 0.01–0.08 Hz) in 69 patients with schizophrenia and 62 healthy controls. Compared with controls, schizophrenia patients exhibited decreased ReHo in the precentral gyrus, middle occipital gyrus, and posterior insula, whereas increased ReHo in the medial prefrontal cortex and anterior insula. Significant differences in ReHo between the two bands were found in fusiform gyrus and superior frontal gyrus (slow-4> slow-5), and in basal ganglia, parahippocampus, and dorsal middle prefrontal gyrus (slow-5> slow-4). Importantly, we identified significant interaction between frequency bands and groups in the inferior occipital gyrus and caudate body. This study demonstrates that ReHo changes in schizophrenia are widespread and frequency dependent. PMID:23483911

  14. Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson's Disease.

    PubMed

    Xiang, Jie; Jia, Xiuqin; Li, Huizhuo; Qin, Jiawei; Liang, Peipeng; Li, Kuncheng

    2016-01-01

    Purpose. The present study aimed to explore the changes of amplitude of low-frequency fluctuations (ALFF) at rest in patients with Parkinson's disease (PD). Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two-sample t-test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6) and dorsolateral prefrontal cortex (BA 9/10). Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease.

  15. Altered Spontaneous Brain Activity in Cortical and Subcortical Regions in Parkinson's Disease

    PubMed Central

    Xiang, Jie; Jia, Xiuqin; Li, Huizhuo; Qin, Jiawei; Li, Kuncheng

    2016-01-01

    Purpose. The present study aimed to explore the changes of amplitude of low-frequency fluctuations (ALFF) at rest in patients with Parkinson's disease (PD). Methods. Twenty-four PD patients and 22 healthy age-matched controls participated in the study. ALFF was measured on the whole brain of all participants. A two-sample t-test was then performed to detect the group differences with age, gender, education level, head motion, and gray matter volume as covariates. Results. It was showed that PD patients had significantly decreased ALFF in the left thalamus/caudate and right insula/inferior prefrontal gyrus, whereas they had increased ALFF in the right medial prefrontal cortex (BA 8/6) and dorsolateral prefrontal cortex (BA 9/10). Conclusions. Our results indicated that significant alterations of ALFF in the subcortical regions and prefrontal cortex have been detected in PD patients, independent of age, gender, education, head motion, and structural atrophy. The current findings further provide insights into the biological mechanism of the disease. PMID:27413576

  16. Alterations in brain activation during cognitive empathy are related to social functioning in schizophrenia.

    PubMed

    Smith, Matthew J; Schroeder, Matthew P; Abram, Samantha V; Goldman, Morris B; Parrish, Todd B; Wang, Xue; Derntl, Birgit; Habel, Ute; Decety, Jean; Reilly, James L; Csernansky, John G; Breiter, Hans C

    2015-01-01

    Impaired cognitive empathy (ie, understanding the emotional experiences of others) is associated with poor social functioning in schizophrenia. However, it is unclear whether the neural activity underlying cognitive empathy relates to social functioning. This study examined the neural activation supporting cognitive empathy performance and whether empathy-related activation during correctly performed trials was associated with self-reported cognitive empathy and measures of social functioning. Thirty schizophrenia outpatients and 24 controls completed a cognitive empathy paradigm during functional magnetic resonance imaging. Neural activity corresponding to correct judgments about the expected emotional expression in a social interaction was compared in schizophrenia subjects relative to control subjects. Participants also completed a self-report measure of empathy and 2 social functioning measures (social competence and social attainment). Schizophrenia subjects demonstrated significantly lower accuracy in task performance and were characterized by hypoactivation in empathy-related frontal, temporal, and parietal regions as well as hyperactivation in occipital regions compared with control subjects during accurate cognitive empathy trials. A cluster with peak activation in the supplementary motor area (SMA) extending to the anterior midcingulate cortex (aMCC) correlated with social competence and social attainment in schizophrenia subjects but not controls. These results suggest that neural correlates of cognitive empathy may be promising targets for interventions aiming to improve social functioning and that brain activation in the SMA/aMCC region could be used as a biomarker for monitoring treatment response.

  17. Neurophysiological activity underlying altered brain metabolism in epileptic encephalopathies with CSWS.

    PubMed

    De Tiège, Xavier; Trotta, Nicola; Op de Beeck, Marc; Bourguignon, Mathieu; Marty, Brice; Wens, Vincent; Nonclercq, Antoine; Goldman, Serge; Van Bogaert, Patrick

    2013-08-01

    We investigated the neurophysiological correlate of altered regional cerebral glucose metabolism observed in children with epileptic encephalopathy with continuous spike-waves during sleep (CSWS) by using a multimodal approach combining time-sensitive magnetic source imaging (MSI) and positron emission tomography with [(18)F]-fluorodeoxyglucose (FDG-PET). Six patients (4 boys and 2 girls, age range: 4-8 years, 3 patients with Landau-Kleffner syndrome (LKS), 3 patients with atypical rolandic epilepsy (ARE)) were investigated by FDG-PET and MSI at the acute phase of CSWS. In all patients, the onset(s) of spike-waves discharges were associated with significant focal hypermetabolism. The propagation of epileptic discharges to other brain areas was associated with focal hypermetabolism (five patients), hypometabolism (one patient) or the absence of any significant metabolic change (one patient). Interestingly, most of the hypometabolic areas were not involved in the epileptic network per se. This study shows that focal hypermetabolism observed at the acute phase of CSWS are related to the onset or propagation sites of spike-wave discharges. Spike-wave discharges propagation can be associated to other types of metabolic changes, suggesting the occurrence of various neurophysiological mechanisms at the cellular level. Most of the hypometabolic areas are not involved in the epileptic network as such and are probably related to a mechanism of remote inhibition. These findings highlight the critical value of combining FDG-PET with time-sensitive functional neuroimaging approaches such as MSI to assess CSWS epileptic network when surgery is considered as a therapeutic approach.

  18. Prenatal drug exposure to illicit drugs alters working memory-related brain activity and underlying network properties in adolescence.

    PubMed

    Schweitzer, Julie B; Riggins, Tracy; Liang, Xia; Gallen, Courtney; Kurup, Pradeep K; Ross, Thomas J; Black, Maureen M; Nair, Prasanna; Salmeron, Betty Jo

    2015-01-01

    The persistence of effects of prenatal drug exposure (PDE) on brain functioning during adolescence is poorly understood. We explored neural activation to a visuospatial working memory (VSWM) versus a control task using functional magnetic resonance imaging (fMRI) in adolescents with PDE and a community comparison group (CC) of non-exposed adolescents. We applied graph theory metrics to resting state data using a network of nodes derived from the VSWM task activation map to further explore connectivity underlying WM functioning. Participants (ages 12-15 years) included 47 adolescents (27 PDE and 20 CC). All analyses controlled for potentially confounding differences in birth characteristics and postnatal environment. Significant group by task differences in brain activation emerged in the left middle frontal gyrus (BA 6) with the CC group, but not the PDE group, activating this region during VSWM. The PDE group deactivated the culmen, whereas the CC group activated it during the VSWM task. The CC group demonstrated a significant relation between reaction time and culmen activation, not present in the PDE group. The network analysis underlying VSWM performance showed that PDE group had lower global efficiency than the CC group and a trend level reduction in local efficiency. The network node corresponding to the BA 6 group by task interaction showed reduced nodal efficiency and fewer direct connections to other nodes in the network. These results suggest that adolescence reveals altered neural functioning related to response planning that may reflect less efficient network functioning in youth with PDE.

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-30

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

  1. Alterations in regional homogeneity of resting-state brain activity in internet gaming addicts

    PubMed Central

    2012-01-01

    Backgrounds Internet gaming addiction (IGA), as a subtype of internet addiction disorder, is rapidly becoming a prevalent mental health concern around the world. The neurobiological underpinnings of IGA should be studied to unravel the potential heterogeneity of IGA. This study investigated the brain functions in IGA patients with resting-state fMRI. Methods Fifteen IGA subjects and fourteen healthy controls participated in this study. Regional homogeneity (ReHo) measures were used to detect the abnormal functional integrations. Results Comparing to the healthy controls, IGA subjects show enhanced ReHo in brainstem, inferior parietal lobule, left posterior cerebellum, and left middle frontal gyrus. All of these regions are thought related with sensory-motor coordination. In addition, IGA subjects show decreased ReHo in temporal, occipital and parietal brain regions. These regions are thought responsible for visual and auditory functions. Conclusions Our results suggest that long-time online game playing enhanced the brain synchronization in sensory-motor coordination related brain regions and decreased the excitability in visual and auditory related brain regions. PMID:22901705

  2. Alterations in Error-Related Brain Activity and Post-Error Behavior over Time

    ERIC Educational Resources Information Center

    Themanson, Jason R.; Rosen, Peter J.; Pontifex, Matthew B.; Hillman, Charles H.; McAuley, Edward

    2012-01-01

    This study examines the relation between the error-related negativity (ERN) and post-error behavior over time in healthy young adults (N = 61). Event-related brain potentials were collected during two sessions of an identical flanker task. Results indicated changes in ERN and post-error accuracy were related across task sessions, with more…

  3. Zebrafish locomotor capacity and brain acetylcholinesterase activity is altered by Aphanizomenon flos-aquae DC-1 aphantoxins.

    PubMed

    Zhang, De Lu; Hu, Chun Xiang; Li, Dun Hai; Liu, Yong Ding

    2013-08-15

    Aphanizomenon flos-aquae (A. flos-aquae) is a source of neurotoxins known as aphantoxins or paralytic shellfish poisons (PSPs) that present a major threat to the environment and to human health. Generally, altered neurological function is reflected in behavior. Although the molecular mechanism of action of PSPs is well known, its neurobehavioral effects on adult zebrafish and its relationship with altered neurological functions are poorly understood. Aphantoxins purified from a natural isolate of A. flos-aquae DC-1 were analyzed by HPLC. The major analogs found in the toxins were the gonyautoxins 1 and 5 (GTX1 and GTX5; 34.04% and 21.28%, respectively) and the neosaxitoxin (neoSTX, 12.77%). Zebrafish (Danio rerio) were intraperitoneally injected with 5.3 and 7.61 μg STXeq/kg (low and high dose, respectively) of A. flos-aquae DC-1 aphantoxins. The swimming activity was investigated by observation combined with video at 6 timepoints from 1 to 24 h post-exposure. Both aphantoxin doses were associated with delayed touch responses, reduced head-tail locomotory abilities, inflexible turning of head, and a tailward-shifted center of gravity. The normal S-pattern (or undulating) locomotor trajectory was replaced by a mechanical motor pattern of swinging the head after wagging the tail. Finally, these fish principally distributed at the top and/or bottom water of the aquarium, and showed a clear polarized distribution pattern at 12 h post-exposure. Further analysis of neurological function demonstrated that both aphantoxin doses inhibited brain acetylcholinesterase activity. All these changes were dose- and time-dependent. These results demonstrate that aphantoxins can alter locomotor capacity, touch responses and distribution patterns by damaging the cholinergic system of zebrafish, and suggest that zebrafish locomotor behavior and acetylcholinesterase can be used as indicators for investigating aphantoxins and blooms in nature. PMID:23792258

  4. Prenatal ethanol exposure alters ethanol-induced Fos immunoreactivity and dopaminergic activity in the mesocorticolimbic pathway of the adolescent brain.

    PubMed

    Fabio, M C; Vivas, L M; Pautassi, R M

    2015-08-20

    Prenatal ethanol exposure (PEE) promotes alcohol intake during adolescence, as shown in clinical and pre-clinical animal models. The mechanisms underlying this effect of prenatal ethanol exposure on postnatal ethanol intake remain, however, mostly unknown. Few studies assessed the effects of moderate doses of prenatal ethanol on spontaneous and ethanol-induced brain activity on adolescence. This study measured, in adolescent (female) Wistar rats prenatally exposed to ethanol (0.0 or 2.0g/kg/day, gestational days 17-20) or non-manipulated (NM group) throughout pregnancy, baseline and ethanol-induced cathecolaminergic activity (i.e., colocalization of c-Fos and tyrosine hydroxylase) in ventral tegmental area (VTA), and baseline and ethanol-induced Fos immunoreactivity (ir) in nucleus accumbens shell and core (AcbSh and AcbC, respectively) and prelimbic (PrL) and infralimbic (IL) prefrontal cortex. The rats were challenged with ethanol (dose: 0.0, 1.25, 2.5 or 3.25g/kg, i.p.) at postnatal day 37. Rats exposed to vehicle prenatally (VE group) exhibited reduced baseline dopaminergic tone in VTA; an effect that was inhibited by prenatal ethanol exposure (PEE group). Dopaminergic activity in VTA after the postnatal ethanol challenge was greater in PEE than in VE or NM animals. Ethanol-induced Fos-ir at AcbSh was found after 1.25g/kg and 2.5g/kg ethanol, in VE and PEE rats, respectively. PEE did not alter ethanol-induced Fos-ir at IL but reduced ethanol-induced Fos-ir at PrL. These results suggest that prenatal ethanol exposure heightens dopaminergic activity in the VTA and alters the response of the mesocorticolimbic pathway to postnatal ethanol exposure. These effects may underlie the enhanced vulnerability to develop alcohol-use disorders of adolescents with a history of in utero ethanol exposure.

  5. Age-related learning and memory deficits in rats: role of altered brain neurotransmitters, acetylcholinesterase activity and changes in antioxidant defense system.

    PubMed

    Haider, Saida; Saleem, Sadia; Perveen, Tahira; Tabassum, Saiqa; Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Madiha, Syeda

    2014-06-01

    Oxidative stress from generation of increased reactive oxygen species or free radicals of oxygen has been reported to play an important role in the aging. To investigate the relationship between the oxidative stress and memory decline during aging, we have determined the level of lipid peroxidation, activities of antioxidant enzymes, and activity of acetylcholine esterase (AChE) in brain and plasma as well as biogenic amine levels in brain from Albino-Wistar rats at age of 4 and 24 months. The results showed that the level of lipid peroxidation in the brain and plasma was significantly higher in older than that in the young rats. The activities of antioxidant enzymes displayed an age-dependent decline in both brain and plasma. Glutathione peroxidase and catalase activities were found to be significantly decreased in brain and plasma of aged rats. Superoxide dismutase (SOD) was also significantly decreased in plasma of aged rats; however, a decreased tendency (non-significant) of SOD in brain was also observed. AChE activity in brain and plasma was significantly decreased in aged rats. Learning and memory of rats in the present study was assessed by Morris Water Maze (MWM) and Elevated plus Maze (EPM) test. Short-term memory and long-term memory was impaired significantly in older rats, which was evident by a significant increase in the latency time in MWM and increase in transfer latency in EPM. Moreover, a marked decrease in biogenic amines (NA, DA, and 5-HT) was also found in the brain of aged rats. In conclusion, our data suggest that increased oxidative stress, decline of antioxidant enzyme activities, altered AChE activity, and decreased biogenic amines level in the brain of aged rats may potentially be involved in diminished memory function.

  6. Gestational exposure to cadmium alters crucial offspring rat brain enzyme activities: the role of cadmium-free lactation.

    PubMed

    Liapi, Charis; Stolakis, Vasileios; Zarros, Apostolos; Zissis, Konstantinos M; Botis, John; Al-Humadi, Hussam; Tsakiris, Stylianos

    2013-11-01

    The present study aimed to shed more light on the effects of gestational (in utero) exposure to cadmium (Cd) on crucial brain enzyme activities of Wistar rat offspring, as well as to assess the potential protective/restorative role that a Cd-free lactation might have on these effects. In contrast to earlier findings of ours regarding the pattern of effects that adult-onset exposure to Cd has on brain AChE, Na(+),K(+)- and Mg(2+)-ATPase activities, as well as in contrast to similar experimental approaches implementing the sacrificing mode of anaesthesia, in utero exposure to Cd-chloride results in increased AChE and Na(+),K(+)-ATPase activities in the newborn rat brain homogenates that were ameliorated through a Cd-free lactation (as assessed in the brain of 21-day-old offspring). Mg(2+)-ATPase activity was not found to be significantly modified under the examined experimental conditions. These findings could provide the basis for a further evaluation of the herein discussed neurotoxic effects of in utero exposure to Cd, in a brain region-specific manner.

  7. Altered Spontaneous Brain Activity in Primary Open Angle Glaucoma: A Resting-State Functional Magnetic Resonance Imaging Study

    PubMed Central

    Lin, Fuchun; Chen, Zhiqi; Yan, Xiaoqin; Hao, Yonghong; Zhu, Wenzhen; Zhang, Hong

    2014-01-01

    Background Previous studies demonstrated that primary open angle glaucoma (POAG) is associated with abnormal brain structure; however, little is known about the changes in the local synchronization of spontaneous activity. The main objective of this study was to investigate spontaneous brain activity in patients with POAG using regional homogeneity (ReHo) analysis based on resting state functional magnetic resonance imaging (rs-fMRI). Methodology/Principal Findings Thirty-nine POAG patients and forty-one age- and gender- matched healthy controls were finally included in the study. ReHo values were used to evaluate spontaneous brain activity and whole brain voxel-wise analysis of ReHo was carried out to detect differences by region in spontaneous brain activity between groups. Compared to controls, POAG patients showed increased ReHo in the right dorsal anterior cingulated cortex, the bilateral medial frontal gyrus and the right cerebellar anterior lobe, and decreased ReHo in the bilateral calcarine, bilateral precuneus gryus, bilateral pre/postcentral gyrus, left inferior parietal lobule and left cerebellum posterior lobe. A multiple linear regression analysis was performed to explore the relationships between clinical measures and ReHo by region showed significant group differences in the POAG group. Negative correlations were found between age and the ReHo values of the superior frontal gyrus (r = −0.323, p = 0.045), left calcarine (r = −0.357, p = 0.026) and inferior parietal lobule (r = −0.362, p = 0.024). A negative correlation was found between the ReHo values of the left precuneus and the cumulative mean defect (r = −0.400, p = 0.012). Conclusions POAG was associated with abnormal brain spontaneous activity in some brain regions and such changed regional activity may be associated with clinical parameters. Spontaneous brain activity may play a role in POAG initiation and progression. PMID:24586822

  8. A novel fMRI paradigm suggests that pedaling-related brain activation is altered after stroke

    PubMed Central

    Promjunyakul, Nutta-on; Schmit, Brian D.; Schindler-Ivens, Sheila M.

    2015-01-01

    The purpose of this study was to examine the feasibility of using functional magnetic resonance imaging (fMRI) to measure pedaling-related brain activation in individuals with stroke and age-matched controls. We also sought to identify stroke-related changes in brain activation associated with pedaling. Fourteen stroke and 12 control subjects were asked to pedal a custom, MRI-compatible device during fMRI. Subjects also performed lower limb tapping to localize brain regions involved in lower limb movement. All stroke and control subjects were able to pedal while positioned for fMRI. Two control subjects were withdrawn due to claustrophobia, and one control data set was excluded from analysis due to an incidental finding. In the stroke group, one subject was unable to enter the gantry due to excess adiposity, and one stroke data set was excluded from analysis due to excessive head motion. Consequently, 81% of subjects (12/14 stroke, 9/12 control) completed all procedures and provided valid pedaling-related fMRI data. In these subjects, head motion was ≤3 mm. In both groups, brain activation localized to the medial aspect of M1, S1, and Brodmann’s area 6 (BA6) and to the cerebellum (vermis, lobules IV, V, VIII). The location of brain activation was consistent with leg areas. Pedaling-related brain activation was apparent on both sides of the brain, with values for laterality index (LI) of –0.06 (0.20) in the stroke cortex, 0.05 (±0.06) in the control cortex, 0.29 (0.33) in the stroke cerebellum, and 0.04 (0.15) in the control cerebellum. In the stroke group, activation in the cerebellum – but not cortex – was significantly lateralized toward the damaged side of the brain (p = 0.01). The volume of pedaling-related brain activation was smaller in stroke as compared to control subjects. Differences reached statistical significance when all active regions were examined together [p = 0.03; 27,694 (9,608) μL stroke; 37,819 (9,169) μL control]. When individual

  9. Altered brain arginine metabolism in schizophrenia

    PubMed Central

    Liu, P; Jing, Y; Collie, N D; Dean, B; Bilkey, D K; Zhang, H

    2016-01-01

    Previous research implicates altered metabolism of l-arginine, a versatile amino acid with a number of bioactive metabolites, in the pathogenesis of schizophrenia. The present study, for we believe the first time, systematically compared the metabolic profile of l-arginine in the frontal cortex (Brodmann's area 8) obtained post-mortem from schizophrenic individuals and age- and gender-matched non-psychiatric controls (n=20 per group). The enzyme assays revealed no change in total nitric oxide synthase (NOS) activity, but significantly increased arginase activity in the schizophrenia group. Western blot showed reduced endothelial NOS protein expression and increased arginase II protein level in the disease group. High-performance liquid chromatography and liquid chromatography/mass spectrometric assays confirmed significantly reduced levels of γ-aminobutyric acid (GABA), but increased agmatine concentration and glutamate/GABA ratio in the schizophrenia cases. Regression analysis indicated positive correlations between arginase activity and the age of disease onset and between l-ornithine level and the duration of illness. Moreover, cluster analyses revealed that l-arginine and its main metabolites l-citrulline, l-ornithine and agmatine formed distinct groups, which were altered in the schizophrenia group. The present study provides further evidence of altered brain arginine metabolism in schizophrenia, which enhances our understanding of the pathogenesis of schizophrenia and may lead to the future development of novel preventions and/or therapeutics for the disease. PMID:27529679

  10. Altered intrinsic regional brain spontaneous activity in patients with comitant strabismus: a resting-state functional MRI study

    PubMed Central

    Huang, Xin; Li, Sheng-Hong; Zhou, Fu-Qing; Zhang, Ying; Zhong, Yu-Lin; Cai, Feng-Qin; Shao, Yi; Zeng, Xian-Jun

    2016-01-01

    Objective To investigate the underlying regional homogeneity (ReHo) of brain-activity abnormalities in patients with comitant strabismus (CS) and their relationship with behavioral performance. Methods Twenty patients with CS (ten men and ten women) and 20 (ten men and ten women) age-, sex-, and education-matched healthy controls (HCs) underwent resting-state functional magnetic resonance imaging scans. The ReHo method was used to assess local features of spontaneous brain activities. Patients with CS were distinguished from HCs by receiver operating characteristic curve. Correlation analysis was performed to explore the relationship between the observed mean ReHo values of the different brain areas and behavioral performance. Results Compared to HCs, the patients with CS showed significantly increased ReHo values in the right inferior temporal cortex/fusiform gyrus/cerebellum anterior lobe, right lingual gyrus, and bilateral cingulate gyrus. We did not find any relationship between the observed mean ReHo values of the different brain areas and behavioral performance. Conclusion CS causes dysfunction in many brain regions, which may explain the fusion compensation in CS. PMID:27350747

  11. Development and altered gravity dependent changes in glucose-6-phosphate dehydrogenase activity in the brain of the cichlid fish Oreochromis mossambicus.

    PubMed

    Slenzka, K; Appel, R; Rahmann, H

    1995-06-01

    Glucose-6-phosphate dehydrogenase activity was studied in the brain of the cichlid fish Oreochromis mossambicus during early ontogenetic development. In general a slight but continuous decrease in enzyme activity was found (9.5 +/- 0.5 nmol substrate cleaved per mg protein and per min at developmental stage 13 [= 1 day post hatch at 28 degrees C] to a value of 7.9 +/- 0.6 in adult brain). In order to investigate the possible influence of altered gravity during early ontogenetic brain development, fish larvae were exposed to an increased acceleration of three times earth gravity (3 g) or to functional weightlessness in a fast-rotating clinostat for 7 days. A significant increase of brain G6PDH activity of approx. 15% was found after exposure to hyper gravity, whereas a significant decrease of the enzyme activity, approximately 10%, was detected following functional weightlessness in respect to the corresponding 1 g controls. Analyses concerning the regain of normal control enzyme activity of the larvae revealed dramatic fluctuations within the first 5 h after exposure to an increased acceleration of 3 g. Thereafter, between day 1 and day 3 after exposure, brain glucose-6-phosphate dehydrogenase decreased slowly. At day 3 after exposure no further differences of the hyper-g larvae compared to the controls were found. Only slight changes in total brain glucose-6-phosphate dehydrogenase activity occur during ontogenetic development of cichlid fish. This suggests that a more or less constant enzyme activity is important during brain development, but is reacting very sensitively to changes in the environmental factor gravity.

  12. Prevention of haloperidol-induced alterations in brain acetylcholinesterase activity by vitamins B co-administration in a rodent model of tardive dyskinesia.

    PubMed

    de Oliveira, Gersilene Valente; Gomes, Patrícia Xavier Lima; de Araújo, Fernanda Yvelize Ramos; Vasconcelos, Silvânia Maria Mendes; Júnior, Hélio Vitoriano Nobre; de Sousa, Francisca Cléa Florenço; de Lucena, David F; Hyphantis, Thomas N; Carvalho, André Férrer; Macêdo, Danielle Silveira

    2013-03-01

    Tardive dyskinesia (TD) is an iatrogenic syndrome being a significant adverse outcome of typical and atypical antipsychotic therapy. Recently we demonstrated that vitamins B (B1, B6, B12 alone or in combination) were able to prevent haloperidol-induced orofacial dyskinesia (OD) possibly by their antioxidant activity in the striatum, using a well-established model of TD. Here, based on the fact that alterations in cholinergic neurotransmission are related to TD pathophysiology and that vitamins B seems to influence brain cholinergic neurotransmission, we decided to investigate the effects of vitamins B1, B6, B12 and their association, vitamin B cocktail in haloperidol-induced cholinergic alterations, evaluated by alterations in acetylcholinesterase (AChE) activity, in striatum, prefrontal cortex and hippocampus, as a way to determine the participation of cholinergic neurotransmission, in these vitamins antidyskinetic mechanism. Haloperidol 1 mg/kg i.p. daily administration during 21 days to Wistar rats caused OD while decreased AChE activity in all brain areas studied. Vitamins B administration (B1:B6:B12 at 60:60:0.6 mg/kg, s.c) alone and vitamin B cocktail co-administered with haloperidol prevented OD development and increased AChE activity in all brain areas studied, with the maximum activity increment observed in the hippocampus of the animals co-treated with vitamin B12 and vitamin B cocktail. The antidyskinetic drug, clozapine did not induce OD and increased AChE activity similarly to the groups coadministered with vitamin B and HAL. The present data suggest that vitamins B can prevent haloperidol-induced alterations in AChE activity what can be related to the mechanism underlying their antidyskinetic effect.

  13. Altered spontaneous brain activity in patients with Parkinson's disease accompanied by depressive symptoms, as revealed by regional homogeneity and functional connectivity in the prefrontal-limbic system.

    PubMed

    Sheng, Ke; Fang, Weidong; Su, Meilan; Li, Rong; Zou, Dezhi; Han, Yu; Wang, Xuefeng; Cheng, Oumei

    2014-01-01

    As patients with Parkinson's disease (PD) are at high risk for comorbid depression, it is hypothesized that these two diseases are sharing common pathogenic pathways. Using regional homogeneity (ReHo) and functional connectivity approaches, we characterized human regional brain activity at resting state to examine specific brain networks in patients with PD and those with PD and depression (PDD). This study comprised 41 PD human patients and 25 normal human subjects. The patients completed the Hamilton Depression Rating Scale and were further divided into two groups: patients with depressive symptoms and non-depressed PD patients (nD-PD). Compared with the non-depressed patients, those with depressive symptoms exhibited significantly increased regional activity in the left middle frontal gyrus and right inferior frontal gyrus, and decreased ReHo in the left amygdala and bilateral lingual gyrus. Brain network connectivity analysis revealed decreased functional connectivity within the prefrontal-limbic system and increased functional connectivity in the prefrontal cortex and lingual gyrus in PDD compared with the nD-PD group. In summary, the findings showed regional brain activity alterations and disruption of the mood regulation network in PDD patients. The pathogenesis of PDD may be attributed to abnormal neural activity in multiple brain regions.

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

    PubMed

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

    2014-01-01

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

  15. Variants in the DYX2 locus are associated with altered brain activation in reading-related brain regions in subjects with reading disability.

    PubMed

    Cope, Natalie; Eicher, John D; Meng, Haiying; Gibson, Christopher J; Hager, Karl; Lacadie, Cheryl; Fulbright, Robert K; Constable, R Todd; Page, Grier P; Gruen, Jeffrey R

    2012-10-15

    Reading disability (RD) is a complex genetic disorder with unknown etiology. Genes on chromosome 6p22, including DCDC2, KIAA0319, and TTRAP, have been identified as RD associated genes. Imaging studies have shown both functional and structural differences between brains of individuals with and without RD. There are limited association studies performed between RD genes, specifically genes on 6p22, and regional brain activation during reading tasks. Using fourteen variants in DCDC2, KIAA0319, and TTRAP and exhaustive reading measures, we first tested for association with reading performance in 82 parent-offspring families (326 individuals). Next, we determined the association of these variants with activation of sixteen brain regions of interest during four functional magnetic resonance imaging-reading tasks. We nominally replicated associations between reading performance and variants of DCDC2 and KIAA0319. Furthermore, we observed a number of associations with brain activation patterns during imaging-reading tasks with all three genes. The strongest association occurred between activation of the left anterior inferior parietal lobe and complex tandem repeat BV677278 in DCDC2 (uncorrected p=0.00003, q=0.0442). Our results show that activation patterns across regions of interest in the brain are influenced by variants in the DYX2 locus. The combination of genetic and functional imaging data show a link between genes and brain functioning during reading tasks in subjects with RD. This study highlights the many advantages of imaging data as an endophenotype for discerning genetic risk factors for RD and other communication disorders and underscores the importance of integrating neurocognitive, imaging, and genetic data in future investigations.

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

    PubMed Central

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

    2014-01-01

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

  17. Altered global brain signal in schizophrenia

    PubMed Central

    Yang, Genevieve J.; Murray, John D.; Repovs, Grega; Cole, Michael W.; Savic, Aleksandar; Glasser, Matthew F.; Pittenger, Christopher; Krystal, John H.; Wang, Xiao-Jing; Pearlson, Godfrey D.; Glahn, David C.; Anticevic, Alan

    2014-01-01

    Neuropsychiatric conditions like schizophrenia display a complex neurobiology, which has long been associated with distributed brain dysfunction. However, no investigation has tested whether schizophrenia shows alterations in global brain signal (GS), a signal derived from functional MRI and often discarded as a meaningless baseline in many studies. To evaluate GS alterations associated with schizophrenia, we studied two large chronic patient samples (n = 90, n = 71), comparing them to healthy subjects (n = 220) and patients diagnosed with bipolar disorder (n = 73). We identified and replicated increased cortical power and variance in schizophrenia, an effect predictive of symptoms yet obscured by GS removal. Voxel-wise signal variance was also increased in schizophrenia, independent of GS effects. Both findings were absent in bipolar patients, confirming diagnostic specificity. Biologically informed computational modeling of shared and nonshared signal propagation through the brain suggests that these findings may be explained by altered net strength of overall brain connectivity in schizophrenia. PMID:24799682

  18. Altered baseline brain activity with 72 h of simulated microgravity--initial evidence from resting-state fMRI.

    PubMed

    Liao, Yang; Zhang, Jinsong; Huang, Zhiping; Xi, Yibin; Zhang, Qianru; Zhu, Tianli; Liu, Xufeng

    2012-01-01

    To provide the basis and reference to further insights into the neural activity of the human brain in a microgravity environment, we discuss the amplitude changes of low-frequency brain activity fluctuations using a simulated microgravity model. Twelve male participants between 24 and 31 years old received resting-state fMRI scans in both a normal condition and after 72 hours in a -6° head down tilt (HDT). A paired sample t-test was used to test the amplitude differences of low-frequency brain activity fluctuations between these two conditions. With 72 hours in a -6° HDT, the participants showed a decreased amplitude of low-frequency fluctuations in the left thalamus compared with the normal condition (a combined threshold of P<0.005 and a minimum cluster size of 351 mm(3) (13 voxels), which corresponded with the corrected threshold of P<0.05 determined by AlphaSim). Our findings indicate that a gravity change-induced redistribution of body fluid may disrupt the function of the left thalamus in the resting state, which may contribute to reduced motor control abilities and multiple executive functions in astronauts in a microgravity environment. PMID:23285086

  19. Hind Limb Unloading Model Alters Nuclear Factor kappa B and Activator Protein-1 Signaling in Mouse Brain

    NASA Astrophysics Data System (ADS)

    Ramesh, Govindarajan; Vani, Vani; Renard, Renard; Vera, Vera; Wilosn, Wilosn; Ramesh, Govindarajan

    Microgravity induces inflammatory response and also modulates immune functions, which may increase oxidative stress. Exposure to the microgravity environment induces adverse neurological effects. However, there is little research exploring the etiology of neurological effects of exposure to this environment. To explore this area we evaluated changes in Nuclear Factor kappa B, Activator Protein 1, MAPP kinase and N terminal c-Jun kinase in mouse brain exposed to a simulated microgravity environment using the hindlimb unloading model. BALB/c male mice were randomly assigned to hindlimb unloading group (n=12) and control group (n=12) to simulate a microgravity environment, for 7 days. Changes observed in NF-κB, AP- 1 DNA binding, MAPKK and N terminal c-Jun kinase were measured using electrophoretic mobility shift assay (EMSA) and western blot analysis and compared to unexposed brain regions. Hindlimb unloading exposed mice showed significant increases in generated NF-κB, AP-1, MAPKK and Kinase in all regions of the brain exposed to hindlimb unloading as compared to the control brain regions. Results suggest that exposure to simulated microgravity can induce expression of certain transcription factors and protein kinases. This work was supported by funding from NASA NCC 9-165. 504b030414000600080000002100828abc13fa0000001c020000130000005b436f6e74656e745f54797065735d2e78

  20. Effects of CPAP-therapy on brain electrical activity in obstructive sleep apneic patients: a combined EEG study using LORETA and Omega complexity : reversible alterations of brain activity in OSAS.

    PubMed

    Toth, Marton; Faludi, Bela; Kondakor, Istvan

    2012-10-01

    Effects of initiation of continuous positive airway pressure (CPAP) therapy on EEG background activity were investigated in patients with obstructive sleep apnea syndrome (OSAS, N = 25) to test possible reversibility of alterations of brain electrical activity caused by chronic hypoxia. Normal control group (N = 14) was also examined. Two EEG examinations were done in each groups: at night and in the next morning. Global and regional (left vs. right, anterior vs. posterior) measures of spatial complexity (Omega complexity) were used to characterize the degree of spatial synchrony of EEG. Low resolution electromagnetic tomography (LORETA) was used to localize generators of EEG activity in separate frequency bands. Before CPAP-treatment, a significantly lower Omega complexity was found globally and over the right hemisphere. Due to CPAP-treatment, these significant differences vanished. Significantly decreased Omega complexity was found in the anterior region after treatment. LORETA showed a decreased activity in all of the beta bands after therapy in the right hippocampus, premotor and temporo-parietal cortex, and bilaterally in the precuneus, paracentral and posterior cingulate cortex. No significant changes were seen in control group. Comparing controls and patients before sleep, an increased alpha2 band activity was seen bilaterally in the precuneus, paracentral and posterior cingulate cortex, while in the morning an increased beta3 band activity in the left precentral and bilateral premotor cortex and a decreased delta band activity in the right temporo-parietal cortex and insula were observed. These findings indicate that effect of sleep on EEG background activity is different in OSAS patients and normal controls. In OSAS patients, significant changes lead to a more normal EEG after a night under CPAP-treatment. Compensatory alterations of brain electrical activity in regions associated with influencing sympathetic outflow, visuospatial abilities, long

  1. Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.

    PubMed

    Yang, Hyunwoo; Jung, Seungmoon; Seo, Jinsoo; Khalid, Arshi; Yoo, Jung-Seok; Park, Jihyun; Kim, Soyun; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jeon, Daejong

    2016-09-01

    The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders. PMID:27211331

  2. Altered brain activation during response inhibition and error processing in subjects with Internet gaming disorder: a functional magnetic imaging study.

    PubMed

    Ko, Chih-Hung; Hsieh, Tsyh-Jyi; Chen, Chiao-Yun; Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Wang, Peng-Wei; Liu, Gin-Chung

    2014-12-01

    The aim of the present study was to evaluate the impulsivity and brain correlates of response inhibition and error processing among subjects with Internet gaming disorder (IGD). We evaluated the response inhibition and error processing by functional magnetic resonance imaging (fMRI) in subjects with IGD and controls. Twenty-six men with IGD for at least 2 years and 23 controls with no history of IGD were recruited as the IGD and control groups, respectively. All subjects performed the event-related designed Go/No-go task under fMRI and completed questionnaires related to Internet addiction and impulsivity. The IGD group exhibited a higher score for impulsivity than the control group. The IGD group also exhibited higher brain activation when processing response inhibition over the left orbital frontal lobe and bilateral caudate nucleus than controls. Both the IGD and control groups exhibited activation of the insula and anterior cingulate cortex during error processing. The activation over the right insula was lower in the subjects with IGD than the control group. Our results support the fact that the fronto-striatal network involved in response inhibition, and the salience network, anchored by the anterior cingulate and insula, contributes to error processing. Further, adults with IGD have impaired insular function in error processing and greater activation of the fronto-striatal network in order to maintain their response inhibition performance. PMID:24469099

  3. Altered brain activation during response inhibition and error processing in subjects with Internet gaming disorder: a functional magnetic imaging study.

    PubMed

    Ko, Chih-Hung; Hsieh, Tsyh-Jyi; Chen, Chiao-Yun; Yen, Cheng-Fang; Chen, Cheng-Sheng; Yen, Ju-Yu; Wang, Peng-Wei; Liu, Gin-Chung

    2014-12-01

    The aim of the present study was to evaluate the impulsivity and brain correlates of response inhibition and error processing among subjects with Internet gaming disorder (IGD). We evaluated the response inhibition and error processing by functional magnetic resonance imaging (fMRI) in subjects with IGD and controls. Twenty-six men with IGD for at least 2 years and 23 controls with no history of IGD were recruited as the IGD and control groups, respectively. All subjects performed the event-related designed Go/No-go task under fMRI and completed questionnaires related to Internet addiction and impulsivity. The IGD group exhibited a higher score for impulsivity than the control group. The IGD group also exhibited higher brain activation when processing response inhibition over the left orbital frontal lobe and bilateral caudate nucleus than controls. Both the IGD and control groups exhibited activation of the insula and anterior cingulate cortex during error processing. The activation over the right insula was lower in the subjects with IGD than the control group. Our results support the fact that the fronto-striatal network involved in response inhibition, and the salience network, anchored by the anterior cingulate and insula, contributes to error processing. Further, adults with IGD have impaired insular function in error processing and greater activation of the fronto-striatal network in order to maintain their response inhibition performance.

  4. Exercise Improves Executive Function and Achievement and Alters Brain Activation in Overweight Children: A Randomized Controlled Trial

    PubMed Central

    Davis, Catherine L.; Tomporowski, Phillip D.; McDowell, Jennifer E.; Austin, Benjamin P.; Miller, Patricia H.; Yanasak, Nathan E.; Allison, Jerry D.; Naglieri, Jack A.

    2010-01-01

    Objective This experiment tested the hypothesis that exercise would improve executive function. Design Sedentary, overweight 7- to 11-year-old children (N = 171, 56% female, 61% Black, M ± SD age 9.3 ± 1.0 yrs, body mass index (BMI) 26 ± 4.6 kg/m2, BMI z-score 2.1 ± 0.4) were randomized to 13 ± 1.6 weeks of an exercise program (20 or 40 minutes/day), or a control condition. Main outcome measures Blinded, standardized psychological evaluations (Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III) assessed cognition and academic achievement. Functional magnetic resonance imaging measured brain activity during executive function tasks. Results Intent to treat analysis revealed dose response benefits of exercise on executive function and mathematics achievement. Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity due to exercise was also observed. Conclusion Consistent with results obtained in older adults, a specific improvement on executive function and brain activation changes due to exercise were observed. The cognitive and achievement results add evidence of dose response, and extend experimental evidence into childhood. This study provides information on an educational outcome. Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic, physical activity may prove to be a simple, important method of enhancing aspects of children’s mental functioning that are central to cognitive development. This information may persuade educators to implement vigorous physical activity. PMID:21299297

  5. α2-Null mutant mice have altered levels of neuronal activity in restricted midbrain and limbic brain regions during nicotine withdrawal as demonstrated by cfos expression.

    PubMed

    Upton, Montana; Lotfipour, Shahrdad

    2015-10-15

    Neuronal nicotinic acetylcholine receptors (nAChRs) are the primary binding sites for nicotine within the brain. Using alpha(α)2 nAChR subunit-null mutant mice, the current study evaluates whether the absence of this gene product during mecamylamine-precipitated nicotine withdrawal eliminates neuronal activity within selective midbrain and limbic brain regions, as determined by the expression of the immediate early gene, cfos. Our results demonstrate that nicotine withdrawal enhances neuronal activity within the interpeduncular nucleus and dorsal hippocampus, which is absent in mice null for α2-containing nAChRs. In contrast, we observe that α2-null mutant mice exhibit a suppression of neuronal activity in the dentate gyrus in mice undergoing nicotine withdrawal. Interestingly, α2-null mutant mice display potentiated neuronal activity specifically within the stratum lacunosum moleculare layer of the hippocampus, independent of nicotine withdrawal. Overall, our findings demonstrate that α2-null mutant mice have altered cfos expression in distinct populations of neurons within selective midbrain and limbic brain structures that mediate baseline and nicotine withdrawal-induced neuronal activity.

  6. Altered spontaneous brain activity patterns in patients with unilateral acute open globe injury using amplitude of low-frequency fluctuation: a functional magnetic resonance imaging study

    PubMed Central

    Tan, Gang; Huang, Xin; Ye, Lei; Wu, An-Hua; He, Li-Xian; Zhong, Yu-Lin; Jiang, Nan; Zhou, Fu-Qing; Shao, Yi

    2016-01-01

    Objective The aim of this study was to evaluate altered spontaneous brain activities in patients with unilateral acute open globe injury (OGI) using amplitude of low-frequency fluctuation (ALFF) method and its relationship with their clinical manifestations. Patients and methods A total of 18 patients with acute OGI (16 males and two females) and 18 healthy controls (HCs, 16 males and two females) closely matched in age, sex, and education were recruited in this study. The ALFF method was used to evaluate the altered spontaneous brain activities. The relationships between the mean ALFF signal values of different brain regions and the clinical features were evaluated by correlation analysis. Acute OGI patients were distinguished from HCs by receiver operating characteristic curve. Results Compared with HCs, acute OGI patients had significantly higher ALFF values in the left cuneus, left middle cingulum cortex, and bilateral precuneus. Furthermore, the age of OGI patients showed a negative correlation with the ALFF signal value of the left middle cingulum cortex (r=−0.557, P=0.016) and a negative correlation with the mean ALFF signal value of the bilateral precuneus (r=−0.746, P<0.001). The ALFF signal value of the bilateral precuneus was negatively correlated with the duration of OGI (r=−0.493, P=0.038) and positively correlated with the vision acuity of the injured eye (r=0.583, P=0.011). Conclusion Acute OGI mainly induces dysfunction in the left cuneus, left middle cingulum cortex, and bilateral precuneus, which may reflect the underlying pathologic mechanisms of abnormal brain activities in OGI patients. PMID:27570455

  7. Activation Changes in Zebra Finch (Taeniopygia guttata) Brain Areas Evoked by Alterations of the Earth Magnetic Field

    PubMed Central

    Keary, Nina; Bischof, Hans-Joachim

    2012-01-01

    Many animals are able to perceive the earth magnetic field and to use it for orientation and navigation within the environment. The mechanisms underlying the perception and processing of magnetic field information within the brain have been thoroughly studied, especially in birds, but are still obscure. Three hypotheses are currently discussed, dealing with ferromagnetic particles in the beak of birds, with the same sort of particles within the lagena organs, or describing magnetically influenced radical-pair processes within retinal photopigments. Each hypothesis is related to a well-known sensory organ and claims parallel processing of magnetic field information with somatosensory, vestibular and visual input, respectively. Changes in activation within nuclei of the respective sensory systems have been shown previously. Most of these previous experiments employed intensity enhanced magnetic stimuli or lesions. We here exposed unrestrained zebra finches to either a stationary or a rotating magnetic field of the local intensity and inclination. C-Fos was used as an activity marker to examine whether the two treatments led to differences in fourteen brain areas including nuclei of the somatosensory, vestibular and visual system. An ANOVA revealed an overall effect of treatment, indicating that the magnetic field change was perceived by the birds. While the differences were too small to be significant in most areas, a significant enhancement of activation by the rotating stimulus was found in a hippocampal subdivision. Part of the hyperpallium showed a strong, nearly significant, increase. Our results are compatible with previous studies demonstrating an involvement of at least three different sensory systems in earth magnetic field perception and suggest that these systems, probably less elaborated, may also be found in nonmigrating birds. PMID:22679515

  8. Altered baseline brain activities before food intake in obese men: a resting state fMRI study.

    PubMed

    Zhang, Bin; Tian, Derun; Yu, Chunshui; Zhang, Jing; Tian, Xiao; von Deneen, Karen M; Zang, Yufeng; Walter, Martin; Liu, Yijun

    2015-01-01

    Obesity as a chronic disease has become a global epidemic. However, why obese individuals eat more still remains unclear. Recent functional neuroimaging studies have found abnormal brain activations in obese people. In the present study, we used resting state functional MRI to observe spontaneous blood-oxygen-level dependent (BOLD) signal fluctuations during both hunger and satiety states in 20 lean and 20 obese men. Using a regional homogeneity (ReHo) analysis method, we measured temporal homogeneity of the regional BOLD signals. We found that, before food intake, obese men had significantly increased synchronicity of activity in the left putamen relative to lean men. Decreased synchronicity of activity was found in the orbitofrontal cortex (OFC) and medial prefrontal cortex(MPFC) in the obese subjects. And, the ratings of hunger of the obese subjects were higher than those of the lean subjects before food intake. After food intake, we did not find the significant differences between the obese men and the lean men. In all participations, synchronicity of activity increased from the fasted to the satiated state in the OFC. The results indicated that OFC plays an important role in feeding behavior, and OFC signaling may be disordered in obesity. Obese men show less inhibitory control during fasting state. This study has provided strong evidence supporting the hypothesis that there is a hypo-functioning reward circuitry in obese individuals, in which the frontal cortex may fail to inhibit the striatum, and consequently lead to overeating and obesity. PMID:25459293

  9. Early adolescence as a critical window during which social stress distinctly alters behavior and brain norepinephrine activity.

    PubMed

    Bingham, Brian; McFadden, Kile; Zhang, Xiaoyan; Bhatnagar, Seema; Beck, Sheryl; Valentino, Rita

    2011-03-01

    Many neural programs that shape behavior become established during adolescence. Adverse events at this age can have enduring consequences for both adolescent and adult mental health. Here we show that repeated social stress at different stages of adolescent development differentially affects rat behavior and neuronal activity. Early-adolescent (PND 28, EA), mid-adolescent (PND 42, MA), and adult (PND 63) rats were subjected to resident-intruder social stress (7 days) and behavior was examined 24-72 h later. In EA rats selectively, resident-intruder stress increased proactive responses in the defensive burying and forced swim tests. In adult rats, resident-intruder stress decreased burying behavior regardless of whether the animal was stressed as an adult or during early adolescence. As the locus coeruleus (LC)-norepinephrine system has been implicated in proactive defense behaviors, LC neuronal activity was quantified in separate cohorts. Stressed EA rats had elevated spontaneous LC discharge rates and diminished responses to sensory stimuli compared with controls. Microinjection of a CRF antagonist into the LC selectively inhibited neurons of stressed EA rats, suggesting that EA social stress induces tonic CRF release onto LC neurons, shifting the mode of discharge to an activated state that promotes active defensive behaviors. In all adult groups, resident-intruder stress resulted in an increased phasic response to sensory stimuli with no change in spontaneous rates. MA was a transition period during which social stress did not affect behavior or LC activity. The results suggest that social stress interacts with the brain norepinephrine system to regulate defensive strategies in an age-dependent manner.

  10. Diet-induced obesity progressively alters cognition, anxiety-like behavior and lipopolysaccharide-induced depressive-like behavior: focus on brain indoleamine 2,3-dioxygenase activation.

    PubMed

    André, Caroline; Dinel, Anne-Laure; Ferreira, Guillaume; Layé, Sophie; Castanon, Nathalie

    2014-10-01

    Obesity is associated with a high prevalence of mood symptoms and cognitive dysfunctions that emerges as significant risk factors for important health complications such as cardiovascular diseases and type 2 diabetes. It is therefore important to identify the dynamic of development and the pathophysiological mechanisms underlying these neuropsychiatric symptoms. Obesity is also associated with peripheral low-grade inflammation and increased susceptibility to immune-mediated diseases. Excessive production of proinflammatory cytokines and the resulting activation of the brain tryptophan catabolizing enzyme indoleamine 2,3-dioxygenase (IDO) have been shown to promote neurobehavioral complications, particularly depression. In that context, questions arise about the impact of diet-induced obesity on the onset of neuropsychiatric alterations and the increased susceptibility to immune-mediated diseases displayed by obese patients, particularly through brain IDO activation. To answer these questions, we used C57Bl/6 mice exposed to standard diet or western diet (WD; consisting of palatable energy-dense food) since weaning and for 20 weeks. We then measured inflammatory and behavioral responses to a systemic immune challenge with lipopolysaccharide (LPS) in experimental conditions known to alter cognitive and emotional behaviors independently of any motor impairment. We first showed that in absence of LPS, 9 weeks of WD is sufficient to impair spatial recognition memory (in the Y-maze). On the other hand, 18 weeks of WD increased anxiety-like behavior (in the elevated plus-maze), but did not affect depressive-like behavior (in the tail-suspension and forced-swim tests). However, 20 weeks of WD altered LPS-induced depressive-like behavior compared to LPS-treated lean mice and exacerbated hippocampal and hypothalamic proinflammatory cytokine expression and brain IDO activation. Taken together, these results show that WD exposure alters cognition and anxiety in unstimulated

  11. Copper deficiency in neonatal mice alters brain catecholamine levels

    SciTech Connect

    Bailey, W.R.; Prohaska, J.R. )

    1991-03-15

    Copper (Cu) deficiency was investigated in Swiss albino mice to develop a model that alters brain catecholamine metabolism without serious growth impairment. Cu deficiency was induced by feeding a diet low in Cu to dams beginning either 7 days (d) prior, 4d prior, 4d after, or on the day of parturition. All 4-week-old male Cu-deficient ({minus}Cu) offspring were anemic and exhibited biochemical characteristics of Cu deficiency when compared to their respective +Cu control mice. However, the best model, which resulted in altered catecholamine metabolism characterized by elevation of dopamine (DA) and depression in norepinephrine (NE) in brain, heart, and spleen, was when treatment began 4d prior to birth. Body and brain weight were not altered. However, levels of Cu in brain and liver of {minus}Cu mice were markedly reduced to 21% and 31% of those measured in +Cu controls, respectively. Furthermore, brain NE and DA concentrations of {minus}Cu mice were 72% and 132% of those quantified in +Cu offspring, respectively. A plausible explanation is that dietary Cu deficiency results in lower activity of brain dopamine-{beta}-monooxygenase, the Cu dependent enzyme that catalyzes conversion of DA to NE. It is not yet known if these changes in Ne and DA pool size altered the quantity or characteristics of the neuronal catecholamine receptors, and more importantly, whether or not the observed changes are reversible by nutritional intervention.

  12. Altered likelihood of brain activation in attention and working memory networks in patients with multiple sclerosis: An ALE meta-analysis☆

    PubMed Central

    Kollndorfer, K.; Krajnik, J.; Woitek, R.; Freiherr, J.; Prayer, D.; Schöpf, V.

    2013-01-01

    Multiple sclerosis (MS) is a chronic neurological disease, frequently affecting attention and working memory functions. Functional imaging studies investigating those functions in MS patients are hard to compare, as they include heterogeneous patient groups and use different paradigms for cognitive testing. The aim of this study was to investigate alterations in neuronal activation between MS patients and healthy controls performing attention and working memory tasks. Two meta-analyses of previously published fMRI studies investigating attention and working memory were conducted for MS patients and healthy controls, respectively. Resulting maps were contrasted to compare brain activation in patients and healthy controls. Significantly increased brain activation in the inferior parietal lobule and the dorsolateral prefrontal cortex was detected for healthy controls. In contrast, higher neuronal activation in MS patients was obtained in the left ventrolateral prefrontal cortex and the right premotor area. With this meta-analytic approach previous results of investigations examining cognitive function using fMRI are summarized and compared. Therefore a more general view on cognitive dysfunction in this heterogeneous disease is enabled. PMID:24056084

  13. Altered Proteins in the Aging Brain

    PubMed Central

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

    2016-01-01

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

  14. Altered Proteins in the Aging Brain.

    PubMed

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

    2016-04-01

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

  15. Altered brain activation in a reversal learning task unmasks adaptive changes in cognitive control in writer's cramp.

    PubMed

    Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver; Sablowsky, Simone; Götz, Julia; Wolff, Stephan; Jansen, Olav; Dressler, Dirk; Schneider, Susanne A; Klein, Christine; Deuschl, Günther; van Eimeren, Thilo; Witt, Karsten

    2016-01-01

    Previous receptor binding studies suggest dopamine function is altered in the basal ganglia circuitry in task-specific dystonia, a condition characterized by contraction of agonist and antagonist muscles while performing specific tasks. Dopamine plays a role in reward-based learning. Using fMRI, this study compared 31 right-handed writer's cramp patients to 35 controls in reward-based learning of a probabilistic reversal-learning task. All subjects chose between two stimuli and indicated their response with their left or right index finger. One stimulus response was rewarded 80%, the other 20%. After contingencies reversal, the second stimulus response was rewarded in 80%. We further linked the DRD2/ANKK1-TaqIa polymorphism, which is associated with 30% reduction of the striatal dopamine receptor density with reward-based learning and assumed impaired reversal learning in A + subjects. Feedback learning in patients was normal. Blood-oxygen level dependent (BOLD) signal in controls increased with negative feedback in the insula, rostral cingulate cortex, middle frontal gyrus and parietal cortex (pFWE < 0.05). In comparison to controls, patients showed greater increase in BOLD activity following negative feedback in the dorsal anterior cingulate cortex (BA32). The genetic status was not correlated with the BOLD activity. The Brodmann area 32 (BA32) is part of the dorsal anterior cingulate cortex (dACC) that plays an important role in coordinating and integrating information to guide behavior and in reward-based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp. PMID:26702397

  16. Altered brain activation in a reversal learning task unmasks adaptive changes in cognitive control in writer's cramp.

    PubMed

    Zeuner, Kirsten E; Knutzen, Arne; Granert, Oliver; Sablowsky, Simone; Götz, Julia; Wolff, Stephan; Jansen, Olav; Dressler, Dirk; Schneider, Susanne A; Klein, Christine; Deuschl, Günther; van Eimeren, Thilo; Witt, Karsten

    2016-01-01

    Previous receptor binding studies suggest dopamine function is altered in the basal ganglia circuitry in task-specific dystonia, a condition characterized by contraction of agonist and antagonist muscles while performing specific tasks. Dopamine plays a role in reward-based learning. Using fMRI, this study compared 31 right-handed writer's cramp patients to 35 controls in reward-based learning of a probabilistic reversal-learning task. All subjects chose between two stimuli and indicated their response with their left or right index finger. One stimulus response was rewarded 80%, the other 20%. After contingencies reversal, the second stimulus response was rewarded in 80%. We further linked the DRD2/ANKK1-TaqIa polymorphism, which is associated with 30% reduction of the striatal dopamine receptor density with reward-based learning and assumed impaired reversal learning in A + subjects. Feedback learning in patients was normal. Blood-oxygen level dependent (BOLD) signal in controls increased with negative feedback in the insula, rostral cingulate cortex, middle frontal gyrus and parietal cortex (pFWE < 0.05). In comparison to controls, patients showed greater increase in BOLD activity following negative feedback in the dorsal anterior cingulate cortex (BA32). The genetic status was not correlated with the BOLD activity. The Brodmann area 32 (BA32) is part of the dorsal anterior cingulate cortex (dACC) that plays an important role in coordinating and integrating information to guide behavior and in reward-based learning. The dACC is connected with the basal ganglia-thalamo-loop modulated by dopaminergic signaling. This finding suggests disturbed integration of reinforcement history in decision making and implicate that the reward system might contribute to the pathogenesis in writer's cramp.

  17. Cigarette smoking leads to persistent and dose-dependent alterations of brain activity and connectivity in anterior insula and anterior cingulate.

