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1

Altered brain activation during visuomotor integration in chronic active cannabis users: relationship to cortisol levels.  

PubMed

Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. Thirty cannabis users (16 men, 14 women, 18-45 years old) and 30 nondrug user controls (16 men, 14 women, 19-44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and with fMRI using a 3 Tesla scanner during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area BA 17 than cannabis users. Cannabis users also had higher salivary cortisol levels than controls (p = 0.002). Chronic active cannabis use is associated with slower and less efficient psychomotor function, especially in male users, as indicated by a shift from regions involved with automated visually guided responses to more executive or attentional control areas. The greater but altered brain activities may be mediated by the higher cortisol levels in the cannabis users, which in turn may lead to less efficient visual-motor function. PMID:22159107

King, George R; Ernst, Thomas; Deng, Weiran; Stenger, Andrew; Gonzales, Rachael M K; Nakama, Helenna; Chang, Linda

2011-12-01

2

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

PubMed Central

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

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

2006-01-01

3

First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo  

PubMed Central

The response to centrally-acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigate the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20 ?g propranolol or 40 ?g propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: a) lower analgesia in the tail-flick test (p<0.05) and lower areas under the analgesia-time curve (p<0.02) within the first hour after 30 mg/kg subcutaneous codeine, b) lower morphine concentrations and morphine to codeine ratios in the brain (p<0.02 and p<0.05, respectively), but not in plasma (p>0.6 and p>0.7, respectively), tested at 30 min after 30 mg/kg subcutaneous codeine, and c) lower morphine formation from codeine ex vivo by brain membranes (p<0.04), but not by liver microsomes (p>0.9). Analgesia trended toward a correlation with brain morphine concentrations (p=0.07) and correlated with brain morphine to codeine ratios (p<0.005), but not with plasma morphine concentrations (p>0.8) or plasma morphine to codeine ratios (p>0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine's therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally-acting drugs. PMID:23623752

Zhou, Kaidi; Khokhar, Jibran Y.; Zhao, Bin; Tyndale, Rachel F.

2013-01-01

4

Altered Spontaneous Brain Activity in Patients with Hemifacial Spasm: A Resting-State Functional MRI Study  

PubMed Central

Resting-state functional magnetic resonance imaging (fMRI) has been used to detect the alterations of spontaneous neuronal activity in various neurological and neuropsychiatric diseases, but rarely in hemifacial spasm (HFS), a nervous system disorder. We used resting-state fMRI with regional homogeneity (ReHo) analysis to investigate changes in spontaneous brain activity of patients with HFS and to determine the relationship of these functional changes with clinical features. Thirty patients with HFS and 33 age-, sex-, and education-matched healthy controls were included in this study. Compared with controls, HFS patients had significantly decreased ReHo values in left middle frontal gyrus (MFG), left medial cingulate cortex (MCC), left lingual gyrus, right superior temporal gyrus (STG) and right precuneus; and increased ReHo values in left precentral gyrus, anterior cingulate cortex (ACC), right brainstem, and right cerebellum. Furthermore, the mean ReHo value in brainstem showed a positive correlation with the spasm severity (r = 0.404, p = 0.027), and the mean ReHo value in MFG was inversely related with spasm severity in HFS group (r = -0.398, p = 0.028). This study reveals that HFS is associated with abnormal spontaneous brain activity in brain regions most involved in motor control and blinking movement. The disturbances of spontaneous brain activity reflected by ReHo measurements may provide insights into the neurological pathophysiology of HFS. PMID:25603126

Tu, Ye; Wei, Yongxu; Sun, Kun; Zhao, Weiguo; Yu, Buwei

2015-01-01

5

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

PubMed Central

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

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

6

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

PubMed Central

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 potential biomarkers for assessment of neuronal damage and the prediction of clinical outcomes in acute SCI. PMID:25768010

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

2015-01-01

7

Altered resting-state brain activity at functional MRI during automatic memory consolidation of fear conditioning.  

PubMed

Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of automatic memory consolidation of fear conditioning is still unclear. To address this question, we measured brain activity following fear acquisition using resting-state functional magnetic resonance imaging (rs-fMRI). In the current study, we used a marker of fMRI, amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to quantify the spontaneous brain activity. Brain activity correlated to fear memory consolidation was observed in parahippocampus, insula, and thalamus in resting-state. Furthermore, after acquired fear conditioning, compared with control group some brain areas showed ALFF increased in ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) in the experimental group, whereas some brain areas showed decreased ALFF in striatal regions (caudate, putamen). Moreover, the change of ALFF in vmPFC was positively correlated with the subjective fear ratings. These findings suggest that the parahippocampus, insula, and thalamus are the neural substrates of fear memory consolidation. The difference in activity could be attributed to a homeostatic process in which the vmPFC and ACC were involved in the fear recovery process, and change of ALFF in vmPFC predicts subjective fear ratings. PMID:23726994

Feng, Tingyong; Feng, Pan; Chen, Zhencai

2013-07-26

8

Evidence that acute taurine treatment alters extracellular AMP hydrolysis and adenosine deaminase activity in zebrafish brain membranes.  

PubMed

Taurine is one of the most abundant free amino acids in excitable tissues. In the brain, extracellular taurine may act as an inhibitory neurotransmitter, neuromodulator, and neuroprotector. Nucleotides are ubiquitous signaling molecules that play crucial roles for brain function. The inactivation of nucleotide-mediated signaling is controlled by ectonucleotidases, which include the nucleoside triphosphate diphosphohydrolase (NTPDase) family and ecto-5'-nucleotidase. These enzymes hydrolyze ATP/GTP to adenosine/guanosine, which exert a modulatory role controlling several neurotransmitter systems. The nucleoside adenosine can be inactivated in extracellular or intracellular milieu by adenosine deaminase (ADA). In this report, we tested whether acute taurine treatment at supra-physiological concentrations alters NTPDase, ecto-5'-nucleotidase, and ADA activities in zebrafish brain. Fish were treated with 42, 150, and 400 mg L(-1) taurine for 1h, the brains were dissected and the enzyme assays were performed. Although the NTPDase activities were not altered, 150 and 400 mg L(-1) taurine increased AMP hydrolysis (128 and 153%, respectively) in zebrafish brain membranes and significantly decreased ecto-ADA activity (29 and 38%, respectively). In vitro assays demonstrated that taurine did not change AMP hydrolysis, whereas it promoted a significant decrease in ecto-ADA activity at 150 and 400 mg L(-1) (24 and 26%, respectively). Altogether, our data provide the first evidence that taurine exposure modulates the ecto-enzymes responsible for controlling extracellular adenosine levels in zebrafish brain. These findings could be relevant to evaluate potential beneficial effects promoted by acute taurine treatment in the central nervous system (CNS) of this species. PMID:20600599

Rosemberg, Denis Broock; Kist, Luiza Wilges; Etchart, Renata Jardim; Rico, Eduardo Pacheco; Langoni, Andrei Silveira; Dias, Renato Dutra; Bogo, Maurício Reis; Bonan, Carla Denise; Souza, Diogo Onofre

2010-09-01

9

Brain Activation During Working Memory Is Altered in Patients With Type 1 Diabetes During Hypoglycemia  

PubMed Central

OBJECTIVE To investigate the effects of acute hypoglycemia on working memory and brain function in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS Using blood oxygen level–dependent (BOLD) functional magnetic resonance imaging during euglycemic (5.0 mmol/L) and hypoglycemic (2.8 mmol/L) hyperinsulinemic clamps, we compared brain activation response to a working-memory task (WMT) in type 1 diabetic subjects (n = 16) with that in age-matched nondiabetic control subjects (n = 16). Behavioral performance was assessed by percent correct responses. RESULTS During euglycemia, the WMT activated the bilateral frontal and parietal cortices, insula, thalamus, and cerebellum in both groups. During hypoglycemia, activation decreased in both groups but remained 80% larger in type 1 diabetic versus control subjects (P < 0.05). In type 1 diabetic subjects, higher HbA1c was associated with lower activation in the right parahippocampal gyrus and amygdala (R2 = 0.45, P < 0.002). Deactivation of the default-mode network (DMN) also was seen in both groups during euglycemia. However, during hypoglycemia, type 1 diabetic patients deactivated the DMN 70% less than control subjects (P < 0.05). Behavioral performance did not differ between glycemic conditions or groups. CONCLUSIONS BOLD activation was increased and deactivation was decreased in type 1 diabetic versus control subjects during hypoglycemia. This higher level of brain activation required by type 1 diabetic subjects to attain the same level of cognitive performance as control subjects suggests reduced cerebral efficiency in type 1 diabetes. PMID:21984582

Bolo, Nicolas R.; Musen, Gail; Jacobson, Alan M.; Weinger, Katie; McCartney, Richard L.; Flores, Veronica; Renshaw, Perry F.; Simonson, Donald C.

2011-01-01

10

Traumatic alterations in GABA signaling disrupt hippocampal network activity in the developing brain  

PubMed Central

Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl?]i) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl?]i correlated with disruption of neural processes and biomarkers of cell injury. Traumatized neurons with higher [Cl?]i demonstrated excitatory GABA signaling, remained synaptically active, and facilitated network activity as assayed by the frequency of extracellular action potentials and spontaneous network-driven oscillations. These data support a more inhibitory role for GABA in the unperturbed immature brain, demonstrate the utility of the acute brain slice preparation for the study of the consequences of trauma, and provide potential mechanisms for both GABA-mediated excitatory network events in the slice preparation and early post-traumatic seizures. PMID:22442068

Dzhala, Volodymyr; Valeeva, Guzel; Glykys, Joseph; Khazipov, Rustem; Staley, Kevin

2012-01-01

11

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

PubMed

The ?-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. PMID:25600108

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

12

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

PubMed

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

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

2015-01-01

13

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

PubMed Central

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

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

2015-01-01

14

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

PubMed

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 12-15years) 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. PMID:25683798

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

15

Visual Learning Alters the Spontaneous Activity of the Resting Human Brain: An fNIRS Study  

PubMed Central

Resting-state functional connectivity (RSFC) has been widely used to investigate spontaneous brain activity that exhibits correlated fluctuations. RSFC has been found to be changed along the developmental course and after learning. Here, we investigated whether and how visual learning modified the resting oxygenated hemoglobin (HbO) functional brain connectivity by using functional near-infrared spectroscopy (fNIRS). We demonstrate that after five days of training on an orientation discrimination task constrained to the right visual field, resting HbO functional connectivity and directed mutual interaction between high-level visual cortex and frontal/central areas involved in the top-down control were significantly modified. Moreover, these changes, which correlated with the degree of perceptual learning, were not limited to the trained left visual cortex. We conclude that the resting oxygenated hemoglobin functional connectivity could be used as a predictor of visual learning, supporting the involvement of high-level visual cortex and the involvement of frontal/central cortex during visual perceptual learning. PMID:25243168

Niu, Haijing; Li, Hao; Sun, Li; Su, Yongming; Huang, Jing; Song, Yan

2014-01-01

16

Altered Brain Activation in Ventral Frontal-Striatal Regions Following a 16-week Pharmacotherapy in Unmedicated Obsessive-Compulsive Disorder  

PubMed Central

Recent studies have reported that cognitive inflexibility associated with impairments in a frontal-striatal circuit and parietal region is a core cognitive deficit of obsessive-compulsive disorder (OCD). However, few studies have examined progressive changes in these regions following clinical improvement in obsessive-compulsive symptoms. To determine if treatment changes the aberrant activation pattern associated with task switching in OCD, we examined the activation patterns in brain areas after treatment. The study was conducted on 10 unmedicated OCD patients and 20 matched controls using event-related functional magnetic resonance imaging. Treatment improved the clinical symptoms measured by the Yale-Brown Obsessive Compulsive Scale and behavioral flexibility indicated by the switching cost. At baseline, OCD showed significantly less activation in the dorsal and ventral frontal-striatal circuit and parietal regions under the task-switch minus task-repeat condition compared with controls. After treatment, the neural responses in the ventral frontal-striatal circuit in OCD were partially normalized, whereas the activation deficit in dorsal frontoparietal regions that mediate shifting attention or behavioral flexibility persisted. It is suggested that altered brain activation in ventral frontal-striatal regions in OCD patients is associated with their cognitive flexibility and changes in these regions may underlie the pathophysiology of OCD. PMID:21532859

Han, Ji Yeon; Kang, Do-Hyung; Gu, Bon-Mi; Jung, Wi Hoon; Choi, Jung-Seok; Choi, Chi-Hoon; Jang, Joon Hwan

2011-01-01

17

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

ERIC Educational Resources Information Center

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…

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

2012-01-01

18

On Altered Patterns of Brain Activation in At-Risk Adolescents and Young Adults  

E-print Network

in the right dorsolateral prefrontal cortex and greater de- activation within the default mode network than concerning increased activation of the dorsolateral prefrontal cortex during working memory manipulation, dorsolateral prefrontal cortex activity increases with increasing memory load until working memory capacity

19

Preserved Working Memory and Altered Brain Activation in Persons at Risk for Psychosis  

E-print Network

greater right dorsolateral prefrontal cortex activation dur- ing manipulation of letters. Conclusions-related hyperactivation in the right dorsolateral prefrontal cortex, the left inferior parietal lobule, and the anterior (including the ventrolat- eral prefrontal cortex and the anterior insula [25, 26]), the dorsolateral

Adcock, R. Alison

20

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

PubMed Central

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

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

2014-01-01

21

Point mutations in IIS4 alter activation and inactivation of rat brain IIA Na channels in Xenopus oocyte macropatches  

Microsoft Academic Search

Macroscopic currents of wild-type rat brain IIA (RBIIA) and mutant Na channels were recorded in excised patches from Xenopus oocytes. A charge deletion (K859Q) and an adjacent conservative mutation (L860F) in the second domain S4 membrane-spanning region differentially altered voltage sensitivity and kinetics. Analysis of voltage dependence was confined to Na currents with fast inactivation kinetics, although RBIIA and K859Q

Andrea Fleig; James M. Fitch; Alan L. Goldin; Martin D. Rayner; John G. Starkus; Peter C. Ruben

1994-01-01

22

Relationship between behavioral alterations and activities of adenylate kinase and creatine kinase in brain of rats infected by Trypanosoma evansi.  

PubMed

The aim of this study was to investigate the behavioral assessment and activities of important enzymes involved in the phosphoryl transfer network in rat brains that were experimentally infected with Trypanosoma evansi. Behavioral assessment (cognitive performance), pro-inflammatory cytokines in serum and activities of adenylate kinase (AK), pyruvate kinase (PK), and creatine kinase (CK) in brain were evaluated at 5 and 15 days post-infection (PI). Here we demonstrate a cognitive impairment in the rats infected with T.?evansi. At 5 and 15 days PI, a memory deficit and a depressant activity were demonstrated by an inhibition avoidance test and increase in the immobility time in a tail suspension test, respectively. On day 5 PI, a decrease in the CK activity and an increase in the AK activity were observed. On day 15 PI, an increase in the CK activity and a decrease in the AK activity were observed. Considering the importance of energy metabolism for brain functioning, it is possible that the changes in the activity of enzymes involved in the cerebral phosphotransfer network and an increase in the proinflammatory cytokines (TNF and IFN) may be involved at least in part in the cognitive impairment in infected rats with T.?evansi. PMID:25662432

Baldissera, Matheus D; Rech, Virginia C; Da Silva, Aleksandro S; Nishihira, Vivian S K; Ianiski, Francine R; Gressler, Lucas T; Grando, Thirssa H; Vaucher, Rodrigo A; Schwertz, Claiton I; Mendes, Ricardo E; Monteiro, Silvia G

2015-01-01

23

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

PubMed Central

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. PMID:22750057

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.

2012-01-01

24

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

PubMed Central

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

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

2014-01-01

25

Altered baseline brain activity in children with bipolar disorder during mania state: a resting-state study  

PubMed Central

Background Previous functional magnetic resonance imaging (fMRI) studies have shown abnormal functional connectivity in regions involved in emotion processing and regulation in pediatric bipolar disorder (PBD). Recent studies indicate, however, that task-dependent neural changes only represent a small fraction of the brain’s total activity. How the brain allocates the majority of its resources at resting state is still unknown. We used the amplitude of low-frequency fluctuation (ALFF) method of fMRI to explore the spontaneous neuronal activity in resting state in PBD patients. Methods Eighteen PBD patients during the mania phase and 18 sex-, age- and education-matched healthy subjects were enrolled in this study and all patients underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups. Correlation analysis was performed between the ALFF values and Young Mania Rating Scale scores. Results Compared with healthy controls, PBD patients presented increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF in left precuneus, left superior parietal lobule, and bilateral inferior occipital gyrus. Additionally, ALFF values in left pallidum were positively correlated with Young Mania Rating Scale score in PBD. Conclusion The abnormal resting-state neuronal activities of the basal ganglia, parietal cortex, and occipital cortex may play an important role in the pathophysiology in PBD patients. PMID:24570585

Lu, Dali; Jiao, Qing; Zhong, Yuan; Gao, Weijia; Xiao, Qian; Liu, Xiaoqun; Lin, Xiaoling; Cheng, Wentao; Luo, Lanzhu; Xu, Chuanjian; Lu, Guangming; Su, Linyan

2014-01-01

26

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

NASA Astrophysics Data System (ADS)

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-?B, 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-?B, 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

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

27

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

PubMed

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

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

28

Altered Calcium Signaling Following Traumatic Brain Injury  

PubMed Central

Cell death and dysfunction after traumatic brain injury (TBI) is caused by a primary phase, related to direct mechanical disruption of the brain, and a secondary phase which consists of delayed events initiated at the time of the physical insult. Arguably, the calcium ion contributes greatly to the delayed cell damage and death after TBI. A large, sustained influx of calcium into cells can initiate cell death signaling cascades, through activation of several degradative enzymes, such as proteases and endonucleases. However, a sustained level of intracellular free calcium is not necessarily lethal, but the specific route of calcium entry may couple calcium directly to cell death pathways. Other sources of calcium, such as intracellular calcium stores, can also contribute to cell damage. In addition, calcium-mediated signal transduction pathways in neurons may be perturbed following injury. These latter types of alterations may contribute to abnormal physiology in neurons that do not necessarily die after a traumatic episode. This review provides an overview of experimental evidence that has led to our current understanding of the role of calcium signaling in death and dysfunction following TBI. PMID:22518104

Weber, John T.