    PubMed

    Zanchi, Davide; Brody, Arthur L; Montandon, Marie-Louise; Kopel, Rotem; Emmert, Kirsten; Preti, Maria Giulia; Van De Ville, Dimitri; Haller, Sven

    2015-11-01

    Although many smokers try to quit smoking, only about 20-25 percent will achieve abstinence despite 6 months or more of gold-standard treatment. This low success rate suggests long-term changes in the brain related to smoking, which remain poorly understood. We compared ex-smokers to both active smokers and non-smokers using functional magnetic resonance imaging (fMRI) to explore persistent modifications in brain activity and network organization. This prospective and consecutive study includes 18 non-smokers (29.5 ± 6.7 years of age, 11 women), 14 smokers (≥10 cigarettes a day >2 years of smoking, 29.3 ± 6.0 years of age, 10 women) and 14 ex-smokers (>1 year of quitting 30.5 ± 5.7 years of age, 10 women). Participants underwent a block-design fMRI study contrasting smoking cue with control (neutral cue) videos. Data analyses included task-related general linear model, seed-based functional connectivity, voxel-based morphometry (VBM) of gray matter and tract-based spatial statistics (TBSS) of white matter. Smoking cue videos versus control videos activated the right anterior insula in ex-smokers compared with smokers, an effect correlating with cumulative nicotine intake (pack-years). Moreover, ex-smokers had a persistent decrease in functional connectivity between right anterior insula and anterior cingulate cortex (ACC) compared with control participants, but similar to active smokers. Potentially confounding alterations in gray or white matter were excluded in VBM and TBSS analyses. In summary, ex-smokers with long-term nicotine abstinence have persistent and dose-dependent brain network changes notably in the right anterior insula and its connection to the ACC.

  18. Administration of Harmine and Imipramine Alters Creatine Kinase and Mitochondrial Respiratory Chain Activities in the Rat Brain

    PubMed Central

    Réus, Gislaine Z.; Stringari, Roberto B.; Gonçalves, Cinara L.; Scaini, Giselli; Carvalho-Silva, Milena; Jeremias, Gabriela C.; Jeremias, Isabela C.; Ferreira, Gabriela K.; Streck, Emílio L.; Hallak, Jaime E.; Zuardi, Antônio W.; Crippa, José A.; Quevedo, João

    2012-01-01

    The present study evaluated mitochondrial respiratory chain and creatine kinase activities after administration of harmine (5, 10, and 15 mg/kg) and imipramine (10, 20, and 30 mg/kg) in rat brain. After acute treatment occurred an increase of creatine kinase in the prefrontal with imipramine (20 and 30 mg/kg) and harmine in all doses, in the striatum with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg); harmine (15 mg/kg) decreased creatine kinase. In the chronic treatment occurred an increase of creatine kinase with imipramine (20 mg/kg), harmine (5 mg/kg) in the prefrontal with imipramine (20 and 30 mg/kg) and harmine (5 and 10 mg/kg) in the striatum. In the acute treatment, the complex I increased in the prefrontal with harmine (15 mg/kg) and in the striatum with harmine (10 mg/kg); the complex II decreased with imipramine (20 and 30 mg/kg) in the striatum; the complex IV increased with imipramine (30 mg/kg) in the striatum. In the chronic treatment, the complex I increased with harmine (5 mg/kg) in the prefrontal; the complex II increased with imipramine (20 mg/kg) in the prefrontal; the complex IV increased with harmine (5 mg/kg) in the striatum. Finally, these findings further support the hypothesis that harmine and imipramine could be involved in mitochondrial function. PMID:21969912

  19. Heavy Metals and Epigenetic Alterations in Brain Tumors

    PubMed Central

    Caffo, Maria; Caruso, Gerardo; Fata, Giuseppe La; Barresi, Valeria; Visalli, Maria; Venza, Mario; Venza, Isabella

    2014-01-01

    Heavy metals and their derivatives can cause various diseases. Numerous studies have evaluated the possible link between exposure to heavy metals and various cancers. Recent data show a correlation between heavy metals and aberration of genetic and epigenetic patterns. From a literature search we noticed few experimental and epidemiological studies that evaluate a possible correlation between heavy metals and brain tumors. Gliomas arise due to genetic and epigenetic alterations of glial cells. Changes in gene expression result in the alteration of the cellular division process. Epigenetic alterations in brain tumors include the hypermethylation of CpG group, hypomethylation of specific genes, aberrant activation of genes, and changes in the position of various histones. Heavy metals are capable of generating reactive oxygen assumes that key functions in various pathological mechanisms. Alteration of homeostasis of metals could cause the overproduction of reactive oxygen species and induce DNA damage, lipid peroxidation, and alteration of proteins. In this study we summarize the possible correlation between heavy metals, epigenetic alterations and brain tumors. We report, moreover, the review of relevant literature. PMID:25646073

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

    PubMed

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

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

  1. Traumatic Alterations in Consciousness: Traumatic Brain Injury

    PubMed Central

    Blyth, Brian J.; Bazarian, Jeffrey J.

    2010-01-01

    Mild traumatic brain injury (mTBI) refers to the clinical condition of transient alteration of consciousness as a result of traumatic injury to the brain. The priority of emergency care is to identify and facilitate the treatment of rare but potentially life threatening intra-cranial injuries associated with mTBI through the judicious application of appropriate imaging studies and neurosurgical consultation. Although post-mTBI symptoms quickly and completely resolve in the vast majority of cases, a significant number of patients will complain of lasting problems that may cause significant disability. Simple and early interventions such as patient education and appropriate referral can reduce the likelihood of chronic symptoms. Although definitive evidence is lacking, mTBI is likely to be related to significant long-term sequelae such as Alzheimer's disease and other neurodegenerative processes. PMID:20709244

  2. Brain Rhythms Connect Impaired Inhibition to Altered Cognition in Schizophrenia

    PubMed Central

    Pittman-Polletta, Benjamin R.; Kocsis, Bernat; Vijayan, Sujith; Whittington, Miles A.; Kopell, Nancy J.

    2015-01-01

    In recent years, schizophrenia research has focused on inhibitory interneuron dysfunction at the level of neurobiology, and on cognitive impairments at the psychological level. Reviewing both experimental and computational findings, we show how the temporal structure of the activity of neuronal populations, exemplified by brain rhythms, can begin to bridge these levels of complexity. Oscillations in neuronal activity tie the pathophysiology of schizophrenia to alterations in local processing and large-scale coordination, and these alterations in turn can lead to the cognitive and perceptual disturbances observed in schizophrenia. PMID:25850619

  3. Profile of altered brain iron acquisition in restless legs syndrome.

    PubMed

    Connor, James R; Ponnuru, Padmavathi; Wang, Xin-Sheng; Patton, Stephanie M; Allen, Richard P; Earley, Christopher J

    2011-04-01

    of restless legs syndrome brains. This study reveals that there are alterations in the iron management protein profile in restless legs syndrome compared with controls at the site of blood-brain interface suggesting fundamental differences in brain iron acquisition in individuals with restless legs syndrome. Furthermore, the decrease in transferrin receptor expression in the microvasculature in the presence of relative brain iron deficiency reported in restless legs syndrome brains may underlie the problems associated with brain iron acquisition in restless legs syndrome. The consistent finding of loss of iron regulatory protein activity in restless legs syndrome brain tissue further implicates this protein as a factor in the underlying cause of the iron deficiency in the restless legs syndrome brain. The data herein provide evidence for regulation of iron uptake and storage within brain microvessels that challenge the existing paradigm that the blood-brain barrier is merely a transport system.

  4. Altered brain activation and functional connectivity in working memory related networks in patients with type 2 diabetes: An ICA-based analysis

    PubMed Central

    Zhang, Yang; Lu, Shan; Liu, Chunlei; Zhang, Huimei; Zhou, Xuanhe; Ni, Changlin; Qin, Wen; Zhang, Quan

    2016-01-01

    Type 2 diabetes mellitus (T2DM) can cause multidimensional cognitive deficits, among which working memory (WM) is usually involved at an early stage. However, the neural substrates underlying impaired WM in T2DM patients are still unclear. To clarify this issue, we utilized functional magnetic resonance imaging (fMRI) and independent component analysis to evaluate T2DM patients for alterations in brain activation and functional connectivity (FC) in WM networks and to determine their associations with cognitive and clinical variables. Twenty complication-free T2DM patients and 19 matched healthy controls (HCs) were enrolled, and fMRI data were acquired during a block-designed 1-back WM task. The WM metrics of the T2DM patients showed no differences compared with those of the HCs, except for a slightly lower accuracy rate in the T2DM patients. Compared with the HCs, the T2DM patients demonstrated increased activation within their WM fronto-parietal networks, and activation strength was significantly correlated with WM performance. The T2DM patients also showed decreased FC within and between their WM networks. Our results indicate that the functional integration of WM sub-networks was disrupted in the complication-free T2DM patients and that strengthened regional activity in fronto-parietal networks may compensate for the WM impairment caused by T2DM. PMID:27021340

  5. Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain.

    PubMed

    Zimmermann, F F; Altenhofen, S; Kist, L W; Leite, C E; Bogo, M R; Cognato, G P; Bonan, C D

    2016-05-01

    Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8%) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis.

  6. Altered brain energetics induces mitochondrial fission arrest in Alzheimer's Disease.

    PubMed

    Zhang, Liang; Trushin, Sergey; Christensen, Trace A; Bachmeier, Benjamin V; Gateno, Benjamin; Schroeder, Andreas; Yao, Jia; Itoh, Kie; Sesaki, Hiromi; Poon, Wayne W; Gylys, Karen H; Patterson, Emily R; Parisi, Joseph E; Diaz Brinton, Roberta; Salisbury, Jeffrey L; Trushina, Eugenia

    2016-01-01

    Altered brain metabolism is associated with progression of Alzheimer's Disease (AD). Mitochondria respond to bioenergetic changes by continuous fission and fusion. To account for three dimensional architecture of the brain tissue and organelles, we applied 3-dimensional electron microscopy (3D EM) reconstruction to visualize mitochondrial structure in the brain tissue from patients and mouse models of AD. We identified a previously unknown mitochondrial fission arrest phenotype that results in elongated interconnected organelles, "mitochondria-on-a-string" (MOAS). Our data suggest that MOAS formation may occur at the final stages of fission process and was not associated with altered translocation of activated dynamin related protein 1 (Drp1) to mitochondria but with reduced GTPase activity. Since MOAS formation was also observed in the brain tissue of wild-type mice in response to hypoxia or during chronological aging, fission arrest may represent fundamental compensatory adaptation to bioenergetic stress providing protection against mitophagy that may preserve residual mitochondrial function. The discovery of novel mitochondrial phenotype that occurs in the brain tissue in response to energetic stress accurately detected only using 3D EM reconstruction argues for a major role of mitochondrial dynamics in regulating neuronal survival. PMID:26729583

  7. Unpredictable Chronic Stress Alters Adenosine Metabolism in Zebrafish Brain.

    PubMed

    Zimmermann, F F; Altenhofen, S; Kist, L W; Leite, C E; Bogo, M R; Cognato, G P; Bonan, C D

    2016-05-01

    Stress is considered a risk factor for several human disorders. Despite the broad knowledge of stress responses in mammals, data on the relationship between unpredictable chronic stress (UCS) and its effects on purinergic signaling are limited. ATP hydrolysis by ectonucleotidases is an important source of adenosine, and adenosine deaminase (ADA) contributes to the control of the nucleoside concentrations. Considering that some stress models could affect signaling systems, the objective of this study was to investigate whether UCS alters ectonucleotidase and ADA pathway in zebrafish brain. Additionally, we analyzed ATP metabolism as well as ada1, ada2.1, ada2.2, adaL, and adaasi gene expression in zebrafish brain. Our results have demonstrated that UCS did not alter ectonucleotidase and soluble ADA activities. However, ecto-ADA activity was significantly decreased (26.8%) in brain membranes of animals exposed to UCS when compared to the control group. Quantitative reverse transcription PCR (RT-PCR) analysis did not show significant changes on ADA gene expression after the UCS exposure. The brain ATP metabolism showed a marked increase in adenosine levels (ADO) in animals exposed to UCS. These data suggest an increase on extracellular adenosine levels in zebrafish brain. Since this nucleoside has neuromodulatory and anxiolytic effects, changes in adenosine levels could play a role in counteracting the stress, which could be related to a compensatory mechanism in order to restore the homeostasis. PMID:26081145

  8. Benevolent sexism alters executive brain responses.

    PubMed

    Dardenne, Benoit; Dumont, Muriel; Sarlet, Marie; Phillips, Christophe; Balteau, Evelyne; Degueldre, Christian; Luxen, André; Salmon, Eric; Maquet, Pierre; Collette, Fabienne

    2013-07-10

    Benevolence is widespread in our societies. It is defined as considering a subordinate group nicely but condescendingly, that is, with charity. Deleterious consequences for the target have been reported in the literature. In this experiment, we used functional MRI (fMRI) to identify whether being the target of (sexist) benevolence induces changes in brain activity associated with a working memory task. Participants were confronted by benevolent, hostile, or neutral comments before and while performing a reading span test in an fMRI environment. fMRI data showed that brain regions associated previously with intrusive thought suppression (bilateral, dorsolateral, prefrontal, and anterior cingulate cortex) reacted specifically to benevolent sexism compared with hostile sexism and neutral conditions during the performance of the task. These findings indicate that, despite being subjectively positive, benevolence modifies task-related brain networks by recruiting supplementary areas likely to impede optimal cognitive performance.

  9. Precocious Alterations of Brain Oscillatory Activity in Alzheimer's Disease: A Window of Opportunity for Early Diagnosis and Treatment.

    PubMed

    Hamm, Valentine; Héraud, Céline; Cassel, Jean-Christophe; Mathis, Chantal; Goutagny, Romain

    2015-01-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative dementia accounting for 50-80% of all age-related dementia. This pathology is characterized by the progressive and irreversible alteration of cognitive functions, such as memory, leading inexorably to the loss of autonomy for patients with AD. The pathology is linked with aging and occurs most commonly around 65 years old. Its prevalence (5% over 65 years of age and 20% after 80 years) constitutes an economic and social burden for AD patients and their family. At the present, there is still no cure for AD, actual treatments being moderately effective only in early stages of the pathology. A lot of efforts have been deployed with the aim of defining new AD biomarkers. Successful early detection of mild cognitive impairment (MCI) linked to AD requires the identification of biomarkers capable of distinguishing individuals with early stages of AD from other pathologies impacting cognition such as depression. In this article, we will review recent evidence suggesting that electroencephalographic (EEG) recordings, coupled with behavioral assessments, could be a useful approach and easily implementable for a precocious detection of AD.

  10. Precocious Alterations of Brain Oscillatory Activity in Alzheimer’s Disease: A Window of Opportunity for Early Diagnosis and Treatment

    PubMed Central

    Hamm, Valentine; Héraud, Céline; Cassel, Jean-Christophe; Mathis, Chantal; Goutagny, Romain

    2015-01-01

    Alzheimer’s disease (AD) is the most common form of neurodegenerative dementia accounting for 50–80% of all age-related dementia. This pathology is characterized by the progressive and irreversible alteration of cognitive functions, such as memory, leading inexorably to the loss of autonomy for patients with AD. The pathology is linked with aging and occurs most commonly around 65 years old. Its prevalence (5% over 65 years of age and 20% after 80 years) constitutes an economic and social burden for AD patients and their family. At the present, there is still no cure for AD, actual treatments being moderately effective only in early stages of the pathology. A lot of efforts have been deployed with the aim of defining new AD biomarkers. Successful early detection of mild cognitive impairment (MCI) linked to AD requires the identification of biomarkers capable of distinguishing individuals with early stages of AD from other pathologies impacting cognition such as depression. In this article, we will review recent evidence suggesting that electroencephalographic (EEG) recordings, coupled with behavioral assessments, could be a useful approach and easily implementable for a precocious detection of AD. PMID:26733816

  11. Alterations in brain protein kinase C after experimental brain injury.

    PubMed

    Padmaperuma, B; Mark, R; Dhillon, H S; Mattson, M P; Prasad, M R

    1996-04-01

    Regional activities and levels of protein kinase C were measured after lateral fluid percussion brain injury in rats. At 5 min and 20 min after injury, neither cofactor-dependent nor -independent PKC activities in the cytosol and membrane fractions changed in the injured and contralateral cortices or in the ipsilateral hippocampus. Western blot analysis revealed decreases in the levels of cytosolic PKC alpha and PKC beta in the injured cortex after brain injury. In the same site, a significant increase in the levels of membrane PKC alpha and PKC beta was observed after injury. Although the level of PKC alpha did not change and that of PKC beta decreased in the cytosol of the ipsilateral hippocampus, these levels did not increase in the membrane fraction after injury. The levels of PKC gamma were generally unchanged in the cytosol and the membrane, except for its decrease in the cytosol of the hippocampus. There were no changes in the levels of any PKC isoform in either the cytosol or the membrane of the contralateral cortex after injury. The present results suggest a translocation of PKC alpha and PKC beta from the cytosol to the membrane in the injured cortex after brain injury. The observation that such a translocation occurs only in the brain regions that undergo substantial neuronal loss suggests that membrane PKC may play a role in neuronal damage after brain injury. PMID:8861605

  12. Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis

    PubMed Central

    Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

    2016-01-01

    Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS. PMID:26727514

  13. Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

    PubMed

    Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

    2016-01-01

    Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS.

  14. Resting State Brain Entropy Alterations in Relapsing Remitting Multiple Sclerosis.

    PubMed

    Zhou, Fuqing; Zhuang, Ying; Gong, Honghan; Zhan, Jie; Grossman, Murray; Wang, Ze

    2016-01-01

    Brain entropy (BEN) mapping provides a novel approach to characterize brain temporal dynamics, a key feature of human brain. Using resting state functional magnetic resonance imaging (rsfMRI), reliable and spatially distributed BEN patterns have been identified in normal brain, suggesting a potential use in clinical populations since temporal brain dynamics and entropy may be altered in disease conditions. The purpose of this study was to characterize BEN in multiple sclerosis (MS), a neurodegenerative disease that affects millions of people. Since currently there is no cure for MS, developing treatment or medication that can slow down its progression represents a high research priority, for which validating a brain marker sensitive to disease and the related functional impairments is essential. Because MS can start long time before any measurable symptoms and structural deficits, assessing the dynamic brain activity and correspondingly BEN may provide a critical way to study MS and its progression. Because BEN is new to MS, we aimed to assess BEN alterations in the relapsing-remitting MS (RRMS) patients using a patient versus control design, to examine the correlation of BEN to clinical measurements, and to check the correlation of BEN to structural brain measures which have been more often used in MS studies. As compared to controls, RRMS patients showed increased BEN in motor areas, executive control area, spatial coordinating area, and memory system. Increased BEN was related to greater disease severity as measured by the expanded disability status scale (EDSS) and greater tissue damage as indicated by the mean diffusivity. Patients also showed decreased BEN in other places, which was associated with less disability or fatigue, indicating a disease-related BEN re-distribution. Our results suggest BEN as a novel and useful tool for characterizing RRMS. PMID:26727514

  15. Alteration of Interictal Brain Activity in Patients with Temporal Lobe Epilepsy in the Left Dominant Hemisphere: A Resting-State MEG Study

    PubMed Central

    Zhu, Haitao; Zhu, Jinlong; Zhao, Tiezhu; Wu, Yong; Liu, Hongyi; Wu, Ting; Yang, Lu; Zou, Yuanjie; Zhang, Rui; Zheng, Gang

    2014-01-01

    Resting MEG activities were compared between patients with left temporal lobe epilepsy (LTLE) and normal controls. Using SAMg2, the activities of MEG data were reconstructed and normalized. Significantly elevated SAMg2 signals were found in LTLE patients in the left temporal lobe and medial structures. Marked decreases of SAMg2 signals were found in the wide extratemporal lobe regions, such as the bilateral visual cortex. The study also demonstrated a positive correlation between the seizure frequency and brain activities of the abnormal regions after the multiple linear regression analysis. These results suggested that the aberrant brain activities not only were related to the epileptogenic zones, but also existed in other extratemporal regions in patients with LTLE. The activities of the aberrant regions could be further damaged with the increase of the seizure frequency. Our findings indicated that LTLE could be a multifocal disease, including complex epileptic networks and brain dysfunction networks. PMID:25136558

  16. Altered Brain Microstate Dynamics in Adolescents with Narcolepsy.

    PubMed

    Drissi, Natasha M; Szakács, Attila; Witt, Suzanne T; Wretman, Anna; Ulander, Martin; Ståhlbrandt, Henriettae; Darin, Niklas; Hallböök, Tove; Landtblom, Anne-Marie; Engström, Maria

    2016-01-01

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13-20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics. PMID:27536225

  17. Altered Brain Microstate Dynamics in Adolescents with Narcolepsy

    PubMed Central

    Drissi, Natasha M.; Szakács, Attila; Witt, Suzanne T.; Wretman, Anna; Ulander, Martin; Ståhlbrandt, Henriettae; Darin, Niklas; Hallböök, Tove; Landtblom, Anne-Marie; Engström, Maria

    2016-01-01

    Narcolepsy is a chronic sleep disorder caused by a loss of hypocretin-1 producing neurons in the hypothalamus. Previous neuroimaging studies have investigated brain function in narcolepsy during rest using positron emission tomography (PET) and single photon emission computed tomography (SPECT). In addition to hypothalamic and thalamic dysfunction they showed aberrant prefrontal perfusion and glucose metabolism in narcolepsy. Given these findings in brain structure and metabolism in narcolepsy, we anticipated that changes in functional magnetic resonance imaging (fMRI) resting state network (RSN) dynamics might also be apparent in patients with narcolepsy. The objective of this study was to investigate and describe brain microstate activity in adolescents with narcolepsy and correlate these to RSNs using simultaneous fMRI and electroencephalography (EEG). Sixteen adolescents (ages 13–20) with a confirmed diagnosis of narcolepsy were recruited and compared to age-matched healthy controls. Simultaneous EEG and fMRI data were collected during 10 min of wakeful rest. EEG data were analyzed for microstates, which are discrete epochs of stable global brain states obtained from topographical EEG analysis. Functional MRI data were analyzed for RSNs. Data showed that narcolepsy patients were less likely than controls to spend time in a microstate which we found to be related to the default mode network and may suggest a disruption of this network that is disease specific. We concluded that adolescents with narcolepsy have altered resting state brain dynamics. PMID:27536225

  18. Altered baseline brain activity in experts measured by amplitude of low frequency fluctuations (ALFF): a resting state fMRI study using expertise model of acupuncturists

    PubMed Central

    Dong, Minghao; Li, Jun; Shi, Xinfa; Gao, Shudan; Fu, Shijun; Liu, Zongquan; Liang, Fanrong; Gong, Qiyong; Shi, Guangming; Tian, Jie

    2015-01-01

    It is well established that expertise modulates evoked brain activity in response to specific stimuli. Recently, researchers have begun to investigate how expertise influences the resting brain. Among these studies, most focused on the connectivity features within/across regions, i.e., connectivity patterns/strength. However, little concern has been given to a more fundamental issue whether or not expertise modulates baseline brain activity. We investigated this question using amplitude of low-frequency (<0.08 Hz) fluctuation (ALFF) as the metric of brain activity and a novel expertise model, i.e., acupuncturists, due to their robust proficiency in tactile perception and emotion regulation. After the psychophysical and behavioral expertise screening procedure, 23 acupuncturists and 23 matched non-acupuncturists (NA) were enrolled. Our results explicated higher ALFF for acupuncturists in the left ventral medial prefrontal cortex (VMPFC) and the contralateral hand representation of the primary somatosensory area (SI) (corrected for multiple comparisons). Additionally, ALFF of VMPFC was negatively correlated with the outcomes of the emotion regulation task (corrected for multiple comparisons). We suggest that our study may reveal a novel connection between the neuroplasticity mechanism and resting state activity, which would upgrade our understanding of the central mechanism of learning. Furthermore, by showing that expertise can affect the baseline brain activity as indicated by ALFF, our findings may have profound implication for functional neuroimaging studies especially those involving expert models, in that difference in baseline brain activity may either smear the spatial pattern of activations for task data or introduce biased results into connectivity-based analysis for resting data. PMID:25852511

  19. Alteration in synaptic junction proteins following traumatic brain injury.

    PubMed

    Merlo, Lucia; Cimino, Francesco; Angileri, Filippo Flavio; La Torre, Domenico; Conti, Alfredo; Cardali, Salvatore Massimiliano; Saija, Antonella; Germanò, Antonino

    2014-08-15

    Extensive research and scientific efforts have been focused on the elucidation of the pathobiology of cellular and axonal damage following traumatic brain injury (TBI). Conversely, few studies have specifically addressed the issue of synaptic dysfunction. Synaptic junction proteins may be involved in post-TBI alterations, leading to synaptic loss or disrupted plasticity. A Synapse Protein Database on synapse ontology identified 109 domains implicated in synaptic activities and over 5000 proteins, but few of these demonstrated to play a role in the synaptic dysfunction after TBI. These proteins are involved in neuroplasticity and neuromodulation and, most importantly, may be used as novel neuronal markers of TBI for specific intervention.

  20. Violent Video Games Alter Brain Function in Young Men

    MedlinePlus

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

  1. Intensive reasoning training alters patterns of brain connectivity at rest

    PubMed Central

    Mackey, Allyson P.; Miller Singley, Alison T.; Bunge, Silvia A.

    2013-01-01

    Patterns of correlated activity among brain regions reflect functionally relevant networks that are widely assumed to be stable over time. We hypothesized that if these correlations reflect the prior history of co-activation of brain regions, then a marked shift in cognition could alter the strength of coupling between these regions. We sought to test whether intensive reasoning training in humans would result in tighter coupling among regions in the lateral fronto-parietal network, as measured with resting-state fMRI (rs-fMRI). Rather than designing an artificial training program, we studied individuals who were preparing for a standardized test that places heavy demands on relational reasoning, the Law School Admissions Test (LSAT). LSAT questions require test-takers to group or sequence items according to a set of complex rules. We recruited young adults who were enrolled in an LSAT course that offers 70 hours of reasoning instruction (n=25), and age- and IQ-matched controls intending to take the LSAT in the future (n=24). Rs-fMRI data were collected for all subjects during two scanning sessions separated by 90 days. An analysis of pairwise correlations between brain regions implicated in reasoning showed that fronto-parietal connections were strengthened, along with parietal-striatal connections. These findings provide strong evidence for neural plasticity at the level of large-scale networks supporting high-level cognition. PMID:23486950

  2. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients.

  3. Methylglyoxal can mediate behavioral and neurochemical alterations in rat brain.

    PubMed

    Hansen, Fernanda; Pandolfo, Pablo; Galland, Fabiana; Torres, Felipe Vasconcelos; Dutra, Márcio Ferreira; Batassini, Cristiane; Guerra, Maria Cristina; Leite, Marina Concli; Gonçalves, Carlos-Alberto

    2016-10-01

    Diabetes is associated with loss of cognitive function and increased risk for Alzheimer's disease (AD). Advanced glycation end products (AGEs) are elevated in diabetes and AD and have been suggested to act as mediators of the cognitive decline observed in these pathologies. Methylglyoxal (MG) is an extremely reactive carbonyl compound that propagates glycation reactions and is, therefore, able to generate AGEs. Herein, we evaluated persistent behavioral and biochemical parameters to explore the hypothesis that elevated exogenous MG concentrations, induced by intracerebroventricular (ICV) infusion, lead to cognitive decline in Wistar rats. A high and sustained administration of MG (3μmol/μL; subdivided into 6days) was found to decrease the recognition index of rats, as evaluated by the object-recognition test. However, MG was unable to impair learning-memory processes, as shown by the habituation in the open field (OF) and Y-maze tasks. Moreover, a single high dose of MG induced persistent alterations in anxiety-related behavior, diminishing the anxiety-like parameters evaluated in the OF test. Importantly, MG did not alter locomotion behavior in the different tasks performed. Our biochemical findings support the hypothesis that MG induces persistent alterations in the hippocampus, but not in the cortex, related to glyoxalase 1 activity, AGEs content and glutamate uptake. Glial fibrillary acidic protein and S100B content, as well as S100B secretion (astroglial-related parameters of brain injury), were not altered by ICV MG administration. Taken together, our data suggest that MG interferes directly in brain function and that the time and the levels of exogenous MG determine the different features that can be seen in diabetic patients. PMID:27235733

  4. Altered Cognitive Control Activations after Moderate-to-Severe Traumatic Brain Injury and Their Relationship to Injury Severity and Everyday-Life Function.

    PubMed

    Olsen, Alexander; Brunner, Jan Ferenc; Indredavik Evensen, Kari Anne; Finnanger, Torun Gangaune; Vik, Anne; Skandsen, Toril; Landrø, Nils Inge; Håberg, Asta Kristine

    2015-08-01

    This study investigated how the neuronal underpinnings of both adaptive and stable cognitive control processes are affected by traumatic brain injury (TBI). Functional magnetic resonance imaging (fMRI) was undertaken in 62 survivors of moderate-to-severe TBI (>1 year after injury) and 68 healthy controls during performance of a continuous performance test adapted for use in a mixed block- and event-related design. Survivors of TBI demonstrated increased reliance on adaptive task control processes within an a priori core region for cognitive control in the medial frontal cortex. TBI survivors also had increased activations related to time-on-task effects during stable task-set maintenance in right inferior parietal and prefrontal cortices. Increased brain activations in TBI survivors had a dose-dependent linear positive relationship to injury severity and were negatively correlated with self-reported cognitive control problems in everyday-life situations. Results were adjusted for age, education, and fMRI task performance. In conclusion, evidence was provided that the neural underpinnings of adaptive and stable control processes are differently affected by TBI. Moreover, it was demonstrated that increased brain activations typically observed in survivors of TBI might represent injury-specific compensatory adaptations also utilized in everyday-life situations.

  5. Hyaluronan deficiency due to Has3 knock-out causes altered neuronal activity and seizures via reduction in brain extracellular space.

    PubMed

    Arranz, Amaia M; Perkins, Katherine L; Irie, Fumitoshi; Lewis, David P; Hrabe, Jan; Xiao, Fanrong; Itano, Naoki; Kimata, Koji; Hrabetova, Sabina; Yamaguchi, Yu

    2014-04-30

    Hyaluronan (HA), a large anionic polysaccharide (glycosaminoglycan), is a major constituent of the extracellular matrix of the adult brain. To address its function, we examined the neurophysiology of knock-out mice deficient in hyaluronan synthase (Has) genes. Here we report that these Has mutant mice are prone to epileptic seizures, and that in Has3(-/-) mice, this phenotype is likely derived from a reduction in the size of the brain extracellular space (ECS). Among the three Has knock-out models, namely Has3(-/-), Has1(-/-), and Has2(CKO), the seizures were most prevalent in Has3(-/-) mice, which also showed the greatest HA reduction in the hippocampus. Electrophysiology in Has3(-/-) brain slices demonstrated spontaneous epileptiform activity in CA1 pyramidal neurons, while histological analysis revealed an increase in cell packing in the CA1 stratum pyramidale. Imaging of the diffusion of a fluorescent marker revealed that the transit of molecules through the ECS of this layer was reduced. Quantitative analysis of ECS by the real-time iontophoretic method demonstrated that ECS volume was selectively reduced in the stratum pyramidale by ∼ 40% in Has3(-/-) mice. Finally, osmotic manipulation experiments in brain slices from Has3(-/-) and wild-type mice provided evidence for a causal link between ECS volume and epileptiform activity. Our results provide the first direct evidence for the physiological role of HA in the regulation of ECS volume, and suggest that HA-based preservation of ECS volume may offer a novel avenue for development of antiepileptogenic treatments.

  6. Carbofuran induced oxidative stress mediated alterations in Na⁺-K⁺-ATPase activity in rat brain: amelioration by vitamin E.

    PubMed

    Jaiswal, Sunil Kumar; Siddiqi, Nikhat Jamal; Sharma, Bechan

    2014-07-01

    Pesticides cause oxidative stress and adversely influence Na(+)-K(+)-ATPase activity in animals. Since impact of carbofuran has not been properly studied in the mammalian brain, the ability of carbofuran to induce oxidative stress and modulation in Na(+)-K(+)-ATPase activity and its amelioration by vitamin E was performed. The rats divided into six groups received two different doses of carbofuran (15% and 30% LD50) for 15 days. The results suggested that the carbofuran treatment caused a significant elevation in levels of malonaldehyde and reduced glutathione and sharp inhibition in the activities of super oxide dismutase, catalase, and glutathione-S-transferase; the effect being dose dependent. Carbofuran at different doses also caused sharp reduction in the activity of Na(+)-K(+)-ATPase. The pretreatment of vitamin E, however, showed a significant recovery in these indices. The pretreatment of rats with vitamin E offered protection from carbofuran-induced oxidative stress.

  7. Killing two birds with one stone: the potential role of aripiprazole for patients with comorbid major depressive disorder and nicotine dependence via altering brain activity in the anterior cingulate cortex.

    PubMed

    Chu, Che-Sheng; Tzeng, Nian-Sheng; Chang, Hsin-An; Chang, Chuan-Chia; Chen, Tien-Yu

    2014-09-01

    The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study.

  8. Altered balance of functional brain networks in Schizophrenia.

    PubMed

    Woodward, Todd S; Leong, KaWai; Sanford, Nicole; Tipper, Christine M; Lavigne, Katie M

    2016-02-28

    Activity in dorsal attention (DAN) and frontoparietal (FPN) functional brain networks is linked to allocation of attention to external stimuli, and activity in the default-mode network (DMN) is linked to allocation of attention to internal representations. Tasks requiring attention to external stimuli shift activity to the DAN/FPN and away from the DMN, and optimal task performance depends on balancing DAN/FPN against DMN activity. The current functional magnetic resonance imaging (fMRI) study assessed the balance of DAN/FPN and DMN activity in 13 schizophrenia patients and 13 healthy controls while they were engaged in a task switching Stroop paradigm which demanded internally directed attention to task instructions. The typical pattern of reciprocity between the DAN/FPN and DMN was observed for healthy controls but not for patients, suggesting a reduction in the internally focussed thought important for maintenance of instructions and strategies in schizophrenia. The observed alteration in the balance between DAN/FPN and DMN in patients may reflect a general mechanism underlying multiple forms of cognitive impairment in schizophrenia, including global processing deficits such as cognitive inefficiency and impaired context processing.

  9. Altered balance of functional brain networks in Schizophrenia.

    PubMed

    Woodward, Todd S; Leong, KaWai; Sanford, Nicole; Tipper, Christine M; Lavigne, Katie M

    2016-02-28

    Activity in dorsal attention (DAN) and frontoparietal (FPN) functional brain networks is linked to allocation of attention to external stimuli, and activity in the default-mode network (DMN) is linked to allocation of attention to internal representations. Tasks requiring attention to external stimuli shift activity to the DAN/FPN and away from the DMN, and optimal task performance depends on balancing DAN/FPN against DMN activity. The current functional magnetic resonance imaging (fMRI) study assessed the balance of DAN/FPN and DMN activity in 13 schizophrenia patients and 13 healthy controls while they were engaged in a task switching Stroop paradigm which demanded internally directed attention to task instructions. The typical pattern of reciprocity between the DAN/FPN and DMN was observed for healthy controls but not for patients, suggesting a reduction in the internally focussed thought important for maintenance of instructions and strategies in schizophrenia. The observed alteration in the balance between DAN/FPN and DMN in patients may reflect a general mechanism underlying multiple forms of cognitive impairment in schizophrenia, including global processing deficits such as cognitive inefficiency and impaired context processing. PMID:26786152

  10. A functional MRI study of altered spontaneous brain activity pattern in patients with congenital comitant strabismus using amplitude of low-frequency fluctuation

    PubMed Central

    Tan, Gang; Huang, Xin; Zhang, Ying; Wu, An-Hua; Zhong, Yu-Lin; Wu, Kai; Zhou, Fu-Qing; Shao, Yi

    2016-01-01

    Objective The aim of this study was to use amplitude of low-frequency fluctuation (ALFF) to investigate local features of spontaneous brain activity in patients with congenital comitant strabismus and clarify their relationship with emotional and psychosocial problems. Methods A total of 20 patients with congenital comitant strabismus (ten males and ten females), and 20 healthy controls (ten males and ten females) closely matched in age, sex, and education underwent resting-state functional magnetic resonance imaging scans. The ALFF method was used to assess local features of spontaneous brain activity. Congenital comitant strabismus patients were distinguished from healthy controls by receiver operating characteristic curve. Correlation analysis was performed to explore the relationships between the observed mean ALFF signal values of the different areas and the Chinese version of the Hospital Anxiety and Depression Scale. Results Compared with healthy controls, patients with congenital comitant strabismus had significantly lower ALFF in the bilateral medialfrontal gyrus and higher values in the bilateral cerebellum posterior lobe and left angular gyrus. In the congenital comitant strabismus group, the Hospital Anxiety and Depression Scale-depression score showed a negative correlation with the ALFF signal values of the bilateral medial frontal gyrus (r=−0.550, P=0.012) and a negative correlation was noted between the mean ALFF signal values of the left angular gyrus and strabismus duration (r=−0.515, P=0.020). Conclusion Congenital comitant strabismus mainly involves dysfunction in the bilateral medial frontal gyrus, bilateral cerebellum posterior lobe, and left angular gyrus, which may reflect the underlying pathologic mechanism of congenital strabismus. PMID:27284244

  11. Mice lacking brain/kidney phosphate-activated glutaminase have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth.

    PubMed

    Masson, Justine; Darmon, Michèle; Conjard, Agnès; Chuhma, Nao; Ropert, Nicole; Thoby-Brisson, Muriel; Foutz, Arthur S; Parrot, Sandrine; Miller, Gretchen M; Jorisch, Renée; Polan, Jonathan; Hamon, Michel; Hen, René; Rayport, Stephen

    2006-04-26

    Neurotransmitter glutamate has been thought to derive mainly from glutamine via the action of glutaminase type 1 (GLS1). To address the importance of this pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion of a STOP cassette by homologous recombination produced a null allele that blocked transcription, encoded no immunoreactive protein, and abolished GLS1 enzymatic activity. Null mutants were slightly smaller, were deficient in goal-directed behavior, hypoventilated, and died in the first postnatal day. No gross or microscopic defects were detected in peripheral organs or in the CNS. In cultured neurons from the null mutants, miniature EPSC amplitude and duration were normal; however, the amplitude of evoked EPSCs decayed more rapidly with sustained 10 Hz stimulation, consistent with an observed reduction in depolarization-evoked glutamate release. Because of this activity-dependent impairment in glutamatergic transmission, we surmised that respiratory networks, which require temporal summation of synaptic input, would be particularly affected. We found that the amplitude of inspirations was decreased in vivo, chemosensitivity to CO2 was severely altered, and the frequency of pacemaker activity recorded in the respiratory generator in the pre-Bötzinger complex, a glutamatergic brainstem network that can be isolated in vitro, was increased. Our results show that although alternate pathways to GLS1 glutamate synthesis support baseline glutamatergic transmission, the GLS1 pathway is essential for maintaining the function of active synapses, and thus the mutation is associated with impaired respiratory function, abnormal goal-directed behavior, and neonatal demise.

  12. Mice lacking brain/kidney phosphate-activated glutaminase (GLS1) have impaired glutamatergic synaptic transmission, altered breathing, disorganized goal-directed behavior and die shortly after birth

    PubMed Central

    Masson, Justine; Darmon, Michèle; Conjard, Agnès; Chuhma, Nao; Ropert, Nicole; Thoby-Brisson, Muriel; Foutz, Arthur S.; Parrot, Sandrine; Miller, Gretchen M.; Jorisch, Renée; Polan, Jonathan; Hamon, Michel; Hen, René; Rayport, Stephen

    2009-01-01

    Neurotransmitter glutamate has been thought to derive mainly from glutamine via the action of glutaminase type 1 (GLS1). To address the importance of this pathway in glutamatergic transmission, we knocked out GLS1 in mice. The insertion of a STOP cassette by homologous recombination produced a null allele that blocked transcription, encoded no immunoreactive protein and abolished GLS1 enzymatic activity. Null mutants were slightly smaller, were deficient in goal-directed behavior, hypoventilated and died in the first post-natal day. No gross or microscopic defects were detected in peripheral organs or in the central nervous system. In cultured neurons from the null mutants, miniature EPSC amplitude and duration were normal; however, the amplitude of evoked EPSCs decayed more rapidly with sustained 10 Hz stimulation, consistent with an observed reduction in depolarization-evoked glutamate release. Because of this activity-dependent impairment in glutamatergic transmission, we surmised that respiratory networks, which require temporal summation of synaptic input, would be particularly affected. We found that the amplitude of inspirations was decreased in vivo, chemosensitivity to CO2 was severely altered, and the frequency of pacemaker activity recorded in the respiratory generator in the Pre-Bötzinger complex, a glutamatergic brainstem network that can be isolated in vitro, was increased. Our results show that while alternate pathways to GLS1 glutamate synthesis support baseline glutamatergic transmission, the GLS1 pathway is essential for maintaining the function of active synapses, and so the mutation is associated with impaired respiratory function, abnormal goal-directed behavior and neonatal demise. PMID:16641247

  13. Alteration of Political Belief by Non-invasive Brain Stimulation.

    PubMed

    Chawke, Caroline; Kanai, Ryota

    2015-01-01

    People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to.

  14. Alteration of Political Belief by Non-invasive Brain Stimulation

    PubMed Central

    Chawke, Caroline; Kanai, Ryota

    2016-01-01

    People generally have imperfect introspective access to the mechanisms underlying their political beliefs, yet can confidently communicate the reasoning that goes into their decision making process. An innate desire for certainty and security in ones beliefs may play an important and somewhat automatic role in motivating the maintenance or rejection of partisan support. The aim of the current study was to clarify the role of the DLPFC in the alteration of political beliefs. Recent neuroimaging studies have focused on the association between the DLPFC (a region involved in the regulation of cognitive conflict and error feedback processing) and reduced affiliation with opposing political candidates. As such, this study used a method of non-invasive brain simulation (tRNS) to enhance activity of the bilateral DLPFC during the incorporation of political campaign information. These findings indicate a crucial role for this region in political belief formation. However, enhanced activation of DLPFC does not necessarily result in the specific rejection of political beliefs. In contrast to the hypothesis the results appear to indicate a significant increase in conservative values regardless of participant's initial political orientation and the political campaign advertisement they were exposed to. PMID:26834603

  15. Data for mitochondrial proteomic alterations in the developing rat brain.

    PubMed

    Villeneuve, Lance M; Stauch, Kelly L; Fox, Howard S

    2014-12-01

    Mitochondria are a critical organelle involved in many cellular processes, and due to the nature of the brain, neuronal cells are almost completely reliant on these organelles for energy generation. Due to the fact that biomedical research tends to investigate disease state pathogenesis, one area of mitochondrial research commonly overlooked is homeostatic responses to energy demands. Therefore, to elucidate mitochondrial alterations occurring during the developmentally important phase of E18 to P7 in the brain, we quantified the proteins in the mitochondrial proteome as well as proteins interacting with the mitochondria. We identified a large number of significantly altered proteins involved in a variety of pathways including glycolysis, mitochondrial trafficking, mitophagy, and the unfolded protein response. These results are important because we identified alterations thought to be homeostatic in nature occurring within mitochondria, and these results may be used to identify any abnormal deviations in the mitochondrial proteome occurring during this period of brain development. A more comprehensive analysis of this data may be obtained from the article "Proteomic analysis of mitochondria from embryonic and postnatal rat brains reveals response to developmental changes in energy demands" in the Journal of Proteomics. PMID:26217684

  16. Cortical and subcortical brain alterations in Juvenile Absence Epilepsy.

    PubMed

    Tondelli, Manuela; Vaudano, Anna Elisabetta; Ruggieri, Andrea; Meletti, Stefano

    2016-01-01

    Despite the common assumption that genetic generalized epilepsies are characterized by a macroscopically normal brain on magnetic resonance imaging, subtle structural brain alterations have been detected by advanced neuroimaging techniques in Childhood Absence Epilepsy syndrome. We applied quantitative structural MRI analysis to a group of adolescents and adults with Juvenile Absence Epilepsy (JAE) in order to investigate micro-structural brain changes using different brain measures. We examined grey matter volumes, cortical thickness, surface areas, and subcortical volumes in 24 patients with JAE compared to 24 healthy controls; whole-brain voxel-based morphometry (VBM) and Freesurfer analyses were used. When compared to healthy controls, patients revealed both grey matter volume and surface area reduction in bilateral frontal regions, anterior cingulate, and right mesial-temporal lobe. Correlation analysis with disease duration showed that longer disease was correlated with reduced surface area in right pre- and post-central gyrus. A possible effect of valproate treatment on brain structures was excluded. Our results indicate that subtle structural brain changes are detectable in JAE and are mainly located in anterior nodes of regions known to be crucial for awareness, attention and memory. PMID:27551668

  17. Structural brain alterations associated with dyslexia predate reading onset.

    PubMed

    Raschle, Nora Maria; Chang, Maria; Gaab, Nadine

    2011-08-01

    Functional magnetic resonance imaging studies have reported reduced activation in parietotemporal and occipitotemporal areas in adults and children with developmental dyslexia compared to controls during reading and reading related tasks. These patterns of regionally reduced activation have been linked to behavioral impairments of reading-related processes (e.g., phonological skills and rapid automatized naming). The observed functional and behavioral differences in individuals with developmental dyslexia have been complemented by reports of reduced gray matter in left parietotemporal, occipitotemporal areas, fusiform and lingual gyrus and the cerebellum. An important question for education is whether these neural differences are present before reading is taught. Developmental dyslexia can only be diagnosed after formal reading education starts. However, here we investigate whether the previously detected gray matter alterations in adults and children with developmental dyslexia can already be observed in a small group of pre-reading children with a family-history of developmental dyslexia compared to age and IQ-matched children without a family-history (N = 20/mean age: 5:9 years; age range 5:1-6:5 years). Voxel-based morphometry revealed significantly reduced gray matter volume indices for pre-reading children with, compared to children without, a family-history of developmental dyslexia in left occipitotemporal, bilateral parietotemporal regions, left fusiform gyrus and right lingual gyrus. Gray matter volume indices in left hemispheric occipitotemporal and parietotemporal regions of interest also correlated positively with rapid automatized naming. No differences between the two groups were observed in frontal and cerebellar regions. This discovery in a small group of children suggests that previously described functional and structural alterations in developmental dyslexia may not be due to experience-dependent brain changes but may be present at birth or

  18. Drug Metabolism within the Brain Changes Drug Response: Selective Manipulation of Brain CYP2B Alters Propofol Effects

    PubMed Central

    Khokhar, Jibran Y; Tyndale, Rachel F

    2011-01-01

    Drug-metabolizing cytochrome P450 (CYPs) enzymes are expressed in the liver, as well as in extrahepatic tissues such as the brain. Here we show for the first time that drug metabolism by a CYP within the brain, illustrated using CYP2B and the anesthetic propofol (2, 6-diisopropylphenol, Diprivan), can meaningfully alter the pharmacological response to a CNS acting drug. CYP2B is expressed in the brains of animals and humans, and this CYP isoform is able to metabolize centrally acting substrates such as propofol, ecstasy, and serotonin. Rats were given intracerebroventricularly (i.c.v.) injections of vehicle, C8-xanthate, or 8-methoxypsoralen (CYP2B mechanism-based inhibitors) and then tested for sleep time following propofol (80 mg/kg intraperitoneally). Both inhibitors significantly increased sleep-time (1.8- to 2-fold) and brain propofol levels, while having no effect on plasma propofol levels. Seven days of nicotine treatment can induce the expression of brain, but not hepatic, CYP2B, and this induction reduced propofol sleep times by 2.5-fold. This reduction was reversed in a dose-dependent manner by i.c.v. injections of inhibitor. Sleep times correlated with brain (r=0.76, P=0.0009), but not plasma (r=0.24, P=0.39) propofol concentrations. Inhibitor treatments increased brain, but not plasma, propofol levels, and had no effect on hepatic enzyme activity. These data indicate that brain CYP2B can metabolize neuroactive substrates (eg, propofol) and can alter their pharmacological response. This has wider implications for localized CYP-mediated metabolism of drugs, neurotransmitters, and neurotoxins within the brain by this highly variable enzyme family and other CYP subfamilies expressed in the brain. PMID:21107310

  19. Brain Activities and Educational Technology

    ERIC Educational Resources Information Center

    Riza, Emel

    2002-01-01

    There are close relationships between brain activities and educational technology. Brain is very important and so complicated part in our bodies. From long time scientists pay attention to that part and did many experiments, but they just reached little information like a drop in the sea. However from time to time they gave us some light to…

  20. Leptin Therapy Alters Appetite and Neural Responses to Food Stimuli in Brain Areas of Leptin-Sensitive Subjects Without Altering Brain Structure

    PubMed Central

    Farr, Olivia M.; Fiorenza, Christina; Papageorgiou, Panagiotis; Brinkoetter, Mary; Ziemke, Florencia; Koo, Bang-Bon; Rojas, Rafael

    2014-01-01

    acutely hypoleptinemic women did not alter brain structure but did alter functional cortical activity to food cues in key feeding and reward-related areas. PMID:25279500

  1. Piroxicam attenuates 3-nitropropionic acid-induced brain oxidative stress and behavioral alteration in mice.

    PubMed

    C, Jadiswami; H M, Megha; Dhadde, Shivsharan B; Durg, Sharanbasappa; Potadar, Pandharinath P; B S, Thippeswamy; V P, Veerapur

    2014-12-01

    3-Nitropropionic acid (3-NP) is a fungal toxin that produces Huntington's disease like symptoms in both animals and humans. Piroxicam, a non-selective cyclooxygenase (COX) inhibitor, used as anti-inflammatory agent and also known to decrease free oxygen radical production. In this study, the effect of piroxicam was evaluated against 3-NP-induced brain oxidative stress and behavioral alteration in mice. Adult male Swiss albino mice were injected with vehicle/piroxicam (10 and 20 mg/kg, i.p.) 30 min before 3-NP challenge (15 mg/kg, i.p.) regularly for 14 days. Body weights of the mice were measured on alternative days of the experiment. At the end of the treatment schedule, mice were evaluated for behavioral alterations (movement analysis, locomotor test, beam walking test and hanging wire test) and brain homogenates were used for the estimation of oxidative stress markers (lipid peroxidation, reduced glutathione and catalase). Administration of 3-NP significantly altered the behavioral activities and brain antioxidant status in mice. Piroxicam, at both the tested doses, caused a significant reversal of 3-NP-induced behavioral alterations and oxidative stress in mice. These findings suggest piroxicam protects the mice against 3-NP-induced brain oxidative stress and behavioral alteration. The antioxidant properties of piroxicam may be responsible for the observed beneficial actions. PMID:25191831

  2. Brain Gym. Simple Activities for Whole Brain Learning.

    ERIC Educational Resources Information Center

    Dennison, Paul E.; Dennison, Gail E.

    This booklet contains simple movements and activities that are used with students in Educational Kinesiology to enhance their experience of whole brain learning. Whole brain learning through movement repatterning and Brain Gym activities enable students to access those parts of the brain previously unavailable to them. These movements of body and…

  3. Methylphenidate alters NCS-1 expression in rat brain.

    PubMed

    Souza, Renan P; Soares, Eliane C; Rosa, Daniela V F; Souza, Bruno R; Réus, Gislaine Z; Barichello, Tatiana; Gomes, Karin M; Gomez, Marcus V; Quevedo, João; Romano-Silva, Marco A

    2008-07-01

    Methylphenidate has been used as an effective treatment for attention deficit hyperactivity disorder (ADHD). Methylphenidate (MPH) blocks dopamine and norepinephrine transporters causing an increase in extracellular levels. The use of psychomotor stimulants continues to rise due to both the treatment of ADHD and illicit abuse. Methylphenidate sensitization mechanism has still poor knowledge. Neuronal calcium sensor 1 was identified as a dopaminergic receptor interacting protein. When expressed in mammalian cells, neuronal calcium sensor 1 attenuates dopamine-induced D2 receptor internalization by a mechanism that involves a reduction in D2 receptor phosphorylation. Neuronal calcium sensor 1 appears to play a pivotal role in regulating D2 receptor function, it will be important to determine if there are alterations in neuronal calcium sensor 1 in neuropathologies associated with deregulation in dopaminergic signaling. Then, we investigated if methylphenidate could alter neuronal calcium sensor 1 expression in five brain regions (striatum, hippocampus, prefrontal cortex, cortex and cerebellum) in young and adult rats. These regions were chosen because some are located in brain circuits related with attention deficit hyperactivity disorder. Our results showed changes in neuronal calcium sensor 1 expression in hippocampus, prefrontal cortex and cerebellum mainly in adult rats. The demonstration that methylphenidate induces changes in neuronal calcium sensor 1 levels in rat brain may help to understand sensitization mechanisms as well as methylphenidate therapeutic effects to improve attention deficit hyperactivity disorder symptoms.

  4. Repeated swim stress alters brain benzodiazepine receptors measured in vivo

    SciTech Connect

    Weizman, R.; Weizman, A.; Kook, K.A.; Vocci, F.; Deutsch, S.I.; Paul, S.M.

    1989-06-01

    The effects of repeated swim stress on brain benzodiazepine receptors were examined in the mouse using both an in vivo and in vitro binding method. Specific in vivo binding of (/sup 3/H)Ro15-1788 to benzodiazepine receptors was decreased in the hippocampus, cerebral cortex, hypothalamus, midbrain and striatum after repeated swim stress (7 consecutive days of daily swim stress) when compared to nonstressed mice. In vivo benzodiazepine receptor binding was unaltered after repeated swim stress in the cerebellum and pons medulla. The stress-induced reduction in in vivo benzodiazepine receptor binding did not appear to be due to altered cerebral blood flow or to an alteration in benzodiazepine metabolism or biodistribution because there was no difference in (14C)iodoantipyrine distribution or whole brain concentrations of clonazepam after repeated swim stress. Saturation binding experiments revealed a change in both apparent maximal binding capacity and affinity after repeated swim stress. Moreover, a reduction in clonazepam's anticonvulsant potency was also observed after repeated swim stress (an increase in the ED50 dose for protection against pentylenetetrazol-induced seizures), although there was no difference in pentylenetetrazol-induced seizure threshold between the two groups. In contrast to the results obtained in vivo, no change in benzodiazepine receptor binding kinetics was observed using the in vitro binding method. These data suggest that environmental stress can alter the binding parameters of the benzodiazepine receptor and that the in vivo and in vitro binding methods can yield substantially different results.

  5. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-01

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574304

  6. Neuronal networks and mediators of cortical neurovascular coupling responses in normal and altered brain states.

    PubMed

    Lecrux, C; Hamel, E

    2016-10-01

    Brain imaging techniques that use vascular signals to map changes in neuronal activity, such as blood oxygenation level-dependent functional magnetic resonance imaging, rely on the spatial and temporal coupling between changes in neurophysiology and haemodynamics, known as 'neurovascular coupling (NVC)'. Accordingly, NVC responses, mapped by changes in brain haemodynamics, have been validated for different stimuli under physiological conditions. In the cerebral cortex, the networks of excitatory pyramidal cells and inhibitory interneurons generating the changes in neural activity and the key mediators that signal to the vascular unit have been identified for some incoming afferent pathways. The neural circuits recruited by whisker glutamatergic-, basal forebrain cholinergic- or locus coeruleus noradrenergic pathway stimulation were found to be highly specific and discriminative, particularly when comparing the two modulatory systems to the sensory response. However, it is largely unknown whether or not NVC is still reliable when brain states are altered or in disease conditions. This lack of knowledge is surprising since brain imaging is broadly used in humans and, ultimately, in conditions that deviate from baseline brain function. Using the whisker-to-barrel pathway as a model of NVC, we can interrogate the reliability of NVC under enhanced cholinergic or noradrenergic modulation of cortical circuits that alters brain states.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'.

  7. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors.

  8. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed

    Xu, Feng; Liu, Peiying; Pekar, James J; Lu, Hanzhang

    2015-04-15

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain's response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine's effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  9. Fueling and imaging brain activation.

    PubMed

    Dienel, Gerald A

    2012-01-01

    Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron-astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

  10. Fueling and imaging brain activation

    PubMed Central

    Dienel, Gerald A

    2012-01-01

    Metabolic signals are used for imaging and spectroscopic studies of brain function and disease and to elucidate the cellular basis of neuroenergetics. The major fuel for activated neurons and the models for neuron–astrocyte interactions have been controversial because discordant results are obtained in different experimental systems, some of which do not correspond to adult brain. In rats, the infrastructure to support the high energetic demands of adult brain is acquired during postnatal development and matures after weaning. The brain's capacity to supply and metabolize glucose and oxygen exceeds demand over a wide range of rates, and the hyperaemic response to functional activation is rapid. Oxidative metabolism provides most ATP, but glycolysis is frequently preferentially up-regulated during activation. Underestimation of glucose utilization rates with labelled glucose arises from increased lactate production, lactate diffusion via transporters and astrocytic gap junctions, and lactate release to blood and perivascular drainage. Increased pentose shunt pathway flux also causes label loss from C1 of glucose. Glucose analogues are used to assay cellular activities, but interpretation of results is uncertain due to insufficient characterization of transport and phosphorylation kinetics. Brain activation in subjects with low blood-lactate levels causes a brain-to-blood lactate gradient, with rapid lactate release. In contrast, lactate flooding of brain during physical activity or infusion provides an opportunistic, supplemental fuel. Available evidence indicates that lactate shuttling coupled to its local oxidation during activation is a small fraction of glucose oxidation. Developmental, experimental, and physiological context is critical for interpretation of metabolic studies in terms of theoretical models. PMID:22612861

  11. Brain responses to altered auditory feedback during musical keyboard production: an fMRI study.

    PubMed

    Pfordresher, Peter Q; Mantell, James T; Brown, Steven; Zivadinov, Robert; Cox, Jennifer L

    2014-03-27

    Alterations of auditory feedback during piano performance can be profoundly disruptive. Furthermore, different alterations can yield different types of disruptive effects. Whereas alterations of feedback synchrony disrupt performed timing, alterations of feedback pitch contents can disrupt accuracy. The current research tested whether these behavioral dissociations correlate with differences in brain activity. Twenty pianists performed simple piano keyboard melodies while being scanned in a 3-T magnetic resonance imaging (MRI) scanner. In different conditions they experienced normal auditory feedback, altered auditory feedback (asynchronous delays or altered pitches), or control conditions that excluded movement or sound. Behavioral results replicated past findings. Neuroimaging data suggested that asynchronous delays led to increased activity in Broca's area and its right homologue, whereas disruptive alterations of pitch elevated activations in the cerebellum, area Spt, inferior parietal lobule, and the anterior cingulate cortex. Both disruptive conditions increased activations in the supplementary motor area. These results provide the first evidence of neural responses associated with perception/action mismatch during keyboard production. PMID:24513403

  12. Brain responses to altered auditory feedback during musical keyboard production: an fMRI study.

    PubMed

    Pfordresher, Peter Q; Mantell, James T; Brown, Steven; Zivadinov, Robert; Cox, Jennifer L

    2014-03-27

    Alterations of auditory feedback during piano performance can be profoundly disruptive. Furthermore, different alterations can yield different types of disruptive effects. Whereas alterations of feedback synchrony disrupt performed timing, alterations of feedback pitch contents can disrupt accuracy. The current research tested whether these behavioral dissociations correlate with differences in brain activity. Twenty pianists performed simple piano keyboard melodies while being scanned in a 3-T magnetic resonance imaging (MRI) scanner. In different conditions they experienced normal auditory feedback, altered auditory feedback (asynchronous delays or altered pitches), or control conditions that excluded movement or sound. Behavioral results replicated past findings. Neuroimaging data suggested that asynchronous delays led to increased activity in Broca's area and its right homologue, whereas disruptive alterations of pitch elevated activations in the cerebellum, area Spt, inferior parietal lobule, and the anterior cingulate cortex. Both disruptive conditions increased activations in the supplementary motor area. These results provide the first evidence of neural responses associated with perception/action mismatch during keyboard production.

  13. Does acute caffeine ingestion alter brain metabolism in young adults?

    PubMed Central

    Xu, Feng; Liu, Peiying; Pekar, James J.; Lu, Hanzhang

    2015-01-01

    Caffeine, as the most commonly used stimulant drug, improves vigilance and, in some cases, cognition. However, the exact effect of caffeine on brain activity has not been fully elucidated. Because caffeine has a pronounced vascular effect which is independent of any neural effects, many hemodynamics-based methods such as fMRI cannot be readily applied without a proper calibration. The scope of the present work is two-fold. In Study 1, we used a recently developed MRI technique to examine the time-dependent changes in whole-brain cerebral metabolic rate of oxygen (CMRO2) following the ingestion of 200mg caffeine. It was found that, despite a pronounced decrease in CBF (p<0.001), global CMRO2 did not change significantly. Instead, the oxygen extraction fraction (OEF) was significantly elevated (p=0.002) to fully compensate for the reduced blood supply. Using the whole-brain finding as a reference, we aim to investigate whether there are any regional differences in the brain’s response to caffeine. Therefore, in Study 2, we examined regional heterogeneities in CBF changes following the same amount of caffeine ingestion. We found that posterior brain regions such as posterior cingulate cortex and superior temporal regions manifested a slower CBF reduction, whereas anterior brain regions including dorsolateral prefrontal cortex and medial frontal cortex showed a faster rate of decline. These findings have a few possible explanations. One is that caffeine may result in a region-dependent increase or decrease in brain activity, resulting in an unaltered average brain metabolic rate. The other is that caffeine’s effect on vasculature may be region-specific. Plausibility of these explanations is discussed in the context of spatial distribution of the adenosine receptors. PMID:25644657

  14. Myriocin, a serine palmitoyltransferase inhibitor, alters regional brain neurotransmitter levels without concurrent inhibition of the brain sphingolipid biosynthesis in mice.

    PubMed

    Osuchowski, Marcin F; Johnson, Victor J; He, Quanren; Sharma, Raghubir P

    2004-02-28

    Myriocin is a specific serine palmitoyltransferase (SPT) inhibitor whose effect on the brain is unknown. Brain amine metabolism and sphingolipid biosynthesis were studied in mice treated intraperitoneally with 0, 0.1, 0.3 or 1 mg/kg per day of myriocin for 5 days. Regional concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), 5-hydroxytryptamine (5-HT, serotonin), 5-hydroxyindoleacetic acid (5-HIAA) and norepinephrine (NE), were determined. Sphinganine (Sa) and sphingosine (So) concentrations and SPT activity in brain and liver were used to evaluate the impact of myriocin on sphingolipid biosynthesis. Myriocin treatment increased DA in striatum and hippocampus and reduced it in cortex. NE concentration decreased in cerebellum and 5-HT levels were reduced in cortex and in medulla oblongata. Changes in ratios for DOPAC/DA and HVA/DA were observed in hippocampus, cortex and midbrain. Brain Sa, So and SPT activity remained unchanged, whereas Sa and SPT activity decreased in liver. Results showed that myriocin may alter the levels and metabolism of brain amines and this effect is not related with inhibition of sphingolipid biosynthesis in the nervous system. PMID:14700532

  15. Preterm birth and structural brain alterations in early adulthood

    PubMed Central

    Nosarti, Chiara; Nam, Kie Woo; Walshe, Muriel; Murray, Robin M.; Cuddy, Marion; Rifkin, Larry; Allin, Matthew P.G.

    2014-01-01

    Alterations in cortical development and impaired neurodevelopmental outcomes have been described following very preterm (VPT) birth in childhood and adolescence, but only a few studies to date have investigated grey matter (GM) and white matter (WM) maturation in VPT samples in early adult life. Using voxel-based morphometry (VBM) we studied regional GM and WM volumes in 68 VPT-born individuals (mean gestational age 30 weeks) and 43 term-born controls aged 19–20 years, and their association with cognitive outcomes (Hayling Sentence Completion Test, Controlled Oral Word Association Test, Visual Reproduction test of the Wechsler Memory Scale-Revised) and gestational age. Structural MRI data were obtained with a 1.5 Tesla system and analysed using the VBM8 toolbox in SPM8 with a customized study-specific template. Similarly to results obtained at adolescent assessment, VPT young adults compared to controls demonstrated reduced GM volume in temporal, frontal, insular and occipital areas, thalamus, caudate nucleus and putamen. Increases in GM volume were noted in medial/anterior frontal gyrus. Smaller subcortical WM volume in the VPT group was observed in temporal, parietal and frontal regions, and in a cluster centred on posterior corpus callosum/thalamus/fornix. Larger subcortical WM volume was found predominantly in posterior brain regions, in areas beneath the parahippocampal and occipital gyri and in cerebellum. Gestational age was associated with GM and WM volumes in areas where VPT individuals demonstrated GM and WM volumetric alterations, especially in temporal, parietal and occipital regions. VPT participants scored lower than controls on measures of IQ, executive function and non-verbal memory. When investigating GM and WM alterations and cognitive outcome scores, subcortical WM volume in an area beneath the left inferior frontal gyrus accounted for 14% of the variance of full-scale IQ (F = 12.9, p < 0.0001). WM volume in posterior corpus callosum

  16. Smoking, alcoholism and genetic polymorphisms alter CYP2B6 levels in human brain.

    PubMed

    Miksys, Sharon; Lerman, Caryn; Shields, Peter G; Mash, Deborah C; Tyndale, Rachel F

    2003-07-01

    CYP2B6 metabolizes drugs such as nicotine and bupropion, and many toxins and carcinogens. Nicotine induces CYP2B1 in rat brain and in humans polymorphic variation in CYP2B6 affects smoking cessation rates. The aim of this study was to compare CYP2B6 expression in brains of human smokers and non-smokers and alcoholics and non-alcoholics (n=26). CYP2B6 expression was brain region-specific, and was observed in both neurons and astrocytes. CYP2B6 levels were higher in brains of smokers and alcoholics, particularly in cerebellar Purkinje cells and hippocampal pyramidal neurons, cells known to be damaged in alcoholics. Significantly more (p<0.05) CYP2B6 protein was seen in four brain regions of smoking alcoholics compared to non-smoking non-alcoholics: hippocampus (5.8-fold), caudate nucleus (3.3-fold), putamen (3.0-fold) and cerebellar hemisphere (1.6-fold). The genetic variant C1459T (R487C) has been associated with reduced hepatic enzyme levels, stability and activity. Preliminary genotyping of this small sample (n=24) suggested that individuals with the CC genotype had higher brain CYP2B6 than those with the CT or TT genotype. Higher brain CYP2B6 activity in smokers and alcoholics may cause altered sensitivity to centrally acting drugs, increased susceptibility to neurotoxins and carcinogenic xenobiotics and contribute to central tolerance to nicotine.

  17. Altered brain response for semantic knowledge in Alzheimer's disease.

    PubMed

    Wierenga, Christina E; Stricker, Nikki H; McCauley, Ashley; Simmons, Alan; Jak, Amy J; Chang, Yu-Ling; Nation, Daniel A; Bangen, Katherine J; Salmon, David P; Bondi, Mark W

    2011-02-01

    Word retrieval deficits are common in Alzheimer's disease (AD) and are thought to reflect a degradation of semantic memory. Yet, the nature of semantic deterioration in AD and the underlying neural correlates of these semantic memory changes remain largely unknown. We examined the semantic memory impairment in AD by investigating the neural correlates of category knowledge (e.g., living vs. nonliving) and featural processing (global vs. local visual information). During event-related fMRI, 10 adults diagnosed with mild AD and 22 cognitively normal (CN) older adults named aloud items from three categories for which processing of specific visual features has previously been dissociated from categorical features. Results showed widespread group differences in the categorical representation of semantic knowledge in several language-related brain areas. For example, the right inferior frontal gyrus showed selective brain response for nonliving items in the CN group but living items in the AD group. Additionally, the AD group showed increased brain response for word retrieval irrespective of category in Broca's homologue in the right hemisphere and rostral cingulate cortex bilaterally, which suggests greater recruitment of frontally mediated neural compensatory mechanisms in the face of semantic alteration. PMID:21163275

  18. Antenatal Maternal Stress Alters Functional Brain Responses In Adult Offspring During Conditioned Fear

    PubMed Central

    Sadler, Theodore R.; Nguyen, Peter T.; Yang, Jun; Givrad, Tina K.; Mayer, Emeran A.; Maarek, Jean-Michel I.; Hinton, David R.; Holschneider, Daniel P.

    2011-01-01

    Antenatal maternal stress has been shown in rodent models and in humans to result in altered behavioral and neuroendocrine responses, yet little is known about its effects on functional brain activation. Pregnant female rats received a daily foot-shock stress or sham-stress two days after testing plug-positive and continuing for the duration of their pregnancy. Adult male offspring (age 14 weeks) with and without prior maternal stress (MS) were exposed to an auditory fear conditioning (CF) paradigm. Cerebral blood flow (CBF) was assessed during recall of the tone cue in the nonsedated, nontethered animal using the 14C-iodoantipyrine method, in which the tracer was administered intravenously by remote activation of an implantable minipump. Regional CBF distribution was examined by autoradiography and analyzed by statistical parametric mapping in the three-dimensionally reconstructed brains. Presence of fear memory was confirmed by behavioral immobility (‘freezing’). Corticosterone plasma levels during the CF paradigm were measured by ELISA in a separate group of rats. Antenatal MS exposure altered functional brain responses to the fear conditioned cue in adult offspring. Rats with prior MS exposure compared to those without demonstrated heightened fear responsivity, exaggerated and prolonged corticosterone release, increased functional cerebral activation of limbic/paralimbic regions (amygdala, ventral hippocampus, insula, ventral striatum, nucleus acumbens), the locus coeruleus, and white matter, and deactivation of medial prefrontal cortical regions. Dysregulation of corticolimbic circuits may represent risk factors in the future development of anxiety disorders and associated alterations in emotional regulation. PMID:21300034

  19. Analysis of Functional Pathways Altered after Mild Traumatic Brain Injury

    PubMed Central

    Redell, John B.; Moore, Anthony N.; Grill, Raymond J.; Johnson, Daniel; Zhao, Jing; Liu, Yin

    2013-01-01

    Abstract Concussive injury (or mild traumatic brain injury; mTBI) can exhibit features of focal or diffuse injury patterns. We compared and contrasted the cellular and molecular responses after mild controlled cortical impact (mCCI; a focal injury) or fluid percussion injury (FPI; a diffuse injury) in rats. The rationale for this comparative analysis was to investigate the brain's response to mild diffuse versus mild focal injury to identify common molecular changes triggered by these injury modalities and to determine the functional pathways altered after injury that may provide novel targets for therapeutic intervention. Microarrays containing probes against 21,792 unique messenger RNAs (mRNAs) were used to investigate the changes in cortical mRNA expression levels at 3 and 24 h postinjury. Of the 354 mRNAs with significantly altered expression levels after mCCI, over 89% (316 mRNAs) were also contained within the mild FPI (mFPI) data set. However, mFPI initiated a more widespread molecular response, with over 2300 mRNAs differentially expressed. Bioinformatic analysis of annotated Gene Ontology molecular function and biological pathway terms showed a significant overrepresentation of genes belonging to inflammation, stress, and signaling categories in both data sets. We therefore examined changes in the protein levels of a panel of 23 cytokines and chemokines in cortical extracts using a Luminex-based bead immunoassay and detected significant increases in macrophage inflammatory protein (MIP)-1α (CCL3), GRO-KC (CXCL1), interleukin (IL)-1α, IL-1β, and IL-6. Immunohistochemical localization of MIP-1α and IL-1β showed marked increases at 3 h postinjury in the cortical vasculature and microglia, respectively, that were largely resolved by 24 h postinjury. Our findings demonstrate that both focal and diffuse mTBI trigger many shared pathobiological processes (e.g., inflammatory responses) that could be targeted for mechanism-based therapeutic interventions

  20. Experimental traumatic brain injury alters ethanol consumption and sensitivity.

    PubMed

    Lowing, Jennifer L; Susick, Laura L; Caruso, James P; Provenzano, Anthony M; Raghupathi, Ramesh; Conti, Alana C

    2014-10-15

    Altered alcohol consumption patterns after traumatic brain injury (TBI) can lead to significant impairments in TBI recovery. Few preclinical models have been used to examine alcohol use across distinct phases of the post-injury period, leaving mechanistic questions unanswered. To address this, the aim of this study was to describe the histological and behavioral outcomes of a noncontusive closed-head TBI in the mouse, after which sensitivity to and consumption of alcohol were quantified, in addition to dopaminergic signaling markers. We hypothesized that TBI would alter alcohol consumption patterns and related signal transduction pathways that were congruent to clinical observations. After midline impact to the skull, latency to right after injury, motor deficits, traumatic axonal injury, and reactive astrogliosis were evaluated in C57BL/6J mice. Amyloid precursor protein (APP) accumulation was observed in white matter tracts at 6, 24, and 72 h post-TBI. Increased intensity of glial fibrillary acidic protein (GFAP) immunoreactivity was observed by 24 h, primarily under the impact site and in the nucleus accumbens, a striatal subregion, as early as 72 h, persisting to 7 days, after TBI. At 14 days post-TBI, when mice were tested for ethanol sensitivity after acute high-dose ethanol (4 g/kg, intraperitoneally), brain-injured mice exhibited increased sedation time compared with uninjured mice, which was accompanied by deficits in striatal dopamine- and cAMP-regulated neuronal phosphoprotein, 32 kDa (DARPP-32) phosphorylation. At 17 days post-TBI, ethanol intake was assessed using the Drinking-in-the-Dark paradigm. Intake across 7 days of consumption was significantly reduced in TBI mice compared with sham controls, paralleling the reduction in alcohol consumption observed clinically in the initial post-injury period. These data demonstrate that TBI increases sensitivity to ethanol-induced sedation and affects downstream signaling mediators of striatal

  1. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  2. Blood-Brain Barrier Alterations Provide Evidence of Subacute Diaschisis in an Ischemic Stroke Rat Model

    PubMed Central

    Garbuzova-Davis, Svitlana; Rodrigues, Maria C. O.; Hernandez-Ontiveros, Diana G.; Tajiri, Naoki; Frisina-Deyo, Aric; Boffeli, Sean M.; Abraham, Jerry V.; Pabon, Mibel; Wagner, Andrew; Ishikawa, Hiroto; Shinozuka, Kazutaka; Haller, Edward; Sanberg, Paul R.; Kaneko, Yuji; Borlongan, Cesario V.

    2013-01-01

    Background Comprehensive stroke studies reveal diaschisis, a loss of function due to pathological deficits in brain areas remote from initial ischemic lesion. However, blood-brain barrier (BBB) competence in subacute diaschisis is uncertain. The present study investigated subacute diaschisis in a focal ischemic stroke rat model. Specific focuses were BBB integrity and related pathogenic processes in contralateral brain areas. Methodology/Principal Findings In ipsilateral hemisphere 7 days after transient middle cerebral artery occlusion (tMCAO), significant BBB alterations characterized by large Evans Blue (EB) parenchymal extravasation, autophagosome accumulation, increased reactive astrocytes and activated microglia, demyelinization, and neuronal damage were detected in the striatum, motor and somatosensory cortices. Vascular damage identified by ultrastuctural and immunohistochemical analyses also occurred in the contralateral hemisphere. In contralateral striatum and motor cortex, major ultrastructural BBB changes included: swollen and vacuolated endothelial cells containing numerous autophagosomes, pericyte degeneration, and perivascular edema. Additionally, prominent EB extravasation, increased endothelial autophagosome formation, rampant astrogliosis, activated microglia, widespread neuronal pyknosis and decreased myelin were observed in contralateral striatum, and motor and somatosensory cortices. Conclusions/Significance These results demonstrate focal ischemic stroke-induced pathological disturbances in ipsilateral, as well as in contralateral brain areas, which were shown to be closely associated with BBB breakdown in remote brain microvessels and endothelial autophagosome accumulation. This microvascular damage in subacute phase likely revealed ischemic diaschisis and should be considered in development of treatment strategies for stroke. PMID:23675488

  3. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells

    PubMed Central

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-01-01

    Blood–brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0·05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. PMID:24801999

  4. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells.

    PubMed

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-11-01

    Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0 · 05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings.

  5. Transcriptional profiling reveals that C5a alters microRNA in brain endothelial cells.

    PubMed

    Eadon, Michael T; Jacob, Alexander; Cunningham, Patrick N; Quigg, Richard J; Garcia, Joe G N; Alexander, Jessy J

    2014-11-01

    Blood-brain barrier (BBB) disturbance is a crucial occurrence in many neurological diseases, including systemic lupus erythematosus (SLE). Our previous studies showed that experimental lupus serum altered the integrity of the mouse brain endothelial layer, an important constituent of the BBB. Complement activation occurs in lupus with increased circulating complement components. Using a genomics approach, we identified the microRNA (miRNA) altered in mouse brain endothelial cells (bEnd3) by lupus serum and the complement protein, C5a. Of the 318 miRNA evaluated, 23 miRNAs were altered by lupus serum and 32 were altered by C5a alone compared with controls. Seven miRNAs (P < 0 · 05) were differentially expressed by both treatments: mmu-miR-133a*, mmu-miR-193*, mmu-miR-26b, mmu-miR-28*, mmu-miR-320a, mmu-miR-423-3p and mmu-miR-509-5p. The microarray results were validated by quantitative RT-PCR. In line with the in vitro results, expression of miR-26b and miR-28* were also significantly up-regulated in lupus mouse brain which was reduced by C5a receptor inhibition. Target prediction analysis revealed miR gene targets encoding components involved in inflammation, matrix arrangement, and apoptosis, pathways known to play important roles in central nervous system lupus. Our findings suggest that the miRNAs reported in this study may represent novel therapeutic targets in central nervous system lupus and other similar neuroinflammatory settings. PMID:24801999

  6. Altered oscillatory brain dynamics after repeated traumatic stress

    PubMed Central

    Kolassa, Iris-Tatjana; Wienbruch, Christian; Neuner, Frank; Schauer, Maggie; Ruf, Martina; Odenwald, Michael; Elbert, Thomas

    2007-01-01

    Background Repeated traumatic experiences, e.g. torture and war, lead to functional and structural cerebral changes, which should be detectable in cortical dynamics. Abnormal slow waves produced within circumscribed brain regions during a resting state have been associated with lesioned neural circuitry in neurological disorders and more recently also in mental illness. Methods Using magnetoencephalographic (MEG-based) source imaging, we mapped abnormal distributions of generators of slow waves in 97 survivors of torture and war with posttraumatic stress disorder (PTSD) in comparison to 97 controls. Results PTSD patients showed elevated production of focally generated slow waves (1–4 Hz), particularly in left temporal brain regions, with peak activities in the region of the insula. Furthermore, differential slow wave activity in right frontal areas was found in PTSD patients compared to controls. Conclusion The insula, as a site of multimodal convergence, could play a key role in understanding the pathophysiology of PTSD, possibly accounting for what has been called posttraumatic alexithymia, i.e., reduced ability to identify, express and regulate emotional responses to reminders of traumatic events. Differences in activity in right frontal areas may indicate a dysfunctional PFC, which may lead to diminished extinction of conditioned fear and reduced inhibition of the amygdala. PMID:17941996

  7. Traumatic Brain Injury Alters Methionine Metabolism: Implications for Pathophysiology

    PubMed Central

    Dash, Pramod K.; Hergenroeder, Georgene W.; Jeter, Cameron B.; Choi, H. Alex; Kobori, Nobuhide; Moore, Anthony N.

    2016-01-01

    Methionine is an essential proteinogenic amino acid that is obtained from the diet. In addition to its requirement for protein biosynthesis, methionine is metabolized to generate metabolites that play key roles in a number of cellular functions. Metabolism of methionine via the transmethylation pathway generates S-adenosylmethionine (SAM) that serves as the principal methyl (−CH3) donor for DNA and histone methyltransferases (MTs) to regulate epigenetic changes in gene expression. SAM is also required for methylation of other cellular proteins that serve various functions and phosphatidylcholine synthesis that participate in cellular signaling. Under conditions of oxidative stress, homocysteine (which is derived from SAM) enters the transsulfuration pathway to generate glutathione, an important cytoprotective molecule against oxidative damage. As both experimental and clinical studies have shown that traumatic brain injury (TBI) alters DNA and histone methylation and causes oxidative stress, we examined if TBI alters the plasma levels of methionine and its metabolites in human patients. Blood samples were collected from healthy volunteers (HV; n = 20) and patients with mild TBI (mTBI; GCS > 12; n = 20) or severe TBI (sTBI; GCS < 8; n = 20) within the first 24 h of injury. The levels of methionine and its metabolites in the plasma samples were analyzed by either liquid chromatography-mass spectrometry or gas chromatography-mass spectrometry (LC-MS or GC-MS). sTBI decreased the levels of methionine, SAM, betaine and 2-methylglycine as compared to HV, indicating a decrease in metabolism through the transmethylation cycle. In addition, precursors for the generation of glutathione, cysteine and glycine were also found to be decreased as were intermediate metabolites of the gamma-glutamyl cycle (gamma-glutamyl amino acids and 5-oxoproline). mTBI also decreased the levels of methionine, α-ketobutyrate, 2 hydroxybutyrate and glycine, albeit to lesser degrees than

  8. Age- and brain region-dependent α-synuclein oligomerization is attributed to alterations in intrinsic enzymes regulating α-synuclein phosphorylation in aging monkey brains

    PubMed Central

    Chen, Min; Yang, Weiwei; Li, Xin; Li, Xuran; Wang, Peng; Yue, Feng; Yang, Hui; Chan, Piu; Yu, Shun

    2016-01-01

    We previously reported that the levels of α-syn oligomers, which play pivotal pathogenic roles in age-related Parkinson's disease (PD) and dementia with Lewy bodies, increase heterogeneously in the aging brain. Here, we show that exogenous α-syn incubated with brain extracts from older cynomolgus monkeys and in Lewy body pathology (LBP)-susceptible brain regions (striatum and hippocampus) forms higher amounts of phosphorylated and oligomeric α-syn than that in extracts from younger monkeys and LBP-insusceptible brain regions (cerebellum and occipital cortex). The increased α-syn phosphorylation and oligomerization in the brain extracts from older monkeys and in LBP-susceptible brain regions were associated with higher levels of polo-like kinase 2 (PLK2), an enzyme promoting α-syn phosphorylation, and lower activity of protein phosphatase 2A (PP2A), an enzyme inhibiting α-syn phosphorylation, in these brain extracts. Further, the extent of the age- and brain-dependent increase in α-syn phosphorylation and oligomerization was reduced by inhibition of PLK2 and activation of PP2A. Inversely, phosphorylated α-syn oligomers reduced the activity of PP2A and showed potent cytotoxicity. In addition, the activity of GCase and the levels of ceramide, a product of GCase shown to activate PP2A, were lower in brain extracts from older monkeys and in LBP-susceptible brain regions. Our results suggest a role for altered intrinsic metabolic enzymes in age- and brain region-dependent α-syn oligomerization in aging brains. PMID:27032368

  9. Right Brain Activities to Improve Analytical Thinking.

    ERIC Educational Resources Information Center

    Lynch, Marion E.

    Schools tend to have a built-in bias toward left brain activities (tasks that are linear and sequential in nature), so the introduction of right brain activities (functions related to music, rhythm, images, color, imagination, daydreaming, dimensions) brings a balance into the classroom and helps those students who may be right brain oriented. To…

  10. Altered Brain Reactivity to Game Cues After Gaming Experience.

    PubMed

    Ahn, Hyeon Min; Chung, Hwan Jun; Kim, Sang Hee

    2015-08-01

    Individuals who play Internet games excessively show elevated brain reactivity to game-related cues. This study attempted to test whether this elevated cue reactivity observed in game players is a result of repeated exposure to Internet games. Healthy young adults without a history of excessively playing Internet games were recruited, and they were instructed to play an online Internet game for 2 hours/day for five consecutive weekdays. Two control groups were used: the drama group, which viewed a fantasy TV drama, and the no-exposure group, which received no systematic exposure. All participants performed a cue reactivity task with game, drama, and neutral cues in the brain scanner, both before and after the exposure sessions. The game group showed an increased reactivity to game cues in the right ventrolateral prefrontal cortex (VLPFC). The degree of VLPFC activation increase was positively correlated with the self-reported increase in desire for the game. The drama group showed an increased cue reactivity in response to the presentation of drama cues in the caudate, posterior cingulate, and precuneus. The results indicate that exposure to either Internet games or TV dramas elevates the reactivity to visual cues associated with the particular exposure. The exact elevation patterns, however, appear to differ depending on the type of media experienced. How changes in each of the regions contribute to the progression to pathological craving warrants a future longitudinal study. PMID:26252933

  11. Altered Brain Reactivity to Game Cues After Gaming Experience.

    PubMed

    Ahn, Hyeon Min; Chung, Hwan Jun; Kim, Sang Hee

    2015-08-01

    Individuals who play Internet games excessively show elevated brain reactivity to game-related cues. This study attempted to test whether this elevated cue reactivity observed in game players is a result of repeated exposure to Internet games. Healthy young adults without a history of excessively playing Internet games were recruited, and they were instructed to play an online Internet game for 2 hours/day for five consecutive weekdays. Two control groups were used: the drama group, which viewed a fantasy TV drama, and the no-exposure group, which received no systematic exposure. All participants performed a cue reactivity task with game, drama, and neutral cues in the brain scanner, both before and after the exposure sessions. The game group showed an increased reactivity to game cues in the right ventrolateral prefrontal cortex (VLPFC). The degree of VLPFC activation increase was positively correlated with the self-reported increase in desire for the game. The drama group showed an increased cue reactivity in response to the presentation of drama cues in the caudate, posterior cingulate, and precuneus. The results indicate that exposure to either Internet games or TV dramas elevates the reactivity to visual cues associated with the particular exposure. The exact elevation patterns, however, appear to differ depending on the type of media experienced. How changes in each of the regions contribute to the progression to pathological craving warrants a future longitudinal study.

  12. Altering 5-hydroxymethylcytosine modification impacts ischemic brain injury.

    PubMed

    Miao, Zhigang; He, Yuquan; Xin, Ning; Sun, Miao; Chen, Li; Lin, Li; Li, Jizhen; Kong, Jiming; Jin, Peng; Xu, Xingshun

    2015-10-15

    Epigenetic modifications such as cytosine methylation and histone modification are linked to the pathology of ischemic brain injury. Recent research has implicated 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine (5mC) via oxidation by ten-eleven translocation (Tet) enzymes, in DNA methylation-related plasticity. Here we show that 5hmC abundance was increased after ischemic injury, and Tet2 was responsible for this increase; furthermore, inhibiting Tet2 expression abolished the increase of 5hmC caused by ischemic injury. The decrease in 5hmC modifications from inhibiting Tet2 activity was accompanied by increased infarct volume after ischemic injury. Genome-wide profiling of 5hmC revealed differentially hydroxymethylated regions (DhMRs) associated with ischemic injury, and DhMRs were enriched among the genes involved in cell junction, neuronal morphogenesis and neurodevelopment. In particular, we found that 5hmC modifications at the promoter region of brain-derived neurotrophic factor (BDNF) increased, which was accompanied by increased BDNF mRNA, whereas the inhibition of Tet2 reduced BDNF mRNA and protein expression. Finally, we show that the abundance of 5hmC in blood samples from patients with acute ischemic stroke was also significantly increased. Together, these data suggest that 5hmC modification could serve as both a potential biomarker and a therapeutic target for the treatment of ischemic stroke.

  13. Decoding patterns of human brain activity.

    PubMed

    Tong, Frank; Pratte, Michael S

    2012-01-01

    Considerable information about mental states can be decoded from noninvasive measures of human brain activity. Analyses of brain activity patterns can reveal what a person is seeing, perceiving, attending to, or remembering. Moreover, multidimensional models can be used to investigate how the brain encodes complex visual scenes or abstract semantic information. Such feats of "brain reading" or "mind reading," though impressive, raise important conceptual, methodological, and ethical issues. What does successful decoding reveal about the cognitive functions performed by a brain region? How should brain signals be spatially selected and mathematically combined to ensure that decoding reflects inherent computations of the brain rather than those performed by the decoder? We highlight recent advances and describe how multivoxel pattern analysis can provide a window into mind-brain relationships with unprecedented specificity, when carefully applied. However, as brain-reading technology advances, issues of neuroethics and mental privacy will be important to consider.

  14. Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self.

    PubMed

    Lehmann, D; Faber, P L; Achermann, P; Jeanmonod, D; Gianotti, L R; Pizzagalli, D

    2001-11-30

    Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions.

  15. Brain sources of EEG gamma frequency during volitionally meditation-induced, altered states of consciousness, and experience of the self.

    PubMed

    Lehmann, D; Faber, P L; Achermann, P; Jeanmonod, D; Gianotti, L R; Pizzagalli, D

    2001-11-30

    Multichannel EEG of an advanced meditator was recorded during four different, repeated meditations. Locations of intracerebral source gravity centers as well as Low Resolution Electromagnetic Tomography (LORETA) functional images of the EEG 'gamma' (35-44 Hz) frequency band activity differed significantly between meditations. Thus, during volitionally self-initiated, altered states of consciousness that were associated with different subjective meditation states, different brain neuronal populations were active. The brain areas predominantly involved during the self-induced meditation states aiming at visualization (right posterior) and verbalization (left central) agreed with known brain functional neuroanatomy. The brain areas involved in the self-induced, meditational dissolution and reconstitution of the experience of the self (right fronto-temporal) are discussed in the context of neural substrates implicated in normal self-representation and reality testing, as well as in depersonalization disorders and detachment from self after brain lesions. PMID:11738545

  16. Altered resting-state activity in seasonal affective disorder.

    PubMed

    Abou Elseoud, Ahmed; Nissilä, Juuso; Liettu, Anu; Remes, Jukka; Jokelainen, Jari; Takala, Timo; Aunio, Antti; Starck, Tuomo; Nikkinen, Juha; Koponen, Hannu; Zang, Yu-Feng; Tervonen, Osmo; Timonen, Markku; Kiviniemi, Vesa

    2014-01-01

    At present, our knowledge about seasonal affective disorder (SAD) is based mainly up on clinical symptoms, epidemiology, behavioral characteristics and light therapy. Recently developed measures of resting-state functional brain activity might provide neurobiological markers of brain disorders. Studying functional brain activity in SAD could enhance our understanding of its nature and possible treatment strategies. Functional network connectivity (measured using ICA-dual regression), and amplitude of low-frequency fluctuations (ALFF) were measured in 45 antidepressant-free patients (39.78 ± 10.64, 30 ♀, 15 ♂) diagnosed with SAD and compared with age-, gender- and ethnicity-matched healthy controls (HCs) using resting-state functional magnetic resonance imaging. After correcting for Type 1 error at high model orders (inter-RSN correction), SAD patients showed significantly increased functional connectivity in 11 of the 47 identified RSNs. Increased functional connectivity involved RSNs such as visual, sensorimotor, and attentional networks. Moreover, our results revealed that SAD patients compared with HCs showed significant higher ALFF in the visual and right sensorimotor cortex. Abnormally altered functional activity detected in SAD supports previously reported attentional and psychomotor symptoms in patients suffering from SAD. Further studies, particularly under task conditions, are needed in order to specifically investigate cognitive deficits in SAD.

  17. C5a alters blood-brain barrier integrity in experimental lupus

    PubMed Central

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G. N.; Quigg, Richard J.; Alexander, Jessy J.

    2010-01-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6lpr (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL+/+ mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases

  18. Simulation of Local Blood Flow in Human Brain under Altered Gravity

    NASA Technical Reports Server (NTRS)

    Kim, Chang Sung; Kiris, Cetin; Kwak, Dochan

    2003-01-01

    In addition to the altered gravitational forces, specific shapes and connections of arteries in the brain vary in the human population (Cebral et al., 2000; Ferrandez et al., 2002). Considering the geometric variations, pulsatile unsteadiness, and moving walls, computational approach in analyzing altered blood circulation will offer an economical alternative to experiments. This paper presents a computational approach for modeling the local blood flow through the human brain under altered gravity. This computational approach has been verified through steady and unsteady experimental measurements and then applied to the unsteady blood flows through a carotid bifurcation model and an idealized Circle of Willis (COW) configuration under altered gravity conditions.

  19. Intrahippocampal Infusion of Crotamine Isolated from Crotalus durissus terrificus Alters Plasma and Brain Biochemical Parameters †

    PubMed Central

    Gonçalves, Rithiele; Vargas, Liane S.; Lara, Marcus V. S.; Güllich, Angélica; Mandredini, Vanusa; Ponce-Soto, Luis; Marangoni, Sergio; Dal Belo, Cháriston A.; Mello-Carpes, Pâmela B.

    2014-01-01

    Crotamine is one of the main constituents of the venom of the South American rattlesnake Crotalus durissus terrificus. Here we sought to investigate the inflammatory and toxicological effects induced by the intrahippocampal administration of crotamine isolated from Crotalus whole venom. Adult rats received an intrahippocampal infusion of crotamine or vehicle and were euthanized 24 h or 21 days after infusion. Plasma and brain tissue were collected for biochemical analysis. Complete blood count, creatinine, urea, glutamic oxaloacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), creatine-kinase (CK), creatine kinase-muscle B (CK-MB) and oxidative parameters (assessed by DNA damage and micronucleus frequency in leukocytes, lipid peroxidation and protein carbonyls in plasma and brain) were quantified. Unpaired and paired t-tests were used for comparisons between saline and crotamine groups, and within groups (24 h vs. 21 days), respectively. After 24 h crotamine infusion promoted an increase of urea, GOT, GPT, CK, and platelets values (p ≤ 0.01), while red blood cells, hematocrit and leukocytes values decreased (p ≤ 0.01). Additionally, 21 days after infusion crotamine group showed increased creatinine, leukocytes, TBARS (plasma and brain), carbonyl (plasma and brain) and micronucleus compared to the saline-group (p ≤ 0.01). Our findings show that crotamine infusion alter hematological parameters and cardiac markers, as well as oxidative parameters, not only in the brain, but also in the blood, indicating a systemic pro-inflammatory and toxicological activity. A further scientific attempt in terms of preserving the beneficial activity over toxicity is required. PMID:25380458

  20. Sleep Deprivation Reveals Altered Brain Perfusion Patterns in Somnambulism

    PubMed Central

    Dang-Vu, Thien Thanh; Zadra, Antonio; Labelle, Marc-Antoine; Petit, Dominique; Soucy, Jean-Paul; Montplaisir, Jacques

    2015-01-01

    Background Despite its high prevalence, relatively little is known about the pathophysiology of somnambulism. Increasing evidence indicates that somnambulism is associated with functional abnormalities during wakefulness and that sleep deprivation constitutes an important drive that facilitates sleepwalking in predisposed patients. Here, we studied the neural mechanisms associated with somnambulism using Single Photon Emission Computed Tomography (SPECT) with 99mTc-Ethylene Cysteinate Dimer (ECD), during wakefulness and after sleep deprivation. Methods Ten adult sleepwalkers and twelve controls with normal sleep were scanned using 99mTc-ECD SPECT in morning wakefulness after a full night of sleep. Eight of the sleepwalkers and nine of the controls were also scanned during wakefulness after a night of total sleep deprivation. Between-group comparisons of regional cerebral blood flow (rCBF) were performed to characterize brain activity patterns during wakefulness in sleepwalkers. Results During wakefulness following a night of total sleep deprivation, rCBF was decreased bilaterally in the inferior temporal gyrus in sleepwalkers compared to controls. Conclusions Functional neural abnormalities can be observed during wakefulness in somnambulism, particularly after sleep deprivation and in the inferior temporal cortex. Sleep deprivation thus not only facilitates the occurrence of sleepwalking episodes, but also uncovers patterns of neural dysfunction that characterize sleepwalkers during wakefulness. PMID:26241047

  1. Developmental Hypothyroidism Alters Brain-Derived Neurotrophic Factor (BDNF) Expression in Adulthood.

    EPA Science Inventory

    Severe developmental thyroid hormone (TH) insufficiency results in alterations in brain structure/function and lasting behavioral impairments. Environmental toxicants reduce circulating levels of TH, but the disruption is modest and the doseresponse relationships of TH and neuro...

  2. Altered resting brain connectivity in persistent cancer related fatigue

    PubMed Central

    Hampson, Johnson P.; Zick, Suzanna M.; Khabir, Tohfa; Wright, Benjamin D.; Harris, Richard E.

    2015-01-01

    There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected). This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected). Mental fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = −0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As

  3. Altered resting brain connectivity in persistent cancer related fatigue.

    PubMed

    Hampson, Johnson P; Zick, Suzanna M; Khabir, Tohfa; Wright, Benjamin D; Harris, Richard E

    2015-01-01

    There is an estimated 3 million women in the US living as breast cancer survivors and persistent cancer related fatigue (PCRF) disrupts the lives of an estimated 30% of these women. PCRF is associated with decreased quality of life, decreased sleep quality, impaired cognition and depression. The mechanisms of cancer related fatigue are not well understood; however, preliminary findings indicate dysfunctional activity in the brain as a potential factor. Here we investigate the relationship between PCRF on intrinsic resting state connectivity in this population. Twenty-three age matched breast cancer survivors (15 fatigued and 8 non-fatigued) who completed all cancer-related treatments at least 12 weeks prior to the study, were recruited to undergo functional connectivity magnetic resonance imaging (fcMRI). Intrinsic resting state networks were examined with both seed based and independent component analysis methods. Comparisons of brain connectivity patterns between groups as well as correlations with self-reported fatigue symptoms were performed. Fatigued patients displayed greater left inferior parietal lobule to superior frontal gyrus connectivity as compared to non-fatigued patients (P < 0.05 FDR corrected). This enhanced connectivity was associated with increased physical fatigue (P = 0.04, r = 0.52) and poor sleep quality (P = 0.04, r = 0.52) in the fatigued group. In contrast greater connectivity in the non-fatigued group was found between the right precuneus to the periaqueductal gray as well as the left IPL to subgenual cortex (P < 0.05 FDR corrected). Mental fatigue scores were associated with greater default mode network (DMN) connectivity to the superior frontal gyrus (P = 0.05 FDR corrected) among fatigued subjects (r = 0.82) and less connectivity in the non-fatigued group (r = -0.88). These findings indicate that there is enhanced intrinsic DMN connectivity to the frontal gyrus in breast cancer survivors with persistent fatigue. As

  4. Psychiatric implications of altered limbic-hypothalamic-pituitary-adrenocortical activity.

    PubMed

    Holsboer, F

    1989-01-01

    Hormones of the limbic-hypothalamic-pituitary-adrenocortical (LHPA) system are much involved in central nervous system regulation. The major LHPA neuropeptides, corticotropin-releasing hormone (CRH), vasopressin (AVP) and corticotropin (ACTH) do not only coordinate the neuroendocrine response to stress, but also induce behavioral adaptation. Transcription and post-translational processing of these neuropeptides is regulated by corticosteroids secreted from the adrenal cortex after stimulation by ACTH and other proopiomelanocortin derived peptides. These steroids play a key role as regulators of cell development, homeostatic maintenance and adaptation to environmental challenges. They execute vitally important actions through genomic effects resulting in altered gene expression and nongenomic effects leading to altered neuronal excitability. Since excessive secretory activity of this particular neuroendocrine system is part of an acute stress response or depressive symptom pattern, there is good reason to suspect that central actions of these steroids and peptides are involved in pathophysiology determining the clinical phenotype, drug response and relapse liability. This overview summarizes the clinical neuroendocrine investigations of the author and his collaborators, while they worked at the Department of Psychiatry in Mainz. The major conclusions from this work were: (1) aberrant hormonal responses to challenges with dexamethasone, ACTH or CRH are reflecting altered brain physiology in affective illness and related disorders; (2) hormones of the LHPA axis influence also nonendocrine behavioral systems such as sleep EEG; (3) physiologically significant interactions exist between LHPA hormones, the thyroid, growth hormone, gonadal and other neuroendocrine systems; (4) hormones of the LHPA axis constitute a bidirectional link between immunoregulation and brain activity; and (5) future psychiatric research topics such as molecular genetics of affective disorders

  5. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    PubMed

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder. PMID:26498253

  6. Developmental Vitamin D3 deficiency alters the adult rat brain.

    PubMed

    Féron, F; Burne, T H J; Brown, J; Smith, E; McGrath, J J; Mackay-Sim, A; Eyles, D W

    2005-03-15

    There is growing evidence that Vitamin D(3) (1,25-dihydroxyvitamin D(3)) is involved in brain development. We have recently shown that the brains of newborn rats from Vitamin D(3) deficient dams were larger than controls, had increased cell proliferation, larger lateral ventricles, and reduced cortical thickness. Brains from these animals also had reduced expression of nerve growth factor (NGF) and glial cell line-derived neurotrophic factor. The aim of the current study was to examine if there were any permanent outcomes into adulthood when the offspring of Vitamin D(3) deficient dams were restored to a normal diet. The brains of adult rats were examined at 10 weeks of age after Vitamin D(3) deficiency until birth or weaning. Compared to controls animals that were exposed to transient early Vitamin D(3) deficiency had larger lateral ventricles, reduced NGF protein content, and reduced expression of a number genes involved in neuronal structure, i.e. neurofilament or MAP-2 or neurotransmission, i.e. GABA-A(alpha4). We conclude that transient early life hypovitaminosis D(3) not only disrupts brain development but leads to persistent changes in the adult brain. In light of the high incidence of hypovitaminosis D(3) in women of child-bearing age, the public health implications of these findings warrant attention. PMID:15763180

  7. Morphine-conditioned cue alters c-Fos protein expression in the brain of crayfish.

    PubMed

    Dziopa, Leah; Imeh-Nathaniel, Adebobola; Baier, Dana; Kiel, Michael; Sameera, Sayeed; Brager, Adam; Beatriz, Vega; Nathaniel, Thomas I

    2011-07-15

    With a highly organized stereotypic behavior and a simplified neuronal system that is characterized by cellular modularity, crayfish (Orconectes rusticus) represents an excellent model that we used in this study to explore how a drug-conditioned-cue alters c-Fos protein expression in the brain of an invertebrate species. The first set of experiments revealed that a single injection of different doses of morphine (3.0 μg/g, 6.0 μg/g and 12.0 μg/g) into the circulatory system of crayfish significantly increased locomotor activity. Repeated injections of morphine increased locomotion at lower doses (3.0 μg/g and 6.0 μg/g), and decreased locomotion at a higher dose of 12.0 μg/g. The second experiment revealed that a repeated or single injection of morphine serves as reward when paired with a distinct visual environment. In the third experiment, we found that the c-Fos profile of morphine treated crayfish in an unconditioned environment did not show a significant increase from the basal level comparable to saline treated crayfish. The brains of crayfish were more active during exposure to the cue-elicited drug conditioned environment than the unconditioned environment. These results indicate that chronic morphine treatment alone is not sufficient to induce changes in the expression of c-Fos; instead, morphine-environment pairing in a specific context contributes to the expression of alterations in c-Fos regulation. The enhancement of c-Fos expression in the brain of crayfish seems to reflect the sensory or anticipatory facets of conditioning that suggests that potential and even unanticipated hypotheses in drug addiction can emerge from studies of addiction in crayfish.

  8. 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

  9. 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.

  10. In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

    PubMed

    Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

    2016-09-01

    During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery. PMID:27324381

  11. In Vivo Tumour Mapping Using Electrocorticography Alterations During Awake Brain Surgery: A Pilot Study.

    PubMed

    Boussen, Salah; Velly, Lionel; Benar, Christian; Metellus, Philippe; Bruder, Nicolas; Trébuchon, Agnès

    2016-09-01

    During awake brain surgery for tumour resection, in situ EEG recording (ECoG) is used to identify eloquent areas surrounding the tumour. We used the ECoG setup to record the electrical activity of cortical and subcortical tumours and then performed frequency and connectivity analyses in order to identify ECoG impairments and map tumours. We selected 16 patients with cortical (8) and subcortical (8) tumours undergoing awake brain surgery. For each patient, we computed the spectral content of tumoural and healthy areas in each frequency band. We computed connectivity of each electrode using connectivity markers (linear and non-linear correlations, phase-locking and coherence). We performed comparisons between healthy and tumour electrodes. The ECoG alterations were used to implement automated classification of the electrodes using clustering or neural network algorithms. ECoG alterations were used to image cortical tumours.Cortical tumours were found to profoundly alter all frequency contents (normalized and absolute power), with an increase in the δ activity and a decreases for the other bands (P < 0.05). Cortical tumour electrodes showed high level of connectivity compared to surrounding electrodes (all markers, P < 0.05). For subcortical tumours, a relative decrease in the γ1 band and in the alpha band in absolute amplitude (P < 0.05) were the only abnormalities. The neural network algorithm classification had a good performance: 93.6 % of the electrodes were classified adequately on a test subject. We found significant spectral and connectivity ECoG changes for cortical tumours, which allowed tumour recognition. Artificial neural algorithm pattern recognition seems promising for electrode classification in awake tumour surgery.

  12. Perinatal Risk Factors Altering Regional Brain Structure in the Preterm Infant

    ERIC Educational Resources Information Center

    Thompson, Deanne K.; Warfield, Simon K.; Carlin, John B.; Pavlovic, Masa; Wang, Hong X.; Bear, Merilyn; Kean, Michael J.; Doyle, Lex W.; Egan, Gary F.; Inder, Terrie E.

    2007-01-01

    Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between…

  13. Sleep variability in adolescence is associated with altered brain development.

    PubMed

    Telzer, Eva H; Goldenberg, Diane; Fuligni, Andrew J; Lieberman, Matthew D; Gálvan, Adriana

    2015-08-01

    Despite the known importance of sleep for brain development, and the sharp increase in poor sleep during adolescence, we know relatively little about how sleep impacts the developing brain. We present the first longitudinal study to examine how sleep during adolescence is associated with white matter integrity. We find that greater variability in sleep duration one year prior to a DTI scan is associated with lower white matter integrity above and beyond the effects of sleep duration, and variability in bedtime, whereas sleep variability a few months prior to the scan is not associated with white matter integrity. Thus, variability in sleep duration during adolescence may have long-term impairments on the developing brain. White matter integrity should be increasing during adolescence, and so sleep variability is directly at odds with normative developmental trends.

  14. Meditation may predispose to epilepsy: an insight into the alteration in brain environment induced by meditation.

    PubMed

    Jaseja, Harinder

    2005-01-01

    Stress-induced diseases in modern life are on an alarming rise not only in developed countries but also in developing ones. To alleviate stress, one practice that is being commonly and increasingly adapted to is meditation. Limited studies on meditation have reported occurrence of mental calmness along with apparently favorable changes in certain autonomic functional parameters like heart rate, blood pressure, respiration and skin resistance. Recently, meditation is also being practiced and advised for alleviation of epilepsy; however, very little work is available to comprehend effect and utility of meditation on epilepsy. Neuro-imaging and in-depth studies during the course and attainment of meditational state have revealed alteration in neuro-chemistry and neuro-physiology of brain environment that could favor epileptogenesis. The rise in brain glutamate and serotonin along with development of 'hypersynchrony' of EEG activity (which occur during the course and attainment of meditational state) are well documented to form the underlying basis of epilepsy. Each of the above-mentioned factors is individually capable of inducing susceptibility and decreasing threshold to epilepsy. Based on these changes in brain, this paper raises a grave possibility and risk of meditation in developing epilepsy or increasing the severity and frequency of attacks in an already epileptic state, contrary to the popular belief of its remedial role in alleviating epilepsy.

  15. Altered brain rhythms and functional network disruptions involved in patients with generalized fixation-off epilepsy.

    PubMed

    Solana, Ana Beatriz; Martínez, Kenia; Hernández-Tamames, Juan Antonio; San Antonio-Arce, Victoria; Toledano, Rafael; García-Morales, Irene; Alvárez-Linera, Juan; Gil-Nágel, Antonio; Del Pozo, Francisco

    2016-06-01

    Generalized Fixation-off Sensitivity (CGE-FoS) patients present abnormal EEG patterns when losing fixation. In the present work, we studied two CGE-FoS epileptic patients with simultaneous EEG-fMRI. We aim to identify brain areas that are specifically related to the pathology by identifying the brain networks that are related to the EEG brain altered rhythms. Three main analyses were performed: EEG standalone, where the voltage fluctuations in delta, alpha, and beta EEG bands were obtained; fMRI standalone, where resting-state fMRI ICA analyses for opened and closed eyes conditions were computed per subject; and, EEG-informed fMRI, where EEG delta, alpha and beta oscillations were used to analyze fMRI. Patient 1 showed EEG abnormalities for lower beta band EEG brain rhythm. Fluctuations of this rhythm were correlated with a brain network mainly composed by temporo-frontal areas only found in the closed eyes condition. Patient 2 presented alterations in all the EEG brain rhythms (delta, alpha, beta) under study when closing eyes. Several biologically relevant brain networks highly correlated (r > 0.7) to each other in the closed eyes condition were found. EEG-informed fMRI results in patient 2 showed hypersynchronized patterns in the fMRI correlation spatial maps. The obtained findings allow a differential diagnosis for each patient and different profiles with respect to healthy volunteers. The results suggest a different disruption in the functional brain networks of these patients that depends on their altered brain rhythms. This knowledge could be used to treat these patients by novel brain stimulation approaches targeting specific altered brain networks in each patient.

  16. [Brain, psyche and physical activity].

    PubMed

    Hollmann, W; Strüder, H K

    2000-11-01

    Modern technical and biochemical methods allow investigation of hemodynamic and metabolic responses of the human brain during muscular work. Following a general introduction to the topic results from selected studies on endogenous opioid peptides, pain sensitivity and psyche, regional cerebral blood flow and cerebral glucose metabolism, amino acid transport across the blood-brain barrier, impact of physical work on the serotonergic system, influence of oxygen partial pressure on neurotransmitters and hormones during exercise, role of the brain as performance limiting factor as well as age-related changes in cerebral blood flow and hypothalamo-pituitary-adrenal/-gonadal axis function will be presented. PMID:11149280

  17. Methamphetamine neurotoxicity increases brain expression and alters behavioral functions of CB₁ cannabinoid receptors.

    PubMed

    Bortolato, Marco; Frau, Roberto; Bini, Valentina; Luesu, William; Loriga, Roberta; Collu, Maria; Gessa, Gian Luigi; Ennas, M Grazia; Castelli, M Paola

    2010-10-01

    Cannabis is the most common secondary illicit substance in methamphetamine (METH) users, yet the outcomes of the concurrent consumption of both substances remain elusive. Capitalizing on recent findings on the implication of CB₁ cannabinoid receptors in the behavioral effects of METH, we hypothesized that METH-induced neurotoxicity may alter the brain expression of CB₁, thereby affecting its role in behavioral functions. To test this possibility, we subjected rats to a well-characterized model of METH neurotoxicity (4 mg/kg, subcutaneous × 4 injections, 2 h apart), and analyzed their CB₁ receptor brain expression three weeks later. METH exposure resulted in significant enhancements of CB₁ receptor expression across several brain regions, including prefrontal cortex, caudate-putamen, basolateral amygdala, CA1 hippocampal region and perirhinal cortex. In parallel, a different group of METH-exposed rats was used to explore the responsiveness to the potent cannabinoid agonist WIN 55,212-2 (WIN) (0.5-1 mg/kg, intraperitoneal), within several paradigms for the assessment of emotional and cognitive functions, such as open field, object exploration and recognition, and startle reflex. WIN induced anxiolytic-like effects in METH-exposed rats and anxiogenic-like effects in saline-treated controls. Furthermore, METH-exposed animals exhibited a significantly lower impact of WIN on the attenuation of exploratory behaviors and short-term (90 min) recognition memory. Conversely, METH neurotoxicity did not significantly affect WIN-induced reductions in locomotor activity, exploration time and acoustic startle. These results suggest that METH neurotoxicity may alter the vulnerability to select behavioral effects of cannabis, by inducing distinct regional variations in the expression of CB₁ receptors.

  18. Altered effective connectivity of default model brain network underlying amnestic MCI

    NASA Astrophysics Data System (ADS)

    Yan, Hao; Wang, Yonghui; Tian, Jie

    2012-02-01

    Mild cognitive impairment (MCI) is the transitional, heterogeneous continuum from healthy elderly to Alzheimer's disease (AD). Previous studies have shown that brain functional activity in the default mode network (DMN) is impaired in MCI patients. However, the altered effective connectivity of the DMN in MCI patients remains largely unknown. The present study combined an independent component analysis (ICA) approach with Granger causality analysis (mGCA) to investigate the effective connectivity within the DMN in 12 amnestic MCI patients and 12 age-matched healthy elderly. Compared to the healthy control, the MCI exhibited decreased functional activity in the posterior DMN regions, as well as a trend towards activity increases in anterior DMN regions. Results from mGCA further supported this conclusion that the causal influence projecting to the precuneus/PCC became much weaker in MCI, while stronger interregional interactions emerged within the frontal-parietal cortices. These findings suggested that abnormal effective connectivity within the DMN may elucidate the dysfunctional and compensatory processes in MCI brain networks.