2012-01-01

29

Brain alterations in paedophilia: a critical review.  

PubMed

Psychosocial and biological factors have been implicated in paedophilia, such as alterations in brain structure and function. The purpose of this paper is to review the expanding body of literature on this topic including brain abnormality case reports, as well as structural and functional neuroimaging studies. Case studies of men who have committed sexual offences against children implicate frontal and temporal abnormalities that may be associated with impaired impulse inhibition. Structural neuroimaging investigations show volume reductions in paedophilic men. Although the findings have been heterogeneous, smaller amygdala volume has been replicated repeatedly. Functional neuroimaging investigations demonstrate an overlap between paedophiles and teleiophiles during sexual arousal processing. While it is controversial among studies regarding group differences, reliable discrimination between paedophilic and teleiophilic men may be achieved using functional activation patterns. Nevertheless, the heterogeneous findings published so far suggest further research is necessary to disentangle the neurobiological mechanisms of paedophilic preference. A number of methodological confounds have been identified, which may account for the inconsistent results that could prove to be beneficial for future investigations. PMID:25116710

Mohnke, Sebastian; Müller, Sabine; Amelung, Till; Krüger, Tillmann H C; Ponseti, Jorge; Schiffer, Boris; Walter, Martin; Beier, Klaus M; Walter, Henrik

2014-11-01

30

Activation changes in zebra finch (Taeniopygia guttata) brain areas evoked by alterations of the earth magnetic field.  

PubMed

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

Keary, Nina; Bischof, Hans-Joachim

2012-01-01

31

Brain dysfunction during motor activation and corpus callosum alterations in schizophrenia measured by cerebral blood flow and magnetic resonance imaging.  

PubMed

Sixteen unmedicated (14 never-medicated, 2 with washout periods of 1-2 weeks) schizophrenic patients displaying positive symptoms (e.g., formal thought disorder, hallucinations, delusions) without negative symptoms (e.g., flattening of affect, loss of energy, anhedonia--type I patients), 15 unmedicated (with washout periods from 1 week to 2 years) patients with marked negative symptomatology [type II patients; criterion score below 15/above 35 on the Munich version of the Scale of Assessment of Negative Symptoms (SANS), respectively], and 31 matched normal controls were investigated using regional cerebral blood flow [rCBF; dynamic single-photon emission computerized tomography (SPECT) with Xenon-133 as tracer] and magnetic resonance imaging (MRI; spin-echo technique, T1 weighted, midsagittal cuts). rCBF measurements were performed during both resting conditions and simple motor activation. Separately, on the same day, we performed a planimetric evaluation of the callosal-brain ratio in all subjects using MRI. In accordance with previous results on a smaller sample, we found signs of diffuse bilateral rCBF hyperactivation in type I patients, as compared with signs of nonreactivity in type II schizophrenics. Both activation patterns were different from a strictly contralateral sensorimotor rCBF activation seen in normal persons (only 8 studied with SPECT). The planimetry of relative callosal area did not reveal differences compared to normal persons, when type I/II patients were taken together. However, the threefold increased variance as compared with that found in normal persons suggested biological heterogeneity in patients. We found an increase of relative callosal size in type I as compared with type II patients. In the light of some recent findings linking lack of laterality of several brain functions to increased callosal size, we propose lack of laterality/diffuse hyperactivation and increased callosal size to be connected with positive symptomatology/good prognosis schizophrenia, and vice versa. PMID:1905162

Günther, W; Petsch, R; Steinberg, R; Moser, E; Streck, P; Heller, H; Kurtz, G; Hippius, H

1991-03-15

32

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

PubMed Central

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

Keary, Nina; Bischof, Hans-Joachim

2012-01-01

33

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

PubMed

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 conditions and enhances activation of neurobiological mechanisms underlying depression after immune stimulation. They suggest therefore that obesity, and possibly obesity-associated inflammatory priming, may represent a vulnerability state to immune-mediated depressive symptoms. PMID:24681251

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

2014-10-01

34

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

PubMed Central

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

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

35

Pre-Symptomatic Activation of Antioxidant Responses and Alterations in Glucose and Pyruvate Metabolism in Niemann-Pick Type C1-Deficient Murine Brain  

PubMed Central

Niemann-Pick Type C (NPC) disease is an autosomal recessive neurodegenerative disorder caused in most cases by mutations in the NPC1 gene. NPC1-deficiency is characterized by late endosomal accumulation of cholesterol, impaired cholesterol homeostasis, and a broad range of other cellular abnormalities. Although neuronal abnormalities and glial activation are observed in nearly all areas of the brain, the most severe consequence of NPC1-deficiency is a near complete loss of Purkinje neurons in the cerebellum. The link between cholesterol trafficking and NPC pathogenesis is not yet clear; however, increased oxidative stress in symptomatic NPC disease, increases in mitochondrial cholesterol, and alterations in autophagy/mitophagy suggest that mitochondria play a role in NPC disease pathology. Alterations in mitochondrial function affect energy and neurotransmitter metabolism, and are particularly harmful to the central nervous system. To investigate early metabolic alterations that could affect NPC disease progression, we performed metabolomics analyses of different brain regions from age-matched wildtype and Npc1-/- mice at pre-symptomatic, early symptomatic and late stage disease by 1H-NMR spectroscopy. Metabolic profiling revealed markedly increased lactate and decreased acetate/acetyl-CoA levels in Npc1-/- cerebellum and cerebral cortex at all ages. Protein and gene expression analyses indicated a pre-symptomatic deficiency in the oxidative decarboxylation of pyruvate to acetyl-CoA, and an upregulation of glycolytic gene expression at the early symptomatic stage. We also observed a pre-symptomatic increase in several indicators of oxidative stress and antioxidant response systems in Npc1-/- cerebellum. Our findings suggest that energy metabolism and oxidative stress may present additional therapeutic targets in NPC disease, especially if intervention can be started at an early stage of the disease. PMID:24367541

Kennedy, Barry E.; LeBlanc, Veronique G.; Mailman, Tiffany M.; Fice, Debra; Burton, Ian; Karakach, Tobias K.; Karten, Barbara

2013-01-01

36

Heavy metals and epigenetic alterations in brain tumors.  

PubMed

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

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

2014-12-01

37

Altered intrinsic regional brain spontaneous activity and subjective sleep quality in patients with chronic primary insomnia: a resting-state fMRI study  

PubMed Central

Study objective To prospectively explore the underlying regional homogeneity (ReHo) brain-activity deficit in patients with chronic primary insomnia (PCPIs) and its relationship with clinical features. Design The ReHo method and Statistical Parametric Mapping 8 software were used to evaluate whether resting-state localized brain activity was modulated between PCPIs and good sleepers (GSs), and correlation analysis between altered regional brain areas and clinical features was calculated. Patients and participants Twenty-four PCPIs (17 females, seven males) and 24 (12 females, 12 males) age-, sex-, and education-matched GSs. Measurements and results PCPIs disturbed subjective sleep quality, split positive mood, and exacerbated negative moods. Compared with GSs, PCPIs showed higher ReHo in left fusiform gyrus, and lower ReHo in bilateral cingulate gyrus and right cerebellum anterior lobe. Compared with female GSs, female PCPIs showed higher ReHo in the left fusiform gyrus and right posterior cingulate, and lower ReHo in the left cerebellum anterior lobe and left superior frontal gyrus. Compared with male GSs, male PCPIs showed higher ReHo in the right temporal lobe and lower ReHo in the bilateral frontal lobe. The fusiform gyrus showed strong positive correlations and the frontal lobe showed negative correlations with the clinical measurements. Conclusion The ReHo analysis is a useful noninvasive imaging tool for the detection of cerebral changes and the indexing of clinical features. The abnormal spontaneous activity areas provided important information on the neural mechanisms underlying emotion and sleep-quality impairment in PCPIs. PMID:25484585

Dai, Xi-Jian; Peng, De-Chang; Gong, Hong-Han; Wan, Ai-Lan; Nie, Xiao; Li, Hai-Jun; Wang, Yi-Xiang J

2014-01-01

38

Imaging Brain Electrial Activity  

Microsoft Academic Search

\\u000a Brain activation is a spatio-temporally-distributed process. While the electroencephalogram (EEG) offers excellent temporal\\u000a resolution to characterize rapidly changing patterns of brain activation, conventional EEG techniques are limited mainly due\\u000a to their inability to provide spatial information regarding brain activity. As a result, invasive mapping procedures have\\u000a been increasingly used [Towle et al, 1995]. It is extremely desirable to image spatially

Bin He; Dezhong Yao; Dongsheng Wu

39

When “altering brain function” becomes “mind control”  

PubMed Central

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

Koivuniemi, Andrew; Otto, Kevin

2014-01-01

40

Manganese alters rat brain amino acids levels  

PubMed Central

Manganese (Mn) is an essential element and it acts as a cofactor for a number of enzymatic reactions, including those involved in amino acid, lipid, protein and carbohydrate metabolism. Excessive exposure to Mn can lead to poisoning, characterized by psychiatric disturbances and an extrapyramidal disorder. Mn-induced neuronal degeneration is associated with alterations in amino acids metabolism. In the present study, we analyzed whole rat brain amino acid content subsequent to 4 or 8 intraperitoneal (ip) injections, with 25 mg MnCl2/kg/day, at 48-hour (h) intervals. We noted a significant increase in glycine brain levels after 4 or 8 Mn injections (p<0.05 and p<0.01, respectively) and arginine also after 4 or 8 injections (p<0.001). Significant increases were also noted in brain proline (p<0.01), cysteine (p<0.05), phenylalanine (p<0.01) and tyrosine (p<0.01) levels after 8 Mn injections vs. the control group. These findings suggest that Mn-induced alterations in amino acid levels secondary to Mn affect the neurochemical milieu. PMID:22971893

Santos, Dinamene; Batoreu, M. Camila; Almeida, Isabel; Ramos, Ruben; Sidoryk-Wegrzynowicz, M.; Aschner, Michael; Marreilha dos Santos, A.P.

2012-01-01

41

REPEATED ANABOLIC/ANDROGENIC STEROID EXPOSURE DURING ADOLESCENCE ALTERS PHOSPHATE-ACTIVATED GLUTAMINASE AND GLUTAMATE RECEPTOR 1 SUBUNIT IMMUNOREACTIVITY IN HAMSTER BRAIN: CORRELATION WITH OFFENSIVE AGGRESSION  

PubMed Central

Male Syrian hamsters (Mesocricetus auratus) treated with moderately high doses (5.0mg/kg/day) of anabolic/androgenic steroids (AAS) during adolescence (P27–P56) display highly escalated offensive aggression. The current study examined whether adolescent AAS-exposure influenced the immunohistochemical localization of phosphate-activated glutaminase (PAG), the rate-limiting enzyme in the synthesis of glutamate, a fast-acting neurotransmitter implicated in the modulation of aggression in various species and models of aggression, as well as glutamate receptor 1 subunit (GluR1). Hamsters were administered AAS during adolescence, scored for offensive aggression using the resident-intruder paradigm, and then examined for changes in PAG and GluR1 immunoreactivity in areas of the brain implicated in aggression control. When compared with sesame oil-treated control animals, aggressive AAS-treated hamsters displayed a significant increase in the number of PAG- and area density of GluR1- containing neurons in several notable aggression regions, although the differential pattern of expression did not appear to overlap across brain regions. Together, these results suggest that altered glutamate synthesis and GluR1 receptor expression in specific aggression areas may be involved in adolescent AAS-induced offensive aggression. PMID:17418431

Fischer, Shannon G.; Ricci, Lesley A.; Melloni, Richard H.

2007-01-01

42

Traumatic Alterations in Consciousness: Traumatic Brain Injury  

PubMed Central

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

Blyth, Brian J.; Bazarian, Jeffrey J.

2010-01-01

43

Understanding Alterations in Brain Connectivity in Attention-Deficit/Hyperactivity Disorder Using  

E-print Network

COMMENTARY Understanding Alterations in Brain Connectivity in Attention of neural systems and brain connections is an important new area of research to understand both normal brain connectivity and alterations in brain connectivity in neuropsychiatric disorders. The study of brain

44

Altered Brain Activation in Early Drug-Naive Parkinson's Disease during Heat Pain Stimuli: An fMRI Study  

PubMed Central

Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by motor and nonmotor signs and symptoms. To date, many studies of PD have focused on its cardinal motor symptoms. To study the nonmotor signs of early PD, we investigated the reactions solicited by heat pain stimuli in early untreated PD patients without pain using fMRI. The activation patterns of contact heat stimuli (51°C) were assessed in 14 patients and 17 age- and sex-matched healthy controls. Patients with PD showed significant decreases in activation of the superior temporal gyrus (STG) and insula compared with controls. In addition, a significant relationship between activation of the insula and STG and the pain scores was observed in healthy controls but not in PD. This study provided further support that the insula and STG are important parts of the somatosensory circuitry recruited during the period of pain. The hypoactivity of the STG and insula in PD implied that functions including affective, cognitive, and sensory-discriminative processes, which are associated with the insula and STG, were disturbed. This finding supports the view that leaving early PD untreated could be tied directly to central nervous system dysfunction. PMID:25628915

Tan, Ying; Tan, Juan; Cui, Wenjuan; He, Hui; Bin, Yi; Deng, Jiayan; Tan, Rui; Tan, Wenrong; Liu, Tao; Zeng, Nanlin; Xiao, Ruhui; Yao, Dezhong; Wang, Xiaoming

2015-01-01

45

Dietary animal proteins alter monoamine metabolism in the brain.  

PubMed

Several amino acids have effects on mental function, including sedative, antidepressant-like and anxiolytic-like effects. However, the influence of integrated amino acid nutrition as protein constituents on mental function remains unclear. Therefore, the purpose of the present study was to compare the influence of chicken, pork and beef protein extracts on brain monoamine metabolism in mice. Changes in monoamine levels and their turnover rates in the brain were induced by different protein sources. In particular, chicken protein group showed the highest norepinephrine levels in the hippocampus and hypothalamus, and beef protein extract caused an activation of the serotonergic system in the hypothalamus, although there were no significant differences in amino acid compositions of these protein extracts. Therefore, it was revealed that amino acid compositions in dietary protein did not induce alteration in monoamine metabolism. However, there were differences in small molecular peptides, such as creatine, carnosine and anserine levels in animal protein extracts. In conclusion, monoamine metabolism was altered by dietary protein sources. However, it was indicated that the alteration in monoamine metabolism may be independent from amino acid compositions in dietary protein. In addition, alteration in monoamine metabolism depending on the dietary protein sources may be induced by small molecular peptides. PMID:22694334

Nagasawa, Mao; Murakami, Tatsuro; Sato, Mikako; Takahata, Yoshihisa; Morimatsu, Fumiki; Furuse, Mitsuhiro

2012-06-01

46

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

PubMed Central

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

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

2014-01-01

47

The Brain Activity Map  

PubMed Central

Neuroscientists have made impressive advances in understanding the microscale function of single neurons and the macroscale activity of the human brain. One can probe molecular and biophysical aspects of individual neurons and also view the human brain in action with magnetic resonance imaging (MRI) or magnetoencephalography (MEG). However, the mechanisms of perception, cognition, and action remain mysterious because they emerge from the real-time interactions of large sets of neurons in densely interconnected, widespread neural circuits. PMID:23470729

Alivisatos, A. Paul; Chun, Miyoung; Church, George M.; Deisseroth, Karl; Donoghue, John P.; Greenspan, Ralph J.; McEuen, Paul L.; Roukes, Michael L.; Sejnowski, Terrence J.; Weiss, Paul S.; Yuste, Rafael

2013-01-01

48

Mapping Structural Brain Alterations in Obsessive-Compulsive Disorder  

Microsoft Academic Search

Background: Recent technical developments have made it feasible to comprehensively assess brain anatomy in psychiatric populations. Objective: To describe the structural brain alterations detected in the magnetic resonance images of a large se- ries of patients with obsessive-compulsive disorder (OCD) using imaging procedures that allow the evaluation of vol- ume changes throughout the brain. Design: Case-control study. Setting: Referral OCD

Jesus Pujol; Carles Soriano-Mas; Pino Alonso; Narcõ ´ s Cardoner; Jose M. Menchon; Joan Deus; Julio Vallejo

2004-01-01

49

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

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

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

2015-01-01

50

Altered functional brain networks in Prader–Willi syndrome  

PubMed Central

Prader–Willi syndrome (PWS) is a genetic imprinting disorder characterized mainly by hyperphagia and early childhood obesity. Previous functional neuroimaging studies used visual stimuli to examine abnormal activities in the eating-related neural circuitry of patients with PWS. It was found that patients with PWS exhibited both excessive hunger and hyperphagia consistently, even in situations without any food stimulation. In the present study, we employed resting-state functional MRI techniques to investigate abnormal brain networks related to eating disorders in children with PWS. First, we applied amplitude of low-frequency fluctuation analysis to define the regions of interest that showed significant alterations in resting-state brain activity levels in patients compared with their sibling control group. We then applied a functional connectivity (FC) analysis to these regions of interest in order to characterize interactions among the brain regions. Our results demonstrated that patients with PWS showed decreased FC strength in the medial prefrontal cortex (MPFC)/inferior parietal lobe (IPL), MPFC/precuneus, IPL/precuneus and IPL/hippocampus in the default mode network; decreased FC strength in the pre-/postcentral gyri and dorsolateral prefrontal cortex (DLPFC)/orbitofrontal cortex (OFC) in the motor sensory network and prefrontal cortex network, respectively; and increased FC strength in the anterior cingulate cortex/insula, ventrolateral prefrontal cortex (VLPFC)/OFC and DLPFC/VLPFC in the core network and prefrontal cortex network, respectively. These findings indicate that there are FC alterations among the brain regions implicated in eating as well as rewarding, even during the resting state, which may provide further evidence supporting the use of PWS as a model to study obesity and to provide information on potential neural targets for the medical treatment of overeating. PMID:23335390

Zhang, Yi; Zhao, Heng; Qiu, Siyou; Tian, Jie; Wen, Xiaotong; Miller, Jennifer L.; von Deneen, Karen M.; Zhou, Zhenyu; Gold, Mark S.; Liu, Yijun

2013-01-01

51

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 Central

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. PMID:24404185

Su, Meilan; Li, Rong; Zou, Dezhi; Han, Yu; Wang, Xuefeng; Cheng, Oumei

2014-01-01

52

RESEARCH Open Access Brain white matter microstructure alterations in  

E-print Network

RESEARCH Open Access Brain white matter microstructure alterations in adolescent rhesus monkeys including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying adolescence, its behavioral correlates, and the relationship with early levels of stress hormones. Methods

Maestripieri, Dario

53

Alterations in Brain Connectivity Underlying Beta Oscillations in Parkinsonism  

E-print Network

Alterations in Brain Connectivity Underlying Beta Oscillations in Parkinsonism Rosalyn J. Moran1, London, United Kingdom, 2 Medical Research Council Anatomical Neuropharmacology Unit and Oxford Parkinson are severely disrupted by the dopamine depletion of Parkinson's disease (PD), leading to pathologically

Moran, Rosalyn

54

Intensive reasoning training alters patterns of brain connectivity at rest  

PubMed Central

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

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

2013-01-01

55

Intensive reasoning training alters patterns of brain connectivity at rest.  