  19. Alterations of Amino Acid Level in Depressed Rat Brain

    PubMed Central

    Yang, Pei; Li, Xuechun; Tian, Jingchen; Jing, Fu; Qu, Changhai; Lin, Longfei; Zhang, Hui

    2014-01-01

    Amino-acid neurotransmitter system dysfunction plays a major role in the pathophysiology of depression. Several studies have demonstrated the potential of amino acids as a source of neuro-specific biomarkers could be used in future diagnosis of depression. Only partial amino acids such as glycine and asparagine were determined from certain parts of rats' brain included hippocampi and cerebral cortex in previous studies. However, according to systematic biology, amino acids in different area of brain are interacted and interrelated. Hence, the determination of 34 amino acids through entire rats' brain was conducted in this study in order to demonstrate more possibilities for biomarkers of depression by discovering other potential amino acids in more areas of rats' brain. As a result, 4 amino acids (L-aspartic acid, L-glutamine, taurine and γ-amino-n-butyric acid) among 34 were typically identified as potentially primary biomarkers of depression by data statistics. Meanwhile, an antidepressant called Fluoxetine was employed to verify other potential amino acids which were not identified by data statistics. Eventually, we found L-α-amino-adipic acid could also become a new potentially secondary biomarker of depression after drug validation. In conclusion, we suggested that L-aspartic acid, L-glutamine, taurine, γ-amino-n-butyric acid and L-α-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant. PMID:25352755

  20. Behavioral alterations following blood-brain barrier disruption stimulated by focused ultrasound

    PubMed Central

    Yang, Feng-Yi; Huang, Sheng-Fang; Cheng, Irene Han-Juo

    2016-01-01

    The purpose of this study was to investigate the behavioral alterations and histological changes of the brain after FUS-induced BBB disruption (BBBD). Rats were behaviorally tested using the open field, hole-board, and grip strength tests from day 1 through day 32 after undergoing BBBD induced by FUS with either a mild or heavy parameter. In the open field test, we found an increase in center entries on day 1 and day 9 following heavy FUS treatment and a decrease in center entries at day 18 following mild FUS treatment. With regard to memory-related alterations, rats subjected to heavy FUS treatment exhibited longer latency to start exploring and to find the first baited hole. However, rats subjected to mild FUS treatment exhibited no significant differences in terms of memory performance or grip force. The obtained data suggest that heavy FUS treatment might induce hyperactivity, spatial memory impairment, and forelimb gripping deficits. Furthermore, while mild FUS treatment may have an impact on anxiety-related behaviors, the data suggested it had no impact on locomotor activity, memory, or grip force. Thus, the behavioral alterations following FUS-induced BBBD require further investigation before clinical application. PMID:27034007

  1. Brain network alterations and vulnerability to simulated neurodegeneration in breast cancer.

    PubMed

    Kesler, Shelli R; Watson, Christa L; Blayney, Douglas W

    2015-08-01

    Breast cancer and its treatments are associated with mild cognitive impairment and brain changes that could indicate an altered or accelerated brain aging process. We applied diffusion tensor imaging and graph theory to measure white matter organization and connectivity in 34 breast cancer survivors compared with 36 matched healthy female controls. We also investigated how brain networks (connectomes) in each group responded to simulated neurodegeneration based on network attack analysis. Compared with controls, the breast cancer group demonstrated significantly lower fractional anisotropy, altered small-world connectome properties, lower brain network tolerance to systematic region (node), and connection (edge) attacks and significant cognitive impairment. Lower tolerance to network attack was associated with cognitive impairment in the breast cancer group. These findings provide further evidence of diffuse white matter pathology after breast cancer and extend the literature in this area with unique data demonstrating increased vulnerability of the post-breast cancer brain network to future neurodegenerative processes.

  2. Altered processing of sweet taste in the brain of diet soda drinkers.

    PubMed

    Green, Erin; Murphy, Claire

    2012-11-01

    Artificially sweetened beverage consumption has been linked to obesity, and it has been hypothesized that considerable exposure to nonnutritive sweeteners may be associated with impaired energy regulation. The reward system plays an integral role in modulating energy intake, but little is known about whether habitual use of artificial sweetener (i.e., diet soda consumption) may be related to altered reward processing of sweet taste in the brain. To investigate this, we examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener) and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated greater activation to sweet taste in the dopaminergic midbrain (including ventral tegmental area) and right amygdala. Saccharin elicited a greater response in the right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet soda drinkers. There was no difference in fMRI response to the nutritive or nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers, fMRI activation of the right caudate head in response to saccharin was negatively associated with the amount of diet sodas consumed per week; individuals who consumed a greater number of diet sodas had reduced caudate head activation. These findings suggest that there are alterations in reward processing of sweet taste in individuals who regularly consume diet soda, and this is associated with the degree of consumption. These findings may provide some insight into the link between diet soda consumption and obesity.

  3. Protein kinase activators alter glial cholesterol esterification

    SciTech Connect

    Jeng, I.; Dills, C.; Klemm, N.; Wu, C.

    1986-05-01

    Similar to nonneural tissues, the activity of glial acyl-CoA cholesterol acyltransferase is controlled by a phosphorylation and dephosphorylation mechanism. Manipulation of cyclic AMP content did not alter the cellular cholesterol esterification, suggesting that cyclic AMP is not a bioregulator in this case. Therefore, the authors tested the effect of phorbol-12-myristate 13-acetate (PMA) on cellular cholesterol esterification to determine the involvement of protein kinase C. PMA has a potent effect on cellular cholesterol esterification. PMA depresses cholesterol esterification initially, but cells recover from inhibition and the result was higher cholesterol esterification, suggesting dual effects of protein kinase C. Studies of other phorbol analogues and other protein kinase C activators such as merezein indicate the involvement of protein kinase C. Oleoyl-acetyl glycerol duplicates the effect of PMA. This observation is consistent with a diacyl-glycerol-protein kinase-dependent reaction. Calcium ionophore A23187 was ineffective in promoting the effect of PMA. They concluded that a calcium-independent and protein C-dependent pathway regulated glial cholesterol esterification.

  4. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  5. C5a alters blood-brain barrier integrity in experimental lupus.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chiang, Eddie; Garcia, Joe G N; Quigg, Richard J; Alexander, Jessy J

    2010-06-01

    The blood-brain barrier (BBB) is a crucial anatomic location in the brain. Its dysfunction complicates many neurodegenerative diseases, from acute conditions, such as sepsis, to chronic diseases, such as systemic lupus erythematosus (SLE). Several studies suggest an altered BBB in lupus, but the underlying mechanism remains unknown. In the current study, we observed a definite loss of BBB integrity in MRL/MpJ-Tnfrsf6(lpr) (MRL/lpr) lupus mice by IgG infiltration into brain parenchyma. In line with this result, we examined the role of complement activation, a key event in this setting, in maintenance of BBB integrity. Complement activation generates C5a, a molecule with multiple functions. Because the expression of the C5a receptor (C5aR) is significantly increased in brain endothelial cells treated with lupus serum, the study focused on the role of C5a signaling through its G-protein-coupled receptor C5aR in brain endothelial cells, in a lupus setting. Reactive oxygen species production increased significantly in endothelial cells, in both primary cells and the bEnd3 cell line treated with lupus serum from MRL/lpr mice, compared with those treated with control serum from MRL(+/+) mice. In addition, increased permeability monitored by changes in transendothelial electrical resistance, cytoskeletal remodeling caused by actin fiber rearrangement, and increased iNOS mRNA expression were observed in bEnd3 cells. These disruptive effects were alleviated by pretreating cells with a C5a receptor antagonist (C5aRant) or a C5a antibody. Furthermore, the structural integrity of the vasculature in MRL/lpr brain was maintained by C5aR inhibition. These results demonstrate the regulation of BBB integrity by the complement system in a neuroinflammatory setting. For the first time, a novel role of C5a in the maintenance of BBB integrity is identified and the potential of C5a/C5aR blockade highlighted as a promising therapeutic strategy in SLE and other neurodegenerative diseases

  6. Recording of brain activity across spatial scales.

    PubMed

    Lewis, C M; Bosman, C A; Fries, P

    2015-06-01

    Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage. PMID:25544724

  7. Activities That Build the Young Child's Brain.

    ERIC Educational Resources Information Center

    Gellens, Suzanne R.

    This book presents 350 classroom-tested activities for use with children to create an environment that will stimulate young children's brains. Designed to be used by families, classroom teachers, family childcare providers, or others caring for young children, the book includes information on current brain research and describes interest areas in…

  8. Increased brain activation during working memory processing after pediatric mild traumatic brain injury (mTBI)

    PubMed Central

    Westfall, Daniel R.; West, John D.; Bailey, Jessica N.; Arnold, Todd W.; Kersey, Patrick A.; Saykin, Andrew J.; McDonald, Brenna C.

    2016-01-01

    Purpose The neural substrate of post-concussive symptoms following the initial injury period after mild traumatic brain injury (mTBI) in pediatric populations remains poorly elucidated. This study examined neuropsychological, behavioral, and brain functioning in adolescents post-mTBI to assess whether persistent differences were detectable up to a year post-injury. Methods Nineteen adolescents (mean age 14.7 years) who experienced mTBI 3–12 months previously (mean 7.5 months) and 19 matched healthy controls (mean age 14.0 years) completed neuropsychological testing and an fMRI auditory-verbal N-back working memory task. Parents completed behavioral ratings. Results No between-group differences were found for cognition, behavior, or N-back task performance, though the expected decreased accuracy and increased reaction time as task difficulty increased were apparent. However, the mTBI group showed significantly greater brain activation than controls during the most difficult working memory task condition. Conclusion Greater working memory task-related activation was found in adolescents up to one year post-mTBI relative to controls, potentially indicating compensatory activation to support normal task performance. Differences in brain activation in the mTBI group so long after injury may indicate residual alterations in brain function much later than would be expected based on the typical pattern of natural recovery, which could have important clinical implications. PMID:26684070

  9. Resting-state brain functional connectivity is altered in type 2 diabetes.

    PubMed

    Musen, Gail; Jacobson, Alan M; Bolo, Nicolas R; Simonson, Donald C; Shenton, Martha E; McCartney, Richard L; Flores, Veronica L; Hoogenboom, Wouter S

    2012-09-01

    Type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer disease (AD). Populations at risk for AD show altered brain activity in the default mode network (DMN) before cognitive dysfunction. We evaluated this brain pattern in T2DM patients. We compared T2DM patients (n = 10, age = 56 ± 2.2 years, fasting plasma glucose [FPG] = 8.4 ± 1.3 mmol/L, HbA(1c) = 7.5 ± 0.54%) with nondiabetic age-matched control subjects (n = 11, age = 54 ± 1.8 years, FPG = 4.8 ± 0.2 mmol/L) using resting-state functional magnetic resonance imaging to evaluate functional connectivity strength among DMN regions. We also evaluated hippocampal volume, cognition, and insulin sensitivity by homeostasis model assessment of insulin resistance (HOMA-IR). Control subjects showed stronger correlations versus T2DM patients in the DMN between the seed (posterior cingulate) and bilateral middle temporal gyrus (β = 0.67 vs. 0.43), the right inferior and left medial frontal gyri (β = 0.75 vs. 0.54), and the left thalamus (β = 0.59 vs. 0.37), respectively, with no group differences in cognition or hippocampal size. In T2DM patients, HOMA-IR was inversely correlated with functional connectivity in the right inferior frontal gyrus and precuneus. T2DM patients showed reduced functional connectivity in the DMN compared with control subjects, which was associated with insulin resistance in selected brain regions, but there were no group effects of brain structure or cognition.

  10. Understanding the brain by controlling neural activity

    PubMed Central

    Krug, Kristine; Salzman, C. Daniel; Waddell, Scott

    2015-01-01

    Causal methods to interrogate brain function have been employed since the advent of modern neuroscience in the nineteenth century. Initially, randomly placed electrodes and stimulation of parts of the living brain were used to localize specific functions to these areas. Recent technical developments have rejuvenated this approach by providing more precise tools to dissect the neural circuits underlying behaviour, perception and cognition. Carefully controlled behavioural experiments have been combined with electrical devices, targeted genetically encoded tools and neurochemical approaches to manipulate information processing in the brain. The ability to control brain activity in these ways not only deepens our understanding of brain function but also provides new avenues for clinical intervention, particularly in conditions where brain processing has gone awry. PMID:26240417

  11. Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

    PubMed Central

    Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

    2014-01-01

    Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620

  12. HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-associated neurocognitive disorders.

    PubMed

    Fields, Jerel Adam; Serger, Elisabeth; Campos, Sofia; Divakaruni, Ajit S; Kim, Changyoun; Smith, Kendall; Trejo, Margarita; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; Murphy, Anne N; Ellis, Ronald J; Letendre, Scott; Grant, Igor; Masliah, Eliezer

    2016-02-01

    HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of HIV patients, and therapies to combat HAND progression are urgently needed. HIV proteins are released from infected cells and cause neuronal damage, possibly through mitochondrial abnormalities. Altered mitochondrial fission and fusion is implicated in several neurodegenerative disorders. Here, we hypothesized that mitochondrial fission/fusion may be dysregulated in neurons during HAND. We have identified decreased mitochondrial fission protein (dynamin 1-like; DNM1L) in frontal cortex tissues of HAND donors, along with enlarged and elongated mitochondria localized to the soma of damaged neurons. Similar pathology was observed in the brains of GFAP-gp120 tg mice. In vitro, recombinant gp120 decreased total and active DNM1L levels, reduced the level of Mitotracker staining, and increased extracellular acidification rate (ECAR) in primary neurons. DNM1L knockdown enhanced the effects of gp120 as measured by reduced Mitotracker signal in the treated cells. Interestingly, overexpression of DNM1L increased the level of Mitotracker staining in primary rat neurons and reduced neuroinflammation and neurodegeneration in the GFAP-gp120-tg mice. These data suggest that mitochondrial biogenesis dynamics are shifted towards mitochondrial fusion in brains of HAND patients and this may be due to gp120-induced reduction in DNM1L activity. Promoting mitochondrial fission during HIV infection of the CNS may restore mitochondrial biogenesis and prevent neurodegeneration.

  13. HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-Associated Neurocognitive Disorders

    PubMed Central

    Fields, Jerel Adam; Serger, Elisabeth; Campos, Sofia; Divakaruni, Ajit S.; Kim, Changyoun; Smith, Kendall; Trejo, Margarita; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; Murphy, Anne N.; Ellis, Ronald J.; Letendre, Scott; Grant, Igor; Masliah, Eliezer

    2015-01-01

    HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of HIV patients, and therapies to combat HAND progression are urgently needed. HIV proteins are released from infected cells and cause neuronal damage, possibly through mitochondrial abnormalities. Altered mitochondrial fission and fusion is implicated in several neurodegenerative disorders. Here, we hypothesized that mitochondrial fission/fusion may be dysregulated in neurons during HAND. We have identified decreased mitochondrial fission protein (dynamin 1-like; DNM1L) in frontal cortex tissues of HAND donors, along with enlarged and elongated mitochondria localized to the soma of damaged neurons. Similar pathology was observed in the brains of GFAP-gp120 tg mice. In vitro, recombinant gp120 decreased total and active DNM1L levels, reduced the level of Mitotracker staining, and increased extracellular acidification rate (ECAR) in primary neurons. DNM1L knockdown enhanced the effects of gp120 as measured by reduced Mitotracker signal in the treated cells. Interestingly, overexpression of DNM1L increased the level of Mitotracker staining in primary rat neurons and reduced neuroinflammation and neurodegeneration in the GFAP-gp120-tg mice. These data suggest that mitochondrial biogenesis dynamics are shifted towards mitochondrial fusion in brains of HAND patients and this may be due to gp120-induced reduction in DNM1L activity. Promoting mitochondrial fission during HIV infection of the CNS may restore mitochondrial biogenesis and prevent neurodegeneration. PMID:26611103

  14. Female Mice are Resistant to Fabp1 Gene Ablation-Induced Alterations in Brain Endocannabinoid Levels.

    PubMed

    Martin, Gregory G; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K; Dangott, Lawrence J; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J; Kier, Ann B; Schroeder, Friedhelm

    2016-09-01

    Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in the brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing EC, i.e. arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: (1) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; (2) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or (3) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO). PMID:27450559

  15. Altered brain iron homeostasis and dopaminergic function in Restless Legs Syndrome (Willis-Ekbom Disease).

    PubMed

    Earley, Christopher J; Connor, James; Garcia-Borreguero, Diego; Jenner, Peter; Winkelman, John; Zee, Phyllis C; Allen, Richard

    2014-11-01

    Restless legs syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder for which the exact pathophysiology remains unclear. Brain iron insufficiency and altered dopaminergic function appear to play important roles in the etiology of the disorder. This concept is based partly on extensive research studies using cerebrospinal fluid (CSF), autopsy material, and brain imaging indicating reduced regional brain iron and on the clinical efficacy of dopamine receptor agonists for alleviating RLS symptoms. Finding causal relations, linking low brain iron to altered dopaminergic function in RLS, has required however the use of animal models. These models have provided insights into how alterations in brain iron homeostasis and dopaminergic system may be involved in RLS. The results of animal models of RLS and biochemical, postmortem, and imaging studies in patients with the disease suggest that disruptions in brain iron trafficking lead to disturbances in striatal dopamine neurotransmission for at least some patients with RLS. This review examines the data supporting an iron deficiency-dopamine metabolic theory of RLS by relating the results from animal model investigations of the influence of brain iron deficiency on dopaminergic systems to data from clinical studies in patients with RLS.

  16. 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

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

    PubMed

    Hubbard, Catherine S; 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

  18. Protective effect of naringin against ischemic reperfusion cerebral injury: possible neurobehavioral, biochemical and cellular alterations in rat brain.

    PubMed

    Gaur, Vaibhav; Aggarwal, Aditi; Kumar, Anil

    2009-08-15

    The present study was conducted with an aim to explore the possible role of naringin against ischemia reperfusion induced-neurobehavioral alterations, oxidative damage, cellular and histopathological alterations in cortex, striatum, hippocampus areas of brain. Male Wistar rats (200-220 g) were subjected to bilateral carotid artery occlusion for 30 min followed by reperfusion for 24 h to induce reperfusion (I/R) cerebral injury. Naringin (50, 100 mg/kg, i.p.) was administered for 7 days continuously before animals were subjected to ischemia reperfusion injury. Various behavioral tests [locomotor activity, neurological score (inclined beam test), transfer latency, resistance to lateral push] and biochemical parameters (lipid peroxidation, nitrite level, reduced glutathione, superoxide dismutase and catalase activity), mitochondrial enzyme dysfunctions (Complex I, II, III and IV) in cortex, striatum, hippocampus of brain and histopathological alterations were assessed subsequently. Seven days naringin (50 and 100 mg/kg) treatment significantly improved neurobehavioral alterations (improved locomotor activity, inclined beam walking and reduced resistance to lateral push, transfer latency) as compared to control ischemia reperfusion. Naringin (50 mg/kg and 100 mg/kg) treatment significantly attenuated oxidative damage as indicated by reduced lipid peroxidation, nitrite concentration, restored reduced glutathione and catalase activity and mitochondrial enzyme activities in cortex, striatum, cerebellum as compared to control (ischemia reperfusion) animals. In addition, naringin treatment significantly reversed histopathological alterations in cortex, striatum, hippocampus areas as compared to control (ischemia reperfusion). Present study suggests the protective effect of naringin and its therapeutic potential against ischemia reperfusion induced and related behavioral alterations in rats. PMID:19577560

  19. Phosphorylation and actin activation of brain myosin.

    PubMed Central

    Barylko, B; Sobieszek, A

    1983-01-01

    A method is described for obtaining brain myosin that shows significant actin activation, after phosphorylation with chicken gizzard myosin light chain kinase. Myosin with this activity could be obtained only via the initial purification of brain actomyosin. The latter complex, isolated by a method similar to that used for smooth muscle, contained actin, myosin, tropomyosin of the non-muscle type and another actin-binding protein of approximately 100,000 daltons. From the presence of a specific myosin light chain kinase and phosphatase in brain tissue it is suggested that the regulation of actin-myosin interaction operates via phosphorylation and dephosphorylation of myosin. Images Fig. 1. Fig. 3. PMID:11894951

  20. Phylogenetic origins of early alterations in brain region proportions.

    PubMed

    Charvet, Christine J; Sandoval, Alexis L; Striedter, Georg F

    2010-01-01

    Adult galliform birds (e.g. chickens) exhibit a relatively small telencephalon and a proportionately large optic tectum compared with parrots and songbirds. We previously examined the embryonic origins of these adult species differences and found that the optic tectum is larger in quail than in parakeets and songbirds at early stages of development, prior to tectal neurogenesis onset. The aim of this study was to determine whether a proportionately large presumptive tectum is a primitive condition within birds or a derived feature of quail and other galliform birds. To this end, we examined embryonic brains of several avian species (emus, parrots, songbirds, waterfowl, galliform birds), reptiles (3 lizard species, alligators, turtles) and a monotreme (platypuses). Brain region volumes were estimated from serial Nissl-stained sections. We found that the embryos of galliform birds and lizards exhibit a proportionally larger presumptive tectum than all the other examined species. The presumptive tectum of the platypus is unusually small. The most parsimonious interpretation of these data is that the expanded embryonic tectum of lizards and galliform birds is a derived feature in both of these taxonomic groups.

  1. [The child's brain: normal (unaltered) development and development altered by perinatal injury].

    PubMed

    Marín-Padilla, Miguel

    2013-09-01

    In this study we analyse some of the morphological and functional aspects of normal and altered development (the latter due to perinatal injury) in the child's brain. Both normal and altered development are developmental processes that progressively interconnect the different regions. The neuropathological development of subpial and periventricular haemorrhages, as well as that of white matter infarct, are analysed in detail. Any kind of brain damage causes a local lesion with possible remote repercussions. All the components (neurons, fibres, blood capillaries and neuroglias) of the affected region undergo alterations. Those that are destroyed are eliminated by the inflammatory process and those that survive are transformed. The pyramidal neurons with amputated apical dendrites are transformed and become stellate cells, the axonal terminals and those of the radial glial cells are regenerated and the region involved is reinnervated and revascularised with an altered morphology and function (altered local corticogenesis). The specific microvascular system of the grey matter protects its neurons from infarction of the white matter. Although it survives, the grey matter is left disconnected from the afferent and efferent fibres, amputated by the infarct with alterations affecting its morphology and possibly its functioning (altered local corticogenesis). Any local lesion can modify the morphological and functional development of remote regions that are functionally interconnected with it (altered remote corticogenesis). We suggest that any local brain injury can alter the morphology and functioning of the regions that are morphologically and functionally interconnected with it and thus end up affecting the child's neurological and psychological development. These changes can cross different regions of the brain (epileptic auras) and, if they eventually reach the motor region, will give rise to the motor storm that characterises epilepsy.

  2. Low HDL cholesterol, aggression and altered central serotonergic activity.

    PubMed

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P

    2000-03-01

    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

  3. Mutations in XPR1 cause primary familial brain calcification associated with altered phosphate export

    PubMed Central

    Legati, Andrea; Giovannini, Donatella; Nicolas, Gaël; López-Sánchez, Uriel; Quintáns, Beatriz; Oliveira, João; Sears, Renee L.; Marisa Ramos, Eliana; Spiteri, Elizabeth; Sobrido, María-Jesús; Carracedo, Ángel; Castro-Fernández, Cristina; Cubizolle, Stéphanie; Fogel, Brent L.; Goizet, Cyril; Jen, Joanna C.; Kirdlarp, Suppachok; Lang, Anthony E.; Miedzybrodzka, Zosia; Mitarnun, Witoon; Paucar, Martin; Paulson, Henry; Pariente, Jérémie; Richard, Anne-Claire; Salins, Naomi S.; Simpson, Sheila A.; Striano, Pasquale; Svenningsson, Per; Tison, François; Unni, Vivek K.; Vanakker, Olivier; Wessels, Marja W.; Wetchaphanphesat, Suppachok; Yang, Michele; Boller, Francois; Campion, Dominique; Hannequin, Didier; Sitbon, Marc; Geschwind, Daniel H.; Battini, Jean-Luc; Coppola, Giovanni

    2015-01-01

    Primary familial brain calcification (PFBC) is a neurological disease characterized by calcium phosphate deposits in the basal ganglia and other brain regions, thus far associated with SLC20A2, PDGFB, or PDGFRB mutations. We identified in multiple PFBC families mutations in XPR1, a gene encoding a retroviral receptor with phosphate export function. These mutations alter phosphate export, providing a direct evidence of an impact of XPR1 and phosphate homeostasis in PFBC. PMID:25938945

  4. Altered subcellular localization of ornithine decarboxylase in Alzheimer's disease brain

    SciTech Connect

    Nilsson, Tatjana . E-mail: Tatjana.Nilsson@ki.se; Bogdanovic, Nenad; Volkman, Inga; Winblad, Bengt; Folkesson, Ronnie; Benedikz, Eirikur

    2006-06-02

    The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD) brains. In frontal cortex and hippocampus of control cases, the most pronounced ODC immunoreactivity was found in the nucleus. In possible and definite AD the immunoreactivity had shifted to the cytoplasm. In cerebellum of control cases, ODC staining was found in a small portion of Purkinje cells, mostly in the nucleus. In AD, both possible and definite, the number of stained Purkinje cells increased significantly and immunoreactivity was shifted to the cytoplasm, even though it was still prominent in the nucleus. In conclusion, our study reveals an early shift of the ODC immunoreactivity in AD from the nuclear compartment towards the cytoplasm.

  5. Alterations in Sociability and Functional Brain Connectivity Caused by Early-Life Seizures is Reversed by Bumetanide

    PubMed Central

    Holmes, Gregory L.; Tian, Chengju; Hernan, Amanda E.; Flynn, Sean; Camp, Devon; Barry, Jeremy

    2015-01-01

    There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P) day 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

  6. Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide.

    PubMed

    Holmes, Gregory L; Tian, Chengju; Hernan, Amanda E; Flynn, Sean; Camp, Devon; Barry, Jeremy

    2015-05-01

    There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P)days 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-P25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

  7. Alterations in sociability and functional brain connectivity caused by early-life seizures are prevented by bumetanide.

    PubMed

    Holmes, Gregory L; Tian, Chengju; Hernan, Amanda E; Flynn, Sean; Camp, Devon; Barry, Jeremy

    2015-05-01

    There is a well-described association between infantile epilepsy and pervasive cognitive and behavioral deficits, including a high incidence of autism spectrum disorders. Despite the robustness of the relationship between early-life seizures and the development of autism, the pathophysiological mechanism by which this occurs has not been explored. As a result of increasing evidence that autism is a disorder of brain connectivity we hypothesized that early-life seizures would interrupt normal brain connectivity during brain maturation and result in an autistic phenotype. Normal rat pups underwent recurrent flurothyl-induced seizures from postnatal (P)days 5-14 and then tested, along with controls, for developmental alterations of development brain oscillatory activity from P18-P25. Specifically we wished to understand how normal changes in rhythmicity in and between brain regions change as a function of age and if this rhythmicity is altered or interrupted by early life seizures. In rat pups with early-life seizures, field recordings from dorsal and ventral hippocampus and prefrontal cortex demonstrated marked increase in coherence as well as a decrease in voltage correlation at all bandwidths compared to controls while there were minimal differences in total power and relative power spectral densities. Rats with early-life seizures had resulting impairment in the sociability and social novelty tests but demonstrated no evidence of increased activity or generalized anxiety as measured in the open field. In addition, rats with early-life seizures had lower seizure thresholds than controls, indicating long-standing alterations in the excitatory/inhibition balance. Bumetanide, a pharmacological agent that blocks the activity of NKCC1 and induces a significant shift of ECl toward more hyperpolarized values, administration at the time of the seizures precluded the subsequent abnormalities in coherence and voltage correlation and resulted in normal sociability and seizure

  8. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior

    PubMed Central

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2016-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning. PMID:26793069

  9. Central Thalamic Deep-Brain Stimulation Alters Striatal-Thalamic Connectivity in Cognitive Neural Behavior.

    PubMed

    Lin, Hui-Ching; Pan, Han-Chi; Lin, Sheng-Huang; Lo, Yu-Chun; Shen, Elise Ting-Hsin; Liao, Lun-De; Liao, Pei-Han; Chien, Yi-Wei; Liao, Kuei-Da; Jaw, Fu-Shan; Chu, Kai-Wen; Lai, Hsin-Yi; Chen, You-Yin

    2015-01-01

    Central thalamic deep brain stimulation (CT-DBS) has been proposed as an experimental therapeutic approach to produce consistent sustained regulation of forebrain arousal for several neurological diseases. We investigated local field potentials (LFPs) induced by CT-DBS from the thalamic central lateral nuclei (CL) and the striatum as potential biomarkers for the enhancement of lever-pressing skill learning. LFPs were simultaneously recorded from multiple sites in the CL, ventral striatum (Vstr), and dorsal striatum (Dstr). LFP oscillation power and functional connectivity were assessed and compared between the CT-DBS and sham control groups. The theta and alpha LFP oscillations were significantly increased in the CL and striatum in the CT-DBS group. Furthermore, interhemispheric coherences between bilateral CL and striatum were increased in the theta band. Additionally, enhancement of c-Fos activity, dopamine D2 receptor (Drd2), and α4-nicotinic acetylcholine receptor (α4-nAChR) occurred after CT-DBS treatment in the striatum and hippocampus. CT-DBS strengthened thalamic-striatal functional connectivity, which demonstrates that the inter-regional connectivity enhancement might contribute to synaptic plasticity in the striatum. Altered dopaminergic and cholinergic receptors resulted in modulation of striatal synaptic plasticity's ability to regulate downstream signaling cascades for higher brain functions of lever-pressing skill learning. PMID:26793069

  10. Altered Cerebellar White Matter Integrity in Patients with Mild Traumatic Brain Injury in the Acute Stage

    PubMed Central

    Wang, Zhongqiu; Wu, Wenzhong; Liu, Yongkang; Wang, Tianyao; Chen, Xiao; Zhang, Jianhua; Zhou, Guoxing; Chen, Rong

    2016-01-01

    Background and Purpose Imaging studies of traumatic brain injury demonstrate that the cerebellum is often affected. We aim to examine fractional anisotropy alteration in acute-phase mild traumatic brain injury patients in cerebellum-related white matter tracts. Materials and Methods This prospective study included 47 mild traumatic brain injury patients in the acute stage and 37 controls. MR imaging and neurocognitive tests were performed in patients within 7 days of injury. White matter integrity was examined by using diffusion tensor imaging. We used three approaches, tract-based spatial statistics, graphical-model-based multivariate analysis, and region-of-interest analysis, to detect altered cerebellar white matter integrity in mild traumatic brain injury patients. Results Results from three analysis methods were in accordance with each other, and suggested fractional anisotropy in the middle cerebellar peduncle and the pontine crossing tract was changed in the acute-phase mild traumatic brain injury patients, relative to controls (adjusted p-value < 0.05). Higher fractional anisotropy in the middle cerebellar peduncle was associated with worse performance in the fluid cognition composite (r = -0.289, p-value = 0.037). Conclusion Altered cerebellar fractional anisotropy in acute-phase mild traumatic brain injury patients is localized in specific regions and statistically associated with cognitive deficits detectable on neurocognitive testing. PMID:26967320

  11. Whole-brain activity mapping onto a zebrafish brain atlas

    PubMed Central

    Randlett, Owen; Wee, Caroline L.; Naumann, Eva A.; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E.; Portugues, Ruben; Lacoste, Alix M.B.; Riegler, Clemens; Engert, Florian; Schier, Alexander F.

    2015-01-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open source atlas containing molecular labels and anatomical region definitions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated-Extracellular signal-regulated kinase (ERK/MAPK) as a readout of neural activity, we have developed a system to create and contextualize whole brain maps of stimulus- and behavior-dependent neural activity. This MAP-Mapping (Mitogen Activated Protein kinase – Mapping) assay is technically simple, fast, inexpensive, and data analysis is completely automated. Since MAP-Mapping is performed on fish that are freely swimming, it is applicable to nearly any stimulus or behavior. We demonstrate the utility of our high-throughput approach using hunting/feeding, pharmacological, visual and noxious stimuli. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

  12. Whole-brain activity mapping onto a zebrafish brain atlas.

    PubMed

    Randlett, Owen; Wee, Caroline L; Naumann, Eva A; Nnaemeka, Onyeka; Schoppik, David; Fitzgerald, James E; Portugues, Ruben; Lacoste, Alix M B; Riegler, Clemens; Engert, Florian; Schier, Alexander F

    2015-11-01

    In order to localize the neural circuits involved in generating behaviors, it is necessary to assign activity onto anatomical maps of the nervous system. Using brain registration across hundreds of larval zebrafish, we have built an expandable open-source atlas containing molecular labels and definitions of anatomical regions, the Z-Brain. Using this platform and immunohistochemical detection of phosphorylated extracellular signal–regulated kinase (ERK) as a readout of neural activity, we have developed a system to create and contextualize whole-brain maps of stimulus- and behavior-dependent neural activity. This mitogen-activated protein kinase (MAP)-mapping assay is technically simple, and data analysis is completely automated. Because MAP-mapping is performed on freely swimming fish, it is applicable to studies of nearly any stimulus or behavior. Here we demonstrate our high-throughput approach using pharmacological, visual and noxious stimuli, as well as hunting and feeding. The resultant maps outline hundreds of areas associated with behaviors. PMID:26778924

  13. Persistent behavioral impairments and alterations of brain dopamine system after early postnatal administration of thimerosal in rats.

    PubMed

    Olczak, Mieszko; Duszczyk, Michalina; Mierzejewski, Pawel; Meyza, Ksenia; Majewska, Maria Dorota

    2011-09-30

    The neurotoxic organomercurial thimerosal (THIM), used for decades as vaccine preservative, is a suspected factor in the pathogenesis of some neurodevelopmental disorders. Previously we showed that neonatal administration of THIM at doses equivalent to those used in infant vaccines or higher, causes lasting alterations in the brain opioid system in rats. Here we investigated neonatal treatment with THIM (at doses 12, 240, 1440 and 3000 μg Hg/kg) on behaviors, which are characteristically altered in autism, such as locomotor activity, anxiety, social interactions, spatial learning, and on the brain dopaminergic system in Wistar rats of both sexes. Adult male and female rats, which were exposed to the entire range of THIM doses during the early postnatal life, manifested impairments of locomotor activity and increased anxiety/neophobia in the open field test. In animals of both sexes treated with the highest THIM dose, the frequency of prosocial interactions was reduced, while the frequency of asocial/antisocial interactions was increased in males, but decreased in females. Neonatal THIM treatment did not significantly affect spatial learning and memory. THIM-exposed rats also manifested reduced haloperidol-induced catalepsy, accompanied by a marked decline in the density of striatal D₂ receptors, measured by immunohistochemical staining, suggesting alterations to the brain dopaminergic system. Males were more sensitive than females to some neurodisruptive/neurotoxic actions of THIM. These data document that early postnatal THIM administration causes lasting neurobehavioral impairments and neurochemical alterations in the brain, dependent on dose and sex. If similar changes occur in THIM/mercurial-exposed children, they could contribute do neurodevelopmental disorders. PMID:21549155

  14. Surface visualization of electromagnetic brain activity.

    PubMed

    Badea, Alexandra; Kostopoulos, George K; Ioannides, Andreas A

    2003-08-15

    Advances in hardware and software have made possible the reconstruction of brain activity from non-invasive electrophysiological measurements over a large part of the brain. The appreciation of the information content in the data is enhanced when relevant anatomical detail is also available for visualization. Different neuroscientific questions give rise to different requirements for optimal superposition of structure and function. Most available software deal with scalar measures of activity, especially hemodynamic changes. In contrast, the electrophysiological observables are generated by electrical activity, which depends on the synchrony of neuronal assemblies and the geometry of the local cortical surface. We describe methods for segmentation and visualization of spatio-temporal brain activity, which allow the interplay of geometry and scalar as well as vector properties of the current density directly in the representations. The utility of these methods is demonstrated through displays of tomographic reconstructions of early sensory processing in the somatosensory and visual modality extracted from magnetoencephalography (MEG) data. The activation course characteristic to a specific area could be observed as current density or statistical maps independently and/or contrasted to the activity in other areas or the whole brain. MEG and functional magnetic resonance imaging (fMRI) activations were simultaneously visualized. Integrating and visualizing complementary functional data into a single environment helps evaluating analysis and understanding structure/function relationships in normal and diseased brain.

  15. Evidence for centrophenoxine as a protective drug in aluminium induced behavioral and biochemical alteration in rat brain.

    PubMed

    Nehru, Bimla; Bhalla, Punita; Garg, Aarti

    2006-10-01

    Potential use of various nootropic drugs have been a burning area of research on account of various physical and chemical insult in brain under different toxicological conditions. One of the nootropic drug centrophenoxine, also known as an anti-aging drug has been exploited in the present experiment under aluminium toxic conditions. Aluminium was administered by oral gavage at a dose level of 100 mg/Kg x b x wt/day for a period of six weeks. To elucidate the region specific response, study was carried out in two different regions of brain namely cerebrum and cerebellum. Following aluminium exposure, a significant decrease in the activities of enzymes namely Hexokinase, Lactate dehydrogenase, Succinate dehydrogenase, Mg(2+) dependent ATPase was observed in both the regions. Moreover, the activity of acetylcholinesterase was also reported to be significantly decreased. Post-treatment with centrophenoxine was able to restore the altered enzyme activities and the effect was observed in both the regions of brain although the activity of lactate dehydrogenase and acetylcholinesterase did not register significant increase in the cerebellum region. Further, centrophenoxine was able to improve the altered short-term memory and cognitive performance resulted from aluminium exposure. From the present study, it can be concluded that centrophenoxine has a potential and can be exploited in other toxicological conditions also.

  16. Repeated forced swimming impairs prepulse inhibition and alters brain-derived neurotrophic factor and astroglial parameters in rats.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Müller, Liz Girardi; Viana, Alice Fialho; Hertzfeldt, Vivian; Lunardi, Paula Santana; Zanotto, Caroline; Nardin, Patrícia; Ravazzolo, Ana Paula; Rates, Stela Maris Kuze; Gonçalves, Carlos-Alberto

    2015-01-01

    Glutamate perturbations and altered neurotrophin levels have been strongly associated with the neurobiology of neuropsychiatric disorders. Environmental stress is a risk factor for mood disorders, disrupting glutamatergic activity in astrocytes in addition to cognitive behaviours. Despite the negative impact of stress-induced neuropsychiatric disorders on public health, the molecular mechanisms underlying the response of the brain to stress has yet to be fully elucidated. Exposure to repeated swimming has proven useful for evaluating the loss of cognitive function after pharmacological and behavioural interventions, but its effect on glutamate function has yet to be fully explored. In the present study, rats previously exposed to repeated forced swimming were evaluated using the novel object recognition test, object location test and prepulse inhibition (PPI) test. In addition, quantification of brain-derived neurotrophic factor (BDNF) mRNA expression and protein levels, glutamate uptake, glutathione, S100B, GluN1 subunit of N-methyl-D-aspartate receptor and calmodulin were evaluated in the frontal cortex and hippocampus after various swimming time points. We found that swimming stress selectively impaired PPI but did not affect memory recognition. Swimming stress altered the frontal cortical and hippocampal BDNF expression and the activity of hippocampal astrocytes by reducing hippocampal glutamate uptake and enhancing glutathione content in a time-dependent manner. In conclusion, these data support the assumption that astrocytes may regulate the activity of brain structures related to cognition in a manner that alters complex behaviours. Moreover, they provide new insight regarding the dynamics immediately after an aversive experience, such as after behavioural despair induction, and suggest that forced swimming can be employed to study altered glutamatergic activity and PPI disruption in rodents. PMID:25444867

  17. Repeated forced swimming impairs prepulse inhibition and alters brain-derived neurotrophic factor and astroglial parameters in rats.

    PubMed

    Borsoi, Milene; Antonio, Camila Boque; Müller, Liz Girardi; Viana, Alice Fialho; Hertzfeldt, Vivian; Lunardi, Paula Santana; Zanotto, Caroline; Nardin, Patrícia; Ravazzolo, Ana Paula; Rates, Stela Maris Kuze; Gonçalves, Carlos-Alberto

    2015-01-01

    Glutamate perturbations and altered neurotrophin levels have been strongly associated with the neurobiology of neuropsychiatric disorders. Environmental stress is a risk factor for mood disorders, disrupting glutamatergic activity in astrocytes in addition to cognitive behaviours. Despite the negative impact of stress-induced neuropsychiatric disorders on public health, the molecular mechanisms underlying the response of the brain to stress has yet to be fully elucidated. Exposure to repeated swimming has proven useful for evaluating the loss of cognitive function after pharmacological and behavioural interventions, but its effect on glutamate function has yet to be fully explored. In the present study, rats previously exposed to repeated forced swimming were evaluated using the novel object recognition test, object location test and prepulse inhibition (PPI) test. In addition, quantification of brain-derived neurotrophic factor (BDNF) mRNA expression and protein levels, glutamate uptake, glutathione, S100B, GluN1 subunit of N-methyl-D-aspartate receptor and calmodulin were evaluated in the frontal cortex and hippocampus after various swimming time points. We found that swimming stress selectively impaired PPI but did not affect memory recognition. Swimming stress altered the frontal cortical and hippocampal BDNF expression and the activity of hippocampal astrocytes by reducing hippocampal glutamate uptake and enhancing glutathione content in a time-dependent manner. In conclusion, these data support the assumption that astrocytes may regulate the activity of brain structures related to cognition in a manner that alters complex behaviours. Moreover, they provide new insight regarding the dynamics immediately after an aversive experience, such as after behavioural despair induction, and suggest that forced swimming can be employed to study altered glutamatergic activity and PPI disruption in rodents.

  18. In situ biospectroscopic investigation of rapid ischemic and postmortem induced biochemical alterations in the rat brain.

    PubMed

    Hackett, Mark J; Britz, Carter J; Paterson, Phyllis G; Nichol, Helen; Pickering, Ingrid J; George, Graham N

    2015-02-18

    Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into

  19. Perinatal Iron and Copper Deficiencies Alter Neonatal Rat Circulating and Brain Thyroid Hormone Concentrations

    PubMed Central

    Bastian, Thomas W.; Prohaska, Joseph R.; Georgieff, Michael K.; Anderson, Grant W.

    2010-01-01

    Copper (Cu), iron (Fe), and iodine/thyroid hormone (TH) deficiencies lead to similar defects in late brain development, suggesting that these micronutrient deficiencies share a common mechanism contributing to the observed derangements. Previous studies in rodents (postweanling and adult) and humans (adolescent and adult) indicate that Cu and Fe deficiencies affect the hypothalamic-pituitary-thyroid axis, leading to altered TH status. Importantly, however, relationships between Fe and Cu deficiencies and thyroidal status have not been assessed in the most vulnerable population, the developing fetus/neonate. We hypothesized that Cu and Fe deficiencies reduce circulating and brain TH levels during development, contributing to the defects in brain development associated with these deficiencies. To test this hypothesis, pregnant rat dams were rendered Cu deficient (CuD), FeD, or TH deficient from early gestation through weaning. Serum thyroxine (T4) and triiodothyronine (T3), and brain T3 levels, were subsequently measured in postnatal d 12 (P12) pups. Cu deficiency reduced serum total T3 by 48%, serum total T4 by 21%, and whole-brain T3 by 10% at P12. Fe deficiency reduced serum total T3 by 43%, serum total T4 by 67%, and whole-brain T3 by 25% at P12. Brain mRNA analysis revealed that expression of several TH-responsive genes were altered in CuD or FeD neonates, suggesting that reduced TH concentrations were sensed by the FeD and CuD neonatal brain. These results indicate that at least some of the brain defects associated with neonatal Fe and Cu deficiencies are mediated through reductions in circulating and brain TH levels. PMID:20573724

  20. Physical exercise improves brain cortex and cerebellum mitochondrial bioenergetics and alters apoptotic, dynamic and auto(mito)phagy markers.

    PubMed

    Marques-Aleixo, I; Santos-Alves, E; Balça, M M; Rizo-Roca, D; Moreira, P I; Oliveira, P J; Magalhães, J; Ascensão, A

    2015-08-20

    We here investigate the effects of two exercise modalities (endurance treadmill training-TM and voluntary free-wheel activity-FW) on the brain cortex and cerebellum mitochondrial bioenergetics, permeability transition pore (mPTP), oxidative stress, as well as on proteins involved in mitochondrial biogenesis, apoptosis, and quality control. Eighteen male rats were assigned to sedentary-SED, TM and FW groups. Behavioral alterations and ex vivo brain mitochondrial function endpoints were assessed. Proteins involved in oxidative phosphorylation (OXPHOS, including the adenine nucleotide translocator), oxidative stress markers and regulatory proteins (SIRT3, p66shc, UCP2, carbonyls, MDA, -SH, aconitase, Mn-SOD), as well as proteins involved in mitochondrial biogenesis (PGC1α, TFAM) were evaluated. Apoptotic signaling was measured through quantifying caspase 3, 8 and 9-like activities, Bax, Bcl2, CypD, and cofilin expression. Mitochondrial dynamics (Mfn1/2, OPA1 and DRP1) and auto(mito)phagy (LC3II, Beclin1, Pink1, Parkin, p62)-related proteins were also measured by Western blotting. Only the TM exercise group showed increased spontaneous alternation and exploratory activity. Both exercise regimens improved mitochondrial respiratory activity, increased OXPHOS complexes I, III and V subunits in both brain subareas and decreased oxidative stress markers. Increased resistance to mPTP and decreased apoptotic signaling were observed in the brain cortex from TM and in the cerebellum from TM and FW groups. Also, exercise increased the expression of proteins involved in mitochondrial biogenesis, autophagy and fusion, simultaneous with decreased expression of mitochondrial fission-related protein DRP1. In conclusion, physical exercise improves brain cortex and cerebellum mitochondrial function, decreasing oxidative stress and apoptotic related markers. It is also possible that favorable alterations in mitochondrial biogenesis, dynamics and autophagy signaling induced by exercise

  1. GH and Pituitary Hormone Alterations After Traumatic Brain Injury.

    PubMed

    Karaca, Züleyha; Tanrıverdi, Fatih; Ünlühızarcı, Kürşad; Kelestimur, Fahrettin

    2016-01-01

    Traumatic brain injury (TBI) is a crucially important public health problem around the world, which gives rise to increased mortality and is the leading cause of physical and psychological disability in young adults, in particular. Pituitary dysfunction due to TBI was first described 95 years ago. However, until recently, only a few papers have been published in the literature and for this reason, TBI-induced hypopituitarism has been neglected for a long time. Recent studies have revealed that TBI is one of the leading causes of hypopituitarism. TBI which causes hypopituitarism may be characterized by a single head injury such as from a traffic accident or by chronic repetitive head trauma as seen in combative sports including boxing, kickboxing, and football. Vascular damage, hypoxic insult, direct trauma, genetic predisposition, autoimmunity, and neuroinflammatory changes may have a role in the development of hypopituitarism after TBI. Because of the exceptional structure of the hypothalamo-pituitary vasculature and the special anatomic location of anterior pituitary cells, GH is the most commonly lost hormone after TBI, and the frequency of isolated GHD is considerably high. TBI-induced pituitary dysfunction remains undiagnosed and therefore untreated in most patients because of the nonspecific and subtle clinical manifestations of hypopituitarism. Treatment of TBI-induced hypopituitarism depends on the deficient anterior pituitary hormones. GH replacement therapy has some beneficial effects on metabolic parameters and neurocognitive dysfunction. Patients with TBI without neuroendocrine changes and those with TBI-induced hypopituitarism share the same clinical manifestations, such as attention deficits, impulsion impairment, depression, sleep abnormalities, and cognitive disorders. For this reason, TBI-induced hypopituitarism may be neglected in TBI victims and it would be expected that underlying hypopituitarism would aggravate the clinical picture of TBI

  2. The interconnectivity of mind, brain, and behavior in altered states of consciousness: focus on shamanism.

    PubMed

    Wright, P A

    1995-07-01

    This paper examines possible interconnections between mind, brain, and behavior in the area of shamanism and altered states of consciousness. It offers a neurophysiological theory of shamanic altered states of consciousness that integrates theories by Mandell, Persinger, Prince, Winkelman, and Wright. Topics include the shamanic call and temporal lobe phenomena, possible neurological correlates of shamanic ecstasy, and the neurophysiological roles of endorphins, plant substances, and genetic factors in shamanic altered states of consciousness. The difficulty of developing such a theory because of the complexity of human physiology and psychological experience and because of the paucity of neurophysiological data from the field is acknowledged.

  3. Nanotools for Neuroscience and Brain Activity Mapping

    PubMed Central

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

    2013-01-01

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

  4. Altered processing of sweet taste in the brain of diet soda drinkers

    PubMed Central

    Green, Erin; Murphy, Claire

    2012-01-01

    Artificially sweetened beverage consumption has been linked to obesity, and it has been hypothesized that considerable exposure to nonnutritive sweeteners may be associated with impaired energy regulation. The reward system plays an integral role in modulating energy intake, but little is known about whether habitual use of artificial sweetener (i.e., diet soda consumption) may be related to altered reward processing of sweet taste in the brain. To investigate this, we examined fMRI response after a 12-hour fast to sucrose (a nutritive sweetener) and saccharin (a nonnutritive sweetener) during hedonic evaluation in young adult diet soda drinkers and non-diet soda drinkers. Diet soda drinkers demonstrated greater activation to sweet taste in the dopaminergic midbrain (including ventral tegmental area) and right amygdala. Saccharin elicited a greater response in the right orbitofrontal cortex (Brodmann Area 47) relative to sucrose in non-diet soda drinkers. There was no difference in fMRI response to the nutritive or nonnutritive sweetener for diet soda drinkers. Within the diet soda drinkers, fMRI activation of the right caudate head in response to saccharin was negatively associated with the amount of diet sodas consumed per week; individuals who consumed a greater number of diet sodas had reduced caudate head activation. These findings suggest that there are alterations in reward processing of sweet taste in individuals who regularly consume diet soda, and this is associated with the degree of consumption. These findings may provide some insight into the link between diet soda consumption and obesity. PMID:22583859

  5. Early life stress affects limited regional brain activity in depression.

    PubMed

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-05-03

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients.

  6. Early life stress affects limited regional brain activity in depression

    PubMed Central

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-01-01

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients. PMID:27138376

  7. Heritability of working memory brain activation.

    PubMed

    Blokland, Gabriëlla A M; McMahon, Katie L; Thompson, Paul M; Martin, Nicholas G; de Zubicaray, Greig I; Wright, Margaret J

    2011-07-27

    Although key to understanding individual variation in task-related brain activation, the genetic contribution to these individual differences remains largely unknown. Here we report voxel-by-voxel genetic model fitting in a large sample of 319 healthy, young adult, human identical and fraternal twins (mean ± SD age, 23.6 ± 1.8 years) who performed an n-back working memory task during functional magnetic resonance imaging (fMRI) at a high magnetic field (4 tesla). Patterns of task-related brain response (BOLD signal difference of 2-back minus 0-back) were significantly heritable, with the highest estimates (40-65%) in the inferior, middle, and superior frontal gyri, left supplementary motor area, precentral and postcentral gyri, middle cingulate cortex, superior medial gyrus, angular gyrus, superior parietal lobule, including precuneus, and superior occipital gyri. Furthermore, high test-retest reliability for a subsample of 40 twins indicates that nongenetic variance in the fMRI brain response is largely due to unique environmental influences rather than measurement error. Individual variations in activation of the working memory network are therefore significantly influenced by genetic factors. By establishing the heritability of cognitive brain function in a large sample that affords good statistical power, and using voxel-by-voxel analyses, this study provides the necessary evidence for task-related brain activation to be considered as an endophenotype for psychiatric or neurological disorders, and represents a substantial new contribution to the field of neuroimaging genetics. These genetic brain maps should facilitate discovery of gene variants influencing cognitive brain function through genome-wide association studies, potentially opening up new avenues in the treatment of brain disorders. PMID:21795540

  8. *C5a/CD88 signaling alters blood-brain barrier integrity in lupus through NFκb

    PubMed Central

    Jacob, Alexander; Hack, Bradley; Chen, Peili; Quigg, Richard J.; Alexander, Jessy J.

    2011-01-01

    Inflammation is a key factor in a number of neurodegenerative diseases including systemic lupus erythematosus (SLE). The complement system is an important mechanism in initiating and amplifying inflammation. Our recent studies demonstrate that C5a, a protein fragment generated during complement activation could alter the blood-brain barrier (BBB) integrity, and thereby disturb the brain microenvironment. To understand the mechanism by which this occurs, we examined the effects of C5a on apoptosis, translocation of nuclear factor-κB (NFκb) and the expression of Iκbα, MAPK, CREB and TJ protein, zona occludens (ZO-1) in mouse brain endothelial cells. Apoptosis was examined by DNA laddering and caspase-3 activity and the distribution of the ZO-1 and the p65 subunit of NFκB were determined by immunofluorescence. Inhibition of CD88 reduced translocation of NFκb into the nucleus, altered ZO-1 at the interfaces of neighboring cells, decreased caspase-3 activity and prevented apoptosis in these cells. Our results indicate that signaling through CD88 regulates the BBB in a NFκb dependent manner. These studies suggest that the C5a receptor, CD88 is a promising therapeutic target that will reduce NFκb signaling cascades in inflammatory settings. PMID:21929539

  9. Silver and titanium dioxide nanoparticles alter oxidative/inflammatory response and renin-angiotensin system in brain.

    PubMed

    Krawczyńska, Agata; Dziendzikowska, Katarzyna; Gromadzka-Ostrowska, Joanna; Lankoff, Anna; Herman, Andrzej Przemysław; Oczkowski, Michał; Królikowski, Tomasz; Wilczak, Jacek; Wojewódzka, Maria; Kruszewski, Marcin

    2015-11-01

    The study was designed to examine the effects of silver AgNPs, 20 nm) and titanium dioxide (Aeroxide(®) P25 TiO2NPs, 21 nm) nanoparticles on brain oxidative stress parameters, its antioxidant potential and brain renin-angiotensin system (RAS) in vivo. The analysis was performed 28 days after single dose injection of TiO2NPs and AgNPs (10 or 5 mg/kg body weight, respectively). The AgNPs, but not TiO2NPs, administration resulted in decreased lipid and cholesterol peroxidation. Antioxidant enzymes gene expression and/or activity were changed differently for TiO2NPs and AgNPs group. The TiO2NPs decreased aromatase gene expression, and glutathione peroxidase and reductase activities. In AgNPs group the sodium dismutase 1 and glutathione reductase mRNA levels were decreased as opposed to their activities. Both NPs altered the expression of brain RAS genes (angiotensinogen, renin, angiotensin I converting enzyme 1 and 2), but only TiO2NPs caused similar changes on protein level. The expression of amyloid beta precursor protein gene was not altered by any kind of injected NPs. The TiO2NPs were more potent modulator of gene expression in the brain than AgNPs, despite the two times lower dosage. These results suggest that AgNPs and TiO2NPs exposure may modulate the brain function, but with different strength.

  10. Altered Neuroinflammation and Behavior after Traumatic Brain Injury in a Mouse Model of Alzheimer's Disease.

    PubMed

    Kokiko-Cochran, Olga; Ransohoff, Lena; Veenstra, Mike; Lee, Sungho; Saber, Maha; Sikora, Matt; Teknipp, Ryan; Xu, Guixiang; Bemiller, Shane; Wilson, Gina; Crish, Samuel; Bhaskar, Kiran; Lee, Yu-Shang; Ransohoff, Richard M; Lamb, Bruce T

    2016-04-01

    Traumatic brain injury (TBI) has acute and chronic sequelae, including an increased risk for the development of Alzheimer's disease (AD). TBI-associated neuroinflammation is characterized by activation of brain-resident microglia and infiltration of monocytes; however, recent studies have implicated beta-amyloid as a major manipulator of the inflammatory response. To examine neuroinflammation after TBI and development of AD-like features, these studies examined the effects of TBI in the presence and absence of beta-amyloid. The R1.40 mouse model of cerebral amyloidosis was used, with a focus on time points well before robust AD pathologies. Unexpectedly, in R1.40 mice, the acute neuroinflammatory response to TBI was strikingly muted, with reduced numbers of CNS myeloid cells acquiring a macrophage phenotype and decreased expression of inflammatory cytokines. At chronic time points, macrophage activation substantially declined in non-Tg TBI mice; however, it was relatively unchanged in R1.40 TBI mice. The persistent inflammatory response coincided with significant tissue loss between 3 and 120 days post-injury in R1.40 TBI mice, which was not observed in non-Tg TBI mice. Surprisingly, inflammatory cytokine expression was enhanced in R1.40 mice compared with non-Tg mice, regardless of injury group. Although R1.40 TBI mice demonstrated task-specific deficits in cognition, overall functional recovery was similar to non-Tg TBI mice. These findings suggest that accumulating beta-amyloid leads to an altered post-injury macrophage response at acute and chronic time points. Together, these studies emphasize the role of post-injury neuroinflammation in regulating long-term sequelae after TBI and also support recent studies implicating beta-amyloid as an immunomodulator.