PubMed

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 coactivation 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 frontoparietal 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 h 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 d. 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

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

2013-03-13

56

Hyaluronan Deficiency Due to Has3 Knock-Out Causes Altered Neuronal Activity and Seizures via Reduction in Brain Extracellular Space  

PubMed Central

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 Has2CKO, 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. PMID:24790187

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

2014-01-01

57

Altered brain reward circuits in eating disorders: chicken or egg?  

PubMed

The eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are severe psychiatric disorders with high mortality. Our knowledge about the neurobiology of eating disorders is very limited, and the question remains whether alterations in brain structure or function in eating disorders are state related, remnants of the illness or premorbid traits. The brain reward system is a relatively well-characterized brain circuitry that plays a central role in the drive to eat and individuals with current or past eating disorders showed alterations in those pathways compared to controls. Here we propose that structural and functional alterations in the insula and frontal cortex, including orbitofrontal and cingulate regions, areas that contribute to reward and anxiety processing, could predispose to developing an eating disorder and that adaptive changes in those circuits in response to malnutrition or repeated binge eating and purging could further promote illness behavior, hinder recovery and contribute to relapse. PMID:23963630

Frank, Guido K W

2013-10-01

58

Altered Brain Reward Circuits in Eating Disorders: Chicken or Egg?  

PubMed Central

The eating disorders anorexia nervosa (AN) and bulimia nervosa (BN) are severe psychiatric disorders with high mortality. Our knowledge about the neurobiology of eating disorders is very limited, and the question remains whether alterations in brain structure or function in eating disorders are state related, remnants of the illness or premorbid traits. The brain reward system is a relatively well-characterized brain circuitry that plays a central role in the drive to eat and individuals with current or past eating disorders showed alterations in those pathways compared to controls. Here we propose that structural and functional alterations in the insula and frontal cortex, including orbitofrontal and cingulate regions, areas that contribute to reward and anxiety processing, could predispose to developing an eating disorder and that adaptive changes in those circuits in response to malnutrition or repeated binge eating and purging could further promote illness behavior, hinder recovery and contribute to relapse. PMID:23963630

2013-01-01

59

Altered Hippocampal Connectivity and Midline Brain Anomalies in Children  

E-print Network

Altered Hippocampal Connectivity and Midline Brain Anomalies in Children with Chromosome 22q11.Wandell, Tony J. Simon 8th Biennial International 22q11.2 Deletion Syndrome Meeting July 6-10, 2012 MIND. (2007) Hippocampus · Hippocampal ­ prefrontal functional connectivity impairments in 22q11.2DS mice

Nguyen, Danh

60

Brain alterations in the classical form of congenital muscular dystrophy  

Microsoft Academic Search

In the classical form of congenital muscular dystrophy (CMD), subclinical brain involvement is frequent. In order to establish the natural evolution of CNS alterations in this type of CMD, the cerebral functions of 12 cases were examined longitudinally for a mean period of 8 years. There were 7 boys and 5 girls, with a mean age of 5 years at

Carlo P. Trevisan; Francesco Martinello; Emilia Ferruzza; Marina Fanin; Martine Chevallay; Fernando M. S. Tomé

1996-01-01

61

Acute or chronic stress induce cell compartment-specific phosphorylation of glucocorticoid receptor and alter its transcriptional activity in Wistar rat brain.  

PubMed

Chronic stress and impaired glucocorticoid receptor (GR) feedback are important factors for the compromised hypothalamic-pituitary-adrenal (HPA) axis activity. We investigated the effects of chronic 21 day isolation of Wistar rats on the extrinsic negative feedback part of HPA axis: hippocampus (HIPPO) and prefrontal cortex (PFC). In addition to serum corticosterone (CORT), we followed GR subcellular localization, GR phosphorylation at serine 232 and serine 246, expression of GR regulated genes: GR, CRF and brain-derived neurotropic factor (BDNF), and activity of c-Jun N-terminal kinase (JNK) and Cdk5 kinases that phosphorylate GR. These parameters were also determined in animals subjected to acute 30 min immobilization, which was taken as 'normal' adaptive response to stress. In isolated animals, we found decreased CORT, whereas in animals exposed to acute immobilization, CORT was markedly increased. Even though the GR was predominantly localized in the nucleus of HIPPO and PFC in acute, but not in chronic stress, the expression of GR, CRF, and BDNF genes was similarly regulated under both acute and chronic stresses. Thus, the transcriptional activity of GR under chronic isolation did not seem to be exclusively dependent on high serum CORT levels nor on the subcellular location of the GR protein. Rather, it resulted from the increased Cdk5 activation and phosphorylation of the nuclear GR at serine 232 and the decreased JNK activity reflected in decreased phosphorylation of the nuclear GR at serine 246. Our study suggests that this nuclear isoform of hippocampal and cortical GR may be related to hypocorticism i.e. HPA axis hypoactivity under chronic isolation stress. PMID:19406955

Adzic, Miroslav; Djordjevic, Jelena; Djordjevic, Ana; Niciforovic, Ana; Demonacos, Constantinos; Radojcic, Marija; Krstic-Demonacos, Marija

2009-07-01

62

Lesions of area postrema and subfornical organ alter exendin-4-induced brain activation without preventing the hypophagic effect of the GLP-1 receptor agonist.  

PubMed

The mechanism and route whereby glucagon-like peptide 1 (GLP-1) receptor agonists, such as GLP-1 and exendin-4 (Ex-4), access the central nervous system (CNS) to exert their metabolic effects have yet to be clarified. The primary objective of the present study was to investigate the potential role of two circumventricular organs (CVOs), the area postrema (AP) and the subfornical organ (SFO), in mediating the metabolic and CNS-stimulating effects of Ex-4. We demonstrated that electrolytic ablation of the AP, SFO, or AP + SFO does not acutely prevent the anorectic effects of Ex-4. AP + SFO lesion chronically decreased food intake and body weight and also modulated the effect of Ex-4 on the neuronal activation of brain structures involved in the hypothalamic-pituitary-adrenal axis and glucose metabolism. The results of the study also showed that CVO lesions blunted Ex-4-induced expression of c-fos mRNA (a widely used neuronal activity marker) in 1) limbic structures (bed nucleus of the stria terminalis and central amygdala), 2) hypothalamus (paraventricular hypothalamic nucleus, supraoptic nucleus, and arcuate nucleus), and 3) hindbrain (lateral and lateral-external parabrachial nucleus, medial nucleus of the solitary tract, and ventrolateral medulla). In conclusion, although the present results do not support a role for the CVOs in the anorectic effect induced by a single injection of Ex-4, they suggest that the CVOs play important roles in mediating the actions of Ex-4 in the activation of CNS structures involved in homeostatic control. PMID:20106992

Baraboi, Elena-Dana; Smith, Pauline; Ferguson, Alastair V; Richard, Denis

2010-04-01

63

Altered Resting State Brain Networks in Parkinson’s Disease  

PubMed Central

Parkinson’s disease (PD) is a neurodegenerative disorder affecting dopaminergic neurons in the substantia nigra leading to dysfunctional cortico-striato-thalamic-cortical loops. In addition to the characteristic motor symptoms, PD patients often show cognitive impairments, affective changes and other non-motor symptoms, suggesting system-wide effects on brain function. Here, we used functional magnetic resonance imaging and graph-theory based analysis methods to investigate altered whole-brain intrinsic functional connectivity in PD patients (n?=?37) compared to healthy controls (n?=?20). Global network properties indicated less efficient processing in PD. Analysis of brain network modules pointed to increased connectivity within the sensorimotor network, but decreased interaction of the visual network with other brain modules. We found lower connectivity mainly between the cuneus and the ventral caudate, medial orbitofrontal cortex and the temporal lobe. To identify regions of altered connectivity, we mapped the degree of intrinsic functional connectivity both on ROI- and on voxel-level across the brain. Compared to healthy controls, PD patients showed lower connectedness in the medial and middle orbitofrontal cortex. The degree of connectivity was also decreased in the occipital lobe (cuneus and calcarine), but increased in the superior parietal cortex, posterior cingulate gyrus, supramarginal gyrus and supplementary motor area. Our results on global network and module properties indicated that PD manifests as a disconnection syndrome. This was most apparent in the visual network module. The higher connectedness within the sensorimotor module in PD patients may be related to compensation mechanism in order to overcome the functional deficit of the striato-cortical motor loops or to loss of mutual inhibition between brain networks. Abnormal connectivity in the visual network may be related to adaptation and compensation processes as a consequence of altered motor function. Our analysis approach proved sensitive for detecting disease-related localized effects as well as changes in network functions on intermediate and global scale. PMID:24204812

Göttlich, Martin; Münte, Thomas F.; Heldmann, Marcus; Kasten, Meike; Hagenah, Johann; Krämer, Ulrike M.

2013-01-01

64

Structural brain alterations associated with dyslexia predate reading onset  

PubMed Central

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 develop in early childhood prior to reading onset. Further studies using larger sample sizes and longitudinal analyses are needed in order to determine whether the identified structural alterations may be utilized as structural markers for the early identification of children at risk, which may prevent the negative clinical, social and psychological outcome of developmental dyslexia. PMID:20884362

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

2012-01-01

65

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

PubMed

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

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

2014-12-01

66

Brain Gym. Simple Activities for Whole Brain Learning.  

ERIC Educational Resources Information Center

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…

Dennison, Paul E.; Dennison, Gail E.

67

Alterations in resting-state brain networks in concussed adolescent athletes.  

PubMed

Sports-related concussion in adolescents is a major public health issue; however, little is known about the underlying changes in functional brain connectivity. We evaluated connectivity of resting-state brain networks to determine whether alterations in specific networks distinguish adolescents with sports-related concussion from a group of healthy, active control adolescents. Twelve adolescents with a clinical diagnosis of subacute concussion and ten healthy adolescents matched for age, gender, and physical activity completed functional magnetic resonance imaging (fMRI) scanning. Functional connectivity of resting-state brain networks was evaluated in both groups using probabilistic independent component analysis (ICA). Altered functional connectivity was found within three resting-state networks in adolescents with concussion. Specifically, we noted: a) alterations within the default mode network; b) increased connectivity in the right frontal pole in the executive function network; and c) increased connectivity in the left frontal operculum cortex associated with the ventral attention network. This preliminary report shows that whole-brain functional connectivity is altered in networks related to cognition and attention in adolescents in the subacute phase following sports-related concussion. This first report in adolescents should be used to inform future studies in larger cohorts of adolescents with sports-related concussion. Increased knowledge of these changes may lead to improvements in clinical management and help to develop rehabilitation programs. PMID:25010041

Borich, Michael; Babul, Aliya-Nur; Yuan, Po Hsiang; Boyd, Lara; Virji-Babul, Naznin

2015-02-15

68

Behavioural alteration in chronic pain: are brain glia involved?  

PubMed

Behavioural symptoms such as abnormal emotionality (including anxious and depressive episodes) and cognition (for instance weakened decision-making) are highly frequent in both chronic pain patients and their animal models. The theory developed in the present article posits that alterations in glial cells (astrocytes and microglia) in cortical and limbic brain regions might be the origin of such emotional and cognitive chronic pain-associated impairments. Indeed, in mood disorders (unipolar depression, anxiety disorders, autism or schizophrenia) glial changes in brain regions involved in mood control (prefrontal and cingulate cortices, amygdala and the hippocampus) have been recurrently described. Besides, glial cells have been undoubtedly identified as key actors in the sensory component of chronic pain, owing to the profound phenotypical changes they undergo throughout the sensory pathway. Hence, the possibility arises that brain astrocytes and microglia react in upper brain structures as well, mediating the related mood and cognitive dysfunctions in chronic pain. So far, only very few studies have provided results in this prospect, mainly indirectly in pain-independent researches. Nevertheless, the first scant available data seem to merge in a unified description of a brain glial reaction occurring after chronic peripheral lesion. The present article uses this scarce literature to formulate the provocative theory of a glia-driven mood and cognitive dysfunction in chronic pain, expounding upon its validity and putative therapeutical impact as well as its current limitations and expected future developments. PMID:21741179

Panigada, T; Gosselin, R-D

2011-10-01

69

Fueling and imaging brain activation  

PubMed Central

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

Dienel, Gerald A

2012-01-01

70

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

PubMed

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

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

2014-03-27

71

Does acute caffeine ingestion alter brain metabolism in young adults?  

PubMed

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

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

2015-04-15

72

Introducing graph theory to track for neuroplastic alterations in the resting human brain: A transcranial direct current stimulation study  

Microsoft Academic Search

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that alters cortical excitability and activity in a polarity-dependent way. Stimulation for a few minutes has been shown to induce plastic alterations of cortical excitability and to improve cognitive performance. These effects might be related to stimulation-induced alterations of functional cortical network connectivity. We aimed to investigate the impact

Rafael Polanía; Walter Paulus; Andrea Antal; Michael A. Nitsche

2011-01-01

73

The Epoch Times | Cocaine Alters Brain Cells, Impairs Impulse Control < Back to previous page  

E-print Network

The Epoch Times | Cocaine Alters Brain Cells, Impairs Impulse Control > Health Cocaine Alters Brain Cells, Impairs Impulse Control Reuters Oct 18, 2006 NEW YORK--A number in Atlanta, show that cocaine use negatively affects the functioning of neurons (cells located in the brain

Goldstein, Rita

74

Brain activity and fatigue during prolonged exercise in the heat  

Microsoft Academic Search

We hypothesized that fatigue due to hyperthermia during prolonged exercise in the heat is in part related to alterations in frontal cortical brain activity. The electroencephalographic activity (EEG) of the frontal cortex of the brain was measured in seven cyclists [maximal O2 uptake ($$\\\\dot VO_{2\\\\max }$$ ) 4.8ǂ.1 (SE) l min-1] cycling at 60% $$\\\\dot VO_{2\\\\max }$$ in a hot

B. Nielsen; T. Hyldig; F. Bidstrup; J. González-Alonso; G. R. J. Christoffersen

2001-01-01

75

Antenatal maternal stress alters functional brain responses in adult offspring during conditioned fear  

Microsoft Academic Search

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 14weeks) with

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

2011-01-01

76

Preterm birth and structural brain alterations in early adulthood  

PubMed Central

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/thalamus/fornix and GM volume in temporal gyri bilaterally, accounted for 21% of the variance of executive function (F = 9.9, p < 0.0001) and WM in the posterior corpus callosum/thalamus/fornix alone accounted for 17% of the variance of total non-verbal memory scores (F = 9.9, p < 0.0001). These results reveal that VPT birth continues to be associated with altered structural brain anatomy in early adult life, although it remains to be ascertained whether these changes reflect neurodevelopmental delays or long lasting structural alterations due to prematurity. GM and WM alterations correlate with length of gestation and mediate cognitive outcome. PMID:25379430

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

2014-01-01

77

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

PubMed Central

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

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

78

Bicuculline microinjections into the ventral tegmental area of the rat: alteration of self-stimulation thresholds and of cytochrome oxidase activity in the brain  

Microsoft Academic Search

Abuse of drugs that potentiate GABAergic neurotransmission, namely benzodiazepines, is difficult to understand because this potentiation should elicit, among other effects, a decrease in activity within the mesolimbic system. Abuse of benzodiazepines is difficult to understand since the opposite, namely an increase in mesolimbic activity, has been implicated in drug abuse as well as in the rewarding effect of direct

Guy Sandner; Catherine Bielajew; George Fouriezos

1996-01-01

79

Common DNA methylation alterations in multiple brain regions in autism.  