  11. Thinking Patterns, Brain Activity and Strategy Choice

    NASA Astrophysics Data System (ADS)

    Nishimura, Kazuo; Okada, Akira; Inagawa, Michiyo; Tobinaga, Yoshikazu

    2012-03-01

    In this study we analyzed the relationship between thinking patterns, behavior and associated brain activity. Subjects completed a self-report assessing whether they could voluntarily stop thinking or not, and were then divided into two groups: those with the ability to stop thinking and those without. We measured subjects' brain activity using magnetoencephalography while giving them a series of tasks intended to encourage or discourage spontaneous thinking. Our findings revealed differences between the two groups in terms of which portions of the brain were active during the two types of task. A second questionnaire confirmed a relationship between the ability to stop thinking and strategy choices in a dilemma game. We found that subjects without the ability to stop thinking had a tendency to choose cooperative behavior.

  12. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling

    PubMed Central

    Hagmann, Patric; Deco, Gustavo

    2015-01-01

    How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model’s prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information. PMID:26317432

  13. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling.

    PubMed

    Ponce-Alvarez, Adrián; He, Biyu J; Hagmann, Patric; Deco, Gustavo

    2015-08-01

    How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model's prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information.

  14. Altered alpha brain oscillations during multistable perception in schizophrenia.

    PubMed

    Basar-Eroglu, Canan; Mathes, Birgit; Khalaidovski, Ksenia; Brand, Andreas; Schmiedt-Fehr, Christina

    2016-05-01

    Schizophrenia is a complex mental disorder with impairments in integrating sensory and cognitive functions, leading to severe problems in coherent perception. This impairment might be accelerated during multistable perception. Multistable perception is a phenomenon, where a visual pattern gives rise to at least two different perceptual representations. We addressed this issue by assessing event-related alpha oscillations during continuous viewing of an ambiguous and unambiguous control stimulus. Perceptual reversals were indicated by a manual response, allowing differentiation between phases of reversion and non-reversion (that is perceptual stability) in both tasks. During the ambiguous task, patients and controls showed a comparable number of perceptual reversals. Alpha amplitudes in patients were larger in non-reversion phases, accompanied by a stronger decrease of alpha activity preceding the perceptual reversal. This group difference was pronounced for lower alpha activity and not apparent during the unambiguous task. This indicates that ambiguous perception taps into the specific deficits that patients experience in maintaining coherent perception. Given that top-down influences in generating a meaningful percept seems to be low in patients, they appear more dependent on sensory information. Similar, bottom-up mechanisms might be more important in triggering perceptual reversals in patients than in controls.

  15. Listening to the Human Voice Alters Sensorimotor Brain Rhythms

    PubMed Central

    Lévêque, Yohana; Schön, Daniele

    2013-01-01

    While neuronal desynchronization in the mu (≈10Hz) and beta (≈20Hz) frequency bands has long been known to be an EEG index of sensorimotor activity, this method has rarely been employed to study auditory perception. In the present study, we measured mu and beta event-related desynchronisation (ERD) while participants were asked to listen to vocal and triangle-wave melodies and to sing them back. Results showed that mu and beta ERD began earlier and were stronger when listening to vocal compared to non-vocal melodies. Interestingly, this humanness effect was stronger for less accurate singers. These results show that voice perception favors an early involvement of motor representations. PMID:24265836

  16. Maternal vitamin D depletion alters neurogenesis in the developing rat brain.

    PubMed

    Cui, Xiaoying; McGrath, John J; Burne, Thomas H J; Mackay-Sim, Alan; Eyles, Darryl W

    2007-06-01

    Evidence is accumulating that normal levels of vitamin D are important for brain development. Vitamin D acts as an anti-proliferative agent in a wide variety of tissues and developmental vitamin D (DVD) deficiency has been shown to alter brain structure and function. The aim of this study was to investigate the effect of DVD deficiency on neuroprogenitor formation in the neonatal brain. We show that DVD deficiency increased the number of neurospheres formed in cultures from the neonatal subventricular zone. Exogenous vitamin D added to the culture medium reduced neurosphere number in control but not DVD cultures. We show the receptor for vitamin D is concentrated in the subventricular zone and is also present in cultured neurospheres prepared from this region. These results show that vitamin D can regulate cell proliferation in the developing brain. Further studies are warranted to examine the underlying mechanisms for these findings. PMID:17467223

  17. Cortisol alters reward processing in the human brain.

    PubMed

    Kinner, Valerie L; Wolf, Oliver T; Merz, Christian J

    2016-08-01

    Dysfunctional reward processing is known to play a central role for the development of psychiatric disorders. Glucocorticoids that are secreted in response to stress have been shown to attenuate reward sensitivity and thereby might promote the onset of psychopathology. However, the underlying neurobiological mechanisms mediating stress hormone effects on reward processing as well as potential sex differences remain elusive. In this neuroimaging study, we administered 30mg cortisol or a placebo to 30 men and 30 women and subsequently tested them in the Monetary Incentive Delay Task. Cortisol attenuated anticipatory neural responses to a verbal and a monetary reward in the left pallidum and the right anterior parahippocampal gyrus. Furthermore, in men, activation in the amygdala, the precuneus, the anterior cingulate, and in hippocampal regions was reduced under cortisol, whereas in cortisol-treated women a signal increase was observed in these regions. Behavioral performance also indicated that reward learning in men is impaired under high cortisol concentrations, while it is augmented in women. These findings illustrate that the stress hormone cortisol substantially diminishes reward anticipation and provide first evidence that cortisol effects on the neural reward system are sensitive to sex differences, which might translate into different vulnerabilities for psychiatric disorders.

  18. Chronic noise stress-induced alterations of glutamate and gamma-aminobutyric acid and their metabolism in the rat brain.

    PubMed

    Kazi, Amajad Iqbal; Oommen, Anna

    2014-01-01

    Chronic stress induces neurochemical changes that include neurotransmitter imbalance in the brain. Noise is an environmental factor inducing stress. Chronic noise stress affects monoamine neurotransmitter systems in the central nervous system. The effect on other excitatory and inhibitory neurotransmitter systems is not known. The aim was to study the role of chronic noise stress on the glutamatergic and gamma-aminobutyric acid (GABA)ergic systems of the brain. Female Wistar rats (155 ± 5 g) were unintentionally exposed to noise due to construction (75-95 db, 3-4 hours/day, 5 days a week for 7-8 weeks) in the vicinity of the animal care facility. Glutamate/GABA levels and their metabolic enzymes were evaluated in different rat brain regions (cortex, hippocampus, striatum, and cerebellum) and compared with age and gender matched nonexposed rats. Chronic noise stress decreased glutamate levels and glutaminase activity 27% and 33% in the cortex, 15% and 24% in the cerebellum. Glutamate levels increased 10% in the hippocampus, 28% in striatum and glutaminase activity 15% in striatum. Glutamine synthetase activity increased significantly in all brain regions studied, that is, cortex, hippocampus, striatum, and cerebellum (P < 0.05). Noise stress-increased GABA levels and glutamate alpha decarboxylase activity 20% and 45% in the cortex, 13% and 28% in the hippocampus respectively. GABA levels and glutamate alpha decarboxylase activity decreased 15% and 14%, respectively in the striatum. GABA transaminase activity was significantly reduced in the cortex (55%), hippocampus (17%), and cerebellum (33%). Chronic noise stress differentially affected glutamatergic and GABAergic neurotransmitter systems in the rat brain, which may alter glutamate and GABA neurotransmission.

  19. Growth-Related Neural Reorganization and the Autism Phenotype: A Test of the Hypothesis that Altered Brain Growth Leads to Altered Connectivity

    ERIC Educational Resources Information Center

    Lewis, John D.; Elman, Jeffrey L.

    2008-01-01

    Theoretical considerations, and findings from computational modeling, comparative neuroanatomy and developmental neuroscience, motivate the hypothesis that a deviant brain growth trajectory will lead to deviant patterns of change in cortico-cortical connectivity. Differences in brain size during development will alter the relative cost and…

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

    PubMed Central

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

    2016-01-01

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

  1. Radiation-Induced Alterations in Mouse Brain Development Characterized by Magnetic Resonance Imaging

    SciTech Connect

    Gazdzinski, Lisa M.; Cormier, Kyle; Lu, Fred G.; Lerch, Jason P.; Wong, C. Shun; Nieman, Brian J.

    2012-12-01

    Purpose: The purpose of this study was to identify regions of altered development in the mouse brain after cranial irradiation using longitudinal magnetic resonance imaging (MRI). Methods and Materials: Female C57Bl/6 mice received a whole-brain radiation dose of 7 Gy at an infant-equivalent age of 2.5 weeks. MRI was performed before irradiation and at 3 time points following irradiation. Deformation-based morphometry was used to quantify volume and growth rate changes following irradiation. Results: Widespread developmental deficits were observed in both white and gray matter regions following irradiation. Most of the affected brain regions suffered an initial volume deficit followed by growth at a normal rate, remaining smaller in irradiated brains compared with controls at all time points examined. The one exception was the olfactory bulb, which in addition to an early volume deficit, grew at a slower rate thereafter, resulting in a progressive volume deficit relative to controls. Immunohistochemical assessment revealed demyelination in white matter and loss of neural progenitor cells in the subgranular zone of the dentate gyrus and subventricular zone. Conclusions: MRI can detect regional differences in neuroanatomy and brain growth after whole-brain irradiation in the developing mouse. Developmental deficits in neuroanatomy persist, or even progress, and may serve as useful markers of late effects in mouse models. The high-throughput evaluation of brain development enabled by these methods may allow testing of strategies to mitigate late effects after pediatric cranial irradiation.

  2. Maternal vitamin D deficiency alters fetal brain development in the BALB/c mouse.

    PubMed

    Hawes, Jazmin E; Tesic, Dijana; Whitehouse, Andrew J; Zosky, Graeme R; Smith, Jeremy T; Wyrwoll, Caitlin S

    2015-06-01

    Prenatal exposure to vitamin D is thought to be critical for optimal fetal neurodevelopment, yet vitamin D deficiency is apparent in a growing proportion of pregnant women. The aim of this study was to determine whether a mouse model of vitamin D-deficiency alters fetal neurodevelopment. Female BALB/c mice were placed on either a vitamin D control (2,195 IU/kg) or deficient (0 IU/kg) diet for 5 weeks prior to and during pregnancy. Fetal brains were collected at embryonic day (E) 14.5 or E17.5 for morphological and gene expression analysis. Vitamin D deficiency during pregnancy reduced fetal crown-rump length and head size. Moreover, lateral ventricle volume was reduced in vitamin D-deficient foetuses. Expression of neurotrophin genes brain-derived neurotrophic factor (Bdnf) and transforming growth factor-β1 (Tgf-β1) was altered, with Bdnf reduced at E14.5 and increased at E17.5 following vitamin D deficiency. Brain expression of forkhead box protein P2 (Foxp2), a gene known to be important in human speech and language, was also altered. Importantly, Foxp2 immunoreactive cells in the developing cortex were reduced in vitamin D-deficient female foetuses. At E17.5, brain tyrosine hydroxylase (TH) gene expression was reduced in females, as was TH protein localization (to identify dopamine neurons) in the substantia nigra of vitamin D-deficient female foetuses. Overall, we show that prenatal vitamin D-deficiency leads to alterations in fetal mouse brain morphology and genes related to neuronal survival, speech and language development, and dopamine synthesis. Vitamin D appears to play an important role in mouse neurodevelopment. PMID:25753408

  3. Estrogen alters the diurnal rhythm of alpha 1-adrenergic receptor densities in selected brain regions

    SciTech Connect

    Weiland, N.G.; Wise, P.M.

    1987-11-01

    Norepinephrine regulates the proestrous and estradiol-induced LH surge by binding to alpha 1-adrenergic receptors. The density of alpha 1-receptors may be regulated by estradiol, photoperiod, and noradrenergic neuronal activity. We wished to determine whether alpha 1-receptors exhibit a diurnal rhythm in ovariectomized and/or estradiol-treated female rats, whether estradiol regulates alpha 1-receptors in those areas of brain involved with LH secretion and/or sexual behavior, and whether the concentrations of alpha-receptors vary inversely relative to previously reported norepinephrine turnover patterns. Young female rats, maintained on a 14:10 light-dark cycle were ovariectomized. One week later, half of them were outfitted sc with Silastic capsules containing estradiol. Groups of animals were decapitated 2 days later at 0300, 1000, 1300, 1500, 1800, and 2300 h. Brains were removed, frozen, and sectioned at 20 micron. Sections were incubated with (/sup 3/H)prazosin in Tris-HCl buffer, washed, dried, and exposed to LKB Ultrofilm. The densities of alpha 1-receptors were quantitated using a computerized image analysis system. In ovariectomized rats, the density of alpha 1-receptors exhibited a diurnal rhythm in the suprachiasmatic nucleus (SCN), medial preoptic nucleus (MPN), and pineal gland. In SCN and MPN, receptor concentrations were lowest during the middle of the day and rose to peak levels at 1800 h. In the pineal gland, the density of alpha 1-receptors was lowest at middark phase, rose to peak levels before lights on, and remained elevated during the day. Estradiol suppressed the density of alpha 1 binding sites in the SCN, MPN, median eminence, ventromedial nucleus, and the pineal gland but had no effect on the lateral septum. Estrogen treatment altered the rhythm of receptor densities in MPN, median eminence, and the pineal gland.

  4. Alterations induced by gestational stress in brain morphology and behaviour of the offspring.

    PubMed

    Weinstock, M

    2001-12-01

    Retrospective studies in humans suggest that chronic maternal stress during pregnancy, associated with raised plasma levels of CRH, ACTH and cortisol may increase the likelihood of preterm birth, developmental delays and behavioural abnormalities in the children. In adulthood, it may contribute to the significant association between the incidence of schizophrenia, increased left or mixed handedness, reduction in cerebral asymmetry and anomalies in brain morphology. Our studies and others have shown that prenatal stress in rats can mimic these developmental and behavioural alterations. These rats show a reduced propensity for social interaction, increased anxiety in intimidating or novel situations and a reduction in cerebral asymmetry and dopamine turnover, consistent with those in schizophrenic humans. Prenatally-stressed (PS) rats also show behaviour consistent with depression, including a phase-shift in their circadian rhythm for corticosterone, sleep abnormalities, a hedonic deficit and greater acquisition of learned helplessness under appropriate conditions. These behavioural abnormalities are associated with impaired regulation of the hypothalamic-pituitary-adrenal axis response to stress and increased CRH activity. PS males may show demasculinisation and feminisation of their sexual behaviour. The developmental and behavioural abnormalities in PS offspring could occur through sensitisation of the foetal brain by maternal stress hormones to the action of glucocorticoid and CRH and to neurotransmitters affected by them. This may have long-lasting consequences and could explain the precipitation of depressive symptoms or schizophrenia by psychosocial stress in later life. The character of the behavioural abnormalities probably depends on the timing of the maternal stress in relation to development of the particular neuronal systems. PMID:11689280

  5. Chronic maternal morphine alters calbindin D-28k expression pattern in postnatal mouse brain.

    PubMed

    Mithbaokar, Pratibha; Fiorito, Filomena; Della Morte, Rossella; Maharajan, Veeramani; Costagliola, Anna

    2016-01-01

    The distribution pattern of calbindin (CB)-D28k-expressing neurons results to be altered in several brain regions of chronic morphine exposed adult mice. In this study, the influence of chronic maternal exposure to morphine on the distribution pattern of CB-D28k-expressing neurons in the brain of mouse offspring was investigated. Females of CD-1 mice were daily administered with saline or morphine for 7 days before mating, during the whole gestation period, and until 21 day post-partum. Their offspring were sacrificed on postnatal day 18, and the brains were examined by histology using cresyl violet and by immunohistochemistry using a rabbit polyclonal anti-CB-D28k antibody. Histology revealed no significant differences in the distribution pattern and the number of neurons between the offspring forebrain of the control group of mice and the two groups of mice treated with different doses of morphine. However, immunohistochemical analysis revealed that the number of CB-D28k-immunoreactive neurons remarkably decreased in the cingulate cortex, in the layers II-IV of the parietal cortex and in all regions of the hippocampus, while it increased in the layers V-VI of the parietal cortex and in the subicular region of the offspring brain of morphine treated mice. Overall, our findings demonstrate that maternal exposure to morphine alters the pattern of CB-D28k-expressing neuron pattern in specific regions of murine developing brain, in a layer- and dose-dependent way, thus suggesting that these alterations might represent a mechanism by which morphine modifies the functional aspects of developing brain.

  6. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    PubMed

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases. PMID:26371169

  7. Neurotransmission to parasympathetic cardiac vagal neurons in the brain stem is altered with left ventricular hypertrophy-induced heart failure.

    PubMed

    Cauley, Edmund; Wang, Xin; Dyavanapalli, Jhansi; Sun, Ke; Garrott, Kara; Kuzmiak-Glancy, Sarah; Kay, Matthew W; Mendelowitz, David

    2015-10-01

    Hypertension, cardiac hypertrophy, and heart failure (HF) are widespread and debilitating cardiovascular diseases that affect nearly 23 million people worldwide. A distinctive hallmark of these cardiovascular diseases is autonomic imbalance, with increased sympathetic activity and decreased parasympathetic vagal tone. Recent device-based approaches, such as implantable vagal stimulators that stimulate a multitude of visceral sensory and motor fibers in the vagus nerve, are being evaluated as new therapeutic approaches for these and other diseases. However, little is known about how parasympathetic activity to the heart is altered with these diseases, and this lack of knowledge is an obstacle in the goal of devising selective interventions that can target and selectively restore parasympathetic activity to the heart. To identify the changes that occur within the brain stem to diminish the parasympathetic cardiac activity, left ventricular hypertrophy was elicited in rats by aortic pressure overload using a transaortic constriction approach. Cardiac vagal neurons (CVNs) in the brain stem that generate parasympathetic activity to the heart were identified with a retrograde tracer and studied using patch-clamp electrophysiological recordings in vitro. Animals with left cardiac hypertrophy had diminished excitation of CVNs, which was mediated both by an augmented frequency of spontaneous inhibitory GABAergic neurotransmission (with no alteration of inhibitory glycinergic activity) as well as a diminished amplitude and frequency of excitatory neurotransmission to CVNs. Opportunities to alter these network pathways and neurotransmitter receptors provide future targets of intervention in the goal to restore parasympathetic activity and autonomic balance to the heart in cardiac hypertrophy and other cardiovascular diseases.

  8. Electromagnetic imaging of dynamic brain activity

    SciTech Connect

    Mosher, J.; Leahy, R. . Dept. of Electrical Engineering); Lewis, P.; Lewine, J.; George, J. ); Singh, M. . Dept. of Radiology)

    1991-01-01

    Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.

  9. Electromagnetic imaging of dynamic brain activity

    SciTech Connect

    Mosher, J.; Leahy, R.; Lewis, P.; Lewine, J.; George, J.; Singh, M.

    1991-12-31

    Neural activity in the brain produces weak dynamic electromagnetic fields that can be measured by an array of sensors. Using a spatio-temporal modeling framework, we have developed a new approach to localization of multiple neural sources. This approach is based on the MUSIC algorithm originally developed for estimating the direction of arrival of signals impinging on a sensor array. We present applications of this technique to magnetic field measurements of a phantom and of a human evoked somatosensory response. The results of the somatosensory localization are mapped onto the brain anatomy obtained from magnetic resonance images.

  10. Complex networks in brain electrical activity

    NASA Astrophysics Data System (ADS)

    Ray, C.; Ruffini, G.; Marco-Pallarés, J.; Fuentemilla, L.; Grau, C.

    2007-08-01

    This letter reports a method to extract a functional network of the human brain from electroencephalogram measurements. A network analysis was performed on the resultant network and the statistics of the cluster coefficient, node degree, path length, and physical distance of the links, were studied. Even given the low electrode count of the experimental data the method was able to extract networks with network parameters that clearly depend on the type of stimulus presented to the subject. This type of analysis opens a door to studying the cerebral networks underlying brain electrical activity, and links the fields of complex networks and cognitive neuroscience.

  11. Age and Haplotype Variations within FADS1 Interact and Associate with Alterations in Fatty Acid Composition in Human Male Cortical Brain Tissue

    PubMed Central

    Freemantle, Erika; Lalovic, Aleksandra; Mechawar, Naguib; Turecki, Gustavo

    2012-01-01

    Fatty acids (FA) play an integral role in brain function and alterations have been implicated in a variety of complex neurological disorders. Several recent genomic studies have highlighted genetic variability in the fatty acid desaturase (FADS1/2/3) gene cluster as an important contributor to FA alterations in serum lipids as well as measures of FA desaturase index estimated by ratios of relevant FAs. The contribution to alterations of FAs within the brain by local synthesis is still a matter of debate. Thus, the impact of genetic variants in FADS genes on gene expression and brain FA levels is an important avenue to investigate. Methods Analyses were performed on brain tissue from prefrontal cortex Brodmann area 47 (BA47) of 61 male subjects of French Canadian ancestry ranging in age from young adulthood to middle age (18–58 years old), with the exception of one teenager (15 years old). Haplotype tagging SNPs were selected using the publicly available HapMap genotyping dataset in conjunction with Haploview. DNA sequencing was performed by the Sanger method and gene expression was measured by quantitative real-time PCR. FAs in brain tissue were analysed by gas chromatography. Variants in the FADS1 gene region were sequenced and analyzed for their influence on both FADS gene expression and FAs in brain tissue. Results Our results suggest an association of the minor haplotype with alteration in estimated fatty acid desaturase activity. Analysis of the impact of DNA variants on expression and alternative transcripts of FADS1 and FADS2, however, showed no differences. Furthermore, there was a significant interaction between haplotype and age on certain brain FA levels. Discussion This study suggests that genetic variability in the FADS genes cluster, previously shown to be implicated in alterations in peripheral FA levels, may also affect FA composition in brain tissue, but not likely by local synthesis. PMID:22900039

  12. High-fat diet transition reduces brain DHA levels associated with altered brain plasticity and behaviour.

    PubMed

    Sharma, Sandeep; Zhuang, Yumei; Gomez-Pinilla, Fernando

    2012-01-01

    To assess how the shift from a healthy diet rich in omega-3 fatty acids to a diet rich in saturated fatty acid affects the substrates for brain plasticity and function, we used pregnant rats fed with omega-3 supplemented diet from their 2nd day of gestation period as well as their male pups for 12 weeks. Afterwards, the animals were randomly assigned to either a group fed on the same diet or a group fed on a high-fat diet (HFD) rich in saturated fats for 3 weeks. We found that the HFD increased vulnerability for anxiety-like behavior, and that these modifications harmonized with changes in the anxiety-related NPY1 receptor and the reduced levels of BDNF, and its signalling receptor pTrkB, as well as the CREB protein. Brain DHA contents were significantly associated with the levels of anxiety-like behavior in these rats. PMID:22666534

  13. Imaging brain activity in conscious monkeys following oral MDMA ("ecstasy").

    PubMed

    Brevard, Mathew E; Meyer, Jerrold S; Harder, Josie A; Ferris, Craig F

    2006-07-01

    Recreational use of 3,4-methylenedioxymethamphetamine (MDMA;"ecstasy") poses worldwide potential health problems. Clinical studies show that repeated exposure to low oral doses of MDMA has toxic effects on the brain, altering cognitive and psychosocial behavior. Functional magnetic resonance imaging in conscious marmoset monkeys was used to evaluate the sensitivity of the brain to an oral dose of MDMA (1 mg/kg). Following MDMA administration, the midbrain raphe nuclei and substantia nigra, major sources of serotonin and dopamine, were activated as were the hippocampus, hypothalamus and amygdala. The corticostriatal circuit of dorsal thalamus, sensorimotor cortex and basal ganglia showed a robust, coherent activation pattern. Two key reward areas, the nucleus accumbens and prefrontal cortex, and most other cortical regions showed little activation. The visual cortex, however, showed intense activation without applied visual stimuli. These data identify brain areas and functional circuits sensitive to a recreational dose of MDMA, some of which may be vulnerable to long-term intermittent exposure to this drug.

  14. Altered neurochemical levels in the rat brain following chronic nicotine treatment.

    PubMed

    Falasca, Sara; Ranc, Vaclav; Petruzziello, Filomena; Khani, Abbas; Kretz, Robert; Zhang, Xiaozhe; Rainer, Gregor

    2014-09-01

    Converging evidence shows that neurochemical systems are crucial mediators of nicotine dependence. Our present study evaluates the effect of 3-month chronic nicotine treatment on the levels of multiple quaternary ammonium compounds as well as glutamate and gamma aminobutyric acid in the rat prefrontal cortex, dorsal striatum and hypothalamus. We observed a marked decrease of acetylcholine levels in the dorsal striatum (22.88%, p<0.01), reflecting the impact of chronic nicotine in local interneuron circuits. We found decreases of carnitine in the dorsal striatum and prefrontal cortex (19.44%, p<0.01; 13.58%, p<0.01, respectively), but robust enhancements of carnitine in the hypothalamus (26.59%, p<0.01), which may reflect the alterations in food and water intake during chronic nicotine treatment. Finally, we identified an increase of prefrontal cortex glutamate levels (8.05%, p<0.05), supporting previous studies suggesting enhanced prefrontal activity during chronic drug use. Our study shows that quaternary ammonium compounds are regulated in a highly brain region specific manner during chronic nicotine treatment, and provides novel insights into neurochemical regulation during nicotine use.

  15. Competitive brain activity in visual attention.

    PubMed

    Duncan, J; Humphreys, G; Ward, R

    1997-04-01

    Visual attention can be considered from the perspective of distributed brain activity engendered by visual input. We propose that visual objects compete for representation in multiple brain systems, sensory and motor, cortical and subcortical. Competition is integrated, however, such that multiple systems converge, working on the different properties and action implications of a selected object. Top-down priming biases competition towards objects relevant to current behaviour. Recent single-unit studies have shown widespread suppression of ignored-object representations in extrastriate cortex, and patterns of spatial and nonspatial priming by task relevance. Human and monkey lesion studies have demonstrated the strong integration tendency of different spatial and nonspatial systems, also revealed in recent studies of normal behaviour. In many cases, no unitary brain system may be responsible for unitary cognitive events such as attention. Such events may emerge as distinct systems converge to work on common cognitive problems.

  16. Advanced shotgun lipidomics for characterization of altered lipid patterns in neurodegenerative diseases and brain injury

    PubMed Central

    Wang, Miao; Han, Xianlin

    2016-01-01

    Summary Multi-dimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) is a powerful technology platform among current lipidomics practices due to its high efficiency, sensitivity, and reproducibility, as well as its broad coverage. This platform has been broadly used to determine the altered lipid profiles induced by diseases, injury, genetic manipulations, drug treatments, and aging, among others. Herein, we summarized the principles underlying this platform and presented a protocol for analysis of many of the lipid classes and subclasses covered by MDMS-SL directly from lipid extracts of brain samples. We believe that this protocol could aid the researchers in the field to determine the altered lipid patterns in neurodegenerative diseases and brain injury. PMID:26235081

  17. Altered brain ion gradients following compensation for elevated CO2 are linked to behavioural alterations in a coral reef fish.

    PubMed

    Heuer, R M; Welch, M J; Rummer, J L; Munday, P L; Grosell, M

    2016-01-01

    Neurosensory and behavioural disruptions are some of the most consistently reported responses upon exposure to ocean acidification-relevant CO2 levels, especially in coral reef fishes. The underlying cause of these disruptions is thought to be altered current across the GABAA receptor in neuronal cells due to changes in ion gradients (HCO3(-) and/or Cl(-)) that occur in the body following compensation for elevated ambient CO2. Despite these widely-documented behavioural disruptions, the present study is the first to pair a behavioural assay with measurements of relevant intracellular and extracellular acid-base parameters in a coral reef fish exposed to elevated CO2. Spiny damselfish (Acanthochromis polyacanthus) exposed to 1900 μatm CO2 for 4 days exhibited significantly increased intracellular and extracellular HCO3(-) concentrations and elevated brain pHi compared to control fish, providing evidence of CO2 compensation. As expected, high CO2 exposed damselfish spent significantly more time in a chemical alarm cue (CAC) than control fish, supporting a potential link between behavioural disruption and CO2 compensation. Using HCO3(-) measurements from the damselfish, the reversal potential for GABAA (EGABA) was calculated, illustrating that biophysical properties of the brain during CO2 compensation could change GABAA receptor function and account for the behavioural disturbances noted during exposure to elevated CO2.

  18. Altered brain ion gradients following compensation for elevated CO2 are linked to behavioural alterations in a coral reef fish

    PubMed Central

    Heuer, R. M.; Welch, M. J.; Rummer, J. L.; Munday, P. L.; Grosell, M.

    2016-01-01

    Neurosensory and behavioural disruptions are some of the most consistently reported responses upon exposure to ocean acidification-relevant CO2 levels, especially in coral reef fishes. The underlying cause of these disruptions is thought to be altered current across the GABAA receptor in neuronal cells due to changes in ion gradients (HCO3− and/or Cl−) that occur in the body following compensation for elevated ambient CO2. Despite these widely-documented behavioural disruptions, the present study is the first to pair a behavioural assay with measurements of relevant intracellular and extracellular acid-base parameters in a coral reef fish exposed to elevated CO2. Spiny damselfish (Acanthochromis polyacanthus) exposed to 1900 μatm CO2 for 4 days exhibited significantly increased intracellular and extracellular HCO3− concentrations and elevated brain pHi compared to control fish, providing evidence of CO2 compensation. As expected, high CO2 exposed damselfish spent significantly more time in a chemical alarm cue (CAC) than control fish, supporting a potential link between behavioural disruption and CO2 compensation. Using HCO3− measurements from the damselfish, the reversal potential for GABAA (EGABA) was calculated, illustrating that biophysical properties of the brain during CO2 compensation could change GABAA receptor function and account for the behavioural disturbances noted during exposure to elevated CO2. PMID:27620837

  19. Altered brain ion gradients following compensation for elevated CO2 are linked to behavioural alterations in a coral reef fish.

    PubMed

    Heuer, R M; Welch, M J; Rummer, J L; Munday, P L; Grosell, M

    2016-01-01

    Neurosensory and behavioural disruptions are some of the most consistently reported responses upon exposure to ocean acidification-relevant CO2 levels, especially in coral reef fishes. The underlying cause of these disruptions is thought to be altered current across the GABAA receptor in neuronal cells due to changes in ion gradients (HCO3(-) and/or Cl(-)) that occur in the body following compensation for elevated ambient CO2. Despite these widely-documented behavioural disruptions, the present study is the first to pair a behavioural assay with measurements of relevant intracellular and extracellular acid-base parameters in a coral reef fish exposed to elevated CO2. Spiny damselfish (Acanthochromis polyacanthus) exposed to 1900 μatm CO2 for 4 days exhibited significantly increased intracellular and extracellular HCO3(-) concentrations and elevated brain pHi compared to control fish, providing evidence of CO2 compensation. As expected, high CO2 exposed damselfish spent significantly more time in a chemical alarm cue (CAC) than control fish, supporting a potential link between behavioural disruption and CO2 compensation. Using HCO3(-) measurements from the damselfish, the reversal potential for GABAA (EGABA) was calculated, illustrating that biophysical properties of the brain during CO2 compensation could change GABAA receptor function and account for the behavioural disturbances noted during exposure to elevated CO2. PMID:27620837

  20. Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders

    PubMed Central

    Darby, M M; Yolken, R H; Sabunciyan, S

    2016-01-01

    The measurement of gene expression in postmortem brain is an important tool for understanding the pathogenesis of serious psychiatric disorders. We hypothesized that major molecular deficits associated with psychiatric disease would affect the entire brain, and such deficits may be shared across disorders. We performed RNA sequencing and quantified gene expression in the hippocampus of 100 brains in the Stanley Array Collection followed by replication in the orbitofrontal cortex of 57 brains in the Stanley Neuropathology Consortium. We then identified genes and canonical pathway gene sets with significantly altered expression in schizophrenia and bipolar disorder in the hippocampus and in schizophrenia, bipolar disorder and major depression in the orbitofrontal cortex. Although expression of individual genes varied, gene sets were significantly enriched in both of the brain regions, and many of these were consistent across diagnostic groups. Further examination of core gene sets with consistently increased or decreased expression in both of the brain regions and across target disorders revealed that ribosomal genes are overexpressed while genes involved in neuronal processes, GABAergic signaling, endocytosis and antigen processing have predominantly decreased expression in affected individuals compared to controls without a psychiatric disorder. Our results highlight pathways of central importance to psychiatric health and emphasize messenger RNA processing and protein synthesis as potential therapeutic targets for all three of the disorders. PMID:27622934

  1. Consistently altered expression of gene sets in postmortem brains of individuals with major psychiatric disorders.

    PubMed

    Darby, M M; Yolken, R H; Sabunciyan, S

    2016-01-01

    The measurement of gene expression in postmortem brain is an important tool for understanding the pathogenesis of serious psychiatric disorders. We hypothesized that major molecular deficits associated with psychiatric disease would affect the entire brain, and such deficits may be shared across disorders. We performed RNA sequencing and quantified gene expression in the hippocampus of 100 brains in the Stanley Array Collection followed by replication in the orbitofrontal cortex of 57 brains in the Stanley Neuropathology Consortium. We then identified genes and canonical pathway gene sets with significantly altered expression in schizophrenia and bipolar disorder in the hippocampus and in schizophrenia, bipolar disorder and major depression in the orbitofrontal cortex. Although expression of individual genes varied, gene sets were significantly enriched in both of the brain regions, and many of these were consistent across diagnostic groups. Further examination of core gene sets with consistently increased or decreased expression in both of the brain regions and across target disorders revealed that ribosomal genes are overexpressed while genes involved in neuronal processes, GABAergic signaling, endocytosis and antigen processing have predominantly decreased expression in affected individuals compared to controls without a psychiatric disorder. Our results highlight pathways of central importance to psychiatric health and emphasize messenger RNA processing and protein synthesis as potential therapeutic targets for all three of the disorders. PMID:27622934

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

    PubMed

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

    2016-04-01

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

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

    PubMed

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

    2016-04-01

    Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. PMID:26825441

  4. Loss of neprilysin alters protein expression in the brain of Alzheimer's disease model mice.

    PubMed

    Nilsson, Per; Loganathan, Krishnapriya; Sekiguchi, Misaki; Winblad, Bengt; Iwata, Nobuhisa; Saido, Takaomi C; Tjernberg, Lars O

    2015-10-01

    Alzheimer's disease (AD) is a neurodegenerative disease displaying extracellular plaques formed by the neurotoxic amyloid β-peptide (Aβ), and intracellular neurofibrillary tangles consisting of protein tau. However, how these pathologies relate to the massive neuronal death that occurs in AD brains remain elusive. Neprilysin is the major Aβ-degrading enzyme and a lack thereof increases Aβ levels in the brain twofold. To identify altered protein expression levels induced by increased Aβ levels, we performed a proteomic analysis of the brain of the AD mouse model APPsw and compared it to that of APPsw mice lacking neprilysin. To this end we established an LC-MS/MS method to analyze brain homogenate, using an (18) O-labeled internal standard to accurately quantify the protein levels. To distinguish between alterations in protein levels caused by increased Aβ levels and those induced by neprilysin deficiency independently of Aβ, the brain proteome of neprilysin deficient APPsw mice was also compared to that of neprilysin deficient mice. By this approach we identified approximately 600 proteins and the levels of 300 of these were quantified. Pathway analysis showed that many of the proteins with altered expression were involved in neurological disorders, and that tau, presenilin and APP were key regulators in the identified networks. The data have been deposited to the ProteomeXchange Consortium with identifiers PXD000968 and PXD001786 (http://proteomecentral.proteomexchange.org/dataset/PXD000968 and (http://proteomecentral.proteomexchange.org/dataset/PXD001786). Interestingly, the levels of several proteins, including some not previously reported to be linked to AD, were associated with increased Aβ levels.

  5. Brain activation during a social attribution task in adolescents with moderate to severe traumatic brain injury.

    PubMed

    Scheibel, Randall S; Newsome, Mary R; Wilde, Elisabeth A; McClelland, Michelle M; Hanten, Gerri; Krawczyk, Daniel C; Cook, Lori G; Chu, Zili D; Vásquez, Ana C; Yallampalli, Ragini; Lin, Xiaodi; Hunter, Jill V; Levin, Harvey S

    2011-01-01

    The ability to make accurate judgments about the mental states of others, sometimes referred to as theory of mind (ToM), is often impaired following traumatic brain injury (TBI), and this deficit may contribute to problems with interpersonal relationships. The present study used an animated social attribution task (SAT) with functional magnetic resonance imaging (fMRI) to examine structures mediating ToM in adolescents with moderate to severe TBI. The study design also included a comparison group of matched, typically developing (TD) adolescents. The TD group exhibited activation within a number of areas that are thought to be relevant to ToM, including the medial prefrontal and anterior cingulate cortex, fusiform gyrus, and posterior temporal and parietal areas. The TBI subjects had significant activation within many of these same areas, but their activation was generally more intense and excluded the medial prefrontal cortex. Exploratory regression analyses indicated a negative relation between ToM-related activation and measures of white matter integrity derived from diffusion tensor imaging, while there was also a positive relation between activation and lesion volume. These findings are consistent with alterations in the level and pattern of brain activation that may be due to the combined influence of diffuse axonal injury and focal lesions.

  6. Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

    PubMed

    El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

    2016-04-01

    In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

  7. Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

    PubMed

    El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

    2016-04-01

    In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

  8. The enteric bacterial metabolite propionic acid alters brain and plasma phospholipid molecular species: further development of a rodent model of autism spectrum disorders

    PubMed Central

    2012-01-01

    Gastrointestinal symptoms and altered blood phospholipid profiles have been reported in patients with autism spectrum disorders (ASD). Most of the phospholipid analyses have been conducted on the fatty acid composition of isolated phospholipid classes following hydrolysis. A paucity of information exists on how the intact phospholipid molecular species are altered in ASD. We applied ESI/MS to determine how brain and blood intact phospholipid species were altered during the induction of ASD-like behaviors in rats following intraventricular infusions with the enteric bacterial metabolite propionic acid. Animals were infused daily for 8 days, locomotor activity assessed, and animals killed during the induced behaviors. Propionic acid infusions increased locomotor activity. Lipid analysis revealed treatment altered 21 brain and 30 blood phospholipid molecular species. Notable alterations were observed in the composition of brain SM, diacyl mono and polyunsaturated PC, PI, PS, PE, and plasmalogen PC and PE molecular species. These alterations suggest that the propionic acid rat model is a useful tool to study aberrations in lipid metabolism known to affect membrane fluidity, peroxisomal function, gap junction coupling capacity, signaling, and neuroinflammation, all of which may be associated with the pathogenesis of ASD. PMID:22747852

  9. Alterations in the sense of time, space, and body in the mindfulness-trained brain: a neurophenomenologically-guided MEG study.

    PubMed

    Berkovich-Ohana, Aviva; Dor-Ziderman, Yair; Glicksohn, Joseph; Goldstein, Abraham

    2013-01-01

    Meditation practice can lead to what have been referred to as "altered states of consciousness."One of the phenomenological characteristics of these states is a joint alteration in the sense of time, space, and body. Here, we set out to study the unique experiences of alteration in the sense of time and space by collaborating with a select group of 12 long-term mindfulness meditation (MM) practitioners in a neurophenomenological setup, utilizing first-person data to guide the neural analyses. We hypothesized that the underlying neural activity accompanying alterations in the sense of time and space would be related to alterations in bodily processing. The participants were asked to volitionally bring about distinct states of "Timelessness" (outside time) and "Spacelessness" (outside space) while their brain activity was recorded by MEG. In order to rule out the involvement of attention, memory, or imagination, we used control states of "Then" (past) and "There" (another place). MEG sensors evidencing alterations in power values were identified, and the brain regions underlying these changes were estimated via spatial filtering (beamforming). Particularly, we searched for similar neural activity hypothesized to underlie both the state of "Timelessness" and "Spacelessness." The results were mostly confined to the theta band, and showed that: (1) the "Then"/"There" overlap yielded activity in regions related to autobiographic memory and imagery (right posterior parietal lobule (PPL), right precentral/middle frontal gyrus (MFG), bilateral precuneus); (2) "Timelessness"/"Spacelessness" conditions overlapped in a different network, related to alterations in the sense of the body (posterior cingulate, right temporoparietal junction (TPJ), cerebellum); and (3) phenomenologically-guided neural analyses enabled us to dissociate different levels of alterations in the sense of the body. This study illustrates the utility of employing experienced contemplative practitioners

  10. Altered brain morphology and functional connectivity reflect a vulnerable affective state after cumulative multigenerational stress in rats.

    PubMed

    McCreary, J Keiko; Truica, L Sorina; Friesen, Becky; Yao, Youli; Olson, David M; Kovalchuk, Igor; Cross, Albert R; Metz, Gerlinde A S

    2016-08-25

    Prenatal stress is a risk factor for abnormal neuroanatomical, cognitive, behavioral and mental health outcomes with potentially transgenerational consequences. Females in general seem more resilient to the effects of prenatal stress than males. Here, we examined if repeated stress across generations may diminish stress resiliency and cumulatively enhance the susceptibility for adverse health outcomes in females. Pregnant female rats of three successive generations were exposed to stress from gestational days 12-18 to generate multigenerational prenatal stress (MPS) in the maternal lineage. Stress response was measured by plasma corticosterone levels and open-field exploration in each generation. Neuromorphological consequences of MPS were investigated in the F3 generation using in vivo manganese-enhanced magnetic resonance imaging (MEMRI), T2-relaxometry, and cytoarchitectonics in relation to candidate gene expression involved in brain plasticity and mental health. Each additional generation of prenatal stress incrementally elevated hypothalamic-pituitary-adrenal axis activation, anxiety-like and aversive behaviors in adult female offspring. Elevated stress responses in the MPS F3 generation were accompanied by reduced neural density in prefrontal cortex, hippocampus and whole brain along with altered brain activation patterns in in vivo MEMRI. MPS increased ephrin receptor A5 (Epha5), neuronal growth regulator (Negr1) and synaptosomal-associated protein 25 (Snap25) gene expression and reduced fibroblast growth factor 12 (Fgf12) in prefrontal cortex. These genes regulate neuronal maturation, arborization and synaptic plasticity and may explain altered brain cytoarchitectonics and connectivity. These findings emphasize that recurrent stress across generations may cumulatively increase stress vulnerability and the risk of adverse health outcomes through perinatal programing in females. PMID:27241944

  11. How networks communicate: propagation patterns in spontaneous brain activity.

    PubMed

    Mitra, Anish; Raichle, Marcus E

    2016-10-01

    Initially regarded as 'noise', spontaneous (intrinsic) activity accounts for a large portion of the brain's metabolic cost. Moreover, it is now widely known that infra-slow (less than 0.1 Hz) spontaneous activity, measured using resting state functional magnetic resonance imaging of the blood oxygen level-dependent (BOLD) signal, is correlated within functionally defined resting state networks (RSNs). However, despite these advances, the temporal organization of spontaneous BOLD fluctuations has remained elusive. By studying temporal lags in the resting state BOLD signal, we have recently shown that spontaneous BOLD fluctuations consist of remarkably reproducible patterns of whole brain propagation. Embedded in these propagation patterns are unidirectional 'motifs' which, in turn, give rise to RSNs. Additionally, propagation patterns are markedly altered as a function of state, whether physiological or pathological. Understanding such propagation patterns will likely yield deeper insights into the role of spontaneous activity in brain function in health and disease.This article is part of the themed issue 'Interpreting blood oxygen level-dependent: a dialogue between cognitive and cellular neuroscience'. PMID:27574315

  12. Does mental exertion alter maximal muscle activation?

    PubMed Central

    Rozand, Vianney; Pageaux, Benjamin; Marcora, Samuele M.; Papaxanthis, Charalambos; Lepers, Romuald

    2014-01-01

    Mental exertion is known to impair endurance performance, but its effects on neuromuscular function remain unclear. The purpose of this study was to test the hypothesis that mental exertion reduces torque and muscle activation during intermittent maximal voluntary contractions of the knee extensors. Ten subjects performed in a randomized order three separate mental exertion conditions lasting 27 min each: (i) high mental exertion (incongruent Stroop task), (ii) moderate mental exertion (congruent Stroop task), (iii) low mental exertion (watching a movie). In each condition, mental exertion was combined with 10 intermittent maximal voluntary contractions of the knee extensor muscles (one maximal voluntary contraction every 3 min). Neuromuscular function was assessed using electrical nerve stimulation. Maximal voluntary torque, maximal muscle activation and other neuromuscular parameters were similar across mental exertion conditions and did not change over time. These findings suggest that mental exertion does not affect neuromuscular function during intermittent maximal voluntary contractions of the knee extensors. PMID:25309404

  13. Chlorpyrifos exposure during neurulation: cholinergic synaptic dysfunction and cellular alterations in brain regions at adolescence and adulthood.

    PubMed

    Qiao, Dan; Seidler, Frederic J; Abreu-Villaça, Yael; Tate, Charlotte A; Cousins, Mandy M; Slotkin, Theodore A

    2004-01-31

    The developmental neurotoxicity of chlorpyrifos (CPF) involves multiple mechanisms, thus rendering the immature brain susceptible to adverse effects over a wide window of vulnerability. Earlier work indicated that CPF exposure at the neural tube stage elicits apoptosis and disrupts mitotic patterns in the brain primordium but that rapid recovery ensues before birth. In the current study, we assessed whether defects in cholinergic synaptic activity emerge later in development. CPF was given to pregnant rats on gestational days 9-12, using regimens devoid of overt maternal or fetal toxicity. We then examined subsequent development of acetylcholine systems and compared the effects to those on general biomarkers of cell development. Choline acetyltransferase (ChAT), a constitutive marker for cholinergic nerve terminals, was increased in the hippocampus and striatum in adolescence and adulthood. In contrast, hemicholinium-3 (HC-3) binding to the presynaptic choline transporter, an index of nerve impulse activity, was markedly subnormal. Furthermore, m2-muscarinic cholinergic receptor binding was significantly reduced, instead of showing the expected compensatory upregulation for reduced neural input. CPF also elicited delayed-onset alterations in biomarkers of cell packing density, cell number, cell size and neuritic projections, involving brain regions both with and without reductions in indices of cholinergic activity. In combination with earlier results, the current findings indicate that the developing brain, and especially the hippocampus, is adversely affected by CPF regardless of whether exposure occurs early or late in brain development, and that defects emerge in adolescence or adulthood even in situations where normative values are initially restored in the immediate post-exposure period.

  14. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

    PubMed

    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-01

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly. PMID:26748089

  15. Prolonged Mitosis of Neural Progenitors Alters Cell Fate in the Developing Brain.

    PubMed

    Pilaz, Louis-Jan; McMahon, John J; Miller, Emily E; Lennox, Ashley L; Suzuki, Aussie; Salmon, Edward; Silver, Debra L

    2016-01-01

    Embryonic neocortical development depends on balanced production of progenitors and neurons. Genetic mutations disrupting progenitor mitosis frequently impair neurogenesis; however, the link between altered mitosis and cell fate remains poorly understood. Here we demonstrate that prolonged mitosis of radial glial progenitors directly alters neuronal fate specification and progeny viability. Live imaging of progenitors from a neurogenesis mutant, Magoh(+/-), reveals that mitotic delay significantly correlates with preferential production of neurons instead of progenitors, as well as apoptotic progeny. Independently, two pharmacological approaches reveal a causal relationship between mitotic delay and progeny fate. As mitotic duration increases, progenitors produce substantially more apoptotic progeny or neurons. We show that apoptosis, but not differentiation, is p53 dependent, demonstrating that these are distinct outcomes of mitotic delay. Together our findings reveal that prolonged mitosis is sufficient to alter fates of radial glia progeny and define a new paradigm to understand how mitosis perturbations underlie brain size disorders such as microcephaly.

  16. Integrated genomic and transcriptomic analysis of human brain metastases identifies alterations of potential clinical significance.

    PubMed

    Saunus, Jodi M; Quinn, Michael C J; Patch, Ann-Marie; Pearson, John V; Bailey, Peter J; Nones, Katia; McCart Reed, Amy E; Miller, David; Wilson, Peter J; Al-Ejeh, Fares; Mariasegaram, Mythily; Lau, Queenie; Withers, Teresa; Jeffree, Rosalind L; Reid, Lynne E; Da Silva, Leonard; Matsika, Admire; Niland, Colleen M; Cummings, Margaret C; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Wani, Shivangi; Anderson, Matthew J; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Taylor, Darrin; Waddell, Nick; Wood, Scott; Xu, Qinying; Kassahn, Karin S; Narayanan, Vairavan; Taib, Nur Aishah; Teo, Soo-Hwang; Chow, Yock Ping; kConFab; Jat, Parmjit S; Brandner, Sebastian; Flanagan, Adrienne M; Khanna, Kum Kum; Chenevix-Trench, Georgia; Grimmond, Sean M; Simpson, Peter T; Waddell, Nicola; Lakhani, Sunil R

    2015-11-01

    Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting

  17. Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development.

    PubMed

    Muellner, Julia; Delmaire, Christine; Valabrégue, Romain; Schüpbach, Michael; Mangin, Jean-François; Vidailhet, Marie; Lehéricy, Stéphane; Hartmann, Andreas; Worbe, Yulia

    2015-04-15

    Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS.

  18. Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

    SciTech Connect

    Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.; Lee, Yong Woo

    2012-04-01

    Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR). The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.

  19. Structural alterations of brain grey and white matter in early deaf adults.

    PubMed

    Hribar, Manja; Suput, Dušan; Carvalho, Altiere Araujo; Battelino, Saba; Vovk, Andrej

    2014-12-01

    Functional and structural brain alterations in the absence of the auditory input have been described, but the observed structural brain changes in the deaf are not uniform. Some of the previous researchers focused only on the auditory areas, while others investigated the whole brain or other selected regions of interest. Majority of studies revealed decreased white matter (WM) volume or altered WM microstructure and preserved grey matter (GM) structure of the auditory areas in the deaf. However, preserved WM and increased or decreased GM volume of the auditory areas in the deaf have also been reported. Several structural alterations in the deaf were found also outside the auditory areas, but these regions differ between the studies. The observed differences between the studies could be due to the use of different single-analysis techniques, or the diverse population sample and its size, or possibly due to the usage of hearing aids by some participating deaf subjects. To overcome the aforementioned limitations four different image-processing techniques were used to investigate changes in the brain morphology of prelingually deaf adults who have never used hearing aids. GM and WM volume of the Heschl's gyrus (HG) were measured using manual volumetry, while whole brain GM volume, thickness and surface area were assessed by voxel-based morphometry (VBM) and surface-based analysis. The microstructural properties of the WM were evaluated by diffusion tensor imaging (DTI). The data were compared between 14 congenitally deaf adults and 14 sex- and age-matched normal hearing controls. Manual volumetry revealed preserved GM volume of the bilateral HG and significantly decreased WM volume of the left HG in the deaf. VBM showed increased cerebellar GM volume in the deaf, while no statistically significant differences were observed in the GM thickness or surface area between the groups. The results of the DTI analysis showed WM microstructural alterations between the groups in

  20. The association between regular cannabis exposure and alterations of human brain morphology: an updated review of the literature.

    PubMed

    Lorenzetti, Valentina; Solowij, Nadia; Fornito, Alex; Lubman, Dan Ian; Yucel, Murat

    2014-01-01

    Cannabis is the most widely used illicit drug worldwide, though it is unclear whether its regular use is associated with persistent alterations in brain morphology. This review examines evidence from human structural neuroimaging investigations of regular cannabis users and focuses on achieving three main objectives. These include examining whether the literature to date provides evidence that alteration of brain morphology in regular cannabis users: i) is apparent, compared to non-cannabis using controls; ii) is associated with patterns of cannabis use; and with iii) measures of psychopathology and neurocognitive performance. The published findings indicate that regular cannabis use is associated with alterations in medial temporal, frontal and cerebellar brain regions. Greater brain morphological alterations were evident among samples that used at higher doses for longer periods. However, the evidence for an association between brain morphology and cannabis use parameters was mixed. Further, there is poor evidence for an association between measures of brain morphology and of psychopathology symptoms/neurocognitive performance. Overall, numerous methodological issues characterize the literature to date. These include investigation of small sample sizes, heterogeneity across studies in sample characteristics (e.g., sex, comorbidity) and in employed imaging techniques, as well as the examination of only a limited number of brain regions. These factors make it difficult to draw firm conclusions from the existing findings. Nevertheless, this review supports the notion that regular cannabis use is associated with alterations of brain morphology, and highlights the need to consider particular methodological issues when planning future cannabis research.

  1. Altered human brain anatomy in chronic smokers: a review of magnetic resonance imaging studies.

    PubMed

    Wang, Chao; Xu, Xiaojun; Qian, Wei; Shen, Zhujing; Zhang, Minming

    2015-04-01

    Cigarette smoking is becoming more prevalent in developing countries, such as China, and is the largest single cause of preventable death worldwide. New emerging reports are highlighting how chronic cigarette smoking plays a role in neural dysfunctions, such as cognitive decline. Basic animal experimental studies have shown that rats undergo persistent pathological brain changes after being given chronic levels of nicotine. What is perhaps less appreciated is the fact that chronic cigarette smoking induces subtle anatomical changes in the human brain. Consequently, this chapter aims to summarize and integrate the existing magnetic resonance imaging studies on both gray- and white-matter marcostructural and microstructural changes. The reviewed studies demonstrate that chronic cigarette smoking results in discrete and localized alterations in brain region tissue (both the gray and white matter of different brain regions), which may, in part, be responsible for different neural dysfunctions. In addition, we further discuss the possible pathological and neurobiological mechanisms of these nicotinic effects on the brain tissue. We will also address the limitations of the current studies on this issue and identify opportunities for future research. PMID:25577510

  2. Adolescent binge ethanol treatment alters adult brain regional volumes, cortical extracellular matrix protein and behavioral flexibility

    PubMed Central

    Coleman, Leon Garland; Liu, Wen; Oguz, Ipek; Styner, Martin; Crews, Fulton T.

    2014-01-01

    Adolescents binge drink more than any other age group, increasing risk of disrupting the development of the frontal cortex. We hypothesized that adolescent binge drinking would lead to persistent alterations in adulthood. In this study, we modeled adolescent weekend underage binge-drinking, using adolescent mice (post-natal days [P] 28–37). The adolescent intermittent binge ethanol (AIE) treatment includes 6 binge intragastric doses of ethanol in an intermittent pattern across adolescence. Assessments were conducted in adulthood following extended abstinence to determine if there were persistent changes in adults. Reversal learning, open field and other behavioral assessments as well as brain structure using magnetic imaging and immunohistochemistry were determined. We found AIE did not impact adult Barnes Maze learning. However, AIE did cause reversal learning deficits in adults. AIE also caused structural changes in the adult brain. AIE was associated with adulthood volume enlargements in specific brain regions without changes in total brain volume. Enlarged regions included the orbitofrontal cortex (OFC, 4%), cerebellum (4.5%), thalamus (2%), internal capsule (10%) and genu of the corpus callosum (7%). The enlarged OFC volume in adults after AIE is consistent with previous imaging studies in human adolescents. AIE treatment was associated with significant increases in the expression of several extracellular matrix (ECM) proteins in the adult OFC including WFA (55%), Brevican (32%), Neurocan (105%), Tenacin-C (25%), and HABP (5%). These findings are consistent with AIE causing persistent changes in brain structure that could contribute to a lack of behavioral flexibility. PMID:24275185

  3. Ionizing radiation alters beta-endorphin-like immunoreactivity in brain but not blood

    SciTech Connect

    Mickley, G.A.; Stevens, K.E.; Moore, G.H.; Deere, W.; White, G.A.; Gibbs, G.L.; Mueller, G.P.

    1983-12-01

    Previous behavioral and pharmacological studies have implicated endorphins in radiation-induced locomotor hyperactivity of the C57BL/6J mouse. However, the endogenous opiate(s) responsible for this behavioral change have not been identified. The present study measured beta-endorphin-like immunoreactivity (beta-END-LI) in brain, blood, and combined brain and pituitary samples from irradiated and sham-irradiated C57BL/6J mice. After radiation exposure, levels of beta-END-LI decreased significantly in the brain. A similar, but not statistically significant, decline was measured in combined brain and pituitary samples. Concentrations of blood beta-END-LI were not changed by irradiation. These radiogenic changes in beta-END-LI are in some ways similar to those observed after other stresses. However, radiation-induced locomotor hyperactivity may be mediated more by alterations of beta-END-LI in the brain than in the periphery. Other endogenous opiate systems may also contribute to this behavioral change in the C57BL/6J mouse.