PubMed

Autism spectrum disorders (ASD) are increasingly common neurodevelopmental disorders defined clinically by a triad of features including impairment in social interaction, impairment in communication in social situations and restricted and repetitive patterns of behavior and interests, with considerable phenotypic heterogeneity among individuals. Although heritability estimates for ASD are high, conventional genetic-based efforts to identify genes involved in ASD have yielded only few reproducible candidate genes that account for only a small proportion of ASDs. There is mounting evidence to suggest environmental and epigenetic factors play a stronger role in the etiology of ASD than previously thought. To begin to understand the contribution of epigenetics to ASD, we have examined DNA methylation (DNAm) in a pilot study of postmortem brain tissue from 19 autism cases and 21 unrelated controls, among three brain regions including dorsolateral prefrontal cortex, temporal cortex and cerebellum. We measured over 485,000 CpG loci across a diverse set of functionally relevant genomic regions using the Infinium HumanMethylation450 BeadChip and identified four genome-wide significant differentially methylated regions (DMRs) using a bump hunting approach and a permutation-based multiple testing correction method. We replicated 3/4 DMRs identified in our genome-wide screen in a different set of samples and across different brain regions. The DMRs identified in this study represent suggestive evidence for commonly altered methylation sites in ASD and provide several promising new candidate genes. PMID:23999529

Ladd-Acosta, C; Hansen, K D; Briem, E; Fallin, M D; Kaufmann, W E; Feinberg, A P

2014-08-01

80

Ethanol-induced alteration in N-methyl- d-aspartate receptor 2A C-terminus and protein kinase C activity in rat brain  

Microsoft Academic Search

Ethanol is a potent inhibitor of the N-methyl-d-aspartate (NMDA) subtype of glutamate receptor. In the present study, expression of NR2A and its phosphorylation status were investigated in adult rat cerebral cortex and cerebellum, using an experimental paradigm of in vivo chronic ethanol exposure. In addition, PKC activity was measured in both cytosol and membrane fraction of cerebral cortex and cerebellum

Rukhsana Sultana; Phanithi Prakash Babu

2003-01-01

81

Is anorexia in thioacetamide-induced cirrhosis related to an altered brain serotonin concentration?  

PubMed

Anorexia or loss of appetite, one of the most typical symptoms observed in experimental and human cirrhosis, has been proposed to be associated with altered brain serotonin (5-HT) metabolism. In order to evaluate this hypothesis, brain 5-HT, its precursor tryptophan (TRP) and its metabolite 5-hydroxyindole-acetic acid (5-HIAA) were measured in brains of rats with thioacetamide (TAA)-induced liver cirrhosis. Thioacetamide at a dose of 500 mg/l in drinking water was administered for 6 weeks and during this period food intake was carefully measured in order to monitor the loss of appetite or decrease in food intake observed in cirrhosis. Concentrations of brain TRP, 5-HT and 5-HIAA were measured by HPLC with electrochemical detection. In TAA-treated rats, concentrations of 5-HT, TRP and 5-HIAA were increased in brain (44%, 33% and 36% of controls, p < 0.01). In plasma and liver of cirrhotic rats, TRP levels were increased (195% and 43%; p < 0.01). Plasma glucose and albumin levels were decreased (50%; p < 0.01 and 31%). Food intake, growth rate and locomotor activity of TAA-treated rats also decreased (73%, 22% and 73% of controls; p < 0.01). The results of this study show that brain 5-HT concentration in rats is increased in TAA-treated rats and it may, therefore, play an important role in the pathogenesis of anorexia associated with TAA-induced cirrhosis. PMID:15047980

Haider, Saida; Saleem, Sadia; Shameem, Saima; Ahmed, Shahida P; Parveen, Tahira; Haleem, Darakhshan J

2004-01-01

82

Altered Pattern of Spontaneous Brain Activity in the Patients with End-Stage Renal Disease: A Resting-State Functional MRI Study with Regional Homogeneity Analysis  

PubMed Central

Purpose To investigate the pattern of spontaneous neural activity in patients with end-stage renal disease (ESRD) with and without neurocognitive dysfunction using resting-state functional magnetic resonance imaging (rs-fMRI) with a regional homogeneity (ReHo) algorithm. Materials and Methods rs-fMRI data were acquired in 36 ESRD patients (minimal nephro-encephalopathy [MNE], n?=?19, 13 male, 37±12.07 years; non-nephro-encephalopathy [non-NE], n?=?17, 11 male, 38±12.13 years) and 20 healthy controls (13 male, 7 female, 36±10.27 years). Neuropsychological (number connection test type A [NCT-A], digit symbol test [DST]) and laboratory tests were performed in all patients. The Kendall's coefficient of concordance (KCC) was used to measure the regional homogeneity for each subject. The regional homogeneity maps were compared using ANOVA tests among MNE, non-NE, and healthy control groups and post hoc t -tests between each pair in a voxel-wise way. A multiple regression analysis was performed to evaluate the relationships between ReHo index and NCT-A, DST scores, serum creatinine and urea levels, disease and dialysis duration. Results Compared with healthy controls, both MNE and non-NE patients showed decreased ReHo in the multiple areas of bilateral frontal, parietal and temporal lobes. Compared with the non-NE, MNE patients showed decreased ReHo in the right inferior parietal lobe (IPL), medial frontal cortex (MFC) and left precuneus (PCu). The NCT-A scores and serum urea levels of ESRD patients negatively correlated with ReHo values in the frontal and parietal lobes, while DST scores positively correlated with ReHo values in the bilateral PCC/precuneus, MFC and inferior parietal lobe (IPL) (all P<0.05, AlphaSim corrected). No significant correlations were found between any regional ReHo values and disease duration, dialysis duration and serum creatinine values in ESRD patients (all P>0.05, AlphaSim corrected). Conclusion Diffused decreased ReHo values were found in both MNE and non-NE patients. The progressively decreased ReHo in the default mode network (DMN), frontal and parietal lobes might be trait-related in MNE. The ReHo analysis may be potentially valuable for elucidating neurocognitive abnormalities of ESRD patients and detecting the development from non-NE to MNE. PMID:23990958

Zhong, Jianhui; Qi, Rongfeng; Zhang, Long Jiang; Lu, Guang Ming

2013-01-01

83

Experimental traumatic brain injury alters ethanol consumption and sensitivity.  

PubMed

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 dopaminergic neurotransmission while altering ethanol consumption. Examining TBI effects on ethanol responsitivity will improve our understanding of alcohol use post-TBI in humans. PMID:24934382

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

2014-10-15

84

Melatonin stimulates brain glutathione peroxidase activity  

Microsoft Academic Search

Exogenously administered melatonin causes a 2-fold rise in glutathione peroxidase activity within 30 min in the brain of the rat. Furthermore, brain glutathione peroxidase activity is higher at night than during the day and is correlated with high night-time tissue melatonin levels. Glutathione peroxidase is thought to be the principal enzyme eliminating peroxides in the brain. This antioxidative enzyme reduces

L. R. Barlow-Walden; R. J. Reiter; M. Abe; M. Pablos; A. Menendez-Pelaez; L.-D. Chen; B. Poeggeler

1995-01-01

85

596 Am J Geriatr Psychiatry 12:6, November-December 2004 Altered PET Functional Brain Responses  

E-print Network

596 Am J Geriatr Psychiatry 12:6, November-December 2004 Altered PET Functional Brain Responses tomography (PET), they imaged 32 healthy subjects (26 non- 4 carriers and 6 4 carriers) performing a serial, with the "activation" difference (TD­SD PET counts) as the dependent variable and the APOE genotype (presence versus ab

86

Somatic retrotransposition alters the genetic landscape of the human brain.  

PubMed

Retrotransposons are mobile genetic elements that use a germline 'copy-and-paste' mechanism to spread throughout metazoan genomes. At least 50 per cent of the human genome is derived from retrotransposons, with three active families (L1, Alu and SVA) associated with insertional mutagenesis and disease. Epigenetic and post-transcriptional suppression block retrotransposition in somatic cells, excluding early embryo development and some malignancies. Recent reports of L1 expression and copy number variation in the human brain suggest that L1 mobilization may also occur during later development. However, the corresponding integration sites have not been mapped. Here we apply a high-throughput method to identify numerous L1, Alu and SVA germline mutations, as well as 7,743 putative somatic L1 insertions, in the hippocampus and caudate nucleus of three individuals. Surprisingly, we also found 13,692 somatic Alu insertions and 1,350 SVA insertions. Our results demonstrate that retrotransposons mobilize to protein-coding genes differentially expressed and active in the brain. Thus, somatic genome mosaicism driven by retrotransposition may reshape the genetic circuitry that underpins normal and abnormal neurobiological processes. PMID:22037309

Baillie, J Kenneth; Barnett, Mark W; Upton, Kyle R; Gerhardt, Daniel J; Richmond, Todd A; De Sapio, Fioravante; Brennan, Paul M; Rizzu, Patrizia; Smith, Sarah; Fell, Mark; Talbot, Richard T; Gustincich, Stefano; Freeman, Thomas C; Mattick, John S; Hume, David A; Heutink, Peter; Carninci, Piero; Jeddeloh, Jeffrey A; Faulkner, Geoffrey J

2011-11-24

87

Altered resting-state activity in seasonal affective disorder.  

PubMed

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. PMID:22987670

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

88

C5a alters blood-brain barrier integrity in experimental lupus  

PubMed Central

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.—Jacob, A., Hack, B., Chiang, E., Garcia, J. G. N., Quigg, R. J., Alexander, J. J. C5a alters blood-brain barrier integrity in experimental lupus. PMID:20065106

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

2010-01-01

89

Neuropsychological–Neurophysiological Alterations and Brain Atrophy in Cirrhotic Patients  

Microsoft Academic Search

Psychometric performance has been reported to be related to brain atrophy in cirrhotics, but the relationship between brain atrophy and EEG findings is still unknown. The aim of this study was to ascertain the relationship among brain atrophy, EEG, and cognitive performance in cirrhotics. Sixty-eight cirrhotics (age = 55 ± 10 years; males-66%) underwent psychometric evaluation (Symbol Digit Test, Trail

P. Amodio; A. Pellegrini; P. Amistà; S. Luise; F. Del Piccolo; D. Mapelli; S. Montagnese; C. Musto; P. Valenti; A. Gatta

2003-01-01

90

Aripiprazole brain concentration is altered in P-glycoprotein deficient mice.  

PubMed

P-glycoprotein (P-gp) is a transporter that mediates the tissue disposition of numerous drugs. To evaluate the role of P-glycoprotein (P-gp) in aripiprazole tissue distribution and penetration across the blood-brain barrier, mice deficient in the P-gp gene (Abcb1a/b-/-) were dosed intraperitoneally with 2 microg/g mouse of the antipsychotic drug aripiprazole. Wildtype FVB mice were administered the same dose as transgenic animals. At one, two, and three hours after dosing, blood and tissue samples were collected and assayed for aripiprazole concentration by HPLC. Deficiency of P-gp did not result in significantly altered plasma drug concentrations but had dramatic effects on drug concentrations in brain tissue. At 1, 2, and 3 h after dosing, aripiprazole brain concentrations in the Abcb1a/b-/- mice were 4.6-, 4.1- and 3.0-fold higher, respectively (P<0.01), compared with the wildtype mice. Increases in drug concentration were also observed in testes and muscle in Abcb1a/b -/- mice. All other tissues including gut, lung, heart, kidney, liver, and spleen did not show significant differences between the two groups. These data provide evidence that aripiprazole is a transportable substrate of P-gp. Thus, factors influencing P-gp activity within the blood brain barrier in humans may have implications for the therapeutic effects and tolerability of aripiprazole. PMID:19239981

Wang, Jun-Sheng; Zhu, Hao-Jie; Donovan, Jennifer L; Yuan, Hong-Jie; Markowitz, John S; Geesey, Mark E; Devane, C Lindsay

2009-05-01

91

Simulation of Local Blood Flow in Human Brain under Altered Gravity  

NASA Technical Reports Server (NTRS)

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.

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

2003-01-01

92

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

PubMed Central

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

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

93

Intrahippocampal infusion of crotamine isolated from Crotalus durissus terrificus alters plasma and brain biochemical parameters.  

PubMed

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

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

2014-11-01

94

Alterations in brain antioxidant enzymes and redox proteomic identification of oxidized brain proteins induced by the anti-cancer drug Adriamycin: Implications for oxidative stress-mediated chemobrain  

PubMed Central

Adriamycin (ADR) is a chemotherapeutic for the treatment of solid tumors. This quinone-containing anthracycline is well known to produce large amounts of reactive oxygen species (ROS) in vivo. A common complaint of patients undergoing long-term treatment with ADR is somnolence, often referred to as “chemobrain.” While ADR itself does not cross the blood brain barrier (BBB), we recently showed that ADR administration causes a peripheral increase in tumor necrosis factor ? (TNF- ?), which migrates across the BBB and leads to inflammation and oxidative stress in brain, most likely contributing to the observed decline in cognition. In the current study, we measured levels of the antioxidant glutathione (GSH) in brains of mice injected intraparitoneally (i.p.) with ADR, as well as the levels and activities of several enzymes involved in brain GSH metabolism. We observed significantly decreased GSH levels, as well as altered GSH/GSSG ratio in brains of ADR treated mice relative to saline- treated controls. Also observed in brains of ADR treated mice were increased levels of glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). We also observed increased activity of GPx, but a significant reduction in GST and GR activity in mice brain, 72 hrs post i.p injection of ADR (20 mg/kg body weight). Furthermore, we used redox proteomics to identify specific proteins that are oxidized and/or have differential levels in mice brains as a result of a single i.p. injection of ADR. Visinin like protein 1 (VLP1), peptidyl prolyl isomerase 1 (Pin1), and syntaxin 1 (SYNT1) showed differential levels in ADR treated mice relative to saline-treated controls. Triose phosphate isomerase (TPI), enolase, and peroxiredoxin 1 (PRX-1) showed significantly increased specific carbonylation in ADR treated mice brain. These results further support the notion ADR induces oxidative stress in brain despite not crossing the BBB, and that antioxidant intervention may prevent ADR-induced cognitive dysfunction. PMID:20096337

Joshi, Gururaj; Aluise, Christopher D.; Cole, Marsha Paulette; Sultana, Rukhsana; Vore, Mary; St Clair, Daret K.; Butterfield, D. Allan

2010-01-01

95

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...

96

Cranial irradiation alters the brain's microenvironment and permits CCR2+ macrophage infiltration.  

PubMed

Therapeutic irradiation is commonly used to treat primary or metastatic central nervous system tumors. It is believed that activation of neuroinflammatory signaling pathways contributes to the development of common adverse effects, which may ultimately contribute to cognitive dysfunction. Recent studies identified the chemokine (C-C motif) receptor (CCR2), constitutively expressed by cells of the monocyte-macrophage lineage, as a mediator of cognitive impairments induced by irradiation. In the present study we utilized a unique reporter mouse (CCR2(RFP/+)CX3CR1(GFP/+)) to accurately delineate the resident (CX3CR1+) versus peripheral (CCR2+) innate immune response in the brain following cranial irradiation. Our results demonstrate that a single dose of 10Gy cranial ?-irradiation induced a significant decrease in the percentage of resident microglia, while inducing an increase in the infiltration of peripherally derived CCR2+ macrophages. Although reduced in percentage, there was a significant increase in F4/80+ activated macrophages in irradiated animals compared to sham. Moreover, we found that there were altered levels of pro-inflammatory cytokines, chemokines, adhesion molecules, and growth factors in the hippocampi of wild type irradiated mice as compared to sham. All of these molecules are implicated in the recruitment, adhesion, and migration of peripheral monocytes to injured tissue. Importantly, there were no measureable changes in the expression of multiple markers associated with blood-brain barrier integrity; implicating the infiltration of peripheral CCR2+ macrophages may be due to inflammatory induced chemotactic signaling. Cumulatively, these data provide evidence that therapeutic levels of cranial radiation are sufficient to alter the brain's homeostatic balance and permit the influx of peripherally-derived CCR2+ macrophages as well as the regional susceptibility of the hippocampal formation to ionizing radiation. PMID:24695541

Morganti, Josh M; Jopson, Timothy D; Liu, Sharon; Gupta, Nalin; Rosi, Susanna

2014-01-01

97

r Human Brain Mapping 00:000000 (2012) r Key Functional Circuitry Altered in Schizophrenia  

E-print Network

r Human Brain Mapping 00:000­000 (2012) r Key Functional Circuitry Altered in Schizophrenia functional and structural changes in the brain in schizophrenia are of most importance, although the main schizophrenia patients, and func- tional connectivity changes were analyzed using resting-state fMRI data from

Feng, Jianfeng

98

Serum extravasation and cytoskeletal alterations following traumatic brain injury in rats  

Microsoft Academic Search

Disruption of the blood-brain barrier (BBB) and neuronal cytoskeletal damage were evaluated in two commonly used rat models\\u000a of traumatic brain injury. Adult rats received a lateral cortical impact (CI) or lateral fluid percussion (FP) injury of mild\\u000a or moderate severity or a sham procedure. Six hours after trauma, the brains were removed and analyzed with immunocytochemical\\u000a techniques for alterations

Ramona R. Hicks; Stanley A. Baldwin; Stephen W. Scheff

1997-01-01

99

Myelin alters the inflammatory phenotype of macrophages by activating PPARs  

PubMed Central

Background Foamy macrophages, containing myelin degradation products, are abundantly found in active multiple sclerosis (MS) lesions. Recent studies have described an altered phenotype of macrophages after myelin internalization. However, mechanisms by which myelin affects the phenotype of macrophages and how this phenotype influences lesion progression remain unclear. Results We demonstrate that myelin as well as phosphatidylserine (PS), a phospholipid found in myelin, reduce nitric oxide production by macrophages through activation of peroxisome proliferator-activated receptor ?/? (PPAR?/?). Furthermore, uptake of PS by macrophages, after intravenous injection of PS-containing liposomes (PSLs), suppresses the production of inflammatory mediators and ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The protective effect of PSLs in EAE animals is associated with a reduced immune cell infiltration into the central nervous system and decreased splenic cognate antigen specific proliferation. Interestingly, PPAR?/? is activated in foamy macrophages in active MS lesions, indicating that myelin also activates PPAR?/? in macrophages in the human brain. Conclusion Our data show that myelin modulates the phenotype of macrophages by PPAR activation, which may subsequently dampen MS lesion progression. Moreover, our results suggest that myelin-derived PS mediates PPAR?/? activation in macrophages after myelin uptake. The immunoregulatory impact of naturally-occurring myelin lipids may hold promise for future MS therapeutics. PMID:24252308

2013-01-01

100

Chronic Alcohol Drinking Alters Neuronal Dendritic Spines in the Brain Reward Center Nucleus Accumbens  

E-print Network

Zhou et al 1 Chronic Alcohol Drinking Alters Neuronal Dendritic Spines in the Brain Reward Center Running Title: Chronic Alcohol Alters Neurodendritic Structure 9 figures and 1 table Send all of Neuroscience For Peer Review Only #12;Zhou et al 2 ABSTRACT Alcohol is known to affect glutamate transmission

New York at Stoney Brook, State University of

101

Perinatal Risk Factors Altering Regional Brain Structure in the Preterm Infant  

ERIC Educational Resources Information Center

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…

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

102

Altered effective connectivity of default model brain network underlying amnestic MCI  

NASA Astrophysics Data System (ADS)

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.

Yan, Hao; Wang, Yonghui; Tian, Jie

2012-02-01

103

C5a alters blood-brain barrier integrity in experimental lupus.  

PubMed

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. PMID:20065106

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

2010-06-01

104

Neural Activity and the Development of Brain  

E-print Network

Neural Activity and the Development of Brain Circuits Carsten D Hohnke, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA Mriganka Sur,Massachusetts Institute of Technology, Cambridge, Massachusetts, USA The development of highly interconnected circuits in the brain relies on patterns of neural

Sur, Mriganka

105

C5a/CD88 signaling alters blood-brain barrier integrity in lupus through nuclear factor-?B.  

PubMed

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-?B (NF-?b) and the expression of I?b?, 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-?B were determined by immunofluorescence. Inhibition of CD88 reduced translocation of NF-?b 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-?b-dependent manner. These studies suggest that the C5a receptor, CD88 is a promising therapeutic target that will reduce NF-?b-signaling cascades in inflammatory settings. PMID:21929539

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

2011-12-01

106

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

PubMed Central

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

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

107

Prechemotherapy alterations in brain function in women with breast cancer  

Microsoft Academic Search

Despite clinical reports of cognitive deficits associated with cancer chemotherapy, the underlying brain mechanisms are not clear. This research examined selective attention and working memory using functional magnetic resonance imaging (fMRI) in women before chemotherapy for localized breast cancer. Patients were tested with an established selective attention and working memory task during fMRI. Compared with healthy controls, patients showed (a)

Bernadine Cimprich; Patricia Reuter-Lorenz; James Nelson; Patricia M. Clark; Barbara Therrien; Daniel Normolle; Marc G. Berman; Daniel F. Hayes; Douglas C. Noll; Scott Peltier; Robert C. Welsh

2010-01-01

108

Alterations of amino Acid level in depressed rat brain.  

PubMed

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 ?-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-?-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, ?-amino-n-butyric acid and L-?-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant. PMID:25352755

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

2014-10-01

109

Alterations of Amino Acid Level in Depressed Rat Brain  

PubMed Central

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 ?-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-?-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, ?-amino-n-butyric acid and L-?-amino-adipic acid might become potential biomarkers for future diagnosis of depression and development of antidepressant. PMID:25352755

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

2014-01-01

110

Microwave hyperthermia-induced blood-brain barrier alterations  

SciTech Connect

We have studied the interaction of microwaves with the blood-brain barrier in Wistar rats. Indwelling catheters were placed in the femoral vein. Evans blue in isotonic saline was used as a visual indicator of barrier permeation. Irradiation with pulsed 2450-MHz microwaves for 20 min at average power densities of 0.5 to 2600 mW/cm/sup 2/, which resulted in average specific absorption rages (SARs) of 0.04 to 200 mW/g in the brain, did not produce staining, except in regions that normally are highly permeable. When the incident power density was increased to 3000 mW/cm/sup 2/ (SAR of 240 mW/g), extravasation of Evans blue could be seen in the cortex, hippocampus, and midbrain. The rectal temperature, as monitored by a copper-constantan thermocouple, showed a maximum increase of less than 1.0/sup o/C. the brain temperature recorded in a similar group of animals using a non-field-perturbing thermistor exceeded 43/sup o/C. At the higher power density the extravasation depended on the irradition and euthanization times. In one series of experiments, rats were irradiated at 3000 mW/cm/sup 2/ for 5, 10, 15, and 20 min. Immediately after irradiation all except the 5-min animals exhibited increased permeability in some regions of the brain. Brains of rats euthanized 30 min after irradiation were free of Evans blue, while those euthanized 10 and 20 min postirradiation showed significant dye staining but with less intensity than those euthanized immediately after irradiation.

Lin, J.C.; Lin, M.F.

1982-01-01

111

Nutritional n-3 PUFAs deficiency during perinatal periods alters brain innate immune system and neuronal plasticity-associated genes.  

PubMed

Low dietary intake of the n-3 polyunsaturated fatty acids (PUFAs) is a causative factor of neurodevelopmental disorders. However the mechanisms linking n-3 PUFAs low dietary intake and neurodevelopmental disorders are poorly understood. Microglia, known mainly for their immune function in the injured or infected brain, have recently been demonstrated to play a pivotal role in regulating maturation of neuronal circuits during normal brain development. Disruption of this role during the perinatal period therefore could significantly contribute to psychopathologies with a neurodevelopmental neurodevelopmental component. N-3 PUFAs, essential lipids and key structural components of neuronal membrane phospholipids, are highly incorporated in cell membranes during the gestation and lactation phase. We previously showed that in a context of perinatal n-3 PUFAs deficiency, accretion of these latter is decreased and this is correlated to an alteration of endotoxin-induced inflammatory response. We thus postulated that dietary n-3 PUFAs imbalance alters the activity of microglia in the developing brain, leading to abnormal formation of neuronal networks. We first confirmed that mice fed with a n-3 PUFAs deficient diet displayed decreased n-3 PUFAs levels in the brain at post-natal days (PND)0 and PND21. We then demonstrated that n-3 PUFAs deficiency altered microglia phenotype and motility in the post-natal developing brain. This was paralleled by an increase in pro-inflammatory cytokines expression at PND21 and to modification of neuronal plasticity-related genes expression. Overall, our findings show for the first time that a dietary n-3 PUFAs deficiency from the first day of gestation leads to the development of a pro-inflammatory condition in the central nervous system that may contribute to neurodevelopmental alterations. PMID:24735929

Madore, Charlotte; Nadjar, Agnès; Delpech, Jean-Christophe; Sere, A; Aubert, A; Portal, Céline; Joffre, Corinne; Layé, Sophie

2014-10-01

112

Protein kinase activators alter glial cholesterol esterification  

SciTech Connect

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.

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

1986-05-01

113

Telomerase activity in 144 brain tumours  

Microsoft Academic Search

Unlimited proliferation in immortalized cells is believed to be highly dependent on the activity of telomerase, a ribonucleoprotein that synthesizes telomeric repeats onto chromosome ends. Using a polymerase chain reaction-based telomeric repeat amplification protocol (TRAP) assay, we analysed telomerase activity in 99 benign and 45 malignant brain tumours. The TRAP assay results were quantitated by normalizing the telomerase activity of

T Sano; A Asai; K Mishima; T Fujimaki; T Kirino

1998-01-01

114

EEG Oscillatory States: Universality, Uniqueness and Specificity across Healthy-Normal, Altered and Pathological Brain Conditions  

PubMed Central

For the first time the dynamic repertoires and oscillatory types of local EEG states in 13 diverse conditions (examined over 9 studies) that covered healthy-normal, altered and pathological brain states were quantified within the same methodological and conceptual framework. EEG oscillatory states were assessed by the probability-classification analysis of short-term EEG spectral patterns. The results demonstrated that brain activity consists of a limited repertoire of local EEG states in any of the examined conditions. The size of the state repertoires was associated with changes in cognition and vigilance or neuropsychopathologic conditions. Additionally universal, optional and unique EEG states across 13 diverse conditions were observed. It was demonstrated also that EEG oscillations which constituted EEG states were characteristic for different groups of conditions in accordance to oscillations’ functional significance. The results suggested that (a) there is a limit in the number of local states available to the cortex and many ways in which these local states can rearrange themselves and still produce the same global state and (b) EEG individuality is determined by varying proportions of universal, optional and unique oscillatory states. The results enriched our understanding about dynamic microstructure of EEG-signal. PMID:24505292

Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

2014-01-01

115

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

PubMed

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

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

116

Subtle Alterations in Brain Anatomy May Change an Individual’s Personality in Chronic Pain  

PubMed Central

It is well established that gross prefrontal cortex damage can affect an individual’s personality. It is also possible that subtle prefrontal cortex changes associated with conditions such as chronic pain, and not detectable until recent advances in human brain imaging, may also result in subtle changes in an individual’s personality. In an animal model of chronic neuropathic pain, subtle prefrontal cortex changes including altered basal dendritic length, resulted in altered decision making ability. Using multiple magnetic resonance imaging techniques, we found in humans, although gray matter volume and on-going activity were unaltered, chronic neuropathic pain was associated with reduced free and bound proton movement, indicators of subtle anatomical changes, in the medial prefrontal cortex, anterior cingulate cortex and mediodorsal thalamus. Furthermore, proton spectroscopy revealed an increase in neural integrity in the medial prefrontal cortex in neuropathic pain patients, the degree of which was significantly correlated to the personality temperament of novelty seeking. These data reveal that even subtle changes in prefrontal cortex anatomy may result in a significant change in an individual’s personality. PMID:25291361

Gustin, Sylvia M.; McKay, Jamie G.; Petersen, Esben T.; Peck, Chris C.; Murray, Greg M.; Henderson, Luke A.

2014-01-01

117

Obesity Associated Cerebral Gray and White Matter Alterations Are Interrelated in the Female Brain  

PubMed Central

Obesity is known to affect the brain's gray matter (GM) and white matter (WM) structure but the interrelationship of such changes remains unclear. Here we used T1-weighted magnetic resonance imaging (MRI) in combination with voxel-based morphometry (VBM) and diffusion-tensor imaging (DTI) with tract-based spatial statistics (TBSS) to assess the relationship between obesity-associated alterations of gray matter density (GMD) and anisotropic water diffusion in WM, respectively. In a small cohort of lean to obese women, we confirmed previous reports of obesity-associated alterations of GMD in brain regions involved in executive control (i.e., dorsolateral prefrontal cortex, DLPFC) and habit learning (i.e., dorsal striatum). Gray matter density alterations of the DLPFC were negatively correlated with radial diffusivity in the entire corpus callosum. Within the genu of the corpus callosum we found a positive correlation with axial diffusivity. In posterior region and inferior areas of the body of the corpus callosum, axial diffusivity correlated negatively with altered GMD in the dorsal striatum. These findings suggest that, in women, obesity-related alterations of GMD in brain regions involved in executive control and habit learning might relate to alterations of associated WM fiber bundles within the corpus callosum. PMID:25494174

Möller, Harald E.; Anwander, Alfred; Lepsien, Jöran; Schroeter, Matthias L.; Villringer, Arno; Pleger, Burkhard

2014-01-01

118

Phylogenetic Origins of Early Alterations in Brain Region Proportions  

PubMed Central

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. PMID:20332607

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

2010-01-01

119

Copper deficiency alters the neurochemical profile of developing rat brain  

PubMed Central

Copper deficiency is associated with impaired brain development and mitochondrial dysfunction. Perinatal copper deficiency was produced in Holtzman rats. In vivo proton NMR spectroscopy was used to quantify 18 cerebellar and hippocampal metabolites on postnatal day 21 (P21). Copper status was evaluated in male copper-adequate (CuA) and copper-deficient (CuD) brothers at P19 and at P23, 2 days following NMR experiments, by metal and in vitro metabolite data. Compared to CuA pups, CuD pups had lower ascorbate concentration in both brain regions, confirming prior HPLC data. Both regions of CuD rats also had lower N-acetylaspartate levels consistent with delayed development or impaired mitochondrial function similar to prior work demonstrating elevated lactate and citrate. For other metabolites, the P21 neurochemical profile of CuD rats was remarkably similar to CuA rats but uniquely different from iron-deficient or chronic hypoxia models. Further research is needed to determine the neurochemical consequences of copper deficiency. PMID:19356314

Gybina, Anna A.; Tkac, Ivan; Prohaska, Joseph R.

2009-01-01

120

TITLE: Prefrontal transcranial direct current stimulation alters activation and connectivity in cortical and subcortical reward systems: A tDCS-fMRI study  

E-print Network

TITLE: Prefrontal transcranial direct current stimulation alters activation and connectivity, Human Brain Mapping #12;IN PRESS, HUMAN BRAIN MAPPING Abstract Transcranial direct current stimulation to the electrodes. Introduction Transcranial direct current stimulation (tDCS) is a technique for noninvasive brain

Thompson-Schill, Sharon

121

Nanotools for neuroscience and brain activity mapping.  

PubMed

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

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

2013-03-26

122

Nanotools for Neuroscience and Brain Activity Mapping  

PubMed Central

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

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

123

*C5a/CD88 signaling alters blood-brain barrier integrity in lupus through NF?b  

PubMed Central

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-?B (NF?b) and the expression of I?b?, 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?B were determined by immunofluorescence. Inhibition of CD88 reduced translocation of NF?b 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 NF?b dependent manner. These studies suggest that the C5a receptor, CD88 is a promising therapeutic target that will reduce NF?b signaling cascades in inflammatory settings. PMID:21929539

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

2011-01-01

124

Alterations in brain antioxidant enzymes and redox proteomic identification of oxidized brain proteins induced by the anti-cancer drug adriamycin: implications for oxidative stress-mediated chemobrain.  

PubMed

Adriamycin (ADR) is a chemotherapeutic for the treatment of solid tumors. This quinone-containing anthracycline is well known to produce large amounts of reactive oxygen species (ROS) in vivo. A common complaint of patients undergoing long-term treatment with ADR is somnolence, often referred to as "chemobrain." While ADR itself does not cross the blood brain barrier (BBB), we recently showed that ADR administration causes a peripheral increase in tumor necrosis factor alpha (TNF-alpha), which migrates across the BBB and leads to inflammation and oxidative stress in brain, most likely contributing to the observed decline in cognition. In the current study, we measured levels of the antioxidant glutathione (GSH) in brains of mice injected intraparitoneally (i.p.) with ADR, as well as the levels and activities of several enzymes involved in brain GSH metabolism. We observed significantly decreased GSH levels, as well as altered GSH/GSSG ratio in brains of ADR treated mice relative to saline-treated controls. Also observed in brains of ADR treated mice were increased levels of glutathione peroxidase (GPx), glutathione-S-transferase (GST), and glutathione reductase (GR). We also observed increased activity of GPx, but a significant reduction in GST and GR activity in mice brain, 72 h post i.p. injection of ADR (20 mg/kg body weight). Furthermore, we used redox proteomics to identify specific proteins that are oxidized and/or have differential levels in mice brains as a result of a single i.p. injection of ADR. Visinin like protein 1 (VLP1), peptidyl prolyl isomerase 1 (Pin1), and syntaxin 1 (SYNT1) showed differential levels in ADR treated mice relative to saline-treated controls. Triose phosphate isomerase (TPI), enolase, and peroxiredoxin 1 (PRX-1) showed significantly increased specific carbonylation in ADR treated mice brain. These results further support the notion ADR induces oxidative stress in brain despite not crossing the BBB, and that antioxidant intervention may prevent ADR-induced cognitive dysfunction. PMID:20096337

Joshi, G; Aluise, C D; Cole, M P; Sultana, R; Pierce, W M; Vore, M; St Clair, D K; Butterfield, D A

2010-03-31

125

Genetic Deletion of Rheb1 in the Brain Reduces Food Intake and Causes Hypoglycemia with Altered Peripheral Metabolism  

PubMed Central

Excessive food/energy intake is linked to obesity and metabolic disorders, such as diabetes. The hypothalamus in the brain plays a critical role in the control of food intake and peripheral metabolism. The signaling pathways in hypothalamic neurons that regulate food intake and peripheral metabolism need to be better understood for developing pharmacological interventions to manage eating behavior and obesity. Mammalian target of rapamycin (mTOR), a serine/threonine kinase, is a master regulator of cellular metabolism in different cell types. Pharmacological manipulations of mTOR complex 1 (mTORC1) activity in hypothalamic neurons alter food intake and body weight. Our previous study identified Rheb1 (Ras homolog enriched in brain 1) as an essential activator of mTORC1 activity in the brain. Here we examine whether central Rheb1 regulates food intake and peripheral metabolism through mTORC1 signaling. We find that genetic deletion of Rheb1 in the brain causes a reduction in mTORC1 activity and impairs normal food intake. As a result, Rheb1 knockout mice exhibit hypoglycemia and increased lipid mobilization in adipose tissue and ketogenesis in the liver. Our work highlights the importance of central Rheb1 signaling in euglycemia and energy homeostasis in animals. PMID:24451134

Yang, Wanchun; Jiang, Wanxiang; Luo, Liping; Bu, Jicheng; Pang, Dejiang; Wei, Jing; Du, Chongyangzi; Xia, Xiaoqiang; Cui, Yiyuan; Liu, Shuang; Mao, Qing; Chen, Mina

2014-01-01

126

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

PubMed Central

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

Green, Erin; Murphy, Claire

2012-01-01

127

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

PubMed

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

Green, Erin; Murphy, Claire

2012-11-01

128

Partial loss in septo-hippocampal cholinergic neurons alters memory-dependent measures of brain connectivity without overt memory deficits.  