  4. Altered human brain anatomy in chronic smokers: a review of magnetic resonance imaging studies.

    PubMed

    Wang, Chao; Xu, Xiaojun; Qian, Wei; Shen, Zhujing; Zhang, Minming

    2015-04-01

    Cigarette smoking is becoming more prevalent in developing countries, such as China, and is the largest single cause of preventable death worldwide. New emerging reports are highlighting how chronic cigarette smoking plays a role in neural dysfunctions, such as cognitive decline. Basic animal experimental studies have shown that rats undergo persistent pathological brain changes after being given chronic levels of nicotine. What is perhaps less appreciated is the fact that chronic cigarette smoking induces subtle anatomical changes in the human brain. Consequently, this chapter aims to summarize and integrate the existing magnetic resonance imaging studies on both gray- and white-matter marcostructural and microstructural changes. The reviewed studies demonstrate that chronic cigarette smoking results in discrete and localized alterations in brain region tissue (both the gray and white matter of different brain regions), which may, in part, be responsible for different neural dysfunctions. In addition, we further discuss the possible pathological and neurobiological mechanisms of these nicotinic effects on the brain tissue. We will also address the limitations of the current studies on this issue and identify opportunities for future research.

  5. Physical activity, air pollution and the brain.

    PubMed

    Bos, Inge; De Boever, Patrick; Int Panis, Luc; Meeusen, Romain

    2014-11-01

    This review introduces an emerging research field that is focused on studying the effect of exposure to air pollution during exercise on cognition, with specific attention to the impact on concentrations of brain-derived neurotrophic factor (BDNF) and inflammatory markers. It has been repeatedly demonstrated that regular physical activity enhances cognition, and evidence suggests that BDNF, a neurotrophin, plays a key role in the mechanism. Today, however, air pollution is an environmental problem worldwide and the high traffic density, especially in urban environments and cities, is a major cause of this problem. During exercise, the intake of air pollution increases considerably due to an increased ventilation rate and particle deposition fraction. Recently, air pollution exposure has been linked to adverse effects on the brain such as cognitive decline and neuropathology. Inflammation and oxidative stress seem to play an important role in inducing these health effects. We believe that there is a need to investigate whether the well-known benefits of regular physical activity on the brain also apply when physical activity is performed in polluted air. We also report our findings about exercising in an environment with ambient levels of air pollutants. Based on the latter results, we hypothesize that traffic-related air pollution exposure during exercise may inhibit the positive effect of exercise on cognition. PMID:25119155

  6. Physical activity, air pollution and the brain.

    PubMed

    Bos, Inge; De Boever, Patrick; Int Panis, Luc; Meeusen, Romain

    2014-11-01

    This review introduces an emerging research field that is focused on studying the effect of exposure to air pollution during exercise on cognition, with specific attention to the impact on concentrations of brain-derived neurotrophic factor (BDNF) and inflammatory markers. It has been repeatedly demonstrated that regular physical activity enhances cognition, and evidence suggests that BDNF, a neurotrophin, plays a key role in the mechanism. Today, however, air pollution is an environmental problem worldwide and the high traffic density, especially in urban environments and cities, is a major cause of this problem. During exercise, the intake of air pollution increases considerably due to an increased ventilation rate and particle deposition fraction. Recently, air pollution exposure has been linked to adverse effects on the brain such as cognitive decline and neuropathology. Inflammation and oxidative stress seem to play an important role in inducing these health effects. We believe that there is a need to investigate whether the well-known benefits of regular physical activity on the brain also apply when physical activity is performed in polluted air. We also report our findings about exercising in an environment with ambient levels of air pollutants. Based on the latter results, we hypothesize that traffic-related air pollution exposure during exercise may inhibit the positive effect of exercise on cognition.

  7. Sexual differentiation of the brain: a model for drug-induced alterations of the reproductive system

    SciTech Connect

    Gorski, R.A.

    1986-12-01

    The process of the sexual differentiation of the brain represents a valuable model system for the study of the chemical modification of the mammalian brain. Although there are numerous functional and structural sex differences in the adult brain, these are imposed on an essentially feminine or bipotential brain by testicular hormones during a critical phase of perinatal development in the rat. It is suggested that a relatively marked structural sex difference in the rat brain, the sexually dimorphic nucleus of the preoptic area (SDN-POA), is a morphological signature of the permanent or organizational action of estradiol derived from the aromatization of testicular testosterone. The SDN-POA of the male rat is severalfold larger in volume and is composed of more neurons than that of the female. The observation that the mitotic formation of the neurons of the SDN-POA is specifically prolonged has enabled us to identify the time course and pathway of neuronal migration into the nucleus. Study of the development of the SDN-POA suggests that estradiol in the male increases the number of neurons which survive a phase of neuronal death by exerting a neurite growth promoting action and/or a direct neuronotrophic action. Finally, although it is clear that gonadal hormones have dramatic permanent effects on the brain during perinatal development, even after puberty and in adulthood gonadal steroids can alter neuronal structure and, perhaps as a corollary to this, have permanent effects on reproductive function. Although the brain may be most sensitive to gonadal hormones or exogenous chemical factors during perinatal development, such as sensitivity does not appear limited to this period.

  8. Evidence of altered DNA integrity in the brain regions of suicidal victims of Bipolar Depression

    PubMed Central

    Mustak, Mohammed S.; Hegde, Muralidhar L.; Dinesh, Athira; Britton, Gabrielle B.; Berrocal, Ruben; Subba Rao, K.; Shamasundar, N. M.; Rao, K. S. J; Sathyanarayana Rao, T. S.

    2010-01-01

    Deoxyribonucleic acid (DNA) integrity plays a significant role in cell function. There are limited studies with regard to the role of DNA damage in bipolar affective disorder (BP). In the present study, we have assessed DNA integrity, conformation, and stability in the brain region of bipolar depression (BD) patients (n=10) compared to age-matched controls (n=8). Genomic DNA was isolated from 10 postmortem BD patients’ brain regions (frontal cortex, Pons, medulla, thalamus, cerebellum, hypothalamus, Parietal, temporal, occipital lobe, and hippocampus) and from the age-matched control subjects. DNA from the frontal cortex, pons, medulla, and thalamus showed significantly higher number of strand breaks in BD (P<0.01) compared to the age-matched controls. However, DNA from the hippocampus region was intact and did not show any strand breaks. The stability studies also indicated that the melting temperature and ethidium bromide binding pattern were altered in the DNA of BD patients’ brain regions, except in the hippocampus. The conformation studies showed B-A or secondary B-DNA conformation (instead of the normal B-DNA) in BD patients’ brain regions, with the exception of the hippocampus. The levels of redox metals such as Copper (Cu) and Iron (Fe) were significantly elevated in the brain regions of the sufferers of BD, while the Zinc (Zn) level was decreased. In the hippocampus, there was no change in the Fe or Cu levels, whereas, the Zn level was elevated. There was a clear correlation between Cu and Fe levels versus strand breaks in the brain regions of the BD. To date, as far as we are aware, this is a new comprehensive database on stability and conformations of DNA in different brain regions of patients affected with BD. The biological significance of these findings is discussed here. PMID:21180406

  9. C5a alters blood-brain barrier integrity in a human in vitro model of systemic lupus erythematosus.

    PubMed

    Mahajan, Supriya D; Parikh, Neil U; Woodruff, Trent M; Jarvis, James N; Lopez, Molly; Hennon, Teresa; Cunningham, Patrick; Quigg, Richard J; Schwartz, Stanley A; Alexander, Jessy J

    2015-09-01

    The blood-brain barrier (BBB) plays a crucial role in brain homeostasis, thereby maintaining the brain environment precise for optimal neuronal function. Its dysfunction is an intriguing complication of systemic lupus erythematosus (SLE). SLE is a systemic autoimmune disorder where neurological complications occur in 5-50% of cases and is associated with impaired BBB integrity. Complement activation occurs in SLE and is an important part of the clinical profile. Our earlier studies demonstrated that C5a generated by complement activation caused the loss of brain endothelial layer integrity in rodents. The goal of the current study was to determine the translational potential of these studies to a human system. To assess this, we used a two dimensional in vitro BBB model constructed using primary human brain microvascular endothelial cells and astroglial cells, which closely emulates the in vivo BBB allowing the assessment of BBB integrity. Increased permeability monitored by changes in transendothelial electrical resistance and cytoskeletal remodelling caused by actin fiber rearrangement were observed when the cells were exposed to lupus serum and C5a, similar to the observations in mice. In addition, our data show that C5a/C5aR1 signalling alters nuclear factor-κB translocation into nucleus and regulates the expression of the tight junction proteins, claudin-5 and zonula occludens 1 in this setting. Our results demonstrate for the first time that C5a regulates BBB integrity in a neuroinflammatory setting where it affects both endothelial and astroglial cells. In addition, we also demonstrate that our previous findings in a mouse model, were emulated in human cells in vitro, bringing the studies one step closer to understanding the translational potential of C5a/C5aR1 blockade as a promising therapeutic strategy in SLE and other neurodegenerative diseases.

  10. Using Brain Electrical Activity Mapping to Diagnose Learning Disabilities.

    ERIC Educational Resources Information Center

    Torello, Michael, W.; Duffy, Frank H.

    1985-01-01

    Cognitive neuroscience assumes that measurement of brain electrical activity should relate to cognition. Brain Electrical Activity Mapping (BEAM), a non-invasive technique, is used to record changes in activity from one brain area to another and is 80 to 90 percent successful in classifying subjects as dyslexic or normal. (MT)

  11. [Psychosocial stress induces molecular and structural alterations in the brain - How animal experiments help to understand pathomechanisms of depressive illnesses].

    PubMed

    Fuchs, E; Flügge, G

    2001-01-01

    Affective disorders are accompanied by central nervous changes that may lead to diseases of brain and peripheral organs. To gain an insight into neurobiological mechanisms that underlie such diseases we are studying tree shrews (Tupaia belangeri). This animal model is based on the fact that male tree shrews are very territorial and that under laboratory conditions, two males establish a clear social rank order with a dominant and a subordinate animal. In the visual presence of the dominant, the subordinate shows all typical signs of stress with pronounced activation of the hypothalamic-pituitary-adrenal axis and of the sympathetic nervous system. If there are daily confrontations with the dominant during a time period of several weeks, the subordinate experiences chronic psychosocial stress. Tree shrews can be regarded as a suitable animal model to investigate the neurobiological basis of affective disorders since (1) behavioral and endocrine symptoms of subordinates resemble those of depressive patients, (2) antidepressant treatments lead to an improvement of symptoms, and (3) also in humans chronic stress can lead to depression. Using this model we showed that chronic stress induces changes in the morphology of hippocampal pyramidal neurons, affects neurogenesis in the hippocampal formation, and changes the expression of glucocorticoid, serotonergic and noradrenergic receptors in the brain. These changes depend on the duration of the stress period with some of the alterations being reversible whereas others persist during a longer time period. Since the above receptors modulate neuronal activity, the stress induced alterations lead to an impairment of neuronal activity in distinct brain regions.

  12. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    PubMed

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing.

  13. Brain Activation During Singing: "Clef de Sol Activation" Is the "Concert" of the Human Brain.

    PubMed

    Mavridis, Ioannis N; Pyrgelis, Efstratios-Stylianos

    2016-03-01

    Humans are the most complex singers in nature, and the human voice is thought by many to be the most beautiful musical instrument. Aside from spoken language, singing represents a second mode of acoustic communication in humans. The purpose of this review article is to explore the functional anatomy of the "singing" brain. Methodologically, the existing literature regarding activation of the human brain during singing was carefully reviewed, with emphasis on the anatomic localization of such activation. Relevant human studies are mainly neuroimaging studies, namely functional magnetic resonance imaging and positron emission tomography studies. Singing necessitates activation of several cortical, subcortical, cerebellar, and brainstem areas, served and coordinated by multiple neural networks. Functionally vital cortical areas of the frontal, parietal, and temporal lobes bilaterally participate in the brain's activation process during singing, confirming the latter's role in human communication. Perisylvian cortical activity of the right hemisphere seems to be the most crucial component of this activation. This also explains why aphasic patients due to left hemispheric lesions are able to sing but not speak the same words. The term clef de sol activation is proposed for this crucial perisylvian cortical activation due to the clef de sol shape of the topographical distribution of these cortical areas around the sylvian fissure. Further research is needed to explore the connectivity and sequence of how the human brain activates to sing. PMID:26966964

  14. Magnetic resonance imaging structural alterations in brain of alcohol abusers and its association with impulsivity.

    PubMed

    Asensio, Samuel; Morales, Julia L; Senabre, Isabel; Romero, Maria J; Beltran, Miguel A; Flores-Bellver, Miguel; Barcia, Jorge M; Romero, Francisco J

    2016-07-01

    Despite the suggestion that impulsivity plays a central role in the transfer from a recreational drug use to a substance use disorder, very few studies focused on neurobiological markers for addiction. This study aimed to identify volumetric alterations in a sample of patients with mild alcohol use disorder with a short history of alcohol use, compared with a control group, and also focused on its association with impulsivity levels. Most magnetic resonance imaging studies have focused on severe alcohol use disorder, formerly called alcohol-dependent patients, showing alcohol-related structural alterations and their association with alcohol use history variables but not with personality parameters like impulsivity. Our hypothesis is that our group of alcohol users may already display structural alterations especially in brain regions related to inhibitory control like medial-prefrontal regions, and that those structural alterations could be more associated to personality traits like impulsivity than to drug use variables. Our results clearly demonstrate that our population showed lower regional grey and white matter volumes in the medial-prefrontal and orbitofrontal cortices, as well as higher regional white matter volume in the ventral striatum and the internal capsule. Volumetric alterations were associated to the Barratt's impulsivity score: the more impulsive the subjects, the lower the medial-prefrontal cortex grey matter volume.

  15. Histone deacetylase inhibitors reverse manic-like behaviors and protect the rat brain from energetic metabolic alterations induced by ouabain.

    PubMed

    Lopes-Borges, Jéssica; Valvassori, Samira S; Varela, Roger B; Tonin, Paula T; Vieira, Julia S; Gonçalves, Cinara L; Streck, Emilio L; Quevedo, João

    2015-01-01

    Studies have revealed alterations in mitochondrial complexes in the brains of bipolar patients. However, few studies have examined changes in the enzymes of the tricarboxylic acid cycle. Several preclinical studies have suggested that histone deacetylase inhibitors may have antimanic effects. The present study aims to investigate the effects of lithium, valproate and sodium butyrate, a histone deacetylase inhibitor, on the activity of tricarboxylic acid cycle enzymes in the brains of rats subjected to an animal model of mania induced by ouabain. Wistar rats received a single intracerebroventricular injection of ouabain or cerebrospinal fluid. Starting on the day following the intracerebroventricular injection, the rats were treated for 7days with intraperitoneal injections of saline, lithium, valproate or sodium butyrate. Risk-taking behavior, locomotor and exploratory activities were measured using the open-field test. Citrate synthase, succinate dehydrogenase, and malate dehydrogenase were examined in the frontal cortex and hippocampus. All treatments reversed ouabain-related risk-taking behavior and hyperactivity in the open-field test. Ouabain inhibited tricarboxylic acid cycle enzymes in the brain, and valproate and sodium butyrate but not lithium reversed this ouabain-induced dysfunction. Thus, protecting the tricarboxylic acid cycle may contribute to the therapeutic effects of histone deacetylase inhibitors. PMID:25433326

  16. When “altering brain function” becomes “mind control”

    PubMed Central

    Koivuniemi, Andrew; Otto, Kevin

    2014-01-01

    Functional neurosurgery has seen a resurgence of interest in surgical treatments for psychiatric illness. Deep brain stimulation (DBS) technology is the preferred tool in the current wave of clinical experiments because it allows clinicians to directly alter the functions of targeted brain regions, in a reversible manner, with the intent of correcting diseases of the mind, such as depression, addiction, anorexia nervosa, dementia, and obsessive compulsive disorder. These promising treatments raise a critical philosophical and humanitarian question. “Under what conditions does ‘altering brain function’ qualify as ‘mind control’?” In order to answer this question one needs a definition of mind control. To this end, we reviewed the relevant philosophical, ethical, and neurosurgical literature in order to create a set of criteria for what constitutes mind control in the context of DBS. We also outline clinical implications of these criteria. Finally, we demonstrate the relevance of the proposed criteria by focusing especially on serendipitous treatments involving DBS, i.e., cases in which an unintended therapeutic benefit occurred. These cases highlight the importance of gaining the consent of the subject for the new therapy in order to avoid committing an act of mind control. PMID:25352789

  17. Dido mutations trigger perinatal death and generate brain abnormalities and behavioral alterations in surviving adult mice

    PubMed Central

    Villares, Ricardo; Gutiérrez, Julio; Fütterer, Agnes; Trachana, Varvara; Gutiérrez del Burgo, Fernando; Martínez-A, Carlos

    2015-01-01

    Nearly all vertebrate cells have a single cilium protruding from their surface. This threadlike organelle, once considered vestigial, is now seen as a pivotal element for detection of extracellular signals that trigger crucial morphogenetic pathways. We recently proposed a role for Dido3, the main product of the death inducer-obliterator (dido) gene, in histone deacetylase 6 delivery to the primary cilium [Sánchez de Diego A, et al. (2014) Nat Commun 5:3500]. Here we used mice that express truncated forms of Dido proteins to determine the link with cilium-associated disorders. We describe dido mutant mice with high incidence of perinatal lethality and distinct neurodevelopmental, morphogenetic, and metabolic alterations. The anatomical abnormalities were related to brain and orofacial development, consistent with the known roles of primary cilia in brain patterning, hydrocephalus incidence, and cleft palate. Mutant mice that reached adulthood showed reduced life expectancy, brain malformations including hippocampus hypoplasia and agenesis of corpus callosum, as well as neuromuscular and behavioral alterations. These mice can be considered a model for the study of ciliopathies and provide information for assessing diagnosis and therapy of genetic disorders linked to the deregulation of primary cilia. PMID:25825751

  18. Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats.

    PubMed

    Stengel, Andreas; Goebel, Miriam; Wang, Lixin; Taché, Yvette

    2010-02-01

    Abdominal surgery-induced postoperative gastric ileus is well established to induce Fos expression in specific brain nuclei in rats within 2-h after surgery. However, the phenotype of activated neurons has not been thoroughly characterized. Nesfatin-1 was recently discovered in the rat hypothalamus as a new anorexigenic peptide that also inhibits gastric emptying and is widely distributed in rat brain autonomic nuclei suggesting an involvement in stress responses. Therefore, we investigated whether abdominal surgery activates nesfatin-1-immunoreactive (ir) neurons in the rat brain. Two hours after abdominal surgery with cecal palpation under short isoflurane anesthesia or anesthesia alone, rats were transcardially perfused and brains processed for double immunohistochemical labeling of Fos and nesfatin-1. Abdominal surgery, compared to anesthesia alone, induced Fos expression in neurons of the supraoptic nucleus (SON), paraventricular nucleus (PVN), locus coeruleus (LC), Edinger-Westphal nucleus (EW), rostral raphe pallidus (rRPa), nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM). Double Fos/nesfatin-1 labeling showed that of the activated cells, 99% were nesfatin-1-immunoreactive in the SON, 91% in the LC, 82% in the rRPa, 74% in the EW and VLM, 71% in the anterior parvicellular PVN, 47% in the lateral magnocellular PVN, 41% in the medial magnocellular PVN, 14% in the NTS and 9% in the medial parvicellular PVN. These data established nesfatin-1 immunoreactive neurons in specific nuclei of the hypothalamus and brainstem as part of the neuronal response to abdominal surgery and suggest a possible implication of nesfatin-1 in the alterations of food intake and gastric transit associated with such a stressor. PMID:19944727

  19. Cerebrospinal fluid-derived circulating tumour DNA better represents the genomic alterations of brain tumours than plasma.

    PubMed

    De Mattos-Arruda, Leticia; Mayor, Regina; Ng, Charlotte K Y; Weigelt, Britta; Martínez-Ricarte, Francisco; Torrejon, Davis; Oliveira, Mafalda; Arias, Alexandra; Raventos, Carolina; Tang, Jiabin; Guerini-Rocco, Elena; Martínez-Sáez, Elena; Lois, Sergio; Marín, Oscar; de la Cruz, Xavier; Piscuoglio, Salvatore; Towers, Russel; Vivancos, Ana; Peg, Vicente; Ramon y Cajal, Santiago; Carles, Joan; Rodon, Jordi; González-Cao, María; Tabernero, Josep; Felip, Enriqueta; Sahuquillo, Joan; Berger, Michael F; Cortes, Javier; Reis-Filho, Jorge S; Seoane, Joan

    2015-11-10

    Cell-free circulating tumour DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in tumours and has been used to monitor tumour progression and response to treatments. However, patients with brain tumours do not present with or present with low amounts of ctDNA in plasma precluding the genomic characterization of brain cancer through plasma ctDNA. Here we show that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma. Massively parallel sequencing of CSF ctDNA more comprehensively characterizes the genomic alterations of brain tumours than plasma, allowing the identification of actionable brain tumour somatic mutations. We show that CSF ctDNA levels longitudinally fluctuate in time and follow the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Moreover, CSF ctDNA is shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis.

  20. Altered myoelectric activity in the experimental blind loop syndrome.

    PubMed

    Justus, P G; Fernandez, A; Martin, J L; King, C E; Toskes, P P; Mathias, J R

    1983-09-01

    Nutrient malabsorption and diarrhea are characteristic of the blind loop syndrome. Alterations in motility have been implicated as a cause of bacterial overgrowth, but the possibility that altered motility may result from alterations in the flora has not been explored. The purpose of this study was to characterize the myoelectric activity of the small intestine in the blind loop rat model. Eight groups of rats were studied: rats with self-filling blind loops, which develop bacterial overgrowth; rats with self-emptying blind loops, which are surgical controls that do not develop overgrowth; unoperated litter mates; rats with self-filling blind loops and unoperated controls treated with chloramphenicol, 200 mg/d i.p.; rats with surgically removed self-filling blind loops; operated control rats; and gnotobiotic rats with self-filling blind loops. In the untreated rats with self-filling blind loops, there was altered myoelectric activity characterized by an increased percentage of slow waves occupied by action potentials and by organized activity similar to the migrating action potential complex. Migrating action potential complex activity and percentage of slow waves occupied by action potentials were significantly decreased with chloramphenicol therapy; that decrease correlated with a decrease in aerobes and anaerobes. Migrating action potential complex activity was abolished in rats with surgically removed self-filling blind loops; they also showed a significant decrease in percentage of slow waves occupied by action potentials. Gnotobiotic rats with self-filling blind loops showed no alteration in myoelectric activity. These data indicate: (a) bacterial overgrowth is associated with a significant increase in percentage of slow waves occupied by action potentials and migrating action potential complex activity; (b) chloramphenicol significantly reduced both percentage of slow waves occupied by action potentials and migrating action potential complex activity; and (c

  1. Material and physical model for evaluation of deep brain activity contribution to EEG recordings

    NASA Astrophysics Data System (ADS)

    Ye, Yan; Li, Xiaoping; Wu, Tiecheng; Li, Zhe; Xie, Wenwen

    2015-12-01

    Deep brain activity is conventionally recorded with surgical implantation of electrodes. During the neurosurgery, brain tissue damage and the consequent side effects to patients are inevitably incurred. In order to eliminate undesired risks, we propose that deep brain activity should be measured using the noninvasive scalp electroencephalography (EEG) technique. However, the deeper the neuronal activity is located, the noisier the corresponding scalp EEG signals are. Thus, the present study aims to evaluate whether deep brain activity could be observed from EEG recordings. In the experiment, a three-layer cylindrical head model was constructed to mimic a human head. A single dipole source (sine wave, 10 Hz, altering amplitudes) was embedded inside the model to simulate neuronal activity. When the dipole source was activated, surface potential was measured via electrodes attached on the top surface of the model and raw data were recorded for signal analysis. Results show that the dipole source activity positioned at 66 mm depth in the model, equivalent to the depth of deep brain structures, is clearly observed from surface potential recordings. Therefore, it is highly possible that deep brain activity could be observed from EEG recordings and deep brain activity could be measured using the noninvasive scalp EEG technique.

  2. Scale-free brain activity: past, present and future

    PubMed Central

    He, Biyu J.

    2014-01-01

    Brain activity observed at many spatiotemporal scales exhibits a 1/f-like power spectrum, including neuronal membrane potentials, neural field potentials, noninvasive electroencephalography, magnetoencephalography and functional magnetic resonance imaging signals. A 1/f-like power spectrum is indicative of arrhythmic brain activity that does not contain a predominant temporal scale (hence, “scale-free”). This characteristic of scale-free brain activity distinguishes it from brain oscillations. While scale-free brain activity and brain oscillations coexist, our understanding of the former remains very limited. Recent research has shed light on the spatiotemporal organization, functional significance and potential generative mechanisms of scale-free brain activity, as well as its developmental and clinical relevance. A deeper understanding of this prevalent brain signal should provide new insights and analytical tools for cognitive neuroscience. PMID:24788139

  3. Scale-free brain activity: past, present, and future.

    PubMed

    He, Biyu J

    2014-09-01

    Brain activity observed at many spatiotemporal scales exhibits a 1/f-like power spectrum, including neuronal membrane potentials, neural field potentials, noninvasive electroencephalography (EEG), magnetoencephalography (MEG), and functional magnetic resonance imaging (fMRI) signals. A 1/f-like power spectrum is indicative of arrhythmic brain activity that does not contain a predominant temporal scale (hence, 'scale-free'). This characteristic of scale-free brain activity distinguishes it from brain oscillations. Although scale-free brain activity and brain oscillations coexist, our understanding of the former remains limited. Recent research has shed light on the spatiotemporal organization, functional significance, and potential generative mechanisms of scale-free brain activity, as well as its developmental and clinical relevance. A deeper understanding of this prevalent brain signal should provide new insights into, and analytical tools for, cognitive neuroscience.

  4. Frequency-Dependent Brain Regional Homogeneity Alterations in Patients with Mild Cognitive Impairment during Working Memory State Relative to Resting State.

    PubMed

    Wang, Pengyun; Li, Rui; Yu, Jing; Huang, Zirui; Li, Juan

    2016-01-01

    Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI). However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control (NC) subjects. Therefore, using the index of regional homogeneity (ReHo), we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex (PCC) in the slow-3 band (0.073-0.198 Hz), and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex (PFC), the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01-0.027 Hz). Furthermore, in NCs, the value of ReHo in clusters belonging to the default mode network (DMN) decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients. This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states. PMID:27047375

  5. Frequency-Dependent Brain Regional Homogeneity Alterations in Patients with Mild Cognitive Impairment during Working Memory State Relative to Resting State

    PubMed Central

    Wang, Pengyun; Li, Rui; Yu, Jing; Huang, Zirui; Li, Juan

    2016-01-01

    Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI). However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control (NC) subjects. Therefore, using the index of regional homogeneity (ReHo), we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex (PCC) in the slow-3 band (0.073–0.198 Hz), and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex (PFC), the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01–0.027 Hz). Furthermore, in NCs, the value of ReHo in clusters belonging to the default mode network (DMN) decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients. This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states. PMID:27047375

  6. Altered microstructure within social-cognitive brain networks during childhood in Williams syndrome.

    PubMed

    Haas, Brian W; Barnea-Goraly, Naama; Sheau, Kristen E; Yamagata, Bun; Ullas, Shruti; Reiss, Allan L

    2014-10-01

    Williams syndrome (WS) is a neurodevelopmental condition caused by a hemizygous deletion of ∼26-28 genes on chromosome 7q11.23. WS is associated with a distinctive pattern of social cognition. Accordingly, neuroimaging studies show that WS is associated with structural alterations of key brain regions involved in social cognition during adulthood. However, very little is currently known regarding the neuroanatomical structure of social cognitive brain networks during childhood in WS. This study used diffusion tensor imaging to investigate the structural integrity of a specific set of white matter pathways (inferior fronto-occipital fasciculus [IFOF] and uncinate fasciculus [UF]) and associated brain regions [fusiform gyrus (FG), amygdala, hippocampus, medial orbitofrontal gyrus (MOG)] known to be involved in social cognition in children with WS and a typically developing (TD) control group. Children with WS exhibited higher fractional anisotropy (FA) and axial diffusivity values and lower radial diffusivity and apparent diffusion coefficient (ADC) values within the IFOF and UF, higher FA values within the FG, amygdala, and hippocampus and lower ADC values within the FG and MOG compared to controls. These findings provide evidence that the WS genetic deletion affects the development of key white matter pathways and brain regions important for social cognition.

  7. In vitro study on the alterations of brain tubulin structure and assembly affected by magnetite nanoparticles.

    PubMed

    Dadras, Ali; Riazi, Gholam Hossein; Afrasiabi, Ali; Naghshineh, Ali; Ghalandari, Behafarid; Mokhtari, Farzad

    2013-03-01

    In recent decades, considerable efforts have been made to understand the mechanism of memory, cognition, and relevant neurodegenerative diseases in the human brain. Several studies have shown the importance of microtubule proteins in the memory mechanism and memory dysfunction. Microtubules possess dynamicity, which is essential for functions of neuronal networks. Microtubule-associated proteins, i.e., tau, play vital roles in microtubule stability. On the other hand, the ferromagnetic mineral magnetite (Fe(3)O(4)) has been detected in the normal human brain, and elevated levels of magnetite are also observed in the brains of Alzheimer's disease patients. Therefore, we propose that a relationship between microtubule organization in axons and brain magnetite nanoparticles is possible. In this study we found alterations of microtubule polymerization in the presence of increasing concentrations of magnetite through transmission electron microscopy images and a turbidimetry method. Structural changes of microtubule and tau protein, as an essential microtubule-associated protein for tubulin assembly, were detected via circular dichroism spectroscopy, intrinsic fluorescence, and 8-anilino-1-naphthalenesulfonic acid fluorometry. We predicted three possible binding sites on tau protein and one possible binding site on tubulin dimer for magnetite nanoparticles. Magnetite also causes the morphology of PC12 cells to change abnormally and cell viability to decrease. Finally, we suggest that magnetite changes microtubule dynamics and polymerization through two paths: (1) changing the secondary and tertiary structure of tubulin and (2) binding to either tubulin dimer or tau protein and preventing tau-tubulin interaction.

  8. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

    PubMed Central

    Guillermo, Rosamond B.; Yang, Panzao; Vickers, Mark H.; McJarrow, Paul; Guan, Jian

    2015-01-01

    Background Supplementation with complex milk lipids (CML) during postnatal brain development has been shown to improve spatial reference learning in rats. Objective The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design The study used the brain tissues from the rats (male Wistar, 80 days of age) after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01), but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05), but did not alter glutamate receptors, myelination or vascular density. Conclusion CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling. PMID:25818888

  9. Amelioration of altered antioxidant status and membrane linked functions by vanadium and Trigonella in alloxan diabetic rat brains.

    PubMed

    Siddiqui, Mohammad Rizwan; Taha, Asia; Moorthy, K; Hussain, Mohd Ejaz; Basir, S F; Baquer, Najma Zaheer

    2005-09-01

    Trigonella foenum graecum seed powder (TSP) and sodium orthovanadate (SOV) have been reported to have antidiabetic effects. However, SOV exerts hypoglycemic effects at relatively high doses with several toxic effects. We used low doses of vanadate in combination with TSP and evaluated their antidiabetic effects on anti-oxidant enzymes and membrane-linked functions in diabetic rat brains. In rats, diabetes was induced by alloxan monohydrate (15 mg/100 g body wt.) and they were treated with 2 IU insulin, 0.6 mg/ml SOV, 5% TSP and a combination of 0.2 mg/ml SOV with 5% TSP for 21 days. Blood glucose levels, activity of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), Na+/K+ ATPase, membrane lipid peroxidation and fluidity were determined in different fractions of whole brain after 21 days of treatment. Diabetic rats showed high blood glucose (P less than 0.001), decreased activities of SOD, catalase and Na+/K+ ATPase (P less than 0.01, P less than 0.001 and P less than 0.01), increased levels of GPx and MDA (P less than 0.01 and P less than 0.001) and decreased membrane fluidity (P less than 0.01). Treatment with different antidiabetic compounds restored the above-altered parameters. Combined dose of Trigonella and vanadate was found to be the most effective treatment in normalizing these alterations. Lower doses of vanadate could be used in combination with TSP to effectively counter diabetic alterations without any toxic effects.

  10. Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity

    PubMed Central

    Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

    2016-01-01

    Background Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Methods Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Results Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. Conclusions These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity. PMID:27575491

  11. Hereditary catalepsy in mice is associated with the brain dysmorphology and altered stress response.

    PubMed

    Tikhonova, Maria A; Kulikov, Alexander V; Bazovkina, Daria V; Kulikova, Elizabeth A; Tsybko, Anton S; Bazhenova, Ekaterina Yu; Naumenko, Vladimir S; Akulov, Andrey E; Moshkin, Mikhail P; Popova, Nina K

    2013-04-15

    Catalepsy is a passive defensive strategy in response to threatening stimuli. In exaggerated forms it is associated with brain dysfunctions. The study was aimed to examine (1) possible association of the hereditary catalepsy with neuroanatomical characteristics and (2) sensitivity of the catalepsy expression, HPA and brain serotonin (5-HT) systems to restraint stress (for one hour) in mice of catalepsy-prone (CBA/Lac, ASC (Antidepressant Sensitive Catalepsy), congenic AKR.CBA-D13M76) and catalepsy-resistant (AKR/J) strains. Magnetic resonance imaging showed that the catalepsy-prone mice were characterized by the smaller size of the pituitary gland and the larger size of the thalamus. In ASC mice, diencephalon region (including hypothalamus) and striatum were significantly reduced in size. Restraint stress provoked catalepsy in AKR mice and enhanced it in the catalepsy-prone mice. Stress-induced corticosterone elevation was diminished, while 5-HT metabolism (5-HIAA level or 5-HIAA/5-HT ratio) in the midbrain was significantly augmented by stress in the catalepsy-prone mice. The multivariate factor analysis revealed interactions between the basal levels and the stress-induced alterations of 5-HT metabolism in the hippocampus and midbrain suggesting the interaction between multiple alterations in 5-HT neurotransmission in several brain structures in the regulation of hereditary catalepsy. The study indicated an association between the hereditary catalepsy, neuroanatomical characteristics, and neurochemical responses to emotional stress. The catalepsy-prone genotypes seem to be more susceptible to stress that suggests them as the adequate models to study the genetic predisposition to stress-based neuropathology. The data support the association of hereditary catalepsy with the inherited brain dysfunction of a neurodegenerative nature.

  12. Brain Connectivity Alterations Are Associated with the Development of Dementia in Parkinson's Disease.

    PubMed

    Bertrand, Josie-Anne; McIntosh, Anthony R; Postuma, Ronald B; Kovacevic, Natasha; Latreille, Véronique; Panisset, Michel; Chouinard, Sylvain; Gagnon, Jean-François

    2016-04-01

    Dementia affects a high proportion of Parkinson's disease (PD) patients and poses a burden on caregivers and healthcare services. Electroencephalography (EEG) is a common nonevasive and nonexpensive technique that can easily be used in clinical settings to identify brain functional abnormalities. Only few studies had identified EEG abnormalities that can predict PD patients at higher risk for dementia. Brain connectivity EEG measures, such as multiscale entropy (MSE) and phase-locking value (PLV) analyses, may be more informative and sensitive to brain alterations leading to dementia than previously used methods. This study followed 62 dementia-free PD patients for a mean of 3.4 years to identify cerebral alterations that are associated with dementia. Baseline resting state EEG of patients who developed dementia (N = 18) was compared to those of patients who remained dementia-free (N = 44) and of 37 healthy subjects. MSE and PLV analyses were performed. Partial least squares statistical analysis revealed group differences associated with the development of dementia. Patients who developed dementia showed higher signal complexity and lower PLVs in low frequencies (mainly in delta frequency) than patients who remained dementia-free and controls. Conversely, both patient groups showed lower signal variability and higher PLVs in high frequencies (mainly in gamma frequency) compared to controls, with the strongest effect in patients who developed dementia. These findings suggest that specific disruptions of brain communication can be measured before PD patients develop dementia, providing a new potential marker to identify patients at highest risk of developing dementia and who are the best candidates for neuroprotective trials. PMID:26708056

  13. Alteration of Electro-Cortical Activity in Microgravity

    NASA Astrophysics Data System (ADS)

    Schneider, Stefan; Brummer, Vera; Carnahan, Heather; Askew, Christopher D.; Guardiera, Simon; Struder, Heiko K.

    2008-06-01

    There is growing interest in the effects of weightlessness on central nervous system (CNS) activity. Due to technical and logistical limitations it presently seems impossible to apply imaging techniques as fMRI or PET in weightless environments e.g. on ISS or during parabolic flights. Within this study we evaluated changes in brain cortical activity using low resolution brain electromagnetic tomography (LORETA) during parabolic flights. Results showed a distinct inhibition of right frontal area activity >12Hz during phases of microgravity compared to normal gravity. We conclude that the inhibition of high frequency frontal activity during microgravity may serve as a marker of emotional anxiety and/or indisposition associated with weightlessness. This puts a new light on the debate as to whether cognitive and sensorimotor impairments are attributable to primary physiological effects or secondary psychological effects of a weightless environment.

  14. Cortisol's effects on hippocampal activation in depressed patients are related to alterations in memory formation.

    PubMed

    Abercrombie, Heather C; Jahn, Allison L; Davidson, Richard J; Kern, Simone; Kirschbaum, Clemens; Halverson, Jerry

    2011-01-01

    Many investigators have hypothesized that brain response to cortisol is altered in depression. However, neural activation in response to exogenously manipulated cortisol elevations has not yet been directly examined in depressed humans. Animal research shows that glucocorticoids have robust effects on hippocampal function, and can either enhance or suppress neuroplastic events in the hippocampus depending on a number of factors. We hypothesized that depressed individuals would show 1) altered hippocampal response to exogenous administration of cortisol, and 2) altered effects of cortisol on learning. In a repeated-measures design, 19 unmedicated depressed and 41 healthy individuals completed two fMRI scans. Fifteen mg oral hydrocortisone (i.e., cortisol) or placebo (order randomized and double-blind) was administered 1 h prior to encoding of emotional and neutral words during fMRI scans. Data analysis examined the effects of cortisol administration on 1) brain activation during encoding, and 2) subsequent free recall for words. Cortisol affected subsequent recall performance in depressed but not healthy individuals. We found alterations in hippocampal response to cortisol in depressed women, but not in depressed men (who showed altered response to cortisol in other regions, including subgenual prefrontal cortex). In both depressed men and women, cortisol's effects on hippocampal function were positively correlated with its effects on recall performance assessed days later. Our data provide evidence that in depressed compared to healthy women, cortisol's effects on hippocampal function are altered. Our data also show that in both depressed men and women, cortisol's effects on emotional memory formation and hippocampal function are related.

  15. Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks.

    PubMed

    Kim, Hyungjun; Kim, Jieun; Loggia, Marco L; Cahalan, Christine; Garcia, Ronald G; Vangel, Mark G; Wasan, Ajay D; Edwards, Robert R; Napadow, Vitaly

    2015-01-01

    Altered brain morphometry has been widely acknowledged in chronic pain, and recent studies have implicated altered network dynamics, as opposed to properties of individual brain regions, in supporting persistent pain. Structural covariance analysis determines the inter-regional association in morphological metrics, such as gray matter volume, and such structural associations may be altered in chronic pain. In this study, voxel-based morphometry structural covariance networks were compared between fibromyalgia patients (N = 42) and age- and sex-matched pain-free adults (N = 63). We investigated network topology using spectral partitioning, which can delineate local network submodules with consistent structural covariance. We also explored white matter connectivity between regions comprising these submodules and evaluated the association between probabilistic white matter tractography and pain-relevant clinical metrics. Our structural covariance network analysis noted more connections within the cerebellum for fibromyalgia patients, and more connections in the frontal lobe for healthy controls. For fibromyalgia patients, spectral partitioning identified a distinct submodule with cerebellar connections to medial prefrontal and temporal and right inferior parietal lobes, whose gray matter volume was associated with the severity of depression in these patients. Volume for a submodule encompassing lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and insular cortices was correlated with evoked pain sensitivity. Additionally, the number of white matter fibers between specific submodule regions was also associated with measures of evoked pain sensitivity and clinical pain interference. Hence, altered gray and white matter morphometry in cerebellar and frontal cortical regions may contribute to, or result from, pain-relevant dysfunction in chronic pain patients.

  16. Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks.

    PubMed

    Kim, Hyungjun; Kim, Jieun; Loggia, Marco L; Cahalan, Christine; Garcia, Ronald G; Vangel, Mark G; Wasan, Ajay D; Edwards, Robert R; Napadow, Vitaly

    2015-01-01

    Altered brain morphometry has been widely acknowledged in chronic pain, and recent studies have implicated altered network dynamics, as opposed to properties of individual brain regions, in supporting persistent pain. Structural covariance analysis determines the inter-regional association in morphological metrics, such as gray matter volume, and such structural associations may be altered in chronic pain. In this study, voxel-based morphometry structural covariance networks were compared between fibromyalgia patients (N = 42) and age- and sex-matched pain-free adults (N = 63). We investigated network topology using spectral partitioning, which can delineate local network submodules with consistent structural covariance. We also explored white matter connectivity between regions comprising these submodules and evaluated the association between probabilistic white matter tractography and pain-relevant clinical metrics. Our structural covariance network analysis noted more connections within the cerebellum for fibromyalgia patients, and more connections in the frontal lobe for healthy controls. For fibromyalgia patients, spectral partitioning identified a distinct submodule with cerebellar connections to medial prefrontal and temporal and right inferior parietal lobes, whose gray matter volume was associated with the severity of depression in these patients. Volume for a submodule encompassing lateral orbitofrontal, inferior frontal, postcentral, lateral temporal, and insular cortices was correlated with evoked pain sensitivity. Additionally, the number of white matter fibers between specific submodule regions was also associated with measures of evoked pain sensitivity and clinical pain interference. Hence, altered gray and white matter morphometry in cerebellar and frontal cortical regions may contribute to, or result from, pain-relevant dysfunction in chronic pain patients. PMID:25844321

  17. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats.

    PubMed

    Davies, Daniel R; Olson, Dawne; Meyer, Danielle L; Scholl, Jamie L; Watt, Michael J; Manzerra, Pasquale; Renner, Kenneth J; Forster, Gina L

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  18. Mild Traumatic Brain Injury with Social Defeat Stress Alters Anxiety, Contextual Fear Extinction, and Limbic Monoamines in Adult Rats

    PubMed Central

    Davies, Daniel R.; Olson, Dawne; Meyer, Danielle L.; Scholl, Jamie L.; Watt, Michael J.; Manzerra, Pasquale; Renner, Kenneth J.; Forster, Gina L.

    2016-01-01

    Mild traumatic brain injury (mTBI) produces symptoms similar to those typifying posttraumatic stress disorder (PTSD) in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM), or for contextual fear conditioning and extinction. Brains were collected 24 h after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes. PMID:27147992

  19. Investigating the physiology of brain activation with MRI

    NASA Astrophysics Data System (ADS)

    Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

    2004-04-01

    Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

  20. Invisible Brain: Knowledge in Research Works and Neuron Activity.

    PubMed

    Segev, Aviv; Curtis, Dorothy; Jung, Sukhwan; Chae, Suhyun

    2016-01-01

    If the market has an invisible hand, does knowledge creation and representation have an "invisible brain"? While knowledge is viewed as a product of neuron activity in the brain, can we identify knowledge that is outside the brain but reflects the activity of neurons in the brain? This work suggests that the patterns of neuron activity in the brain can be seen in the representation of knowledge-related activity. Here we show that the neuron activity mechanism seems to represent much of the knowledge learned in the past decades based on published articles, in what can be viewed as an "invisible brain" or collective hidden neural networks. Similar results appear when analyzing knowledge activity in patents. Our work also tries to characterize knowledge increase as neuron network activity growth. The results propose that knowledge-related activity can be seen outside of the neuron activity mechanism. Consequently, knowledge might exist as an independent mechanism. PMID:27439199

  1. The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)

    EPA Science Inventory

    The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...

  2. Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli.

    PubMed

    Hasen, Nina S; Gammie, Stephen C

    2011-03-01

    The trpc2 gene encodes an ion channel involved in pheromonal detection and is found in the vomeronasal organ. In tprc2(-/-) knockout (KO) mice, maternal aggression (offspring protection) is impaired and brain Fos expression in females in response to a male are reduced. Here we examine in lactating wild-type (WT) and KO mice behavioral and brain responses to different olfactory/pheromonal cues. Consistent with previous studies, KO dams exhibited decreased maternal aggression and nest building, but we also identified deficits in nighttime nursing and increases in pup weight. When exposed to the bedding tests, WT dams typically ignored clean bedding, but buried male-soiled bedding from unfamiliar males. In contrast, KO dams buried both clean and soiled bedding. Differences in brain Fos expression were found between WT and KO mice in response to either no bedding, clean bedding, or soiled bedding. In the accessory olfactory bulb, a site of pheromonal signal processing, KO mice showed suppressed Fos activation in the anterior mitral layer relative to WT mice in response to clean and soiled bedding. However, in the medial and basolateral amygdala, KO mice showed a robust Fos response to bedding, suggesting that regions of the amygdala canonically associated with pheromonal sensing can be active in the brains of KO mice, despite compromised signaling from the vomeronasal organ. Together, these results provide further insights into the complex ways by which pheromonal signaling regulates the brain and behavior of the maternal female.

  3. Brain-derived neurotrophic factor in human subjects with function-altering melanocortin-4 receptor variants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In rodents, hypothalamic brain-derived neurotrophic factor (BDNF) expression appears to be regulated by melanocortin-4 receptor (MC4R) activity. The impact of MC4R genetic variation on circulating BDNF in humans is unknown. The objective of this study is to compare BDNF concentrations of subjects wi...

  4. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain.

    PubMed

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn(2+) affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases. PMID:27300264

  5. Alterations in Brain Inflammation, Synaptic Proteins, and Adult Hippocampal Neurogenesis during Epileptogenesis in Mice Lacking Synapsin2.

    PubMed

    Chugh, Deepti; Ali, Idrish; Bakochi, Anahita; Bahonjic, Elma; Etholm, Lars; Ekdahl, Christine T

    2015-01-01

    Synapsins are pre-synaptic vesicle-associated proteins linked to the pathogenesis of epilepsy through genetic association studies in humans. Deletion of synapsins causes an excitatory/inhibitory imbalance, exemplified by the epileptic phenotype of synapsin knockout mice. These mice develop handling-induced tonic-clonic seizures starting at the age of about 3 months. Hence, they provide an opportunity to study epileptogenic alterations in a temporally controlled manner. Here, we evaluated brain inflammation, synaptic protein expression, and adult hippocampal neurogenesis in the epileptogenic (1 and 2 months of age) and tonic-clonic (3.5-4 months) phase of synapsin 2 knockout mice using immunohistochemical and biochemical assays. In the epileptogenic phase, region-specific microglial activation was evident, accompanied by an increase in the chemokine receptor CX3CR1, interleukin-6, and tumor necrosis factor-α, and a decrease in chemokine keratinocyte chemoattractant/ growth-related oncogene. Both post-synaptic density-95 and gephyrin, scaffolding proteins at excitatory and inhibitory synapses, respectively, showed a significant up-regulation primarily in the cortex. Furthermore, we observed an increase in the inhibitory adhesion molecules neuroligin-2 and neurofascin and potassium chloride co-transporter KCC2. Decreased expression of γ-aminobutyric acid receptor-δ subunit and cholecystokinin was also evident. Surprisingly, hippocampal neurogenesis was reduced in the epileptogenic phase. Taken together, we report molecular alterations in brain inflammation and excitatory/inhibitory balance that could serve as potential targets for therapeutics and diagnostic biomarkers. In addition, the regional differences in brain inflammation and synaptic protein expression indicate an epileptogenic zone from where the generalized seizures in synapsin 2 knockout mice may be initiated or spread. PMID:26177381

  6. Obesity and age-related alterations in the gene expression of zinc-transporter proteins in the human brain

    PubMed Central

    Olesen, R H; Hyde, T M; Kleinman, J E; Smidt, K; Rungby, J; Larsen, A

    2016-01-01

    The incidence of Alzheimer's disease (AD) is increasing. Major risk factors for AD are advancing age and diabetes. Lately, obesity has been associated with an increased risk of dementia. Obese and diabetic individuals are prone to decreased circulating levels of zinc, reducing the amount of zinc available for crucial intracellular processes. In the brain, zinc co-localizes with glutamate in synaptic vesicles, and modulates NMDA receptor activity. Intracellular zinc is involved in apoptosis and fluctuations in cytoplasmic Zn2+ affect modulation of intracellular signaling. The ZNT and ZIP proteins participate in intracellular zinc homeostasis. Altered expression of zinc-regulatory proteins has been described in AD patients. Using microarray data from human frontal cortex (BrainCloud), this study investigates expression of the SCLA30A (ZNT) and SCLA39A (ZIP) families of genes in a Caucasian and African-American sample of 145 neurologically and psychiatrically normal individuals. Expression of ZNT3 and ZNT4 were significantly reduced with increasing age, whereas expression of ZIP1, ZIP9 and ZIP13 were significantly increased. Increasing body mass index (BMI) correlated with a significant reduction in ZNT1 expression similar to what is seen in the early stages of AD. Increasing BMI also correlated with reduced expression of ZNT6. In conclusion, we found that the expression of genes that regulate intracellular zinc homeostasis in the human frontal cortex is altered with increasing age and affected by increasing BMI. With the increasing rates of obesity throughout the world, these findings warrant continuous scrutiny of the long-term consequences of obesity on brain function and the development of neurodegenerative diseases. PMID:27300264

  7. Brain mechanical property measurement using MRE with intrinsic activation

    NASA Astrophysics Data System (ADS)

    Weaver, John B.; Pattison, Adam J.; McGarry, Matthew D.; Perreard, Irina M.; Swienckowski, Jessica G.; Eskey, Clifford J.; Lollis, S. Scott; Paulsen, Keith D.

    2012-11-01

    Many pathologies alter the mechanical properties of tissue. Magnetic resonance elastography (MRE) has been developed to noninvasively characterize these quantities in vivo. Typically, small vibrations are induced in the tissue of interest with an external mechanical actuator. The resulting displacements are measured with phase contrast sequences and are then used to estimate the underlying mechanical property distribution. Several MRE studies have quantified brain tissue properties. However, the cranium and meninges, especially the dura, are very effective at damping externally applied vibrations from penetrating deeply into the brain. Here, we report a method, termed ‘intrinsic activation’, that eliminates the requirement for external vibrations by measuring the motion generated by natural blood vessel pulsation. A retrospectively gated phase contrast MR angiography sequence was used to record the tissue velocity at eight phases of the cardiac cycle. The velocities were numerically integrated via the Fourier transform to produce the harmonic displacements at each position within the brain. The displacements were then reconstructed into images of the shear modulus based on both linear elastic and poroelastic models. The mechanical properties produced fall within the range of brain tissue estimates reported in the literature and, equally important, the technique yielded highly reproducible results. The mean shear modulus was 8.1 kPa for linear elastic reconstructions and 2.4 kPa for poroelastic reconstructions where fluid pressure carries a portion of the stress. Gross structures of the brain were visualized, particularly in the poroelastic reconstructions. Intra-subject variability was significantly less than the inter-subject variability in a study of six asymptomatic individuals. Further, larger changes in mechanical properties were observed in individuals when examined over time than when the MRE procedures were repeated on the same day. Cardiac pulsation

  8. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways

    PubMed Central

    Rogers, G B; Keating, D J; Young, R L; Wong, M-L; Licinio, J; Wesselingh, S

    2016-01-01

    The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut–brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies. PMID:27090305

  9. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways.

    PubMed

    Rogers, G B; Keating, D J; Young, R L; Wong, M-L; Licinio, J; Wesselingh, S

    2016-06-01

    The human body hosts an enormous abundance and diversity of microbes, which perform a range of essential and beneficial functions. Our appreciation of the importance of these microbial communities to many aspects of human physiology has grown dramatically in recent years. We know, for example, that animals raised in a germ-free environment exhibit substantially altered immune and metabolic function, while the disruption of commensal microbiota in humans is associated with the development of a growing number of diseases. Evidence is now emerging that, through interactions with the gut-brain axis, the bidirectional communication system between the central nervous system and the gastrointestinal tract, the gut microbiome can also influence neural development, cognition and behaviour, with recent evidence that changes in behaviour alter gut microbiota composition, while modifications of the microbiome can induce depressive-like behaviours. Although an association between enteropathy and certain psychiatric conditions has long been recognized, it now appears that gut microbes represent direct mediators of psychopathology. Here, we examine roles of gut microbiome in shaping brain development and neurological function, and the mechanisms by which it can contribute to mental illness. Further, we discuss how the insight provided by this new and exciting field of research can inform care and provide a basis for the design of novel, microbiota-targeted, therapies. PMID:27090305

  10. In vivo evidence of global and focal brain alterations in anorexia nervosa.

    PubMed

    Boghi, Andrea; Sterpone, Sara; Sales, Stefano; D'Agata, Federico; Bradac, Gianni Boris; Zullo, Giuseppina; Munno, Donato

    2011-06-30

    Brain alterations are known to be associated with anorexia nervosa (AN) and tend to be distributed across brain structures, with only a few reports describing focal damage. Magnetic resonance images of 21 anorexic patients with different disease duration and 27 control subjects were acquired and compared using voxel-based morphometry (VBM). Patients had a significant reduction of total white matter (WM) volume and focal gray matter (GM) atrophy in cerebellum, hypothalamus, caudate nucleus and frontal, parietal and temporal areas. The cerebellum was more affected in patients with longer disease duration, whereas the hypothalamic alterations were more pronounced in patients with shorter food restriction. A correlation with body mass index (BMI) and GM was found in the hypothalamus. Our data demonstrate a diffuse reduction of WM together with focal areas of GM atrophy in AN. The finding of a hypothalamic focal atrophy points to hormonal dysfunction and opens the possibility for a central dysregulation of homeostasis. The involvement of temporoparietal areas could account for body image distortion. Finally, the cerebellar GM atrophy confirms previous findings and seems to be a late consequence of AN that could play a role in the chronic phase of the disease.

  11. Altered spontaneous activity in antisocial personality disorder revealed by regional homogeneity.

    PubMed

    Tang, Yan; Liu, Wangyong; Chen, Jingang; Liao, Jian; Hu, Dewen; Wang, Wei

    2013-08-01

    There is increasing evidence that antisocial personality disorder (ASPD) stems from brain abnormalities. However, there are only a few studies investigating brain structure in ASPD. The aim of this study was to find regional coherence abnormalities in resting-state functional MRI of ASPD. Thirty-two ASPD individuals and 34 controls underwent a resting-state functional MRI scan. The regional homogeneity (ReHo) approach was used to examine whether ASPD was related to alterations in resting-state neural activity. Support vector machine discriminant analysis was used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the ASPD individuals and controls. The results showed that, compared with controls, ASPD individuals show lower ReHo in the right cerebellum posterior lobe (Crus1) and the right middle frontal gyrus, as well as higher ReHo in the right middle occipital gyrus (BA 19), left inferior temporal gyrus (BA 37), and right inferior occipital gyrus (cuneus, BA 18). All alternation regions reported a predictive accuracy above 70%. To our knowledge, this study was the first to study the change in regional activity coherence in the resting brain of ASPD individuals. These results not only elucidated the pathological mechanism of ASPD from a resting-state functional viewpoint but also showed that these alterations in ReHo may serve as potential markers for the detection of ASPD.

  12. Brain activities during synchronized tapping task.

    PubMed

    Hiroyasu, Tomoyuki; Murakami, Akiho; Mao Gto; Yokouchi, Hisatake

    2015-01-01

    This study aims to investigate how people process information about other people to determine a response during human-to-human cooperative work. As a preliminary study, the mechanism of cooperative work was examined using interaction between a machine and a human. This machine was designed to have an "other person" model that simulates an emotional model of another person. The task performed in the experiment was a synchronized tapping task. Two models were prepared for this experiment, a simple model that does not employ the other person model and a synchronized model that employs the other person model. Subjects performed cooperative work with these machines. During the experiment, brain activities were measured using functional near-infrared spectroscopy. It was observed that the left inferior frontal gyrus was activated more with the synchronized model than the simple model. PMID:26737670

  13. Brain Activity with Reading Sentences and Emoticons

    NASA Astrophysics Data System (ADS)

    Yuasa, Masahide; Saito, Keiichi; Mukawa, Naoki

    In this paper, we describe a person's brain activity when he/she sees an emoticon at the end of a sentence. An emoticon consists of some characters that resemble the human face and expresses a sender's emotion. With the help of a computer network, we use e-mail, messenger, avatars and so on, in order to convey what we wish to, to a receiver. Moreover, we send an emotional expression by using an emoticon at the end of a sentence. In this research, we investigate the effect of an emoticon as nonverbal information, using an fMRI study. The experimental results show that the right and left inferior frontal gyrus were activated and we detect a sentence with an emoticon as the verbal and nonverval information.

  14. Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.