PubMed

The functional relevance of septo-hippocampal cholinergic (SHC) degeneration to the degradation of hippocampus-dependent declarative memory (DM) in aging and Alzheimer's disease (AD) remains ill-defined. Specifically, selective SHC lesions often fail to induce overt memory impairments in animal models. In spite of apparent normal performance, however, neuronal activity within relevant brain structures might be altered by SHC disruption. We hypothesized that partial SHC degeneration may contribute to functional alterations within memory circuits occurring in aging before DM decline. In young adult mice, we studied the effects of behaviorally ineffective (saporin-induced) SHC lesions - similar in extent to that seen in aged animals - on activity patterns and functional connectivity between three main neural memory systems: the septo-hippocampal system, the striatum and the amygdala that sustain declarative, procedural and emotional memory, respectively. Animals were trained in a radial maze procedure dissociating the human equivalents of relational/DM and non-R/DM expressions in animals. Test-induced Fos activation pattern revealed that the partial SHC lesion significantly altered the brain's functional activities and connectivity (co-activation pattern) despite the absence of overt behavioral deficit. Specifically, hippocampal CA3 hyperactivity and abnormal septo-hippocampo-amygdalar inter-connectivity resemble those observed in aging and prodromal AD. Hence, SHC neurons critically coordinate hippocampal function in concert with extra-hippocampal structures in accordance with specific mnemonic demand. Although partial SHC degeneration is not sufficient to impact DM performance by itself, the connectivity change might predispose the emergence of subsequent DM loss when, due to additional age-related insults, the brain can no longer compensate the holistic imbalance caused by cholinergic loss. PMID:23376311

Brayda-Bruno, Laurent; Mons, Nicole; Yee, Benjamin K; Micheau, Jacques; Abrous, Djoher Nora; Nogues, Xavier; Marighetto, Aline

2013-06-01

129

r Human Brain Mapping 000:0000 (2012) r Global and Regional Alterations of Hippocampal  

E-print Network

in Long-Term Meditation Practitioners Eileen Luders,1 * Paul M. Thompson,1 Florian Kurth,2 Jui-Yang Hong,2, Arizona r r Abstract: Studies linking meditation and brain structure are still relatively sparse, but the hippocam- pus is consistently implicated as one of the structures altered in meditation practitioners

Wang, Yalin

130

Brain grey matter volume alterations in late-life depression  

PubMed Central

Background Voxel-based morphometry (VBM) studies have demonstrated that grey matter abnormalities are involved in the pathophysiology of late-life depression (LLD), but the findings are inconsistent and have not been quantitatively reviewed. The aim of the present study was to conduct a meta-analysis that integrated the reported VBM studies, to determine consistent grey matter alterations in individuals with LLD. Methods A systematic search was conducted to identify VBM studies that compared patients with LLD and healthy controls. We performed a meta-analysis using the effect size signed differential mapping method to quantitatively estimate regional grey matter abnormalities in patients with LLD. Results We included 9 studies with 11 data sets comprising 292 patients with LLD and 278 healthy controls in our meta-analysis. The pooled and subgroup meta-analyses showed robust grey matter reductions in the right lentiform nucleus extending into the parahippocampus, the hippocampus and the amygdala, the bilateral medial frontal gyrus and the right subcallosal gyrus as well as a grey matter increase in the right lingual gyrus. Meta-regression analyses showed that mean age and the percentage of female patients with LLD were not significantly related to grey matter changes. Limitations The analysis techniques, patient characteristics and clinical variables of the studies included were heterogeneous, and most participants were medicated. Conclusion The present meta-analysis is, to our knowledge, the first to overcome previous inconsistencies in the VBM studies of LLD and provide robust evidence for grey matter alterations within fronto–striatal–limbic networks, thereby implicating them in the pathophysiology of LLD. The mean age and the percentage of female patients with LLD did not appear to have a measurable impact on grey matter changes, although we cannot rule out the contributory effects of medication. PMID:24949867

Du, Mingying; Liu, Jia; Chen, Ziqi; Huang, Xiaoqi; Li, Jing; Kuang, Weihong; Yang, Yanchun; Zhang, Wei; Zhou, Dong; Bi, Feng; Kendrick, Keith Maurice; Gong, Qiyong

2014-01-01

131

CCR2 antagonism alters brain macrophage polarization and ameliorates cognitive dysfunction induced by traumatic brain injury.  

PubMed

Traumatic brain injury (TBI) is a major risk factor for the development of multiple neurodegenerative diseases. With respect to the increasing prevalence of TBI, new therapeutic strategies are urgently needed that will prevent secondary damage to primarily unaffected tissue. Consistently, neuroinflammation has been implicated as a key mediator of secondary damage following the initial mechanical insult. Following injury, there is uncertainty regarding the role that accumulating CCR2(+) macrophages play in the injury-induced neuroinflammatory sequelae and cognitive dysfunction. Using CX3CR1(GFP/+)CCR2(RFP/+) reporter mice, we show that TBI initiated a temporally restricted accumulation of peripherally derived CCR2(+) macrophages, which were concentrated in the hippocampal formation, a region necessary for learning and memory. Multivariate analysis delineated CCR2(+) macrophages' neuroinflammatory response while identifying a novel therapeutic treatment window. As a proof of concept, targeting CCR2(+) macrophages with CCX872, a novel Phase I CCR2 selective antagonist, significantly reduced TBI-induced inflammatory macrophage accumulation. Concomitantly, there was a significant reduction in multiple proinflammatory and neurotoxic mediators with this treatment paradigm. Importantly, CCR2 antagonism resulted in a sparing of TBI-induced hippocampal-dependent cognitive dysfunction and reduced proinflammatory activation profile 1 month after injury. Thus, therapeutically targeting the CCR2(+) subset of monocytes/macrophages may provide a new avenue of clinical intervention following TBI. PMID:25589768

Morganti, Josh M; Jopson, Timothy D; Liu, Sharon; Riparip, Lara-Kirstie; Guandique, Cristian K; Gupta, Nalin; Ferguson, Adam R; Rosi, Susanna

2015-01-14

132

Alteration of brain monoamines & EEG wave pattern in rat model of Alzheimer's disease & protection by Moringa oleifera  

Microsoft Academic Search

Background & objectives: The monoaminergic systems which exert a modulatory role in memory processing, are disturbed in Alzheimer's disease (AD) and Moringa oleifera (MO) has been shown to exert its effect in CNS by altering the brain monoamines. The present study aims to see whether chronic oral treatment of ethanolic extract of MO leaves can alter the brain monoamines (norepinephrine,

R. Ganguly; D. Guha

2008-01-01

133

Low levels of copper disrupt brain amyloid-? homeostasis by altering its production and clearance  

PubMed Central

Whereas amyloid-? (A?) accumulates in the brain of normal animals dosed with low levels of copper (Cu), the mechanism is not completely known. Cu could contribute to A? accumulation by altering its clearance and/or its production. Because Cu homeostasis is altered in transgenic mice overexpressing A? precursor protein (APP), the objective of this study was to elucidate the mechanism of Cu-induced A? accumulation in brains of normal mice and then to explore Cu’s effects in a mouse model of Alzheimer’s disease. In aging mice, accumulation of Cu in brain capillaries was associated with its reduction in low-density lipoprotein receptor-related protein 1 (LRP1), an A? transporter, and higher brain A? levels. These effects were reproduced by chronic dosing with low levels of Cu via drinking water without changes in A? synthesis or degradation. In human brain endothelial cells, Cu, at its normal labile levels, caused LRP1-specific down-regulation by inducing its nitrotyrosination and subsequent proteosomal-dependent degradation due in part to Cu/cellular prion protein/LRP1 interaction. In APPsw/0 mice, Cu not only down-regulated LRP1 in brain capillaries but also increased A? production and neuroinflammation because Cu accumulated in brain capillaries and, unlike in control mice, in the parenchyma. Thus, we have demonstrated that Cu’s effect on brain A? homeostasis depends on whether it is accumulated in the capillaries or in the parenchyma. These findings should provide unique insights into preventative and/or therapeutic approaches to control neurotoxic A? levels in the aging brain. PMID:23959870

Singh, Itender; Sagare, Abhay P.; Coma, Mireia; Perlmutter, David; Gelein, Robert; Bell, Robert D.; Deane, Richard J.; Zhong, Elaine; Parisi, Margaret; Ciszewski, Joseph; Kasper, R. Tristan; Deane, Rashid

2013-01-01

134

Altered brain-gut axis in autism: comorbidity or causative mechanisms?  

PubMed

The concept that alterated communications between the gut microbiome and the brain may play an important role in human brain disorders has recently received considerable attention. This is the result of provocative preclinical and some clinical evidence supporting early hypotheses about such communication in health and disease. Gastrointestinal symptoms are a common comorbidity in patients with autism spectrum disorders (ASD), even though the underlying mechanisms are largely unknown. In addition, alteration in the composition and metabolic products of the gut microbiome has long been implicated as a possible causative mechanism contributing to ASD pathophysiology, and this hypothesis has been supported by several recently published evidence from rodent models of autism induced by prenatal insults to the mother. Recent evidence in one such model involving maternal infection, that is characterized by alterations in behavior, gut physiology, microbial composition, and related metabolite profile, suggests a possible benefit of probiotic treatment on several of the observed abnormal behaviors. PMID:25145752

Mayer, Emeran A; Padua, David; Tillisch, Kirsten

2014-10-01

135

Agrin in Alzheimer's Disease: Altered Solubility and Abnormal Distribution within Microvasculature and Brain Parenchyma  

NASA Astrophysics Data System (ADS)

Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with ? -amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to ? -amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.

Donahue, John E.; Berzin, Tyler M.; Rafii, Michael S.; Glass, David J.; Yancopoulos, George D.; Fallon, Justin R.; Stopa, Edward G.

1999-05-01

136

Directional Connectivity between Frontal and Posterior Brain Regions Is Altered with Increasing Concentrations of Propofol  

PubMed Central

Recent studies using electroencephalography (EEG) suggest that alteration of coherent activity between the anterior and posterior brain regions might be used as a neurophysiologic correlate of anesthetic-induced unconsciousness. One way to assess causal relationships between brain regions is given by renormalized partial directed coherence (rPDC). Importantly, directional connectivity is evaluated in the frequency domain by taking into account the whole multichannel EEG, as opposed to time domain or two channel approaches. rPDC was applied here in order to investigate propofol induced changes in causal connectivity between four states of consciousness: awake (AWA), deep sedation (SED), loss (LOC) and return of consciousness (ROC) by gathering full 10/20 system human EEG data in ten healthy male subjects. The target-controlled drug infusion was started at low rate with subsequent gradual stepwise increases at 10 min intervals in order to carefully approach LOC (defined as loss of motor responsiveness to a verbal stimulus). The direction of the causal EEG-network connections clearly changed from AWA to SED and LOC. Propofol induced a decrease (p?=?0.002–0.004) in occipital-to-frontal rPDC of 8-16 Hz EEG activity and an increase (p?=?0.001–0.040) in frontal-to-occipital rPDC of 10–20 Hz activity on both sides of the brain during SED and LOC. In addition, frontal-to-parietal rPDC within 1–12 Hz increased in the left hemisphere at LOC compared to AWA (p?=?0.003). However, no significant changes were detected between the SED and the LOC states. The observed decrease in back-to-front EEG connectivity appears compatible with impaired information flow from the posterior sensory and association cortices to the executive prefrontal areas, possibly related to decreased ability to perceive the surrounding world during sedation. The observed increase in the opposite (front-to-back) connectivity suggests a propofol concentration dependent association and is not directly related to the level of consciousness per se. PMID:25419791

Maksimow, Anu; Silfverhuth, Minna; Långsjö, Jaakko; Kaskinoro, Kimmo; Georgiadis, Stefanos; Jääskeläinen, Satu; Scheinin, Harry

2014-01-01

137

Brain-Specific Overexpression of Trace Amine-Associated Receptor 1 Alters Monoaminergic Neurotransmission and Decreases Sensitivity to Amphetamine  

PubMed Central

Trace amines (TAs) such as ?-phenylethylamine, p-tyramine, or tryptamine are biogenic amines found in the brain at low concentrations that have been implicated in various neuropsychiatric disorders like schizophrenia, depression, or attention deficit hyperactivity disorder. TAs are ligands for the recently identified trace amine-associated receptor 1 (TAAR1), an important modulator of monoamine neurotransmission. Here, we sought to investigate the consequences of TAAR1 hypersignaling by generating a transgenic mouse line overexpressing Taar1 specifically in neurons. Taar1 transgenic mice did not show overt behavioral abnormalities under baseline conditions, despite augmented extracellular levels of dopamine and noradrenaline in the accumbens nucleus (Acb) and of serotonin in the medial prefrontal cortex. In vitro, this was correlated with an elevated spontaneous firing rate of monoaminergic neurons in the ventral tegmental area, dorsal raphe nucleus, and locus coeruleus as the result of ectopic TAAR1 expression. Furthermore, Taar1 transgenic mice were hyposensitive to the psychostimulant effects of amphetamine, as it produced only a weak locomotor activation and failed to alter catecholamine release in the Acb. Attenuating TAAR1 activity with the selective partial agonist RO5073012 restored the stimulating effects of amphetamine on locomotion. Overall, these data show that Taar1 brain overexpression causes hyposensitivity to amphetamine and alterations of monoaminergic neurotransmission. These observations confirm the modulatory role of TAAR1 on monoamine activity and suggest that in vivo the receptor is either constitutively active and/or tonically activated by ambient levels of endogenous agonist(s). PMID:22763617

Revel, Florent G; Meyer, Claas A; Bradaia, Amyaouch; Jeanneau, Karine; Calcagno, Eleonora; André, Cédric B; Haenggi, Markus; Miss, Marie-Thérèse; Galley, Guido; Norcross, Roger D; Invernizzi, Roberto W; Wettstein, Joseph G; Moreau, Jean-Luc; Hoener, Marius C

2012-01-01

138

Altering cannabinoid signaling during development disrupts neuronal activity  

E-print Network

interneurons neonates drug abuse Marijuana (cannabis) abuse during pregnancy represents a major health problem signaling impairs oviductal transport of embryos (1). Further- more, children of cannabis users display of the brain (2, 3). The action of cannabis in the adult brain includes the activation of presynaptic G protein

Cossart, Rosa

139

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

PubMed Central

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

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

2012-01-01

140

Altered brain response to verbal learning following sleep deprivation  

Microsoft Academic Search

The effects of sleep deprivation on the neural substrates of cognition are poorly understood. Here we used functional magnetic resonance imaging to measure the effects of 35 hours of sleep deprivation on cerebral activation during verbal learning in normal young volunteers. On the basis of a previous hypothesis, we predicted that the prefrontal cortex (PFC) would be less responsive to

Sean P. A. Drummond; Gregory G. Brown; J. Christian Gillin; John L. Stricker; Eric C. Wong; Richard B. Buxton

2000-01-01

141

Monocrotophos induced oxidative stress and alterations in brain dopamine and serotonin receptors in young rats.  

PubMed

Human exposure to monocrotophos, an organophosphate pesticide, could occur due to its high use in agriculture to protect crops. Recently, we found that postlactational exposure to monocrotophos impaired cholinergic mechanisms in young rats and such changes persisted even after withdrawal of monocrotophos exposure. In continuation to this, the effect of monocrotophos on noncholinergic targets and role of oxidative stress in its neurotoxicity has been studied. Exposure of rats from postnatal day (PD)22 to PD49 to monocrotophos (0.50 or 1.0 mg kg(-1) body weight, perorally) significantly impaired motor activity and motor coordination on PD50 as compared to controls. A significant decrease in the binding of (3)H-spiperone to striatal membrane (26%, p < 0.01; 30%, p < 0.05) in rats exposed to monocrotophos at both the doses and increase in the binding of (3)H-ketanserin to frontocortical membrane (14%, p > 0.05; 37%, p < 0.05) in those exposed at a higher dose, respectively, was observed on PD50 compared with the controls. Alterations in the binding persisted even after withdrawal of monocrotophos exposure on PD65. Increased oxidative stress in brain regions following exposure of rats to monocrotophos was also observed on PD50 that persisted 15 days after withdrawal of exposure on PD65. The results suggest that monocrotophos exerts its neurobehavioral toxicity by affecting noncholinergic functions involving dopaminergic and serotonergic systems associated with enhanced oxidative stress. The results also exhibit vulnerability of developing brain to monocrotophos as most of the changes persisted even after withdrawal of its exposure. PMID:24105069

Sankhwar, Madhu L; Yadav, Rajesh S; Shukla, Rajendra K; Singh, Dhirendra; Ansari, Reyaz W; Pant, Aditya B; Parmar, Devendra; Khanna, Vinay K

2013-10-01

142

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

SciTech Connect

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.

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

1987-11-01

143

Patients with Chronic Visceral Pain Show Sex-Related Alterations in Intrinsic Oscillations of the Resting Brain  

PubMed Central

Abnormal responses of the brain to delivered and expected aversive gut stimuli have been implicated in the pathophysiology of irritable bowel syndrome (IBS), a visceral pain syndrome occurring more commonly in women. Task-free resting-state functional magnetic resonance imaging (fMRI) can provide information about the dynamics of brain activity that may be involved in altered processing and/or modulation of visceral afferent signals. Fractional amplitude of low-frequency fluctuation is a measure of the power spectrum intensity of spontaneous brain oscillations. This approach was used here to identify differences in the resting-state activity of the human brain in IBS subjects compared with healthy controls (HCs) and to identify the role of sex-related differences. We found that both the female HCs and female IBS subjects had a frequency power distribution skewed toward high frequency to a greater extent in the amygdala and hippocampus compared with male subjects. In addition, female IBS subjects had a frequency power distribution skewed toward high frequency in the insula and toward low frequency in the sensorimotor cortex to a greater extent than male IBS subjects. Correlations were observed between resting-state blood oxygen level-dependent signal dynamics and some clinical symptom measures (e.g., abdominal discomfort). These findings provide the first insight into sex-related differences in IBS subjects compared with HCs using resting-state fMRI. PMID:23864686

Hong, Jui-Yang; Kilpatrick, Lisa A.; Labus, Jennifer; Gupta, Arpana; Jiang, Zhiguo; Ashe-McNalley, Cody; Stains, Jean; Heendeniya, Nuwanthi; Ebrat, Bahar; Smith, Suzanne; Tillisch, Kirsten; Naliboff, Bruce

2013-01-01

144

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

SciTech Connect

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.

Gazdzinski, Lisa M.; Cormier, Kyle [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada)] [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Lu, Fred G. [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada)] [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Lerch, Jason P. [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada) [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Wong, C. Shun [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada) [Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada); Department of Radiation Oncology, University of Toronto, Toronto (Canada); Nieman, Brian J., E-mail: bjnieman@phenogenomics.ca [Mouse Imaging Centre, Hospital for Sick Children, Toronto (Canada); Department of Medical Biophysics, University of Toronto, Toronto (Canada)

2012-12-01

145

Structural Brain Alterations in Patients with Lumbar Disc Herniation: A Preliminary Study  

PubMed Central

Chronic pain is one of the most common health complaints in industrial nations. For example, chronic low back pain (cLBP) disables millions of people across the world and generates a tremendous economic burden. While previous studies provided evidence of widespread functional as well as structural brain alterations in chronic pain, little is known about cortical changes in patients suffering from lumbar disc herniation. We investigated morphometric alterations of the gray and white matter of the brain in patients suffering from LDH. The volumes of the gray and white matter of 12 LDH patients were determined in a prospective study and compared to the volumes of healthy controls to distinguish local differences. High-resolution MRI brain images of all participants were performed using a 3 Tesla MRI scanner. Voxel-based morphometry was used to investigate local differences in gray and white matter volume between patients suffering from LDH and healthy controls. LDH patients showed significantly reduced gray matter volume in the right anterolateral prefrontal cortex, the right temporal lobe, the left premotor cortex, the right caudate nucleus, and the right cerebellum as compared to healthy controls. Increased gray matter volume, however, was found in the right dorsal anterior cingulate cortex, the left precuneal cortex, the left fusiform gyrus, and the right brainstem. Additionally, small subcortical decreases of the white matter were found adjacent to the left prefrontal cortex, the right premotor cortex and in the anterior limb of the left internal capsule. We conclude that the lumbar disk herniation can lead to specific local alterations of the gray and white matter in the human brain. The investigation of LDH-induced brain alterations could provide further insight into the underlying nature of the chronification processes and could possibly identify prognostic factors that may improve the conservative as well as the operative treatment of the LDH. PMID:24595036

Luchtmann, Michael; Steinecke, Yvonne; Baecke, Sebastian; Lützkendorf, Ralf; Bernarding, Johannes; Kohl, Jana; Jöllenbeck, Boris; Tempelmann, Claus; Ragert, Patrick; Firsching, Raimund

2014-01-01

146

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

PubMed

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 (2195IU/kg) or deficient (0IU/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-?1 (Tgf-?1) 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

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

2015-06-01

147

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

PubMed Central

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 within a neurophenomenological setup for scientifically characterizing a self-induced altered sense of time, space and body, as well as the importance of theta activity in relation with these altered states. PMID:24348455

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

2013-01-01

148

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

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

2012-01-01

149

Electromagnetic imaging of dynamic brain activity  

SciTech Connect

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.

Mosher, J.; Leahy, R. (University of Southern California, Los Angeles, CA (United States). Dept. of Electrical Engineering); Lewis, P.; Lewine, J.; George, J. (Los Alamos National Lab., NM (United States)); Singh, M. (University of Southern California, Los Angeles, CA (United States). Dept. of Radiology)

1991-01-01

150

Electromagnetic imaging of dynamic brain activity  

SciTech Connect

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.

Mosher, J.; Leahy, R. [University of Southern California, Los Angeles, CA (United States). Dept. of Electrical Engineering; Lewis, P.; Lewine, J.; George, J. [Los Alamos National Lab., NM (United States); Singh, M. [University of Southern California, Los Angeles, CA (United States). Dept. of Radiology

1991-12-31

151

Ketogenic Diet Prevents Alterations in Brain Metabolism in Young but not Adult Rats after Traumatic Brain Injury  

PubMed Central

Abstract Previous studies have shown that the change of cerebral metabolic rate of glucose (CMRglc) in response to traumatic brain injury (TBI) is different in young (PND35) and adult rats (PND70), and that prolonged ketogenic diet treatment results in histological and behavioral neuroprotection only in younger rat brains. However, the mechanism(s) through which ketones act in the injured brain and the biochemical markers of their action remain unknown. Therefore, the current study was initiated to: 1) determine the effect of injury on the neurochemical profile in PND35 compared to PND70 rats; and 2) test the effect of early post-injury administration of ketogenic diet on brain metabolism in PND35 versus PND70 rats. The data show that alterations in energy metabolites, amino acid, and membrane metabolites were not evident in PND35 rats on standard diet until 24?h after injury, when the concentration of most metabolites was reduced from sham-injured values. In contrast, acute, but transient deficits in energy metabolism were measured at 6?h in PND70 rats, together with deficits in N-acetylaspartate that endured until 24?h. Administration of a ketogenic diet resulted in significant increases in plasma ?-hydroxybutyrate (?OHB) levels. Similarly, brain ?OHB levels were significantly elevated in all injured rats, but were elevated by 43% more in PND35 rats compared to PND70 rats. As a result, ATP, creatine, and phosphocreatine levels at 24?h after injury were significantly improved in the ketogenic PND35 rats, but not in the PND70 group. The improvement in energy metabolism in the PND35 brains was accompanied by the recovery of NAA and reduction of lactate levels, as well as amelioration of the deficits of other amino acids and membrane metabolites. These results indicate that the PND35 brains are more resistant to the injury, indicated by a delayed deficit in energy metabolism. Moreover, the younger brains revert to ketones metabolism more quickly than do the adult brains, resulting in better neurochemical and cerebral metabolic recovery after injury. PMID:21635175

Prins, Mayumi L.; Hovda, David A.; Harris, Neil G.

2011-01-01

152

Altered glucose metabolism and preserved energy charge and neuronal structures in the brain of mouse intermittently exposed to hypoxia.  

PubMed

The key for an animal to survive prolonged hypoxia is to avoid rapid decline in ATP levels in vital organs such as the brain. This can be well achieved by a very few of hypoxia-tolerant animals such as freshwater turtles and newborn animals, since these animals can substantially suppress their metabolic levels by coordinated regulation of ATP-producing and ATP-demanding pathways. However, most animals, especially adult mammals, can only tolerate a short period of hypoxia since they are unable to maintain constant ATP levels and energy charge in vital organs during prolonged hypoxic exposure. Here, we described a special mouse model, in which a hypoxia intolerant adult mouse gradually built up an ability to survive prolonged hypoxia after intermittent hypoxic exposures. This increased ability was accompanied by reductions in body temperature and O(2) consumption as well as transient variations in blood pCO(2), pO(2) and pH. The glucose and energy metabolism in the brain of the mouse altered similarly to those reported in the brain of hypoxic turtles. Activities of phosphofructokinase and pyruvate kinase, the two rate-limiting enzymes controlling the rate of glycolysis decreased to baseline levels after a short period of increase. In contrast, the activity of complex I, the major enzyme complex controlling oxidative phosphorylation, was kept inhibited. These alterations in the ATP-producing pathway suggest the occurrence of reverse Pasteur effect, indicating that the animal had entered a hypometabolic state favoring maintenance of ATP level and energy charge in hypoxic conditions. In supporting this idea, the ATP levels and energy charge as well as neuronal structures in the brain were well preserved. This study provides evidence for a possibility that a hypoxic intolerant animal can build up an ability to survive prolonged hypoxia through regulation of its glucose and energy metabolism after an appropriate hypoxic training, which deserves further investigation. PMID:21718782

Cheng, Furong; Xie, Shengnan; Guo, Miao; Fang, Haixia; Li, Xin; Yin, Juanjuan; Lu, Guowei; Li, Yaohua; Ji, Xunming; Yu, Shun

2011-09-01

153

Classification of whole brain fMRI activation patterns  

E-print Network

Functional magnetic resonance imaging (fMRI) is an imaging technology which is primarily used to perform brain activation studies by measuring neural activity in the brain. It is an interesting question whether patterns ...

Balc?, Serdar Kemal

2008-01-01

154

Altered localization of Drosophila Smoothened protein activates Hedgehog  

E-print Network

Altered localization of Drosophila Smoothened protein activates Hedgehog signal transduction Alan, Stanford, California 94305-5329, USA Hedgehog (Hh) signaling is critical for many developmental events in Drosophila. [Keywords: Hedgehog; Patched; Smoothened; Drosophila] Supplemental material is available at http

Quake, Stephen R.

155

Variant Brain-Derived Neurotrophic Factor (BDNF) (Met66) Alters the Intracellular Trafficking and Activity-Dependent Secretion of Wild-Type BDNF in Neurosecretory Cells and Cortical Neurons  

Microsoft Academic Search

Brain-derived neurotrophic factor (BDNF) plays a critical role in nervous system and cardiovascular development and function. Re- cently, a common single nucleotide polymorphism in the bdnf gene, resulting in a valine to methionine substitution in the prodomain (BDNFMet ), has been shown to lead to memory impairment and susceptibility to neuropsychiatric disorders in humans heterozygous for the variant BDNF. When

Zhe-Yu Chen; Paresh D. Patel; Gayatree Sant; Chui-Xiang Meng; Kenneth K. Teng; Barbara L. Hempstead; Francis S. Lee

2004-01-01

156

Transgenic overexpression of adenosine kinase in brain leads to multiple learning impairments and altered sensitivity to psychomimetic drugs.  

PubMed

The neuromodulator adenosine fulfills a unique role in the brain affecting glutamatergic neurotransmission and dopaminergic signaling via activation of adenosine A1 and A2A receptors, respectively. The adenosine system is thus ideally positioned to integrate glutamatergic and dopaminergic neurotransmission, which in turn could affect behavior and cognition. In the adult brain, adenosine levels are largely regulated by its key metabolic enzyme adenosine kinase (ADK), which may assume the role of an 'upstream regulator' of these two neurotransmitter pathways. To test this hypothesis, transgenic mice with an overexpression of ADK in brain (Adk-tg), and therefore reduced brain adenosine levels, were evaluated in a panel of behavioral and psychopharmacological assays to assess possible glutamatergic and dopaminergic dysfunction. In comparison to non-transgenic control mice, Adk-tg mice are characterized by severe learning deficits in the Morris water maze task and in Pavlovian conditioning. The Adk-tg mice also exhibited reduced locomotor reaction to systemic amphetamine, whereas their reaction to the non-competitive N-methyl-d-aspartate receptor antagonist MK-801 was enhanced. Our results confirmed that ADK overexpression could lead to functional concomitant alterations in dopaminergic and glutamatergic functions, which is in keeping with the hypothesized role of ADK in the balance and integration between glutamatergic and dopaminergic neurotransmission. The present findings are of relevance to current pathophysiological hypotheses of schizophrenia and its pharmacotherapy. PMID:18005073

Yee, Benjamin K; Singer, Philipp; Chen, Jiang-Fan; Feldon, Joram; Boison, Detlev

2007-12-01

157

Irritable Bowel Syndrome in female patients is associated with alterations in structural brain networks  

PubMed Central

Alterations in gray matter (GM) density/ volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with different chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at UCLA between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32 ± 10 SD, 119 Healthy Controls [HCs], 30± 10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between IBS and HC groups. Relative to HCs, the IBS group had lower volumes in bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found for the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for Early Trauma Inventory global score with the exception of the right amygdala and the left post central gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, the right cingulate gyrus and right thalamus were identified as significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks. PMID:24076048

Labus, Jennifer; Dinov, Ivo D.; Jiang, Zhiguo; Ashe-McNalley, Cody; Zamanyan, Alen; Shi, Yonggang; Hong, Jui-Yang; Gupta, Arpana; Tillisch, Kirsten; Ebrat, Bahar; Hobel, Sam; Gutman, Boris A.; Joshi, Shantanu; Thompson, Paul M.; Toga, Arthur W.; Mayer, Emeran A.

2014-01-01

158

Effects of familiar voices on brain activity.  

PubMed

This study aimed to examine the extent to which a familiar voice influences brain activity. Participants were nine healthy female volunteers aged 21-34 years old (with a mean age of 25.78 ± 4.04 years). Brain activity was recorded during periods of silence, familiar and unfamiliar voices. Electroencephalographic data were collected and analyzed using a frequency rate set at 5 min. To account for emotional influences imbedded into the contents of the voice stimuli, both the voice of a familiar family member and the voice of a stranger were used to record a well-known Japanese fairy tale, 'Momotaro'. Results revealed that listening to familiar voices increased the rate of the ? band (13-30 Hz) in all four brain areas (F3, F4, C3 and C4). In particular, increased activity was observed at F4 and C4. Findings revealed that in study, participants' familiar voices activated cerebral functioning more than unfamiliar voices. PMID:22776531

Tanaka, Yuji L; Kudo, Yumi

2012-07-01

159

Neuroprotective effects of crocin on the histopathological alterations following brain ischemia-reperfusion injury in rat  

PubMed Central

Objective(s): Some histopathological alterations take place in the ischemic regions following brain ischemia. Recent studies have demonstrated some neuroprotective roles of crocin in different models of experimental cerebral ischemia. Here, we investigated the probable neuroprotective effects of crocin on the brain infarction and histopathological changes after transient model of focal cerebral ischemia. Materials and Methods: Experiment was performed in four groups of rats (each group; n=8), sham, control ischemia and ischemia treated rats. Transient focal cerebral ischemia was induced by 80 min middle cerebral artery occlusion (MCAO) followed by 24 hr reperfusion. Crocin, at doses 50 and 80 mg/kg, was injected at the beginning of ischemia (IP injection). Neurologic outcome (Neurological Deficit Score, NDS scale), infarct volume (TTC staining) and histological studies were assessed 24 hr after termination of MCAO. Results: Treatment with crocin, at doses 50 and 80 mg/kg, significantly reduced the cortical infarct volume by 48% and 60%, and also decreased striatal infarct volume by 45% and75%, respectively. Crocin at two different doses significantly improved the NDS of ischemic rats. At histological evaluation, crocin, at dose 80 mg/kg more than 50 mg/kg, decreased the number of eosinophilic (prenecrotic) neurons and reduced the fiber demyelination and axonal damage in ischemic regions. Conclusion: Our findings indicated that crocin effectively reduces brain ischemia-induced injury and improves neurological outcomes. Crocin also is a potent neuroprotective factor that can be able to prevent histopathological alterations following brain ischemia. PMID:25691932

Sarshoori, Javad Raouf; Asadi, Mohammad Hossien; Mohammadi, Mohammad Taghi

2014-01-01

160

Altered topological organization of brain structural network in Chinese children with developmental dyslexia.  