    PubMed

    Palesi, Fulvia; Castellazzi, Gloria; Casiraghi, Letizia; Sinforiani, Elena; Vitali, Paolo; Gandini Wheeler-Kingshott, Claudia A M; D'Angelo, Egidio

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a "disconnection

  15. Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis

    PubMed Central

    Palesi, Fulvia; Castellazzi, Gloria; Casiraghi, Letizia; Sinforiani, Elena; Vitali, Paolo; Gandini Wheeler-Kingshott, Claudia A. M.; D'Angelo, Egidio

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the “disconnection syndrome” hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a

  16. Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis

    PubMed Central

    Palesi, Fulvia; Castellazzi, Gloria; Casiraghi, Letizia; Sinforiani, Elena; Vitali, Paolo; Gandini Wheeler-Kingshott, Claudia A. M.; D'Angelo, Egidio

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the “disconnection syndrome” hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a

  17. Exploring Patterns of Alteration in Alzheimer's Disease Brain Networks: A Combined Structural and Functional Connectomics Analysis.

    PubMed

    Palesi, Fulvia; Castellazzi, Gloria; Casiraghi, Letizia; Sinforiani, Elena; Vitali, Paolo; Gandini Wheeler-Kingshott, Claudia A M; D'Angelo, Egidio

    2016-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by a severe derangement of cognitive functions, primarily memory, in elderly subjects. As far as the functional impairment is concerned, growing evidence supports the "disconnection syndrome" hypothesis. Recent investigations using fMRI have revealed a generalized alteration of resting state networks (RSNs) in patients affected by AD and mild cognitive impairment (MCI). However, it was unclear whether the changes in functional connectivity were accompanied by corresponding structural network changes. In this work, we have developed a novel structural/functional connectomic approach: resting state fMRI was used to identify the functional cortical network nodes and diffusion MRI to reconstruct the fiber tracts to give a weight to internodal subcortical connections. Then, local and global efficiency were determined for different networks, exploring specific alterations of integration and segregation patterns in AD and MCI patients compared to healthy controls (HC). In the default mode network (DMN), that was the most affected, axonal loss, and reduced axonal integrity appeared to compromise both local and global efficiency along posterior-anterior connections. In the basal ganglia network (BGN), disruption of white matter integrity implied that main alterations occurred in local microstructure. In the anterior insular network (AIN), neuronal loss probably subtended a compromised communication with the insular cortex. Cognitive performance, evaluated by neuropsychological examinations, revealed a dependency on integration and segregation of brain networks. These findings are indicative of the fact that cognitive deficits in AD could be associated not only with cortical alterations (revealed by fMRI) but also with subcortical alterations (revealed by diffusion MRI) that extend beyond the areas primarily damaged by neurodegeneration, toward the support of an emerging concept of AD as a "disconnection

  18. Altered long non-coding RNA transcriptomic profiles in brain microvascular endothelium after cerebral ischemia.

    PubMed

    Zhang, J; Yuan, L; Zhang, X; Hamblin, M H; Zhu, T; Meng, F; Li, Y; Chen, Y E; Yin, K J

    2016-03-01

    The brain endothelium is an important therapeutic target for the inhibition of cerebrovascular dysfunction in ischemic stroke. Previously, we documented the important regulatory roles of microRNAs in the cerebral vasculature, in particular the cerebral vascular endothelium. However, the functional significance and molecular mechanisms of other classes of non-coding RNAs in the regulation of cerebrovascular endothelial pathophysiology after stroke are completely unknown. Using RNA sequencing (RNA-seq) technology, we profiled long non-coding RNA (lncRNA) expressional signatures in primary brain microvascular endothelial cells (BMECs) after oxygen-glucose deprivation (OGD), an in vitro mimic of ischemic stroke conditions. After 16h of OGD exposure, the expression levels for 362 of the 10,677 lncRNAs analyzed changed significantly, including a total of 147 lncRNAs increased and 70 lncRNAs decreased by more than 2-fold. Among them, the most highly upregulated lncRNAs include Snhg12, Malat1, and lnc-OGD 1006, whereas the most highly downregulated lncRNAs include 281008D09Rik, Peg13, and lnc-OGD 3916. Alteration of the most highly upregulated/downregulated ODG-responsive lncRNAs was further confirmed in cultured BMECs after OGD as well as isolated cerebral microvessels in mice following transient middle cerebral artery occlusion (MCAO) and 24h reperfusion by the quantitative real-time PCR approach. Moreover, promoter analysis of altered ODG-responsive endothelial lncRNA genes by bioinformatics showed substantial transcription factor binding sites on lncRNAs, implying potential transcriptional regulation of those lncRNAs. These findings are the first to identify OGD-responsive brain endothelial lncRNAs, which suggest potential pathological roles for these lncRNAs in mediating endothelial responses to ischemic stimuli. Endothelial-selective lncRNAs may function as a class of novel master regulators in cerebrovascular endothelial pathologies after ischemic stroke.

  19. An acute dose of gamma-hydroxybutyric acid alters gene expression in multiple mouse brain regions.

    PubMed

    Schnackenberg, B J; Saini, U T; Robinson, B L; Ali, S F; Patterson, T A

    2010-10-13

    Gamma-hydroxybutyric acid (GHB) is normally found in the brain in low concentrations and may function as a neurotransmitter, although the mechanism of action has not been completely elucidated. GHB has been used as a general anesthetic and is currently used to treat narcolepsy and alcoholism. Recreational use of GHB is primarily as a "club drug" and a "date rape drug," due to its amnesic effects. For this study, the hypothesis was that behavioral and neurochemical alterations may parallel gene expression changes in the brain after GHB administration. Adult male C57/B6N mice (n=5/group) were administered a single dose of 500 mg/kg GHB (i.p.) and were sacrificed 1, 2 and 4 h after treatment. Control mice were administered saline. Brains were removed and regionally dissected on ice. Total RNA from the hippocampus, cortex and striatum was extracted, amplified and labeled. Gene expression was evaluated using Agilent whole mouse genome 4x44K oligonucleotide microarrays. Microarray data were analyzed by ArrayTrack and differentially expressed genes (DEGs) were identified using P < or = 0.01 and a fold change > or = 1.7 as the criteria for significance. Principal component analysis (PCA) and Hierarchical Cluster Analysis (HCA) showed that samples from each time point clustered into distinct treatment groups with respect to sacrifice time. Ingenuity pathways analysis (IPA) was used to identify involved pathways. The results show that GHB induces gene expression alterations in hundreds of genes in the hippocampus, cortex and striatum, and the number of affected genes increases throughout a 4-h time course. Many of these DEGs are involved in neurological disease, apoptosis, and oxidative stress.

  20. Structural Alterations of the Social Brain: A Comparison between Schizophrenia and Autism

    PubMed Central

    Radeloff, Daniel; Ciaramidaro, Angela; Siniatchkin, Michael; Hainz, Daniela; Schlitt, Sabine; Weber, Bernhard; Poustka, Fritz; Bölte, Sven; Walter, Henrik; Freitag, Christine Margarete

    2014-01-01

    Autism spectrum disorder and schizophrenia share a substantial number of etiologic and phenotypic characteristics. Still, no direct comparison of both disorders has been performed to identify differences and commonalities in brain structure. In this voxel based morphometry study, 34 patients with autism spectrum disorder, 21 patients with schizophrenia and 26 typically developed control subjects were included to identify global and regional brain volume alterations. No global gray matter or white matter differences were found between groups. In regional data, patients with autism spectrum disorder compared to typically developed control subjects showed smaller gray matter volume in the amygdala, insula, and anterior medial prefrontal cortex. Compared to patients with schizophrenia, patients with autism spectrum disorder displayed smaller gray matter volume in the left insula. Disorder specific positive correlations were found between mentalizing ability and left amygdala volume in autism spectrum disorder, and hallucinatory behavior and insula volume in schizophrenia. Results suggest the involvement of social brain areas in both disorders. Further studies are needed to replicate these findings and to quantify the amount of distinct and overlapping neural correlates in autism spectrum disorder and schizophrenia. PMID:25188200

  1. Motor stereotypies and volumetric brain alterations in children with Autistic Disorder

    PubMed Central

    Goldman, Sylvie; O’Brien, Liam M.; Filipek, Pauline A.; Rapin, Isabelle; Herbert, Martha R.

    2013-01-01

    Motor stereotypies are defined as patterned, repetitive, purposeless movements. These stigmatizing motor behaviors represent one manifestation of the third core criterion for an Autistic Disorder (AD) diagnosis, and are becoming viewed as potential early markers of autism. Moreover, motor stereotypies might be a tangible expression of the underlying neurobiology of this neurodevelopmental disorder. In this study, we videoscored stereotypies recorded during semi-structured play sessions from school age children with AD. We examined the effect of severity and persistence over time of stereotypies on brain volumetric changes. Our findings confirmed that the brain volume of school age children with AD is, on average, larger than that of age-matched typically developing children. However, we have failed to detect any sign of volumetric differences in brain regions thought to be particularly linked to the pathophysiology of stereotypies. This negative finding may suggest that, at least with respect to motor stereotypies, functional rather than structural alterations might be the underpinning of these disruptive motor manifestations of autism. PMID:23637709

  2. Exercise challenge in Gulf War Illness reveals two subgroups with altered brain structure and function.

    PubMed

    Rayhan, Rakib U; Stevens, Benson W; Raksit, Megna P; Ripple, Joshua A; Timbol, Christian R; Adewuyi, Oluwatoyin; VanMeter, John W; Baraniuk, James N

    2013-01-01

    Nearly 30% of the approximately 700,000 military personnel who served in Operation Desert Storm (1990-1991) have developed Gulf War Illness, a condition that presents with symptoms such as cognitive impairment, autonomic dysfunction, debilitating fatigue and chronic widespread pain that implicate the central nervous system. A hallmark complaint of subjects with Gulf War Illness is post-exertional malaise; defined as an exacerbation of symptoms following physical and/or mental effort. To study the causal relationship between exercise, the brain, and changes in symptoms, 28 Gulf War veterans and 10 controls completed an fMRI scan before and after two exercise stress tests to investigate serial changes in pain, autonomic function, and working memory. Exercise induced two clinical Gulf War Illness subgroups. One subgroup presented with orthostatic tachycardia (n = 10). This phenotype correlated with brainstem atrophy, baseline working memory compensation in the cerebellar vermis, and subsequent loss of compensation after exercise. The other subgroup developed exercise induced hyperalgesia (n = 18) that was associated with cortical atrophy and baseline working memory compensation in the basal ganglia. Alterations in cognition, brain structure, and symptoms were absent in controls. Our novel findings may provide an understanding of the relationship between the brain and post-exertional malaise in Gulf War Illness.

  3. Altered Brain Function, Structure, and Developmental Trajectory in Children Born Late Preterm

    PubMed Central

    Brumbaugh, Jane E.; Conrad, Amy L.; Lee, Jessica K.; DeVolder, Ian J.; Zimmerman, M. Bridget; Magnotta, Vincent A.; Axelson, Eric D.; Nopoulos, Peggy C.

    2016-01-01

    Background Late preterm birth (34-36 weeks’ gestation) is a common occurrence with potential for altered brain development. Methods This observational cohort study compared children at age 6-13 years based on the presence or absence of the historical risk factor of late preterm birth. Children completed a battery of cognitive assessments and underwent magnetic resonance imaging of the brain. Results Late preterm children (n=52) demonstrated slower processing speed (p=0.035) and scored more poorly in visual-spatial perception (p=0.032) and memory (p=0.007) than full term children (n=74). Parents of late preterm children reported more behavioral difficulty (p=0.004). There were no group differences in cognitive ability or academic achievement. Imaging revealed similar intracranial volumes but less total tissue and more cerebrospinal fluid (p=0.004) for late preterm children compared to full term children. The tissue difference was driven by differences in the cerebrum (p=0.028) and distributed across cortical (p=0.051) and subcortical tissue (p=0.047). Late preterm children had a relatively smaller thalamus (p=0.012) than full term children. Only full term children demonstrated significant decreases in cortical tissue volume (p<0.001) and thickness (p<0.001) with age. Conclusion Late preterm birth may affect cognition, behavior, and brain structure well beyond infancy. PMID:27064239

  4. Brain structural alterations in obsessive-compulsive disorder patients with autogenous and reactive obsessions.

    PubMed

    Subirà, Marta; Alonso, Pino; Segalàs, Cinto; Real, Eva; López-Solà, Clara; Pujol, Jesús; Martínez-Zalacaín, Ignacio; Harrison, Ben J; Menchón, José M; Cardoner, Narcís; Soriano-Mas, Carles

    2013-01-01

    Obsessive-compulsive disorder (OCD) is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30) and reactive (n = 65) sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally), while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.

  5. The influence of preterm birth on structural alterations of the vision-deprived brain.

    PubMed

    Wan, Catherine Y; Wood, Amanda G; Chen, Jian; Wilson, Sarah J; Reutens, David C

    2013-04-01

    Differences in brain structures between blind and sighted individuals have not been widely investigated. Furthermore, existing studies have included individuals who were blinded by retinopathy of prematurity, a condition that is associated with premature birth. Recent pediatric research has reported structural differences in individuals who were born prematurely, suggesting that some of the structural abnormalities previously observed in blind individuals may be related to prematurity rather than being specific to blindness. In the present study, we used voxel-based morphometry to investigate gray and white matter differences between 24 blind and 16 sighted individuals. Of the blind individuals, six were born prematurely and 18 at term. Compared to those born at term, blind individuals born preterm showed differences in gray, but not white, matter volumes in various brain regions. When the preterm individuals were excluded from analysis, there were significant differences between blind and sighted individuals. Full-term blind individuals showed regional gray matter decreases in the cuneus, lingual gyrus, middle occipital gyrus, precuneus, inferior and superior parietal lobules, and the thalamus, and gray matter increases in the globus pallidus. They also showed regional white matter decreases in the cuneus, lingual gyrus, and the posterior cingulate. These differences were observed in blind individuals irrespective of blindness onset age, providing evidence for structural alterations in the mature brain. Our findings highlight the importance of considering the potential impact of premature birth on neurodevelopmental outcomes in studies of blind individuals.

  6. Chronology and chronicity of altered resting-state functional connectivity after traumatic brain injury.

    PubMed

    Venkatesan, Umesh M; Dennis, Nancy A; Hillary, Frank G

    2015-02-15

    Whereas traumatic brain injury (TBI) results in widespread disruption of neural networks, changes in regional resting-state functional connectivity patterns after insult remain unclear. Specifically, little is known about the chronology of emergent connectivity alterations and whether they persist after a critical recovery window. We used resting-state functional magnetic resonance imaging and seed-voxel correlational analyses in both cross-sectional and longitudinal designs to probe intrinsic connectivity patterns involving the posterior cingulate cortex (PCC) and hippocampi, regions shown to be important in the default mode network (DMN) and vulnerable to neuropathology. A total of 22 participants in the chronic stage of moderate-to-severe TBI and 18 healthy controls were included for cross-sectional study. Longitudinal analyses included 13 individuals in the TBI group for whom data approximately 3 months after injury (subacute) were available. Overall, results indicated dissociable connectivity trajectories of the PCC and hippocampi during recovery from TBI, with PCC alterations characterized by early hypersynchrony with the anterior DMN that is gradually reduced, and hippocampal changes marked by increasing synchrony with proximal cortex and subcortex. The PCC also showed increasing antiphase synchrony with posterior attentional regions, and the hippocampi showed decreasing antiphase synchrony with frontal attentional regions. Antiphase synchrony of the hippocampus and dorsolateral prefrontal cortex at the subacute stage of TBI was positively associated with attentional performance on neuropsychological tests at both the subacute and chronic stages. Our findings highlight the heterogeneity of regional whole-brain connectivity changes after TBI, and suggest that residual connectivity alterations exist in the clinically stable phase of TBI. Parallels between the chronicity of the observed effects and findings in neurodegenerative disease are discussed in the

  7. Chronology and Chronicity of Altered Resting-State Functional Connectivity after Traumatic Brain Injury

    PubMed Central

    Dennis, Nancy A.; Hillary, Frank G.

    2015-01-01

    Abstract Whereas traumatic brain injury (TBI) results in widespread disruption of neural networks, changes in regional resting-state functional connectivity patterns after insult remain unclear. Specifically, little is known about the chronology of emergent connectivity alterations and whether they persist after a critical recovery window. We used resting-state functional magnetic resonance imaging and seed-voxel correlational analyses in both cross-sectional and longitudinal designs to probe intrinsic connectivity patterns involving the posterior cingulate cortex (PCC) and hippocampi, regions shown to be important in the default mode network (DMN) and vulnerable to neuropathology. A total of 22 participants in the chronic stage of moderate-to-severe TBI and 18 healthy controls were included for cross-sectional study. Longitudinal analyses included 13 individuals in the TBI group for whom data approximately 3 months after injury (subacute) were available. Overall, results indicated dissociable connectivity trajectories of the PCC and hippocampi during recovery from TBI, with PCC alterations characterized by early hypersynchrony with the anterior DMN that is gradually reduced, and hippocampal changes marked by increasing synchrony with proximal cortex and subcortex. The PCC also showed increasing antiphase synchrony with posterior attentional regions, and the hippocampi showed decreasing antiphase synchrony with frontal attentional regions. Antiphase synchrony of the hippocampus and dorsolateral prefrontal cortex at the subacute stage of TBI was positively associated with attentional performance on neuropsychological tests at both the subacute and chronic stages. Our findings highlight the heterogeneity of regional whole-brain connectivity changes after TBI, and suggest that residual connectivity alterations exist in the clinically stable phase of TBI. Parallels between the chronicity of the observed effects and findings in neurodegenerative disease are discussed in

  8. A new stress model, a scream sound, alters learning and monoamine levels in rat brain.

    PubMed

    Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen

    2014-01-17

    Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time.

  9. Alterations of motor performance and brain cortex mitochondrial function during ethanol hangover.

    PubMed

    Bustamante, Juanita; Karadayian, Analia G; Lores-Arnaiz, Silvia; Cutrera, Rodolfo A

    2012-08-01

    Ethanol has been known to affect various behavioral parameters in experimental animals, even several hours after ethanol (EtOH) is absent from blood circulation, in the period known as hangover. The aim of this study was to assess the effects of acute ethanol hangover on motor performance in association with the brain cortex energetic metabolism. Evaluation of motor performance and brain cortex mitochondrial function during alcohol hangover was performed in mice 6 hours after a high ethanol dose (hangover onset). Animals were injected i.p. either with saline (control group) or with ethanol (3.8 g/kg BW) (hangover group). Ethanol hangover group showed a bad motor performance compared with control animals (p < .05). Oxygen uptake in brain cortex mitochondria from hangover animals showed a 34% decrease in the respiratory control rate as compared with the control group. Mitochondrial complex activities were decreased being the complex I-III the less affected by the hangover condition; complex II-III was markedly decreased by ethanol hangover showing 50% less activity than controls. Complex IV was 42% decreased as compared with control animals. Hydrogen peroxide production was 51% increased in brain cortex mitochondria from the hangover group, as compared with the control animals. Quantification of the mitochondrial transmembrane potential indicated that ethanol injected animals presented 17% less ability to maintain the polarized condition as compared with controls. These results indicate that a clear decrease in proton motive force occurs in brain cortex mitochondria during hangover conditions. We can conclude that a decreased motor performance observed in the hangover group of animals could be associated with brain cortex mitochondrial dysfunction and the resulting impairment of its energetic metabolism.

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

    PubMed Central

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

    2014-01-01

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

  11. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    PubMed

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing. PMID:25858600

  12. Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments

    PubMed Central

    Siedler, Declan G.; Chuah, Meng Inn; Kirkcaldie, Matthew T. K.; Vickers, James C.; King, Anna E.

    2014-01-01

    Traumatic brain injury (TBI) from penetrating or closed forces to the cranium can result in a range of forms of neural damage, which culminate in mortality or impart mild to significant neurological disability. In this regard, diffuse axonal injury (DAI) is a major neuronal pathophenotype of TBI and is associated with a complex set of cytoskeletal changes. The neurofilament triplet proteins are key structural cytoskeletal elements, which may also be important contributors to the tensile strength of axons. This has significant implications with respect to how axons may respond to TBI. It is not known, however, whether neurofilament compaction and the cytoskeletal changes that evolve following axonal injury represent a component of a protective mechanism following damage, or whether they serve to augment degeneration and progression to secondary axotomy. Here we review the structure and role of neurofilament proteins in normal neuronal function. We also discuss the processes that characterize DAI and the resultant alterations in neurofilaments, highlighting potential clues to a possible protective or degenerative influence of specific neurofilament alterations within injured neurons. The potential utility of neurofilament assays as biomarkers for axonal injury is also discussed. Insights into the complex alterations in neurofilaments will contribute to future efforts in developing therapeutic strategies to prevent, ameliorate or reverse neuronal degeneration in the central nervous system (CNS) following traumatic injury. PMID:25565963

  13. Bilingualism alters brain functional connectivity between "control" regions and "language" regions: Evidence from bimodal bilinguals.

    PubMed

    Li, Le; Abutalebi, Jubin; Zou, Lijuan; Yan, Xin; Liu, Lanfang; Feng, Xiaoxia; Wang, Ruiming; Guo, Taomei; Ding, Guosheng

    2015-05-01

    Previous neuroimaging studies have revealed that bilingualism induces both structural and functional neuroplasticity in the dorsal anterior cingulate cortex (dACC) and the left caudate nucleus (LCN), both of which are associated with cognitive control. Since these "control" regions should work together with other language regions during language processing, we hypothesized that bilingualism may also alter the functional interaction between the dACC/LCN and language regions. Here we tested this hypothesis by exploring the functional connectivity (FC) in bimodal bilinguals and monolinguals using functional MRI when they either performed a picture naming task with spoken language or were in resting state. We found that for bimodal bilinguals who use spoken and sign languages, the FC of the dACC with regions involved in spoken language (e.g. the left superior temporal gyrus) was stronger in performing the task, but weaker in the resting state as compared to monolinguals. For the LCN, its intrinsic FC with sign language regions including the left inferior temporo-occipital part and right inferior and superior parietal lobules was increased in the bilinguals. These results demonstrate that bilingual experience may alter the brain functional interaction between "control" regions and "language" regions. For different control regions, the FC alters in different ways. The findings also deepen our understanding of the functional roles of the dACC and LCN in language processing.

  14. [Cerebral hemodynamics in children of 8-12 years old with alterations of the motor activity of central origin].

    PubMed

    Holovchenko, I V; Haĭdaĭ, M I

    2013-01-01

    In children with altered physical activity there is a lack of brain blood supply, which is the most pronounced in the system of the vertebral arteries right hemisphere, and a low volume speed of blood flow in the internal carotid artery and in the system of the vertebral arteries. Children of the main group have a decreased venous outflow from the cavity of the skull, which is accompanied by altered venous circulation in the sinuses of the brain. It is established that in the system of the vertebral arteries a hemispheric asymmetry of growth in the right hemisphere is observed, in contrast to the left hemisphere, indicators of vascular tone of arterial and venous type of small caliber. Children with altered physical activity have higher values of indicators of venous outflow, than the children of the control group, and they have better venous outflow from the carotid system and a slightly worse with vertebro-basilar.

  15. Human activities change marine ecosystems by altering predation risk.

    PubMed

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises. PMID:26448058

  16. Human activities change marine ecosystems by altering predation risk.

    PubMed

    Madin, Elizabeth M P; Dill, Lawrence M; Ridlon, April D; Heithaus, Michael R; Warner, Robert R

    2016-01-01

    In ocean ecosystems, many of the changes in predation risk - both increases and decreases - are human-induced. These changes are occurring at scales ranging from global to local and across variable temporal scales. Indirect, risk-based effects of human activity are known to be important in structuring some terrestrial ecosystems, but these impacts have largely been neglected in oceans. Here, we synthesize existing literature and data to explore multiple lines of evidence that collectively suggest diverse human activities are changing marine ecosystems, including carbon storage capacity, in myriad ways by altering predation risk. We provide novel, compelling evidence that at least one key human activity, overfishing, can lead to distinct, cascading risk effects in natural ecosystems whose magnitude exceeds that of presumed lethal effects and may account for previously unexplained findings. We further discuss the conservation implications of human-caused indirect risk effects. Finally, we provide a predictive framework for when human alterations of risk in oceans should lead to cascading effects and outline a prospectus for future research. Given the speed and extent with which human activities are altering marine risk landscapes, it is crucial that conservation and management policy considers the indirect effects of these activities in order to increase the likelihood of success and avoid unfortunate surprises.

  17. Parasitic castration by the digenian trematode Allopodocotyle sp. alters gene expression in the brain of the host mollusc Haliotis asinina.

    PubMed

    Rice, Tamika; McGraw, Elizabeth; O'Brien, Elizabeth K; Reverter, Antonio; Jackson, Daniel J; Degnan, Bernard M

    2006-06-26

    Infection of molluscs by digenean trematode parasites typically results in the repression of reproduction -- the so-called parasitic castration. This is known to occur by altering the expression of a range of host neuropeptide genes. Here we analyse the expression levels of 10 members of POU, Pax, Sox and Hox transcription factor gene families, along with genes encoding FMRFamide, prohormone convertase and beta-tubulin, in the brain ganglia of actively reproducing (summer), non-reproducing (winter) and infected Haliotis asinina (a vetigastropod mollusc). A number of the regulatory genes are differentially expressed in parasitised H. asinina, but in only a few cases do expression patterns in infected animals match those occurring in animals where reproduction is normally repressed.

  18. Alzheimer's disease and type 2 diabetes-related alterations in brain mitochondria, autophagy and synaptic markers.

    PubMed

    Carvalho, Cristina; Santos, Maria S; Oliveira, Catarina R; Moreira, Paula I

    2015-08-01

    We aimed to investigate mitochondrial function, biogenesis and autophagy in the brain of type 2 diabetes (T2D) and Alzheimer's disease (AD) mice. Isolated brain mitochondria and homogenates from cerebral cortex and hippocampus of wild-type (WT), triple transgenic AD (3xTg-AD) and T2D mice were used to evaluate mitochondrial functional parameters and protein levels of mitochondrial biogenesis, autophagy and synaptic integrity markers, respectively. A significant decrease in mitochondrial respiration, membrane potential and energy levels was observed in T2D and 3xTg-AD mice. Also, a significant decrease in the levels of autophagy-related protein 7 (ATG7) and glycosylated lysosomal membrane protein 1 (LAMP1) was observed in cerebral cortex and hippocampus of T2D and 3xTg-AD mice. Moreover, both brain regions of 3xTg-AD mice present lower levels of nuclear respiratory factor (NRF) 1 while the levels of NRF2 are lower in both brain regions of T2D and 3xTg-AD mice. A decrease in mitochondrial encoded, nicotinamide adenine dinucleotide dehydrogenase subunit 1 (ND1) was also observed in T2D and 3xTg-AD mice although only statistically significant in T2D cortex. Furthermore, a decrease in the levels of postsynaptic density protein 95 (PSD95) in the cerebral cortex of 3xTg-AD mice and in hippocampus of T2D and 3xTg-AD mice and a decrease in the levels of synaptosomal-associated protein 25 (SNAP 25) in the hippocampus of T2D and 3xTg-AD mice were observed suggesting synaptic integrity loss. These results support the idea that alterations in mitochondrial function, biogenesis and autophagy cause synaptic damage in AD and T2D.

  19. ALTERED EXPRESSION OF NEUROPLASTICITY-RELATED GENES IN THE BRAIN OF DEPRESSED SUICIDES

    PubMed Central

    FUCHSOVA, B.; ALVAREZ JULIÁ, A.; RIZAVI, H. S.; FRASCH, A. C.; PANDEY, G. N.

    2015-01-01

    Background Expression of the neuronal membrane glycoprotein M6a (GPM6A), the proteolipid protein (PLP/DM20) family member, is downregulated in the hippocampus of chronically stressed animals. Its neuroplastic function involves a role in neurite formation, filopodium outgrowth and synaptogenesis through an unknown mechanism. Disruptions in neuroplasticity mechanisms have been shown to play a significant part in the etiology of depression. Thus, the current investigation examined whether GPM6A expression is also altered in human depressed brain. Methods Expression levels and coexpression patterns of GPM6A, GPM6B, and PLP1 (two other members of PLP/DM20 family) as well as of the neuroplasticity-related genes identified to associate with GPM6A were determined using quantitative polymerase chain reaction (qPCR) in postmortem samples from the hippocampus (n =18) and the prefrontal cortex (PFC) (n= 25) of depressed suicide victims and compared with control subjects (hippocampus n= 18; PFC n =25). Neuroplasticity-related proteins that form complexes with GPM6A were identified by coimmunoprecipitation technique followed by mass spectrometry. Results Results indicated transcriptional downregulation of GPM6A and GPM6B in the hippocampus of depressed suicides. The expression level of calcium/calmodulin-dependent protein kinase II alpha (CAMK2A) and coronin1A (CORO1A) was also significantly decreased. Subsequent analysis of coexpression patterns demonstrated coordinated gene expression in the hippocampus and in the PFC indicating that the function of these genes might be coregulated in the human brain. However, in the brain of depressed suicides this coordinated response was disrupted. Conclusions Disruption of coordinated gene expression as well as abnormalities in GPM6A and GPM6B expression and expression of the components of GPM6A complexes were detected in the brain of depressed suicides. PMID:25934039

  20. Brain activation during phonological and semantic processing of Chinese characters in deaf signers

    PubMed Central

    Li, Yanyan; Peng, Danling; Liu, Li; Booth, James R.; Ding, Guosheng

    2014-01-01

    Previous studies found altered brain function in deaf individuals reading alphabetic orthographies. However, it is not known whether similar alterations of brain function are characteristic of non-alphabetic writing systems and whether alterations are specific to certain kinds of lexical tasks. Here we examined differences in brain activation between Chinese congenitally deaf individuals (CD) and hearing controls (HC) during character reading tasks requiring phonological and semantic judgments. For both tasks, we found that CD showed less activation than HC in left inferior frontal gyrus, but greater activation in several right hemisphere regions including inferior frontal gyrus, angular gyrus, and inferior temporal gyrus. Although many group differences were similar across tasks, greater activation in right middle frontal gyrus was more pronounced for the rhyming compared to the meaning task. Finally, within the deaf individuals better performance on the rhyming task was associated with less activation in right inferior parietal lobule and angular gyrus. Our results in Chinese CD are broadly consistent with previous studies in alphabetic languages suggesting greater engagement of inferior frontal gyrus and inferior parietal cortex for reading that is largely independent of task, with the exception of right middle frontal gyrus for phonological processing. The brain behavior correlations potentially indicate that CD that more efficiently use the right hemisphere are better readers. PMID:24795593

  1. Plumbagin alters telomere dynamics, induces DNA damage and cell death in human brain tumour cells.

    PubMed

    Khaw, Aik Kia; Sameni, Safoura; Venkatesan, Shriram; Kalthur, Guruprasad; Hande, M Prakash

    2015-11-01

    Natural plant products may possess much potential in palliative therapy and supportive strategies of current cancer treatments with lesser cytotoxicity to normal cells compared to conventional chemotherapy. In the current study, anti-cancer properties of plumbagin, a plant-derived naphthoquinone, on brain cancer cells were determined. Plumbagin treatment resulted in the induction of DNA damage, cell cycle arrest and apoptosis, followed by suppression of the colony forming ability of the brain tumour cells. These effects were substantiated by upregulation of PTEN, TNFRSF1A and downregulation of E2F1 genes, along with a drop in MDM2, cyclin B1, survivin and BCL2 protein expression. Plumbagin induced elevated levels of caspase-3/7 activity as well. For the first time, we show here that plumbagin inhibits telomerase in brain tumour cells and results in telomere shortening following chronic long-term treatment. This observation implies considerable cytotoxicity of plumbagin towards cancer cells with higher telomerase activity. Collectively, our findings suggest plumbagin as a potential chemotherapeutic phytochemical in brain tumour treatment modalities.

  2. A study on small-world brain functional networks altered by postherpetic neuralgia.

    PubMed

    Zhang, Yue; Liu, Jing; Li, Longchuan; Du, Minyi; Fang, Wenxue; Wang, Dongxin; Jiang, Xuexiang; Hu, Xiaoping; Zhang, Jue; Wang, Xiaoying; Fang, Jing

    2014-05-01

    Understanding the effect of postherpetic neuralgia (PHN) pain on brain activity is important for clinical strategies. This is the first study, to our knowledge, to relate PHN pain to small-world properties of brain functional networks. Functional magnetic resonance imaging (fMRI) was used to construct functional brain networks of the subjects during the resting state. Sixteen patients with PHN pain and 16 (8 males, 8 females for both groups) age-matched controls were studied. The PHN patients exhibited decreased local efficiency along with non-significant changes of global efficiency in comparison with the healthy controls. Moreover, regional nodal efficiency was found to be significantly affected by PHN pain in the areas related to sense (postcentral gyrus, inferior parietal gyrus and thalamus), memory/affective processes (parahippocampal gyrus) and emotional activities (putamen). Significant correlation (p<0.05) was also found between the nodal efficiency of putamen and pain intensity in PHN patients. Our results suggest that PHN modulates the local efficiency, and the small-world properties of brain networks may have potentials to objectively evaluate pain information in clinic.

  3. Motivation alters response bias and neural activation patterns in a perceptual decision-making task.

    PubMed

    Reckless, G E; Bolstad, I; Nakstad, P H; Andreassen, O A; Jensen, J

    2013-05-15

    Motivation has been demonstrated to affect individuals' response strategies in economic decision-making, however, little is known about how motivation influences perceptual decision-making behavior or its related neural activity. Given the important role motivation plays in shaping our behavior, a better understanding of this relationship is needed. A block-design, continuous performance, perceptual decision-making task where participants were asked to detect a picture of an animal among distractors was used during functional magnetic resonance imaging (fMRI). The effect of positive and negative motivation on sustained activity within regions of the brain thought to underlie decision-making was examined by altering the monetary contingency associated with the task. In addition, signal detection theory was used to investigate the effect of motivation on detection sensitivity, response bias and response time. While both positive and negative motivation resulted in increased sustained activation in the ventral striatum, fusiform gyrus, left dorsolateral prefrontal cortex (DLPFC) and ventromedial prefrontal cortex, only negative motivation resulted in the adoption of a more liberal, closer to optimal response bias. This shift toward a liberal response bias correlated with increased activation in the left DLPFC, but did not result in improved task performance. The present findings suggest that motivation alters aspects of the way perceptual decisions are made. Further, this altered response behavior is reflected in a change in left DLPFC activation, a region involved in the computation of perceptual decisions.

  4. On a Quantum Model of Brain Activities

    NASA Astrophysics Data System (ADS)

    Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.

    2010-01-01

    One of the main activities of the brain is the recognition of signals. A first attempt to explain the process of recognition in terms of quantum statistics was given in [6]. Subsequently, details of the mathematical model were presented in a (still incomplete) series of papers (cf. [7, 2, 5, 10]). In the present note we want to give a general view of the principal ideas of this approach. We will introduce the basic spaces and justify the choice of spaces and operations. Further, we bring the model face to face with basic postulates any statistical model of the recognition process should fulfill. These postulates are in accordance with the opinion widely accepted in psychology and neurology.

  5. Dorsal raphe nucleus of brain in the rats flown in space inflight and postflight alteration of structure

    NASA Astrophysics Data System (ADS)

    Krasnov, I.

    structures in DRN of "postflight" rats were not differ significantly fo rm analogous parameters of "inflight" rats. The results of study point out the decrease in mircrogravity in functional activity of DRN - main serotoniner gic center of brain and in combination with the data (Krasnov et. A.; 1998; Krasnov, Dyachkova, 2000) about inflight alteration in locus coeruleus - main noradrenergic center allow to propose the mechanism of decline of growth hormone secretion in mammals during space flight.

  6. C5a/CD88 signaling alters blood-brain barrier integrity in lupus through nuclear factor-κB.

    PubMed

    Jacob, Alexander; Hack, Bradley; Chen, Peili; Quigg, Richard J; Alexander, Jessy J

    2011-12-01

    Inflammation is a key factor in a number of neurodegenerative diseases including systemic lupus erythematosus. The complement system is an important mechanism in initiating and amplifying inflammation. Our recent studies demonstrate that C5a, a protein fragment generated during complement activation could alter the blood-brain barrier integrity, and thereby disturb the brain microenvironment. To understand the mechanism by which this occurs, we examined the effects of C5a on apoptosis, translocation of nuclear factor-κB (NF-κb) and the expression of Iκbα, MAPK, CREB and TJ protein, zona occludens (ZO-1) in mouse brain endothelial cells. Apoptosis was examined by DNA laddering and caspase 3 activity and the distribution of the ZO-1 and the p65 subunit of NF-κB were determined by immunofluorescence. Inhibition of CD88 reduced translocation of NF-κb into the nucleus, altered ZO-1 at the interfaces of neighboring cells, decreased caspase 3 activity and prevented apoptosis in these cells. Our results indicate that signaling through CD88 regulates the blood-brain barrier in a NF-κb-dependent manner. These studies suggest that the C5a receptor, CD88 is a promising therapeutic target that will reduce NF-κb-signaling cascades in inflammatory settings.

  7. Protective effect of resveratrol on fluoride induced alteration in protein and nucleic acid metabolism, DNA damage and biogenic amines in rat brain.

    PubMed

    Pal, Sudipta; Sarkar, Chaitali

    2014-09-01

    Fluoride, a well-established environmental carcinogen, has been found to cause various neurodegenerative diseases in human. Sub-acute exposure to fluoride at a dose of 20mg/kgb.w./day for 30 days caused significant alteration in pro-oxidant/anti-oxidant status of brain tissue as reflected by perturbation of reduced glutathione content, increased lipid peroxidation, protein carbonylation, nitric oxide and free hydroxyl radical production and decreased activities of antioxidant enzymes. Decreased proteolytic and transaminase enzymes' activities, protein and nucleic acid contents and associated DNA damage were observed in the brain of fluoride intoxicated rats. The neurotransmitters dopamine (DA), norepinephrine (NE) and serotonin level was also significantly altered after fluoride exposure. Protective effect of resveratrol on fluoride-induced metabolic and oxidative dysfunctions was evaluated. Resveratrol was found to inhibit changes in metabolic activities restoring antioxidant status, biogenic amine level and structural organization of the brain. Our findings indicated that resveratrol imparted antioxidative role in ameliorating fluoride-induced metabolic and oxidative stress in different regions of the brain.

  8. Physical activity and brain plasticity in late adulthood.

    PubMed

    Erickson, Kirk I; Gildengers, Ariel G; Butters, Meryl A

    2013-03-01

    The human brain shrinks with advancing age, but recent research suggests that it is also capable of remarkable plasticity, even in late life. In this review we summarize the research linking greater amounts of physical activity to less cortical atrophy, better brain function, and enhanced cognitive function, and argue that physical activity takes advantage of the brain's natural capacity for plasticity. Further, although the effects of physical activity on the brain are relatively widespread, there is also some specificity, such that prefrontal and hippocampal areas appear to be more influenced than other areas of the brain. The specificity of these effects, we argue, provides a biological basis for understanding the capacity for physical activity to influence neurocognitive and neuropsychiatric disorders such as depression. We conclude that physical activity is a promising intervention that can influence the endogenous pharmacology of the brain to enhance cognitive and emotional function in late adulthood.

  9. Antagonism of corticotropin-releasing hormone alters serotonergic-induced changes in brain temperature, but not sleep, of rats.

    PubMed

    Imeri, Luca; Bianchi, Susanna; Opp, Mark R

    2005-10-01

    Serotonin is involved in many physiological processes, including the regulation of sleep and body temperature. Administration into rats of low doses (25, 50 mg/kg) of the 5-HT precursor l-5-hydroxytryptophan (5-HTP) at the beginning of the dark period of the 12:12-h light-dark cycle initially increases wakefulness. Higher doses (75, 100 mg/kg) increase nonrapid eye movement (NREM) sleep. The initial enhancement of wakefulness after low-dose 5-HTP administration may be a direct action of 5-HT in brain or due to 5-HT-induced activation of other arousal-promoting systems. One candidate arousal-promoting system is corticotropin-releasing hormone (CRH) and the hypothalamic-pituitary-adrenal axis. Serotonergic activation by 5-HTP at the beginning of the dark period also induces hypothermia. Because sleep and body temperature are influenced by circadian factors, one aim of this study was to determine responses to 5-HTP when administered at a different circadian time, the beginning of the light period. Results obtained show that all doses of 5-HTP (25-100 mg/kg) administered at light onset initially increase wakefulness; NREM sleep increases only after a long delay, during the subsequent dark period. Serotonergic activation by 5-HTP at light onset induces hypothermia, the time course of which is biphasic after higher doses (75, 100 mg/kg). Intracerebroventricular pretreatment with the CRH receptor antagonist alpha-helical CRH does not alter the impact of 5-HTP on sleep-wake behavior but potentiates the hypothermic response to 50 mg/kg 5-HTP. These data suggest that serotonergic activation by peripheral administration of 5-HTP may modulate sleep-wake behavior by mechanisms in addition to direct actions in brain and that circadian systems are important determinants of the impact of serotonergic activation on sleep and body temperature. PMID:15994374

  10. Methamphetamine alters blood brain barrier protein expression in mice, facilitating central nervous system infection by neurotropic Cryptococcus neoformans.

    PubMed

    Eugenin, Eliseo A; Greco, Jade M; Frases, Susana; Nosanchuk, Joshua D; Martinez, Luis R

    2013-08-15

    Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique interface that in part functions to prevent microbial invasion of the CNS. The effects of METH on brain vasculature have not been studied extensively. We hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS infection. Using a murine model of METH administration, we demonstrated that METH alters BBB integrity and modifies the expression of tight junction and adhesion molecules. Additionally, we showed that BBB disruption accelerates transmigration of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after systemic infection. Furthermore, METH-treated mice displayed increased mortality as compared to untreated animals. Our findings provide novel evidence of the impact of METH abuse on the integrity of the cells that comprise the BBB and protect the brain from infection.

  11. Methamphetamine Alters Blood Brain Barrier Protein Expression in Mice, Facilitating Central Nervous System Infection by Neurotropic Cryptococcus neoformans

    PubMed Central

    Eugenin, Eliseo A.; Greco, Jade M.; Frases, Susana; Nosanchuk, Joshua D.; Martinez, Luis R.

    2013-01-01

    Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique interface that in part functions to prevent microbial invasion of the CNS. The effects of METH on brain vasculature have not been studied extensively. We hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS infection. Using a murine model of METH administration, we demonstrated that METH alters BBB integrity and modifies the expression of tight junction and adhesion molecules. Additionally, we showed that BBB disruption accelerates transmigration of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after systemic infection. Furthermore, METH-treated mice displayed increased mortality as compared to untreated animals. Our findings provide novel evidence of the impact of METH abuse on the integrity of the cells that comprise the BBB and protect the brain from infection. PMID:23532099

  12. Binding sites for atrial natriuretic factor (ANF) in brain: alterations in Brattleboro rats

    SciTech Connect

    McCarty, R.; Plunkett, L.M.

    1986-12-01

    Binding sites for atrial natriuretic factor (ANF-28) were analyzed in discrete brain areas of Brattleboro rats with hereditary diabetes insipidus and Long-Evans (LE) controls by quantitative autoradiography. The maximum binding capacity (Bmax) and affinity constant (Ka) for /sup 125/I-ANF-28 were elevated significantly in the subfornical organ of Brattleboro rats compared to matched LE controls. In contrast, values for Bmax and Ka for /sup 125/I-ANF-28 binding in choroid plexus and area postrema were similar for rats of the two strains. These findings are consistent with a selective upregulation of ANF-28 binding sites in the subfornical organ of Brattleboro rats which exhibit a profound disturbance in body fluid homeostasis. These alterations in ANF-28 binding sites in the subfornical organ may represent a compensatory response to the absence of vasopressin in the Brattleboro rat.

  13. Possible nitric oxide modulation in protective effect of FK-506 against 3-nitropropionic acid-induced behavioral, oxidative, neurochemical, and mitochondrial alterations in rat brain.

    PubMed

    Kumar, Puneet; Kalonia, Harikesh; Kumar, Anil

    2010-10-01

    FK-506 is an immunosuppressant being widely used for allograft rejection cases in the present clinical scenario. Recently, the neuroprotective effect of FK-506 has also been reported against a number of neurodegenerative diseases in rodents. This study was designed to explore the possible protective effect of FK-506 and its interaction with nitric-oxide modulators against 3-nitropropionic acid (3-NP)-induced behavioural, biochemical, neurochemical, and mitochondrial alterations in striatum, cortex, and hippocampus regions of the brain. Systemic administration of 3-nitropropionic acid produces Huntington-like symptoms in rats. 3-NP (10 mg/kg) treatment for 14 days impaired locomotor activity, grip strength, and body weight. 3-NP treatment significantly raised malondialdehyde, nitrite concentration, depleted antioxidant enzymes (SOD and catalase), and levels of bioamines (dopamine and norepinephrine) in striatum, cortex, and hippocampus areas of rat brain. Significant alterations in mitochondrial enzyme complexes (I, II, and IV) activities and mitochondrial redox activity have also been altered significantly by 3-NP. Pretreatment with FK-506 (0.5, 1, and 2 mg/kg) significantly reversed these behavioral, biochemical, and cellular alterations. L-arginine treatment with a subeffective dose FK-506 (1 mg/kg) reversed the protective effect of FK-506. However, L-NAME pretreatment with FK-506 (1 mg/kg) potentiated the protective effect of FK-506. The present study shows that FK-506 attenuates 3-NP-induced neurotoxicity and nitric-oxide modulation might be involved in its protective action. PMID:20550427

  14. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains.

    PubMed

    Ledesma, Maria Dolores; Abad-Rodriguez, José; Galvan, Cristian; Biondi, Elisa; Navarro, Pilar; Delacourte, Andre; Dingwall, Colin; Dotti, Carlos G

    2003-12-01

    The serine protease plasmin can efficiently degrade amyloid peptide in vitro, and is found at low levels in the hippocampus of patients with Alzheimer's disease (AD). The cause of such paucity remains unknown. We show here that the levels of total brain plasminogen and plasminogen-binding molecules are normal in these brain samples, yet plasminogen membrane binding is greatly reduced. Biochemical analysis reveals that the membranes of these brains have a mild, still significant, cholesterol reduction compared to age-matched controls, and anomalous raft microdomains. This was reflected by the loss of raft-enriched proteins, including plasminogen-binding and -activating molecules. Using hippocampal neurons in culture, we demonstrate that removal of a similar amount of membrane cholesterol is sufficient to induce raft disorganization, leading to reduced plasminogen membrane binding and low plasmin activity. These results suggest that brain raft alterations may contribute to AD by rendering the plasminogen system inefficient.

  15. Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain

    PubMed Central

    Ngai, Ying Fai; Sulistyoningrum, Dian C.; O'Neill, Ryan; Innis, Sheila M.; Weinberg, Joanne

    2015-01-01

    Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes (Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE. PMID:26180184

  16. Alterations in brain structure and functional connectivity in prescription opioid-dependent patients.

    PubMed

    Upadhyay, Jaymin; Maleki, Nasim; Potter, Jennifer; Elman, Igor; Rudrauf, David; Knudsen, Jaime; Wallin, Diana; Pendse, Gautam; McDonald, Leah; Griffin, Margaret; Anderson, Julie; Nutile, Lauren; Renshaw, Perry; Weiss, Roger; Becerra, Lino; Borsook, David

    2010-07-01

    A dramatic increase in the use and dependence of prescription opioids has occurred within the last 10 years. The consequences of long-term prescription opioid use and dependence on the brain are largely unknown, and any speculation is inferred from heroin and methadone studies. Thus, no data have directly demonstrated the effects of prescription opioid use on brain structure and function in humans. To pursue this issue, we used structural magnetic resonance imaging, diffusion tensor imaging and resting-state functional magnetic resonance imaging in a highly enriched group of prescription opioid-dependent patients [(n=10); from a larger study on prescription opioid dependent patients (n=133)] and matched healthy individuals (n=10) to characterize possible brain alterations that may be caused by long-term prescription opioid use. Criteria for patient selection included: (i) no dependence on alcohol or other drugs; (ii) no comorbid psychiatric or neurological disease; and (iii) no medical conditions, including pain. In comparison to control subjects, individuals with opioid dependence displayed bilateral volumetric loss in the amygdala. Prescription opioid-dependent subjects had significantly decreased anisotropy in axonal pathways specific to the amygdala (i.e. stria terminalis, ventral amygdalofugal pathway and uncinate fasciculus) as well as the internal and external capsules. In the patient group, significant decreases in functional connectivity were observed for seed regions that included the anterior insula, nucleus accumbens and amygdala subdivisions. Correlation analyses revealed that longer duration of prescription opioid exposure was associated with greater changes in functional connectivity. Finally, changes in amygdala functional connectivity were observed to have a significant dependence on amygdala volume and white matter anisotropy of efferent and afferent pathways of the amygdala. These findings suggest that prescription opioid dependence is associated

  17. [Alterations in recruitment and activation of Rab proteins during mycobacterial infection].

    PubMed

    Castaño, Diana; Rojas, Mauricio

    2010-01-01

    At the phagosome level, Mycobacterium spp. alters activation and recruitment of several "Ras gene from rat brain" proteins, commonly known as Rab. Mycobacterial phagosomes have a greater and sustained expression of Rab5, Rab11, Rab14 and Rab22a, and lowered or no expression of Rab7, Rab9 and Rab6. This correlates with increased fusion of the phagosomes with early and recycling endosomes acquiring some features of early phagosomes, allowing the bacteria to gain access to nutrients and preventing the activation of anti-mycobacterial mechanisms. The expression of constitutively active mutants of Rab from the early stage endosomes prevents the maturation of phagosomes containing latex beads or heat-inactivated mycobacteria. Silencing of these mutants by interference RNA or dominant negative forms induces the maturation of mycobacterial phagosomes. The mechanisms have not been established by which mycobacteria alter the expression of these GTPases and thereby shift the phagolysosomal maturation. The problem can be explained by alterations in the recruitment of proteins that interact with Rab, such as phosphoinositide 3-kinases and early endosomal antigen 1. Identifying the mechanisms used by Mycobacterium spp. to disrupt the cycle of Rab activation will be essential to understand the pathophysiology of mycobacterial infections and usefully to potential drug targets.

  18. Supervised learning for neural manifold using spatiotemporal brain activity

    NASA Astrophysics Data System (ADS)

    Kuo, Po-Chih; Chen, Yong-Sheng; Chen, Li-Fen

    2015-12-01

    Objective. Determining the means by which perceived stimuli are compactly represented in the human brain is a difficult task. This study aimed to develop techniques for the construction of the neural manifold as a representation of visual stimuli. Approach. We propose a supervised locally linear embedding method to construct the embedded manifold from brain activity, taking into account similarities between corresponding stimuli. In our experiments, photographic portraits were used as visual stimuli and brain activity was calculated from magnetoencephalographic data using a source localization method. Main results. The results of 10 × 10-fold cross-validation revealed a strong correlation between manifolds of brain activity and the orientation of faces in the presented images, suggesting that high-level information related to image content can be revealed in the brain responses represented in the manifold. Significance. Our experiments demonstrate that the proposed method is applicable to investigation into the inherent patterns of brain activity.

  19. A mouse model of anxiety molecularly characterized by altered protein networks in the brain proteome.

    PubMed

    Szego, Eva M; Janáky, Tamás; Szabó, Zoltán; Csorba, Attila; Kompagne, Hajnalka; Müller, Géza; Lévay, György; Simor, Attila; Juhász, Gábor; Kékesi, Katalin A

    2010-02-01

    Recently, several attempts have been made to describe changes related to certain anxiety states in the proteome of experimental animal models. However, these studies are restricted by limitations regarding the number and correct identification of separated proteins. Moreover, the application of a systems biology approach to discover the molecular mechanisms of anxiety requires genetically homogenous inbred animal models. Therefore, we developed a novel mouse model of anxiety using a combination of crossbreeding (inbred for 35 generations) and behavioral selection. We found significant changes in 82 proteins in the total brain proteome compared to the control proteome. Thirty-four of these proteins had been previously identified in other anxiety, depression or repeated psychosocial stress studies. The identified proteins are associated with different cellular functions, including synaptic transmission, metabolism, proteolysis, protein biosynthesis and folding, cytoskeletal proteins, brain development and neurogenesis, oxidative stress, signal transduction. Our proteomics data suggest that alterations in serotonin receptor-associated proteins, in the carbohydrate metabolism, in the cellular redox system and in synaptic docking are all involved in anxiety.

  20. Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology?

    PubMed

    Faria, Ágatha Cristhina; Rabbi-Bortolini, Eliete; Rebouças, Maria R G O; de S Thiago Pereira, Andréia L A; Frasson, Milena G Tonini; Atique, Rodrigo; Lourenço, Naila Cristina V; Rosenberg, Carla; Kobayashi, Gerson S; Passos-Bueno, Maria Rita; Errera, Flávia Imbroisi Valle

    2016-02-01

    Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault. PMID:26566760

  1. Craniosynostosis in 10q26 deletion patients: A consequence of brain underdevelopment or altered suture biology?

    PubMed

    Faria, Ágatha Cristhina; Rabbi-Bortolini, Eliete; Rebouças, Maria R G O; de S Thiago Pereira, Andréia L A; Frasson, Milena G Tonini; Atique, Rodrigo; Lourenço, Naila Cristina V; Rosenberg, Carla; Kobayashi, Gerson S; Passos-Bueno, Maria Rita; Errera, Flávia Imbroisi Valle

    2016-02-01

    Approximately a hundred patients with terminal 10q deletions have been described. They present with a wide range of clinical features always accompanied by delayed development, intellectual disability and craniofacial dysmorphisms. Here, we report a girl and a boy with craniosynostosis, developmental delay and other congenital anomalies. Karyotyping and molecular analysis including Multiplex Ligation dependent probe amplification (MLPA) and Array Comparative Genomic Hybridization (aCGH) were performed in both patients. We detected a 13.1 Mb pure deletion at 10q26.12-q26.3 in the girl and a 10.9 Mb pure deletion at 10q26.13-q26.3 in the boy, both encompassing about 100 genes. The clinical and molecular findings in these patients reinforce the importance of the DOCK1 smallest region of overlap I (SRO I), previously suggested to explain the clinical signs, and together with a review of the literature suggest a second 3.5 Mb region important for the phenotype (SRO II). Genotype-phenotype correlations and literature data suggest that the craniosynostosis is not directly related to dysregulated signaling in suture development, but may be secondary to alterations in brain development instead. Further, genes at 10q26 may be involved in the molecular crosstalk between brain and cranial vault.

  2. Alterations in the sense of time, space, and body in the mindfulness-trained brain: a neurophenomenologically-guided MEG study

    PubMed Central

    Berkovich-Ohana, Aviva; Dor-Ziderman, Yair; Glicksohn, Joseph; Goldstein, Abraham

    2013-01-01

    Meditation practice can lead to what have been referred to as “altered states of consciousness.”One of the phenomenological characteristics of these states is a joint alteration in the sense of time, space, and body. Here, we set out to study the unique experiences of alteration in the sense of time and space by collaborating with a select group of 12 long-term mindfulness meditation (MM) practitioners in a neurophenomenological setup, utilizing first-person data to guide the neural analyses. We hypothesized that the underlying neural activity accompanying alterations in the sense of time and space would be related to alterations in bodily processing. The participants were asked to volitionally bring about distinct states of “Timelessness” (outside time) and “Spacelessness” (outside space) while their brain activity was recorded by MEG. In order to rule out the involvement of attention, memory, or imagination, we used control states of “Then” (past) and “There” (another place). MEG sensors evidencing alterations in power values were identified, and the brain regions underlying these changes were estimated via spatial filtering (beamforming). Particularly, we searched for similar neural activity hypothesized to underlie both the state of “Timelessness” and “Spacelessness.” The results were mostly confined to the theta band, and showed that: (1) the “Then”/“There” overlap yielded activity in regions related to autobiographic memory and imagery (right posterior parietal lobule (PPL), right precentral/middle frontal gyrus (MFG), bilateral precuneus); (2) “Timelessness”/“Spacelessness” conditions overlapped in a different network, related to alterations in the sense of the body (posterior cingulate, right temporoparietal junction (TPJ), cerebellum); and (3) phenomenologically-guided neural analyses enabled us to dissociate different levels of alterations in the sense of the body. This study illustrates the utility of employing

  3. Brain and hypophyseal acetylcholinesterase activity of pubertal boars fed dietary fumonisin B1.

    PubMed

    Gbore, F A

    2010-10-01

    The effects of dietary fumonisin B(1) (FB(1)) on regional brain and hypophyseal activities of AChE (EC 3117), the enzyme which catalyses the hydrolysis of acetylcholine, were studied using 24 male Large White weanling pigs divided into four groups. Each group received one of the four diets containing 0.2, 5.0, 10.0 and 15.0 mg FB(1)/kg in a 6-month feeding trial. All animals were slaughtered at the end of the feeding trial; the brains and the hypophyses obtained were carefully dissected out. Significant (p < 0.05) influence of dietary FB(1) on regional brain and hypophyseal AChE activities were observed. The AChE activities in the pons, amygdala, hypothalamus and the medulla oblongata declined significantly (p < 0.05) with increased dietary FB(1) concentrations. The findings of this study suggest that diets containing 5.0 mg FB(1)/kg and above significantly (p < 0.05) altered regional brain and hypophyseal AChE activities in the animals. Dietary exposure to FB(1) at a concentration of approximately 5.0 mg/kg or more for a 6-month period is a potential health risk that may induce adverse physiological response resulting from altered brain neurochemistry in growing pigs.

  4. Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain

    PubMed Central

    Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

    2013-01-01

    Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP−) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

  5. Leptin replacement alters brain response to food cues in genetically leptin-deficient adults

    PubMed Central

    Baicy, Kate; London, Edythe D.; Monterosso, John; Wong, Ma-Li; Delibasi, Tuncay; Sharma, Anil; Licinio, Julio

    2007-01-01

    A missense mutation in the ob gene causes leptin deficiency and morbid obesity. Leptin replacement to three adults with this mutation normalized body weight and eating behavior. Because the neural circuits mediating these changes were unknown, we paired functional magnetic resonance imaging (fMRI) with presentation of food cues to these subjects. During viewing of food-related stimuli, leptin replacement reduced brain activation in regions linked to hunger (insula, parietal and temporal cortex) while enhancing activation in regions linked to inhibition and satiety (prefrontal cortex). Leptin appears to modulate feeding behavior through these circuits, suggesting therapeutic targets for human obesity. PMID:17986612

  6. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

    PubMed Central

    Mantua, Janna; Mahan, Keenan M.; Henry, Owen S.; Spencer, Rebecca M. C.

    2015-01-01

    Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18–22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation. PMID:26097451

  7. Selective cortical alteration after hypoxic-ischemic injury in the very immature rat brain.

    PubMed

    Sizonenko, Stephane V; Sirimanne, Ernest; Mayall, Yvette; Gluckman, Peter D; Inder, Terrie; Williams, Chris

    2003-08-01

    Distinctive cerebral lesions with disruptions to the developing white matter are found in very low birth weight (VLBW) infants. Although hypoxia-ischemia (HI) is a causal pathway, the pathogenesis of cerebral white matter injury in the VLBW infant is not fully understood. Pertinent murine models would facilitate the investigation of the processes leading to these cerebral lesions and enable the evaluation of therapeutic strategies. Postnatal d 3 (P3) rats are at a stage of cortical oligodendroglial maturation and axonal outgrowth similar to very preterm infants. Our aim was to characterize the effects of a focal hypoxic-ischemic injury at P3 on subsequent cerebral development. Three groups of P3 Wistar rats were investigated: group I underwent right carotid ligation followed by 6% hypoxia for 30 min (HI), group 2 had carotid ligation only, and group 3 had no intervention. At P21, in the HI group, the right cortical area was reduced compared with controls (p < 0.01). There were no significant alterations in the size of the dorsal hippocampus, striatum, and thalamus. The cortical myelinated area was reduced in the HI animals compared with controls (p < 0.01). There was a corresponding loss of myelinated axons extending up into the cortex, with deep cortical neuronal and axonal architecture markedly disrupted. Glial fibrillary acidic protein immunohistology showed a reactive gliosis in the deep parietal cortex (p < 0.01). Moderate HI injury in the immature rat brain compromised cortical growth and led to a selective alteration of cortical myelinated axons with persistent gliosis. These alterations induced at P3 by unilateral HI share neuropathological similarities with the diffuse white matter lesions found in VLBW infants.

  8. Differences in Functional Brain Connectivity Alterations Associated with Cerebral Amyloid Deposition in Amnestic Mild Cognitive Impairment

    PubMed Central

    Yi, Dahyun; Choe, Young Min; Byun, Min Soo; Sohn, Bo Kyung; Seo, Eun Hyun; Han, Jiyoung; Park, Jinsick; Woo, Jong Inn; Lee, Dong Young

    2015-01-01

    Despite potential implications for the early detection of impending Alzheimer’s disease (AD), very little is known about the differences of large-scale brain networks between amnestic mild cognitive impairment (aMCI) with high cerebral amyloid-beta protein (Aβ) deposition (i.e., aMCI+) and aMCI with no or very little Aβ deposition (i.e., aMCI−). We first aimed to extend the current literature on altering intrinsic functional connectivity (FC) of the default mode network (DMN) and salience network (SN) from cognitively normal (CN) to AD dementia. Second, we further examined the differences of the DMN and the SN between aMCI−, aMCI+, and CN. Forty-three older adult (12 CN, 10 aMCI+, 10 aMCI−, and 11 AD dementia) subjects were included. All participants received comprehensive clinical and neuropsychological assessment, resting-state functional magnetic resonance imaging, structural MRI, and Pittsburgh compound-B-PET scans. FC data were preprocessed using multivariate exploratory linear optimized decomposition into independent components of FMRIB’s Software Library. Group comparisons were carried out using the “dual-regression” approach. In addition, to verify presence of gray matter volume changes with intrinsic functional network alterations, voxel-based morphometry was performed on the acquired T1-weighted data. As expected, AD dementia participants exhibited decreased FC in the DMN compared to CN (particularly in the precuneus and cingulate gyrus). The degree of alteration in the DMN in aMCI+ compared to CN was intermediate to that of AD. In contrast, aMCI− exhibited increased FC in the DMN compared to CN (primarily in the precuneus) as well as aMCI+. In terms of the SN, aMCI− exhibited decreased FC compared to both CN and aMCI+ particularly in the inferior frontal gyrus. FC within the SN in aMCI+ and AD did not differ from CN. Compared to CN, aMCI− showed atrophy in bilateral superior temporal gyri whereas aMCI+ showed atrophy in right

  9. Paternal alcohol exposure in mice alters brain NGF and BDNF and increases ethanol-elicited preference in male offspring.

    PubMed

    Ceccanti, Mauro; Coccurello, Roberto; Carito, Valentina; Ciafrè, Stefania; Ferraguti, Giampiero; Giacovazzo, Giacomo; Mancinelli, Rosanna; Tirassa, Paola; Chaldakov, George N; Pascale, Esterina; Ceccanti, Marco; Codazzo, Claudia; Fiore, Marco

    2016-07-01

    Ethanol (EtOH) exposure during pregnancy induces cognitive and physiological deficits in the offspring. However, the role of paternal alcohol exposure (PAE) on offspring EtOH sensitivity and neurotrophins has not received much attention. The present study examined whether PAE may disrupt nerve growth factor (NGF) and/or brain-derived neurotrophic factor (BDNF) and affect EtOH preference/rewarding properties in the male offspring. CD1 sire mice were chronically addicted for EtOH or administered with sucrose. Their male offsprings when adult were assessed for EtOH preference by a conditioned place preference paradigm. NGF and BDNF, their receptors (p75(NTR) , TrkA and TrkB), dopamine active transporter (DAT), dopamine receptors D1 and D2, pro-NGF and pro-BDNF were also evaluated in brain areas. PAE affected NGF levels in frontal cortex, striatum, olfactory lobes, hippocampus and hypothalamus. BDNF alterations in frontal cortex, striatum and olfactory lobes were found. PAE induced a higher susceptibility to the EtOH rewarding effects mostly evident at the lower concentration (0.5 g/kg) that was ineffective in non-PAE offsprings. Moreover, higher ethanol concentrations (1.5 g/kg) produced an aversive response in PAE animals and a significant preference in non-PAE offspring. PAE affected also TrkA in the hippocampus and p75(NTR) in the frontal cortex. DAT was affected in the olfactory lobes in PAE animals treated with 0.5 g/kg of ethanol while no differences were found on D1/D2 receptors and for pro-NGF or pro-BDNF. In conclusion, this study shows that: PAE affects NGF and BDNF expression in the mouse brain; PAE may induce ethanol intake preference in the male offspring.

  10. Invisible Brain: Knowledge in Research Works and Neuron Activity

    PubMed Central

    Segev, Aviv; Curtis, Dorothy; Jung, Sukhwan; Chae, Suhyun

    2016-01-01

    If the market has an invisible hand, does knowledge creation and representation have an “invisible brain”? While knowledge is viewed as a product of neuron activity in the brain, can we identify knowledge that is outside the brain but reflects the activity of neurons in the brain? This work suggests that the patterns of neuron activity in the brain can be seen in the representation of knowledge-related activity. Here we show that the neuron activity mechanism seems to represent much of the knowledge learned in the past decades based on published articles, in what can be viewed as an “invisible brain” or collective hidden neural networks. Similar results appear when analyzing knowledge activity in patents. Our work also tries to characterize knowledge increase as neuron network activity growth. The results propose that knowledge-related activity can be seen outside of the neuron activity mechanism. Consequently, knowledge might exist as an independent mechanism. PMID:27439199

  11. Brain studies may alter long-held concepts about likely causes of some voice disorders

    SciTech Connect

    Not Available

    1989-02-17

    Two voice disorders long considered to be psychological problems, stuttering and spasmodic dysphonia, have been shown in many persons to have a neurophysiological basis. Investigators at the 155th national meeting of the American Association for the Advancement of Science, in San Francisco, described their findings, which are based on new analytic techniques. The research is being done at the Dallas Center for Vocal Motor Control, Callier Center for Communication Disorders, University of Texas at Dallas Health Science Center. The technology employed to learn what's wrong with the brains, rather than the psyches, of persons with certain speech disorders includes magnetic resonance imaging (MRI), brain electrical activity mapping (BEAM), and single photon emission computerized tomography (SPECT). The results of applying these techniques are combined with quantitative behavioral measures of vocal and nonvocal motor control, language performance, and cognition to arrive at a better understanding of the problem.

  12. Brain activation associated with active and passive lower limb stepping

    PubMed Central

    Jaeger, Lukas; Marchal-Crespo, Laura; Wolf, Peter; Riener, Robert; Michels, Lars; Kollias, Spyros

    2014-01-01

    Reports about standardized and repeatable experimental procedures investigating supraspinal activation in patients with gait disorders are scarce in current neuro-imaging literature. Well-designed and executed tasks are important to gain insight into the effects of gait-rehabilitation on sensorimotor centers of the brain. The present study aims to demonstrate the feasibility of a novel imaging paradigm, combining the magnetic resonance (MR)-compatible stepping robot (MARCOS) with sparse sampling functional magnetic resonance imaging (fMRI) to measure task-related BOLD signal changes and to delineate the supraspinal contribution specific to active and passive stepping. Twenty-four healthy participants underwent fMRI during active and passive, periodic, bilateral, multi-joint, lower limb flexion and extension akin to human gait. Active and passive stepping engaged several cortical and subcortical areas of the sensorimotor network, with higher relative activation of those areas during active movement. Our results indicate that the combination of MARCOS and sparse sampling fMRI is feasible for the detection of lower limb motor related supraspinal activation. Activation of the anterior cingulate and medial frontal areas suggests motor response inhibition during passive movement in healthy participants. Our results are of relevance for understanding the neural mechanisms underlying gait in the healthy. PMID:25389396

  13. Protection against 1,2-di-methylhydrazine-induced systemic oxidative stress and altered brain neurotransmitter status by probiotic Escherichia coli CFR 16 secreting pyrroloquinoline quinone.

    PubMed

    Pandey, Sumeet; Singh, Ashish; Chaudhari, Nirja; Nampoothiri, Laxmipriya P; Kumar, G Naresh

    2015-05-01

    Exposure to environmental pollutant 1,2-dimethylhydrazine (DMH) is attributed to systemic oxidative stress and is known to cause neurotropic effect by altering brain neurotransmitter status. Probiotics are opted as natural therapeutic against oxidative stress and also have the ability to modulate gut-brain axis. Pyrroloquinoline quinone (PQQ) is water-soluble, heat-stable antioxidant molecule. Aim of the present study was to evaluate the antioxidant efficacy of PQQ-producing probiotic E. coli CFR 16 on DMH-induced systemic oxidative damage and altered neurotransmitter status in rat brain. Adult virgin Charles Forster rats (200-250 g) were given DMH dose (25 mg/kg body weight, s.c.) for 8 weeks. Blood lipid peroxidation levels exhibited a marked increase while antioxidant enzyme activities of superoxide dismutase, catalase, glucose-6-phosphate dehydrogenase and glutathione peroxidase were found to be reduced in DMH-treated rats. Likewise, brain serotonin and norepinephrine levels displayed a significant decrease, whereas epinephrine levels demonstrated a marked increase in brain of these rats. PQQ-producing E. coli CFR 16 supplementation reduced systemic oxidative stress and also restored brain neurotransmitter status. However, E. coli CFR 16 did not show any effect on these parameters. In contrast, E. coli CFR 16:: vgb-gfp and E. coli CFR 16:: vgb-gfp vector exhibited some degree of protection again oxidative stress but they were not able to modulate neurotransmitter levels. In conclusion, continuous and sustained release of PQQ by probiotic E. coli in rat intestine ameliorates systemic oxidative stress and restored brain neurotransmitter levels.

  14. Psychoneuroendocrine immunology: perception of stress can alter body temperature and natural killer cell activity.

    PubMed

    Hiramoto, R N; Solvason, H B; Hsueh, C M; Rogers, C F; Demissie, S; Hiramoto, N S; Gauthier, D K; Lorden, J F; Ghanta, V K

    1999-01-01

    Psychoimmunology has been credited with using the mind as a way to alter immunity. The problem with this concept is that many of the current psychoimmunology techniques in use are aimed at alleviating stress effects on the immune system rather than at direct augmentation of immunity by the brain. Studies in animals provide a model that permits us to approach the difficulties associated with gaining an understanding of the CNS-immune system connection. A particular advantage of using animals over humans is that psychological and social contributions play a less prominent role for animals than for human subjects, since the animals are all inbred and reared under identical controlled conditions. If the insightful information provided by animal studies is correct, then psychotherapy for the treatment of diseases might be made more effective if some aspect of this knowledge is included in the design of the treatment. We emphasize conditioning as a regimen and an acceptable way to train the brain to remember an output pathway to raise immunity. We propose that a specific drug or perception (mild stress, represented by rotation, total body heating or handling) could substitute and kindle the same output pathway without the need for conditioning. If this view is correct, then instead of using conditioning, it may be possible to use an antigen to activate desired immune cells, and substitute a drug or an external environmental sensory stimulus (perception) to energize the output pathway to these cells. Alternatively, monitoring alterations of body temperature in response to a drug or perception might allow us to follow how effectively the brain is performing in altering immunity. Studies with animals suggest that there are alternative ways to use the mind to raise natural or acquired immunity in man.

  15. Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

    PubMed Central

    Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

    2015-01-01

    In patients with Parkinson’s disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson’s disease, such as deep brain stimulation (DBS) therapy. PMID:25698937

  16. Brain-Wide Insulin Resistance, Tau Phosphorylation Changes, and Hippocampal Neprilysin and Amyloid-β Alterations in a Monkey Model of Type 1 Diabetes

    PubMed Central

    Morales-Corraliza, Jose; Wong, Harrison; Mazzella, Matthew J.; Che, Shaoli; Lee, Sang Han; Petkova, Eva; Wagner, Janice D.; Hemby, Scott E.; Ginsberg, Stephen D.

    2016-01-01

    Epidemiological findings suggest that diabetic individuals are at a greater risk for developing Alzheimer's disease (AD). To examine the mechanisms by which diabetes mellitus (DM) may contribute to AD pathology in humans, we examined brain tissue from streptozotocin-treated type 1 diabetic adult male vervet monkeys receiving twice-daily exogenous insulin injections for 8–20 weeks. We found greater inhibitory phosphorylation of insulin receptor substrate 1 in each brain region examined of the diabetic monkeys when compared with controls, consistent with a pattern of brain insulin resistance that is similar to that reported in the human AD brain. Additionally, a widespread increase in phosphorylated tau was seen, including brain areas vulnerable in AD, as well as relatively spared structures, such as the cerebellum. An increase in active ERK1/2 was also detected, consistent with DM leading to changes in tau-kinase activity broadly within the brain. In contrast to these widespread changes, we found an increase in soluble amyloid-β (Aβ) levels that was restricted to the temporal lobe, with the greatest increase seen in the hippocampus. Consistent with this localized Aβ increase, a hippocampus-restricted decrease in the protein and mRNA for the Aβ-degrading enzyme neprilysin (NEP) was found, whereas various Aβ-clearing and -degrading proteins were unchanged. Thus, we document multiple biochemical changes in the insulin-controlled DM monkey brain that can link DM with the risk of developing AD, including dysregulation of the insulin-signaling pathway, changes in tau phosphorylation, and a decrease in NEP expression in the hippocampus that is coupled with a localized increase in Aβ. SIGNIFICANCE STATEMENT Given that diabetes mellitus (DM) appears to increase the risk of developing Alzheimer's disease (AD), understanding the mechanisms by which DM promotes AD is important. We report that DM in a nonhuman primate brain leads to changes in the levels or

  17. Altered resting-state functional activity in posttraumatic stress disorder: A quantitative meta-analysis

    PubMed Central

    Wang, Ting; Liu, Jia; Zhang, Junran; Zhan, Wang; Li, Lei; Wu, Min; Huang, Hua; Zhu, Hongyan; Kemp, Graham J.; Gong, Qiyong

    2016-01-01

    Many functional neuroimaging studies have reported differential patterns of spontaneous brain activity in posttraumatic stress disorder (PTSD), but the findings are inconsistent and have not so far been quantitatively reviewed. The present study set out to determine consistent, specific regional brain activity alterations in PTSD, using the Effect Size Signed Differential Mapping technique to conduct a quantitative meta-analysis of resting-state functional neuroimaging studies of PTSD that used either a non-trauma (NTC) or a trauma-exposed (TEC) comparison control group. Fifteen functional neuroimaging studies were included, comparing 286 PTSDs, 203 TECs and 155 NTCs. Compared with NTC, PTSD patients showed hyperactivity in the right anterior insula and bilateral cerebellum, and hypoactivity in the dorsal medial prefrontal cortex (mPFC); compared with TEC, PTSD showed hyperactivity in the ventral mPFC. The pooled meta-analysis showed hypoactivity in the posterior insula, superior temporal, and Heschl’s gyrus in PTSD. Additionally, subgroup meta-analysis (non-medicated subjects vs. NTC) identified abnormal activation in the prefrontal-limbic system. In meta-regression analyses, mean illness duration was positively associated with activity in the right cerebellum (PTSD vs. NTC), and illness severity was negatively associated with activity in the right lingual gyrus (PTSD vs. TEC). PMID:27251865

  18. Altered cross-frequency coupling in resting-state MEG after mild traumatic brain injury.

    PubMed

    Antonakakis, Marios; Dimitriadis, Stavros I; Zervakis, Michalis; Micheloyannis, Sifis; Rezaie, Roozbeh; Babajani-Feremi, Abbas; Zouridakis, George; Papanicolaou, Andrew C

    2016-04-01

    Cross-frequency coupling (CFC) is thought to represent a basic mechanism of functional integration of neural networks across distant brain regions. In this study, we analyzed CFC profiles from resting state Magnetoencephalographic (MEG) recordings obtained from 30 mild traumatic brain injury (mTBI) patients and 50 controls. We used mutual information (MI) to quantify the phase-to-amplitude coupling (PAC) of activity among the recording sensors in six nonoverlapping frequency bands. After forming the CFC-based functional connectivity graphs, we employed a tensor representation and tensor subspace analysis to identify the optimal set of features for subject classification as mTBI or control. Our results showed that controls formed a dense network of stronger local and global connections indicating higher functional integration compared to mTBI patients. Furthermore, mTBI patients could be separated from controls with more than 90% classification accuracy. These findings indicate that analysis of brain networks computed from resting-state MEG with PAC and tensorial representation of connectivity profiles may provide a valuable biomarker for the diagnosis of mTBI.

  19. Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners.

    PubMed

    Fox, Kieran C R; Nijeboer, Savannah; Dixon, Matthew L; Floman, James L; Ellamil, Melissa; Rumak, Samuel P; Sedlmeier, Peter; Christoff, Kalina

    2014-06-01

    Numerous studies have begun to address how the brain's gray and white matter may be shaped by meditation. This research is yet to be integrated, however, and two fundamental questions remain: Is meditation associated with altered brain structure? If so, what is the magnitude of these differences? To address these questions, we reviewed and meta-analyzed 123 brain morphology differences from 21 neuroimaging studies examining ∼300 meditation practitioners. Anatomical likelihood estimation (ALE) meta-analysis found eight brain regions consistently altered in meditators, including areas key to meta-awareness (frontopolar cortex/BA 10), exteroceptive and interoceptive body awareness (sensory cortices and insula), memory consolidation and reconsolidation (hippocampus), self and emotion regulation (anterior and mid cingulate; orbitofrontal cortex), and intra- and interhemispheric communication (superior longitudinal fasciculus; corpus callosum). Effect size meta-analysis (calculating 132 effect sizes from 16 studies) suggests a global 'medium' effect size (Cohen's d¯=0.46; r¯=.19). Publication bias and methodological limitations are strong concerns, however. Further research using rigorous methods is required to definitively link meditation practice to altered brain morphology.

  20. Imatinib Activates Pathological Hypertrophy by Altering Myocyte Calcium Regulation

    PubMed Central

    Barr, Larry; Makarewich, Catherine A.; Berretta, Remus M.; Gao, Hui; Troupes, Constantine D.; Woitek, Felix; Recchia, Fabio; Kubo, Hajime; Force, Thomas; Houser, Steven R.

    2014-01-01

    Background Imatinib mesylate is a selective tyrosine-kinase inhibitor used in the treatment of multiple cancers, most notably chronic myelogenous leukemia (CML). There is evidence that imatinib can induce cardiotoxicity in cancer patients. Our hypothesis is that imatinib alters calcium regulatory mechanisms and can contribute to development of pathological cardiac hypertrophy. Methods/Results Neonatal rat ventricular myocytes (NRVMs) were treated with clinical doses (Low: 2µM, High: 5µM) of imatinib and assessed for molecular changes. Imatinib increased peak systolic Ca2+ and Ca2+ transient decay rates and Western analysis revealed significant increases in phosphorylation of phospholamban (Thr-17) and the ryanodine receptor (Ser-2814), signifying activation of CaMKII. Imatinib significantly increased NRVM volume as assessed by Coulter counter, myocyte surface area and ANP abundance seen by Western. Imatinib induced cell death, but did not activate the classical apoptotic program as assessed by caspase-3 cleavage, indicating a necrotic mechanism of death in myocytes. We expressed AdNFATc3-GFP in NRVMS and showed imatinib treatment significantly increased NFAT translocation that was inhibited by the calcineurin inhibitor FK506 or CaMKII inhibitors. Conclusion These data show that imatinib can activate pathological hypertrophic signaling pathways by altering intracellular Ca2+ dynamics. This is likely a contributing mechanism for the adverse cardiac effects of imatinib. PMID:24931551

  1. Amygdala kindling alters protein kinase C activity in dentate gyrus.

    PubMed

    Chen, S J; Desai, M A; Klann, E; Winder, D G; Sweatt, J D; Conn, P J

    1992-11-01

    Kindling is a use-dependent form of synaptic plasticity and a widely used model of epilepsy. Although kindling has been widely studied, the molecular mechanisms underlying induction of this phenomenon are not well understood. We determined the effect of amygdala kindling on protein kinase C (PKC) activity in various regions of rat brain. Kindling stimulation markedly elevated basal (Ca(2+)-independent) and Ca(2+)-stimulated phosphorylation of an endogenous PKC substrate (which we have termed P17) in homogenates of dentate gyrus, assayed 2 h after kindling stimulation. The increase in P17 phosphorylation appeared to be due at least in part to persistent PKC activation, as basal PKC activity assayed in vitro using an exogenous peptide substrate was increased in kindled dentate gyrus 2 h after the last kindling stimulation. A similar increase in basal PKC activity was observed in dentate gyrus 2 h after the first kindling stimulation. These results document a kindling-associated persistent PKC activation and suggest that the increased activity of PKC could play a role in the induction of the kindling effect.

  2. Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.

    PubMed

    Le Belle, Janel E; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R; López-Aranda, Manuel; Silva, Alcino J; Kornblum, Harley I

    2014-11-11

    A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

  3. Thalidomide combined with irradiation alters the activity of two proteases.

    PubMed

    Şimşek, Ece; Aydemir, Esra; Korcum, Aylin Fidan; Fişkın, Kayahan

    2015-02-01

    The aim of the present study was to investigate the effects of thalidomide, a drug known for its anti‑angiogenic and antitumor properties, at its cytotoxic dose previously determined as 40 µg/ml (according to four cytotoxic test results). The effect of the drug alone and in combination with radiotherapy using Cobalt 60 (60Co) at 45 Gy on the enzymatic activity of substance‑P degrading A disintegrin and metalloproteinase (ADAM)10 and neprilysin (NEP) was investigated in the mouse breast cancer cell lines 4T1 and 4T1 heart metastases post‑capsaicin (4THMpc). Thalidomide (40 µg/ml) exerted differing effects on the activities of ADAM10 and NEP enzymes. In 4T1 cells, 40 µg/ml thalidomide alone did not alter ADAM10 enzyme activity. 60Co irradiation at 45 Gy alone caused a 42% inhibition in ADAM10 activity, however, the inhibition increased to 89% when combined therapy was used. By contrast, in the 4THMpc cell line, 40 µg/ml thalidomide alone induced a 66.6% increase in ADAM10 enzyme activity. Radiotherapy alone and thalidomide with 60Co combined therapy caused a 33.3 and 40% inhibition of ADAM10 activity, respectively. In 4T1 cells, thalidomide alone caused a 40.9% increase in NEP activity. Radiation therapy alone or in combination with the drug caused a 40.7% increase in NEP activity. In more aggressive 4THMpc cells, thalidomide alone caused a 26.6% increase in NEP activity. Radiotherapy alone and combined therapy caused a 33.3 and 37% increase in enzyme activity, respectively. To the best of our knowledge, the present study is the first to demonstrate that thalidomide alone or in combination with radiotherapy exhibits significant cytotoxic effects on 4T1 and 4THMpc mouse breast cancer cell lines indicating that this drug affects the enzymatic activity of ADAM10 and NEP in vitro.

  4. Memory impairment and alterations in prefrontal cortex gamma band activity following methamphetamine sensitization

    PubMed Central

    Linsenbardt, David N.; Lapish, Christopher C.

    2015-01-01

    Rationale Repeated methamphetamine (MA) use leads to increases in the incentive motivational properties of the drug as well as cognitive impairments. These behavioral alterations persist for some time following abstinence, and neuroadaptations in the structure and function of the prefrontal cortex (PFC) are particularly important for their expression. However, there is a weak understanding of the changes in neural firing and oscillatory activity in the PFC evoked by repeated drug use, thus complicating the development of novel treatment strategies for addiction. Objectives The purpose of the current study was to assess changes in cognitive and brain function following MA sensitization. Methods Sensitization was induced in rats, then temporal and recognition memory were assessed after 1 or 30 days of abstinence. Electrophysiological recordings from the medial PFC were also acquired from rats whereupon simultaneous measures of oscillatory and spiking activity were examined. Results Impaired temporal memory was observed after 1 and 30 days of abstinence. However, recognition memory was only impaired after 1 day of abstinence. An injection of MA profoundly decreased neuronal firing rate and the anesthesia-induced slow oscillation (SO) in both sensitized (SENS) and control (CTRL) rats. Strong correlations were observed between the SO and gamma band power, which was altered in SENS animals. A decrease in the number of neurons phase-locked to the gamma oscillation was also observed in SENS animals. Conclusions The changes observed in PFC function may play an integral role in the expression of the altered behavioral phenotype evoked by MA sensitization. PMID:25572530

  5. Brain region-specific altered expression and association of mitochondria-related genes in autism

    PubMed Central

    2012-01-01

    Background Mitochondrial dysfunction (MtD) has been observed in approximately five percent of children with autism spectrum disorders (ASD). MtD could impair highly energy-dependent processes such as neurodevelopment, thereby contributing to autism. Most of the previous studies of MtD in autism have been restricted to the biomarkers of energy metabolism, while most of the genetic studies have been based on mutations in the mitochondrial DNA (mtDNA). Despite the mtDNA, most of the proteins essential for mitochondrial replication and function are encoded by the genomic DNA; so far, there have been very few studies of those genes. Therefore, we carried out a detailed study involving gene expression and genetic association studies of genes related to diverse mitochondrial functions. Methods For gene expression analysis, postmortem brain tissues (anterior cingulate gyrus (ACG), motor cortex (MC) and thalamus (THL)) from autism patients (n=8) and controls (n=10) were obtained from the Autism Tissue Program (Princeton, NJ, USA). Quantitative real-time PCR arrays were used to quantify the expression of 84 genes related to diverse functions of mitochondria, including biogenesis, transport, translocation and apoptosis. We used the delta delta Ct (∆∆Ct) method for quantification of gene expression. DNA samples from 841 Caucasian and 188 Japanese families were used in the association study of genes selected from the gene expression analysis. FBAT was used to examine genetic association with autism. Results Several genes showed brain region-specific expression alterations in autism patients compared to controls. Metaxin 2 (MTX2), neurofilament, light polypeptide (NEFL) and solute carrier family 25, member 27 (SLC25A27) showed consistently reduced expression in the ACG, MC and THL of autism patients. NEFL (P = 0.038; Z-score 2.066) and SLC25A27 (P = 0.046; Z-score 1.990) showed genetic association with autism in Caucasian and Japanese samples, respectively. The expression of

  6. Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles.

    PubMed

    Fukushiro, D F; Olivera, A; Liu, Y; Wang, Z

    2015-10-29

    The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior.

  7. Neonatal exposure to amphetamine alters social affiliation and central dopamine activity in adult male prairie voles.

    PubMed

    Fukushiro, D F; Olivera, A; Liu, Y; Wang, Z

    2015-10-29

    The prairie vole (Microtus ochrogaster) is a socially monogamous rodent species that forms pair bonds after mating. Recent data have shown that amphetamine (AMPH) is rewarding to prairie voles as it induces conditioned place preferences. Further, repeated treatment with AMPH impairs social bonding in adult prairie voles through a central dopamine (DA)-dependent mechanism. The present study examined the effects of neonatal exposure to AMPH on behavior and central DA activity in adult male prairie voles. Our data show that neonatal exposure to AMPH makes voles less social in an affiliation test during adulthood, but does not affect animals' locomotor activity and anxiety-like behavior. Neonatal exposure to AMPH also increases the levels of tyrosine hydroxylase (TH) and DA transporter (DAT) mRNA expression in the ventral tegmental area (VTA) in the brain, indicating an increase in central DA activity. As DA has been implicated in AMPH effects on behavioral and cognitive functions, altered DA activity in the vole brain may contribute to the observed changes in social behavior. PMID:26321240

  8. Optical imaging of neural and hemodynamic brain activity

    NASA Astrophysics Data System (ADS)

    Schei, Jennifer Lynn

    Optical imaging technologies can be used to record neural and hemodynamic activity. Neural activity elicits physiological changes that alter the optical tissue properties. Specifically, changes in polarized light are concomitant with neural depolarization. We measured polarization changes from an isolated lobster nerve during action potential propagation using both reflected and transmitted light. In transmission mode, polarization changes were largest throughout the center of the nerve, suggesting that most of the optical signal arose from the inner nerve bundle. In reflection mode, polarization changes were largest near the edges, suggesting that most of the optical signal arose from the outer sheath. To overcome irregular cell orientation found in the brain, we measured polarization changes from a nerve tied in a knot. Our results show that neural activation produces polarization changes that can be imaged even without regular cell orientations. Neural activation expends energy resources and elicits metabolic delivery through blood vessel dilation, increasing blood flow and volume. We used spectroscopic imaging techniques combined with electrophysiological measurements to record evoked neural and hemodynamic responses from the auditory cortex of the rat. By using implantable optics, we measured responses across natural wake and sleep states, as well as responses following different amounts of sleep deprivation. During quiet sleep, evoked metabolic responses were larger compared to wake, perhaps because blood vessels were more compliant. When animals were sleep deprived, evoked hemodynamic responses were smaller following longer periods of deprivation. These results suggest that prolonged neural activity through sleep deprivation may diminish vascular compliance as indicated by the blunted vascular response. Subsequent sleep may allow vessels to relax, restoring their ability to deliver blood. These results also suggest that severe sleep deprivation or chronic

  9. Active microwave computed brain tomography: the response to a challenge.

    PubMed

    Almirall, H; Broquetas, A; Jofre, L

    1991-02-01

    The potential application of active microwave techniques to brain imaging is studied by numerical simulations and experimentally using a recently developed cylindrical microwave scanner. The potential advantages and limitations of this method in static and dynamic brain imaging are presented and compared with other imaging techniques. PMID:2062119

  10. Altered Amygdala Connectivity in Individuals with Chronic Traumatic Brain Injury and Comorbid Depressive Symptoms

    PubMed Central

    Han, Kihwan; Chapman, Sandra B.; Krawczyk, Daniel C.

    2015-01-01

    Depression is one of the most common psychiatric conditions in individuals with chronic traumatic brain injury (TBI). Though depression has detrimental effects in TBI and network dysfunction is a “hallmark” of TBI and depression, there have not been any prior investigations of connectivity-based neuroimaging biomarkers for comorbid depression in TBI. We utilized resting-state functional magnetic resonance imaging to identify altered amygdala connectivity in individuals with chronic TBI (8 years post-injury on average) exhibiting comorbid depressive symptoms (N = 31), relative to chronic TBI individuals having minimal depressive symptoms (N = 23). Connectivity analysis of these participant sub-groups revealed that the TBI-plus-depressive symptoms group showed relative increases in amygdala connectivity primarily in the regions that are part of the salience, somatomotor, dorsal attention, and visual networks (pvoxel < 0.01, pcluster < 0.025). Relative increases in amygdala connectivity in the TBI-plus-depressive symptoms group were also observed within areas of the limbic–cortical mood-regulating circuit (the left dorsomedial and right dorsolateral prefrontal cortices and thalamus) and the brainstem. Further analysis revealed that spatially dissociable patterns of correlation between amygdala connectivity and symptom severity according to subtypes (Cognitive and Affective) of depressive symptoms (pvoxel < 0.01, pcluster < 0.025). Taken together, these results suggest that amygdala connectivity may be a potentially effective neuroimaging biomarker for comorbid depressive symptoms in chronic TBI. PMID:26581959

  11. Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice

    PubMed Central

    2013-01-01

    Background Traffic-generated air pollution-exposure is associated with adverse effects in the central nervous system (CNS) in both human exposures and animal models, including neuroinflammation and neurodegeneration. While alterations in the blood brain barrier (BBB) have been implicated as a potential mechanism of air pollution-induced CNS pathologies, pathways involved have not been elucidated. Objectives To determine whether inhalation exposure to mixed vehicle exhaust (MVE) mediates alterations in BBB permeability, activation of matrix metalloproteinases (MMP) -2 and −9, and altered tight junction (TJ) protein expression. Methods Apolipoprotein (Apo) E−/− and C57Bl6 mice were exposed to either MVE (100 μg/m3 PM) or filtered air (FA) for 6 hr/day for 30 days and resulting BBB permeability, expression of ROS, TJ proteins, markers of neuroinflammation, and MMP activity were assessed. Serum from study mice was applied to an in vitro BBB co-culture model and resulting alterations in transport and permeability were quantified. Results MVE-exposed Apo E−/− mice showed increased BBB permeability, elevated ROS and increased MMP-2 and −9 activity, compared to FA controls. Additionally, cerebral vessels from MVE-exposed mice expressed decreased levels of TJ proteins, occludin and claudin-5, and increased levels of inducible nitric oxide synthase (iNOS) and interleukin (IL)-1β in the parenchyma. Serum from MVE-exposed animals also resulted in increased in vitro BBB permeability and altered P-glycoprotein transport activity. Conclusions These data indicate that inhalation exposure to traffic-generated air pollutants promotes increased MMP activity and degradation of TJ proteins in the cerebral vasculature, resulting in altered BBB permeability and expression of neuroinflammatory markers. PMID:24344990

  12. Brain activation-based sexual orientation in female-to-male transsexuals.

    PubMed

    Kim, T-H; Kim, G-W; Kim, S-K; Jeong, G-W

    2016-01-01

    This study was performed to identify the sexual orientation in association with brain activation pattern in response to visual erotic stimuli in female-to-male (FtM) transsexuals by using functional magnetic resonance imaging (fMRI). Eleven FtM transsexuals who have had sex-reassignment surgery to alter their natal bodies with the gender-identity disorder were participated. Brain activation for sexual orientation was induced by visual stimuli with female and male erotic nude pictures compared with emotionally-neutral pictures. During viewing the erotic female pictures, the brain areas dominantly activated consist of the superior frontal gyrus, supplementary motor area, anterior/median cingulate gyri and hypothalamus, whereas during viewing male pictures, the brain areas with predominant activities were the middle frontal gyrus, precentral gyrus, middle temporal gyrus, fusiform gyrus, angular gyrus, precuneus, superior/middle occipital gyri, cerebellar cortex and vermis. These findings demonstrate that the brain activation patterns induced by viewing male or female erotic pictures show some correlation to the sexual orientation opposite to the genetic sex in FtM transsexuals. This study would be helpful to understand the neural mechanism associated with visual sexual arousal in patients with gender disorder. PMID:26581912

  13. Brain activation-based sexual orientation in female-to-male transsexuals.

    PubMed

    Kim, T-H; Kim, G-W; Kim, S-K; Jeong, G-W

    2016-01-01

    This study was performed to identify the sexual orientation in association with brain activation pattern in response to visual erotic stimuli in female-to-male (FtM) transsexuals by using functional magnetic resonance imaging (fMRI). Eleven FtM transsexuals who have had sex-reassignment surgery to alter their natal bodies with the gender-identity disorder were participated. Brain activation for sexual orientation was induced by visual stimuli with female and male erotic nude pictures compared with emotionally-neutral pictures. During viewing the erotic female pictures, the brain areas dominantly activated consist of the superior frontal gyrus, supplementary motor area, anterior/median cingulate gyri and hypothalamus, whereas during viewing male pictures, the brain areas with predominant activities were the middle frontal gyrus, precentral gyrus, middle temporal gyrus, fusiform gyrus, angular gyrus, precuneus, superior/middle occipital gyri, cerebellar cortex and vermis. These findings demonstrate that the brain activation patterns induced by viewing male or female erotic pictures show some correlation to the sexual orientation opposite to the genetic sex in FtM transsexuals. This study would be helpful to understand the neural mechanism associated with visual sexual arousal in patients with gender disorder.

  14. Cannabis use and brain structural alterations of the cingulate cortex in early psychosis.

    PubMed

    Rapp, Charlotte; Walter, Anna; Studerus, Erich; Bugra, Hilal; Tamagni, Corinne; Röthlisberger, Michel; Borgwardt, Stefan; Aston, Jacqueline; Riecher-Rössler, Anita

    2013-11-30

    As cannabis use is more frequent in patients with psychosis than in the general population and is known to be a risk factor for psychosis, the question arises whether cannabis contributes to recently detected brain volume reductions in schizophrenic psychoses. This study is the first to investigate how cannabis use is related to the cingulum volume, a brain region involved in the pathogenesis of schizophrenia, in a sample of both at-risk mental state (ARMS) and first episode psychosis (FEP) subjects. A cross-sectional magnetic resonance imaging (MRI) study of manually traced cingulum in 23 FEP and 37 ARMS subjects was performed. Cannabis use was assessed with the Basel Interview for Psychosis. By using repeated measures analyses of covariance, we investigated whether current cannabis use is associated with the cingulum volume, correcting for age, gender, alcohol consumption, whole brain volume and antipsychotic medication. There was a significant three-way interaction between region (anterior/posterior cingulum), hemisphere (left/right cingulum) and cannabis use (yes/no). Post-hoc analyses revealed that this was due to a significant negative effect of cannabis use on the volume of the posterior cingulum which was independent of the hemisphere and diagnostic group and all other covariates we controlled for. In the anterior cingulum, we found a significant negative effect only for the left hemisphere, which was again independent of the diagnostic group. Overall, we found negative associations of current cannabis use with grey matter volume of the cingulate cortex, a region rich in cannabinoid CB1 receptors. As this finding has not been consistently found in healthy controls, it might suggest that both ARMS and FEP subjects are particularly sensitive to exogenous activation of these receptors.

  15. Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice.

    PubMed

    Fatemi, S H; Emamian, E S; Sidwell, R W; Kist, D A; Stary, J M; Earle, J A; Thuras, P

    2002-01-01

    Epidemiological reports describe a strong association between prenatal human influenza viral infection and later development of schizophrenia. Postmodern human brain studies, however, indicate a lack of gliosis in schizophrenic brains presumably secondary to absence of glial cells during the second trimester viral infection in utero. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of glial fibrillary acidic protein (GFAP, an important marker of gliosis, neuron migration, and reactive injury) in developing brains of postnatal days 0, 14 and 35 mice. Determination of cellular GFAP immunoreactivity (IR) expressed as cell density in cortex and hippocampus of control and experimental brains showed increases in GFAP-positive density in exposed cortical (P = 0.03 day 14 vs control) and hippocampal cells (P = 0.035 day 14, P = 0.034 day 35). Similarly, ependymal cell layer GFAP-IR cell counts showed increases with increasing brain age from day 0, to days 14 and 35 in infected groups (P = 0.037, day 14) vs controls. The GFAP-positive cells in prenatally exposed brains showed 'hypertrophy' and more stellate morphology. These results implicate a significant role of prenatal human influenza viral infection on subsequent gliosis, which persists throughout brain development in mice from birth to adolescence.

  16. Ethanol-induced alterations in sup 14 C-glucose utilization: Modulation by brain adenosine in mice

    SciTech Connect

    Anwer, J.; Dar, M.S. )

    1992-02-26

    The possible role of brain adenosine (Ado) in acute ethanol-induced alteration in glucose utilization in the cerebellum and brain stem was investigated. The slices were incubated for 100 min in a glucose medium in Warburg flasks using {sup 14}C-glucose as a tracer. Trapped {sup 14}CO{sub 2} was counted to estimate glucose utilization. Ethanol markedly increased the glucose utilization in both areas of brain. Theophylline, an Ado antagonist, significantly reduced ethanol-induced increase in glucose utilization in both brain areas. Ado agonist CHA significantly accentuated ethanol-induced increase in glucose utilization in both motor areas. Ado agonist CHA significantly accentuated ethanol-induced increase in glucose utilization in both motor areas. Ethanol was still able to produce a smaller but significant increase in glucose utilization in both brain areas when theophylline and CHA were given together, suggesting an additional mechanism. Collectively, the data indicate that ethanol-induced glucose utilization in the cerebellum and brain stem is modulated by brain Ado receptor and by non-adenosinergic mechanism.

  17. Physical activity attenuates age-related biomarker alterations in preclinical AD

    PubMed Central

    Schultz, Stephanie A.; Oh, Jennifer M.; Larson, Jordan; Edwards, Dorothy; Cook, Dane; Koscik, Rebecca; Gallagher, Catherine L.; Dowling, N.M.; Carlsson, Cynthia M.; Bendlin, Barbara B.; LaRue, Asenath; Rowley, Howard A.; Christian, Brad T.; Asthana, Sanjay; Hermann, Bruce P.; Johnson, Sterling C.; Sager, Mark A.

    2014-01-01

    Objective: To examine whether engagement in physical activity might favorably alter the age-dependent evolution of Alzheimer disease (AD)-related brain and cognitive changes in a cohort of at-risk, late-middle-aged adults. Methods: Three hundred seventeen enrollees in the Wisconsin Registry for Alzheimer's Prevention underwent T1 MRI; a subset also underwent 11C-Pittsburgh compound B–PET (n = 186) and 18F-fluorodeoxyglucose–PET (n = 152) imaging. Participants' responses on a self-report measure of current physical activity were used to classify them as either physically active or physically inactive based on American Heart Association guidelines. They also completed a comprehensive neuropsychological battery. Covariate-adjusted regression analyses were used to test whether the adverse effect of age on imaging and cognitive biomarkers was modified by physical activity. Results: There were significant age × physical activity interactions for β-amyloid burden (p = 0.014), glucose metabolism (p = 0.015), and hippocampal volume (p = 0.025) such that, with advancing age, physically active individuals exhibited a lesser degree of biomarker alterations compared with the physically inactive. Similar age × physical activity interactions were also observed on cognitive domains of Immediate Memory (p = 0.042) and Visuospatial Ability (p = 0.016). In addition, the physically active group had higher scores on Speed and Flexibility (p = 0.002) compared with the inactive group. Conclusions: In a middle-aged, at-risk cohort, a physically active lifestyle is associated with an attenuation of the deleterious influence of age on key biomarkers of AD pathophysiology. However, because our observational, cross-sectional design cannot establish causality, randomized controlled trials/longitudinal studies will be necessary for determining whether midlife participation in structured physical exercise forestalls the development of AD and related disorders in later life. PMID:25298312

  18. Altered Intrinsic Regional Activity and Interregional Functional Connectivity in Post-stroke Aphasia

    PubMed Central

    Yang, Mi; Li, Jiao; Li, Yibo; Li, Rong; Pang, Yajing; Yao, Dezhong; Liao, Wei; Chen, Huafu

    2016-01-01

    Several neuroimaging studies have examined cerebral function in patients who suffer from aphasia, but the mechanism underlying this disorder remains poorly understood. In this study, we examined alterations in the local regional and remote interregional network cerebral functions in aphasia combined with amplitude of low-frequency fluctuations and interregional functional connectivity (FC) using resting-state functional magnetic resonance imaging. A total of 17 post-stroke aphasic patients, all having suffered a stroke in the left hemisphere, as well as 20 age- and sex-matched healthy controls, were enrolled in this study. The aphasic patients showed significantly increased intrinsic regional activity mainly in the contralesional mesial temporal (hippocampus/parahippocampus, [HIP/ParaHIP]) and lateral temporal cortices. In addition, intrinsic regional activity in the contralesional HIP/ParaHIP was negatively correlated with construction score. Aphasic patients showed increased remote interregional FC between the contralesional HIP/ParaHIP and fusiform gyrus, but reduced FC in the ipsilesional occipital and parietal cortices. These findings suggested that the intrinsic regional brain dysfunctions in aphasia were related to interregional functional connectivity. Changes in the intrinsic regional brain activity and associated remote functional connectivity pattern would provide valuable information to enhance the understanding of the pathophysiological mechanisms of aphasia. PMID:27091494

  19. Structural brain alterations in heart failure: a review of the literature and implications for risk of Alzheimer's disease.

    PubMed

    Alosco, Michael L; Hayes, Scott M

    2015-09-01

    Cardiovascular disease is a recognized contributor to the pathogenesis of Alzheimer's disease (AD). Heart failure (HF) is a cardiovascular subtype that can be used to model the contribution of cardiovascular disease to AD. Neuroimaging research indicates that HF patients exhibit a diverse range of structural brain alterations and epidemiological studies suggest HF may be an important risk factor for AD. The neural alterations observed in HF may overlap with those observed in AD and contribute to increased risk of AD in HF patients. To examine this possibility, we reviewed structural MRI studies in persons with HF. We examined subcortical brain regions affected in the early stages of AD (medial temporal lobes), as well as cortical alterations that typically occur in the later stages of AD. Our review indicates that patients with HF exhibit greater neural atrophy and white matter microstructural alterations of nearly every region of the Papez circuit (e.g., hippocampus, cingulate gyrus, thalamus, mammillary bodies, and fornix), as well-significant alterations in cortical and cerebellar regions. Based on animal research and past work in AD patients, the mechanisms for structural brain changes in HF may stem from reductions in cerebral blood flow subsequent to cardiac deficiency. This review supports the hypothesis that HF may contribute to AD risk via widespread structural brain changes, including many of the same regions affected by AD. Case-controlled prospective neuroimaging studies with long-term follow-ups are needed to clarify the risk of AD in HF and elucidate the neural underpinnings of AD risk in HF.

  20. The bile acid-sensitive ion channel (BASIC) is activated by alterations of its membrane environment.

    PubMed

    Schmidt, Axel; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Kusch, Jana; Lucas, Susana Dias; Gründer, Stefan; Wiemuth, Dominik

    2014-01-01

    The bile acid-sensitive ion channel (BASIC) is a member of the DEG/ENaC family of ion channels. Channels of this family are characterized by a common structure, their physiological functions and modes of activation, however, are diverse. Rat BASIC is expressed in brain, liver and intestinal tract and activated by bile acids. The physiological function of BASIC and its mechanism of bile acid activation remain a puzzle. Here we addressed the question whether amphiphilic bile acids activate BASIC by directly binding to the channel or indirectly by altering the properties of the surrounding membrane. We show that membrane-active substances other than bile acids also affect the activity of BASIC and that activation by bile acids and other membrane-active substances is non-additive, suggesting that BASIC is sensitive for changes in its membrane environment. Furthermore based on results from chimeras between BASIC and ASIC1a, we show that the extracellular and the transmembrane domains are important for membrane sensitivity.

  1. Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain

    SciTech Connect

    Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

    1986-03-05

    The authors have previously reported that multiple high doses of methamphetamine (METH) alter neuronal monoamine metabolism and release. Recently, Hokfelt et al. showed that neurotensin, a tridecapeptide, has neurotransmitter properties which may be involved with DA neuronal activity. In the present study they investigated the possible effects of METH on the CNS neurotensin system. Five doses of METH (15 mg/kg) were administered every 6 h; control and treated rats were sacrificed 18 h after the last dose and concentrations of neurotensin-like immuno-reactivity (NTLI) were measured by radioimmunoassay. NTLI was elevated 200-300% in the nucleus accumbens, neostriatum, and substantia nigra; 30-40% increases in NTLI were measured in the hippocampus and hypothalamus. No change was observed in amygdala, A-10 or periaqueductal gray. In contrast to the above measured areas, the frontal lobe and olfactory bulb showed decreases of 25-35%. These findings demonstrate that METH treatment alters the activities of several CNS neurotensin systems, possibly due to the influence of this drug on DA pathways. The variability in the type and magnitude of these responses suggests that DA and neurotensin systems interact by more than one mechanism.

  2. Spatial heterogeneity analysis of brain activation in fMRI

    PubMed Central

    Gupta, Lalit; Besseling, René M.H.; Overvliet, Geke M.; Hofman, Paul A.M.; de Louw, Anton; Vaessen, Maarten J.; Aldenkamp, Albert P.; Ulman, Shrutin; Jansen, Jacobus F.A.; Backes, Walter H.

    2014-01-01

    In many brain diseases it can be qualitatively observed that spatial patterns in blood oxygenation level dependent (BOLD) activation maps appear more (diffusively) distributed than in healthy controls. However, measures that can quantitatively characterize this spatial distributiveness in individual subjects are lacking. In this study, we propose a number of spatial heterogeneity measures to characterize brain activation maps. The proposed methods focus on different aspects of heterogeneity, including the shape (compactness), complexity in the distribution of activated regions (fractal dimension and co-occurrence matrix), and gappiness between activated regions (lacunarity). To this end, functional MRI derived activation maps of a language and a motor task were obtained in language impaired children with (Rolandic) epilepsy and compared to age-matched healthy controls. Group analysis of the activation maps revealed no significant differences between patients and controls for both tasks. However, for the language task the activation maps in patients appeared more heterogeneous than in controls. Lacunarity was the best measure to discriminate activation patterns of patients from controls (sensitivity 74%, specificity 70%) and illustrates the increased irregularity of gaps between activated regions in patients. The combination of heterogeneity measures and a support vector machine approach yielded further increase in sensitivity and specificity to 78% and 80%, respectively. This illustrates that activation distributions in impaired brains can be complex and more heterogeneous than in normal brains and cannot be captured fully by a single quantity. In conclusion, heterogeneity analysis has potential to robustly characterize the increased distributiveness of brain activation in individual patients. PMID:25161893

  3. Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

    PubMed Central

    Dawson, N; Kurihara, M; Thomson, D M; Winchester, C L; McVie, A; Hedde, J R; Randall, A D; Shen, S; Seymour, P A; Hughes, Z A; Dunlop, J; Brown, J T; Brandon, N J; Morris, B J; Pratt, J A

    2015-01-01

    Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity. PMID:25989143

  4. Human brain plasticity: evidence from sensory deprivation and altered language experience.

    PubMed

    Neville, Helen; Bavelier, Daphne

    2002-01-01

    The results from the language studies taken as a whole point to different developmental time courses and developmental vulnerabilities of aspects of grammatical and semantic/lexical processing. They thus provide support for conceptions of language that distinguish these subprocesses within language. Similarly, following auditory deprivation, processes associated with the dorsal visual pathway were more altered than were functions associated with the ventral pathway, providing support for conceptions of visual system organization that distinguish functions along these lines. Could the effects observed in blind and deaf adults be accounted for, at least in part, by the redundant connectivity of the immature human brain? One way we tested this hypothesis was to study the differentiation of visual and auditory sensory responses in normal development (Neville, 1995). In normal adults, auditory stimuli elicit ERP responses that are large over temporal brain regions but small or absent over occipital regions. By contrast, in 6-month-old children we observed that auditory ERPs are equally large over temporal and visual brain regions, consistent with the idea that there is less specificity and more redundancy of connections between the auditory and visual cortex at this time. Between 6 and 36 months, however, we observed a gradual decrease in the amplitude of the auditory ERP over visual areas, while the amplitude over the temporal areas was unchanged. These results suggest that early in human development, there exists a redundancy of connections between auditory and visual areas and that this overlap gradually decreases after birth. This loss of redundancy may be a boundary condition that determines when sensory deprivation can result in alterations in the organization of remaining sensory systems. The considerable variability in timing of sensitive periods may also be in part due to temporal differences in the occurrence of redundancy within different systems. Ongoing

  5. Altered Brain Connectivity in Early Postmenopausal Women with Subjective Cognitive Impairment

    PubMed Central

    Vega, Jennifer N.; Zurkovsky, Lilia; Albert, Kimberly; Melo, Alyssa; Boyd, Brian; Dumas, Julie; Woodward, Neil; McDonald, Brenna C.; Saykin, Andrew J.; Park, Joon H.; Naylor, Magdalena; Newhouse, Paul A.

    2016-01-01

    Cognitive changes after menopause are a common complaint, especially as the loss of estradiol at menopause has been hypothesized to contribute to the higher rates of dementia in women. To explore the neural processes related to subjective cognitive complaints, this study examined resting state functional connectivity in 31 postmenopausal women (aged 50–60) in relationship to cognitive complaints following menopause. A cognitive complaint index was calculated using responses to a 120-item questionnaire. Seed regions were identified for resting state brain networks important for higher-order cognitive processes and for areas that have shown differences in volume and functional activity associated with cognitive complaints in prior studies. Results indicated a positive correlation between the executive control network and cognitive complaint score, weaker negative functional connectivity within the frontal cortex, and stronger positive connectivity within the right middle temporal gyrus in postmenopausal women who report more cognitive complaints. While longitudinal studies are needed to confirm this hypothesis, these data are consistent with previous findings suggesting that high levels of cognitive complaints may reflect changes in brain connectivity and may be a potential marker for the risk of late-life cognitive dysfunction in postmenopausal women with otherwise normal cognitive performance. PMID:27721740

  6. BRAIN NETWORKS. Correlated gene expression supports synchronous activity in brain networks.

    PubMed

    Richiardi, Jonas; Altmann, Andre; Milazzo, Anna-Clare; Chang, Catie; Chakravarty, M Mallar; Banaschewski, Tobias; Barker, Gareth J; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Conrod, Patricia; Fauth-Bühler, Mira; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Lemaître, Hervé; Mann, Karl F; Martinot, Jean-Luc; Nees, Frauke; Paus, Tomáš; Pausova, Zdenka; Rietschel, Marcella; Robbins, Trevor W; Smolka, Michael N; Spanagel, Rainer; Ströhle, Andreas; Schumann, Gunter; Hawrylycz, Mike; Poline, Jean-Baptiste; Greicius, Michael D

    2015-06-12

    During rest, brain activity is synchronized between different regions widely distributed throughout the brain, forming functional networks. However, the molecular mechanisms supporting functional connectivity remain undefined. We show that functional brain networks defined with resting-state functional magnetic resonance imaging can be recapitulated by using measures of correlated gene expression in a post mortem brain tissue data set. The set of 136 genes we identify is significantly enriched for ion channels. Polymorphisms in this set of genes significantly affect resting-state functional connectivity in a large sample of healthy adolescents. Expression levels of these genes are also significantly associated with axonal connectivity in the mouse. The results provide convergent, multimodal evidence that resting-state functional networks correlate with the orchestrated activity of dozens of genes linked to ion channel activity and synaptic function.