PubMed

Increasing evidence indicates that developmental dyslexia (DD) is a "disconnection syndrome", and new probes of connectome were applied to investigate the "disconnection" in DD. However, there is a lack of brain connectome studies of Chinese dyslexics, who may have a different neural impairment pattern due to the logographic nature of Chinese. The aim of this study was to investigate the topological organization characteristics of the DD brain using a structural network based analysis on the volumetric covariance, which is a method with the advantage of reflecting brain developmental changes. Twenty-five children diagnosed with DD and twenty-five typically developing controls were included. The structural networks based on the pair-wise correlation of gray matter volume from 90 brain regions were constructed for the two groups and compared. Compared to controls, the structural network of dyslexic children exhibited significantly increased local efficiency combined with a tendency of decreased global efficiency and prolonged characteristic path length, thus reflecting a more locally specialized topological organization. Two brain areas showed significantly altered local regional network properties: the left precentral gyrus with increased bi, and the right Heschl's gyrus with decreased bi and ki. Moreover, a series of hub regions (especially the right fronto-temporal regions) identified in the network of typically developing children were not presented in the brain of DD. To our knowledge, this is the first whole-brain structural network study on Chinese dyslexics. This study provides evidence of brain topological organization changes in Chinese children with DD, and thus may help shed light on its neurobiological basis. PMID:25597882

Liu, Kai; Shi, Lin; Chen, Feiyan; Waye, Mary M Y; Lim, Cadmon K P; Cheng, Pui-Wan; Luk, Sarah S H; Mok, Vincent C T; Chu, Winnie C W; Wang, Defeng

2015-03-01

161

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

PubMed

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. PMID:23829361

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

2014-01-01

162

Long-term sequelae of severe sepsis: cognitive impairment and structural brain alterations – an MRI study (LossCog MRI)  

PubMed Central

Background The number of patients with cognitive impairment after sepsis or septic shock is high. However, the underlying neurophysiological basis of sepsis induced cognitive impairment is not fully understood. Methods/Design This is a prospective, controlled observational study. We are in the process of recruiting 25 survivors of severe sepsis or septic shock who will be investigated with functional MRI (fMRI), T1-weighted MRI und Diffusion Tensor Imaging (DTI) as well as Magnetoencephalography (MEG). Furthermore, patients will undergo neuropsychological evaluation using the DemTect and the clock drawing tests. In addition, verbal and declarative memory is assessed by the Verbal Learning and Memory Test. The primary aim is to determine the volumetry of the amygdala and the hippocampus. The secondary aim is to analyze the relationship between cognitive tests and MEG, and the (f)MRI results. Moreover, a between-group comparison will be evaluated to an age-matched group of healthy controls. Discussion In a previous MEG study, we observed a significant slowing of the prominent background activity in sepsis survivors and hepatic encephalopathy patients in particular shortly after discharge from the ICU. Intriguingly, the rhythmic brain activity after visual flickering stimulation was altered in sepsis survivors in comparison to age-matched healthy volunteers. We propose that this desynchronization is based on affected underlying neuronal responses between various interconnected brain regions. The current project will analyze whether the modifications are related to a damage of the fibers connecting different brain regions or to a disturbance of the functional interaction between different brain regions or even due to an atrophy of certain brain regions. Trial registration “Langzeitfolgen nach schwerer Sepsis: Kognitive Beeinträchtigungen und strukturelle Veränderungen am Gehirn, eine MRT Studie”; German Clinical Trials Register (DRKS00005484). PMID:25027645

2014-01-01

163

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

SciTech Connect

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.

Lee, Won Hee [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Warrington, Junie P.; Sonntag, William E. [Reynolds Oklahoma Center on Aging, Department of Geriatric Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma (United States); Lee, Yong Woo, E-mail: ywlee@vt.edu [School of Biomedical Engineering and Sciences, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States); Department of Biomedical Sciences and Pathobiology, Virginia Polytechnic Institute and State University, Blacksburg, Virginia (United States)

2012-04-01

164

Active ultramicrobacterial alteration of iron in granite  

NASA Astrophysics Data System (ADS)

Microorganisms are able to exist in extreme environments, where they often form biofilms. We are investigating an iron metabolizing biofilm consortium derived from groundwater draining the Canadian Shield. This was first discovered in the Underground Research Laboratory of Atomic Energy of Canada Ltd., where its influence on the management of nuclear fuel waste was examined. Incubations have shown that the microbial consortium contains different morphological forms. Ultramicrobacteria, 0.3 micrometers diameter cocci, are dominant on magnetite surfaces, which they are able to transform rapidly to hematite. Larger rods, 1.0 micrometers long, aggregate on silicon minerals containing little iron. Carbon is limited in these natural groundwaters so that iron is utilized as an alternative energy source. The cell surface of the organisms and the extracellular polymers of the biofilm are both negatively-charged allowing metal cations to be quickly bound by physicochemical sorption, thus providing nucleation sites for mineralization within the boundaries. The biofilm consortium is able to mediate a wide range of iron reactions. Aerobically a ferric gel is precipitated throughout the biofilm slime, which alters first to ferrihydrite and later to hematite. When anaerobic fermentation produces a reducing environment the iron is converted to the ferrous state which may then be precipitated as ferrous hydroxide, vivianite or siderite. Since iron is widespread in the natural environment, these reactions could have important geochemical implications.

Brown, D. Ann; Sherriff, Barbara L.

1997-07-01

165

Physical activity, air pollution and the brain.  

PubMed

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

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

2014-11-01

166

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

PubMed

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 the bilateral auditory areas, including the superior temporal gyrus, the HG, the planum temporale and the planum polare, which were more extensive in the right hemisphere. Fractional anisotropy (FA) was significantly reduced in the right and axial diffusivity (AD) in the left auditory areas in the deaf. FA and AD were significantly reduced also in several other brain areas outside the auditory cortex in the deaf. The use of four different methods used in our study, although showing changes that are not directly related, provides additional information and supports the conclusion that in prelingually deaf subjects structural alterations are present both in the auditory areas and elsewhere. Our results support the findings of those studies showing that early deafness results in decreased WM volume and microstructural WM alterations in the auditory areas. As we observed WM microstructural alteration also in several other areas and increased GM volume in the cerebellum in the deaf, we can conclude that early deafness results in widespread structural brain changes. These probably reflect atrophy or degradation as well as compensatory cross-modal reorganisation in the absence of the auditory input and the use of the sign language. PMID:25262621

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

2014-12-01

167

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

PubMed

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

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

168

New Benzodiazepines Alter Acetylcholinesterase and ATPDase Activities  

Microsoft Academic Search

This study examines the effect of new 1,5 benzodiazepines on acetylcholinesterase (AChE) and ATPDase (apyrase) activities from cerebral cortex of adult rats. Simultaneously, the effects of the classical 1,4-benzodiazepine on these enzymes were also studied for comparative purpose. The compounds 2-trichloromethyl-4-phenyl-3H-1,5-benzodiazepin and 2-trichloromethyl-4-(p-methyl-phenyl)-3H-1,5-benzodiazepin significantly inhibited acetylcholinesterase activity (p < 0.01) when tested in the range of 0.18–0.35 mM. The inhibition

Maria R. C. Schetinger; Neuza M. Porto; Maria B. Moretto; Vera M. Morsch; JoãoBatista T. da Rocha; Vânia Vieira; Franciele Moro; RoseliTatto Neis; Sandra Bittencourt; Hélio G. Bonacorso; Nilo Zanatta

2000-01-01

169

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

PubMed

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

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

2015-04-01

170

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

PubMed Central

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

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

2014-01-01

171

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

SciTech Connect

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.

Gorski, R.A.

1986-12-01

172

Does mental exertion alter maximal muscle activation?  

PubMed Central

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

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

2014-01-01

173

Release of Neuronal HMGB1 by Ethanol through Decreased HDAC Activity Activates Brain Neuroimmune Signaling  

PubMed Central

Neuroimmune gene induction is involved in many brain pathologies including addiction. Although increased expression of proinflammatory cytokines has been found in ethanol-treated mouse brain and rat brain slice cultures as well as in post-mortem human alcoholic brain, the mechanisms remain elusive. High-mobility group box 1 (HMGB1) protein is a nuclear protein that has endogenous cytokine-like activity. We previously found increased HMGB1 in post-mortem alcoholic human brain as well as in ethanol treated mice and rat brain slice cultures. The present study investigated the mechanisms for ethanol-induced release of HMGB1 and neuroimmune activation in a model of rat hippocampal-entorhinal cortex (HEC) brain slice cultures. Ethanol exposure triggered dose-dependent HMGB1 release, predominantly from neuronal cells. Inhibitors of histone deacetylases (HDACs) promoted nucleocytoplasmic mobilization of HDAC1/4 and HMGB1 resulting in increased total HMGB1 and acetylated HMGB1 release. Similarly, ethanol treatment was found to induce the translocation of HDAC1/4 and HMGB1 proteins from nuclear to cytosolic fractions. Furthermore, ethanol treatment reduced HDAC1/4 mRNA and increased acetylated HMGB1 release into the media. These results suggest decreased HDAC activity may be critical in regulating acetylated HMGB1 release from neurons in response to ethanol. Ethanol and HMGB1 treatment increased mRNA expression of proinflammatory cytokines TNF? and IL-1? as well as toll-like receptor 4 (TLR4). Targeting HMGB1 or microglial TLR4 by using siRNAs to HMGB1 and TLR4, HMGB1 neutralizing antibody, HMGB1 inhibitor glycyrrhizin and TLR4 antagonist as well as inhibitor of microglial activation all blocked ethanol-induced expression of proinflammatory cytokines TNF? and IL-1?. These results support the hypothesis that ethanol alters HDACs that regulate HMGB1 release and that danger signal HMGB1 as endogenous ligand for TLR4 mediates ethanol-induced brain neuroimmune signaling through activation of microglial TLR4. These findings provide new therapeutic targets for brain neuroimmune activation and alcoholism. PMID:24551070

Zou, Jian Y.; Crews, Fulton T.

2014-01-01

174

Brain Mechanical Property Measurement Using MRE with Intrinsic Activation  

PubMed Central

Problem Addressed 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. Methodology 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. Results, Significance and Potential Impact 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 6 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, termed intrinsic activation, produces sufficient motion to allow mechanical properties to be recovered. The poroelastic model is more consistent with the measured data from brain at low frequencies than the linear elastic model. Intrinsic activation allows MR elastography to be performed without a device shaking the head so the patient notices no differences between it and the other sequences in an MR examination. PMID:23079508

Pattison, Adam J.; McGarry, Matthew D.; Perreard, Irina M.; Swienckowski, Jessica G.; Eskey, Clifford J.; Lollis, S. Scott; Paulsen, Keith D.

2013-01-01

175

Brain mechanical property measurement using MRE with intrinsic activation  

NASA Astrophysics Data System (ADS)

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, termed intrinsic activation, produces sufficient motion to allow mechanical properties to be recovered. The poroelastic model is more consistent with the measured data from brain at low frequencies than the linear elastic model. Intrinsic activation allows MRE to be performed without a device shaking the head so the patient notices no differences between it and the other sequences in an MR examination.

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

176

Altered spontaneous neural activity in first-episode, unmedicated patients with major depressive disorder.  

PubMed

Abnormal brain function is presumed to be a pathophysiological aspect of major depressive disorder (MDD). However, the underlying patterns of spontaneous neural activity have been poorly characterized and replicated to date. In this study, we applied a novel approach of fractional amplitude of low-frequency fluctuation (fALFF) to investigate the alteration of spontaneous neural activity in MDD. Sixteen first-episode, unmedicated patients with MDD and 16 healthy controls were recruited and subjected to resting-state fMRI scans to measure the fALFF across the whole brain. Compared with healthy controls, MDD patients exhibited decreased fALFF in the right angular gyrus, left middle temporal gyrus, left superior temporal gyrus, right putamen, right precuneus, and the right superior temporal gyrus. Differences in fALFF between MDD patients and controls indicated that altered spontaneous neural activity was distributed across a number of specific brain regions among MDD patients. These atypical functional regions may help explain some of the neural processes underlying the clinical symptoms accompanying MDD. PMID:25229945

Shen, Ting; Qiu, Meihui; Li, Chao; Zhang, Jie; Wu, Zhiguo; Wang, Biao; Jiang, Kaida; Peng, Daihui

2014-11-12

177

Gregarious desert locusts have substantially larger brains with altered proportions compared with the solitarious phase  

PubMed Central

The behavioural demands of group living and foraging have been implicated in both evolutionary and plastic changes in brain size. Desert locusts show extreme phenotypic plasticity, allowing brain morphology to be related to very different lifestyles in one species. At low population densities, locusts occur in a solitarious phase that avoids other locusts and is cryptic in appearance and behaviour. Crowding triggers the transformation into the highly active gregarious phase, which aggregates into dense migratory swarms. We found that the brains of gregarious locusts have very different proportions and are also 30 per cent larger overall than in solitarious locusts. To address whether brain proportions change with size through nonlinear scaling (allometry), we conducted the first comprehensive major axis regression analysis of scaling relations in an insect brain. This revealed that phase differences in brain proportions arise from a combination of allometric effects and deviations from the allometric expectation (grade shifts). In consequence, gregarious locusts had a larger midbrain?optic lobe ratio, a larger central complex and a 50 per cent larger ratio of the olfactory primary calyx to the first olfactory neuropile. Solitarious locusts invest more in low-level sensory processing, having disproportionally larger primary visual and olfactory neuropiles, possibly to gain sensitivity. The larger brains of gregarious locusts prioritize higher integration, which may support the behavioural demands of generalist foraging and living in dense and highly mobile swarms dominated by intense intraspecific competition. PMID:20507896

Ott, Swidbert R.; Rogers, Stephen M.

2010-01-01

178

Exercise Modulates Redox-Sensitive Small GTPase Activity in the Brain Microvasculature in a Model of Brain Metastasis Formation  

PubMed Central

Tumor cell extravasation into the brain requires passage through the blood-brain barrier (BBB). There is evidence that exercise can alter the oxidation status of the brain microvasculature and protect against tumor cell invasion into the brain, although the mechanisms are not well understood. In the current study, we focused on the role of microenvironment generated by exercise and metastasizing tumor cells at the levels of brain microvessels, influencing oxidative stress-mediated responses and activation of redox-sensitive small GTPases. Mature male mice were exercised for four weeks using a running wheel with the average voluntary running distance 9.0±0.3 km/day. Mice were then infused with 1.0×106 D122 (murine Lewis lung carcinoma) cells into the brain microvasculature, and euthanized either 48 hours (in short-term studies) or 2–3 weeks (in long-term studies) post tumor cell administration. A significant increase in the level of reactive oxygen species was observed following 48 hours or 3 weeks of tumor cells growth, which was accompanied by a reduction in MnSOD expression in the exercised mice. Activation of the small GTPase Rho was negatively correlated with running distance in the tumor cell infused mice. Together, these data suggest that exercise may play a significant role during aggressive metastatic invasion, especially at higher intensities in pre-trained individuals. PMID:24804765

Wolff, Gretchen; Balke, Jordan E.; Andras, Ibolya E.; Park, Minseon; Toborek, Michal

2014-01-01

179

Proteome-Wide Lysine Acetylation in Cortical Astrocytes and Alterations That Occur during Infection with Brain Parasite Toxoplasma gondii  

PubMed Central

Lysine acetylation is a reversible post-translational modification (PTM) that has been detected on thousands of proteins in nearly all cellular compartments. The role of this widespread PTM has yet to be fully elucidated, but can impact protein localization, interactions, activity, and stability. Here we present the first proteome-wide survey of lysine acetylation in cortical astrocytes, a subtype of glia that is a component of the blood-brain barrier and a key regulator of neuronal function and plasticity. We identified 529 lysine acetylation sites across 304 proteins found in multiple cellular compartments that largely function in RNA processing/transcription, metabolism, chromatin biology, and translation. Two hundred and seventy-seven of the acetylated lysines we identified on 186 proteins have not been reported previously in any other cell type. We also mapped an acetylome of astrocytes infected with the brain parasite, Toxoplasma gondii. It has been shown that infection with T. gondii modulates host cell gene expression, including several lysine acetyltransferase (KAT) and deacetylase (KDAC) genes, suggesting that the host acetylome may also be altered during infection. In the T. gondii-infected astrocytes, we identified 34 proteins exhibiting a level of acetylation >2-fold and 24 with a level of acetylation <2-fold relative to uninfected astrocytes. Our study documents the first acetylome map for cortical astrocytes, uncovers novel lysine acetylation sites, and demonstrates that T. gondii infection produces an altered acetylome. PMID:25786129

Bouchut, Anne; Chawla, Aarti R.; Jeffers, Victoria; Hudmon, Andy; Sullivan, William J.

2015-01-01

180

Proteome-Wide Lysine Acetylation in Cortical Astrocytes and Alterations That Occur during Infection with Brain Parasite Toxoplasma gondii.  

PubMed

Lysine acetylation is a reversible post-translational modification (PTM) that has been detected on thousands of proteins in nearly all cellular compartments. The role of this widespread PTM has yet to be fully elucidated, but can impact protein localization, interactions, activity, and stability. Here we present the first proteome-wide survey of lysine acetylation in cortical astrocytes, a subtype of glia that is a component of the blood-brain barrier and a key regulator of neuronal function and plasticity. We identified 529 lysine acetylation sites across 304 proteins found in multiple cellular compartments that largely function in RNA processing/transcription, metabolism, chromatin biology, and translation. Two hundred and seventy-seven of the acetylated lysines we identified on 186 proteins have not been reported previously in any other cell type. We also mapped an acetylome of astrocytes infected with the brain parasite, Toxoplasma gondii. It has been shown that infection with T. gondii modulates host cell gene expression, including several lysine acetyltransferase (KAT) and deacetylase (KDAC) genes, suggesting that the host acetylome may also be altered during infection. In the T. gondii-infected astrocytes, we identified 34 proteins exhibiting a level of acetylation >2-fold and 24 with a level of acetylation <2-fold relative to uninfected astrocytes. Our study documents the first acetylome map for cortical astrocytes, uncovers novel lysine acetylation sites, and demonstrates that T. gondii infection produces an altered acetylome. PMID:25786129

Bouchut, Anne; Chawla, Aarti R; Jeffers, Victoria; Hudmon, Andy; Sullivan, William J

2015-01-01

181

Minocycline protects against oxidative damage and alters energy metabolism parameters in the brain of rats subjected to chronic mild stress.  

PubMed

Studies have been suggested that minocycline can be a potential new agent for the treatment of depression. In addition, both oxidative stress and energy metabolism present an important role in pathophysiology of depression. So, the present study was aimed to evaluate the effects of minocycline on stress oxidative parameters and energy metabolism in the brain of adult rats submitted to the chronic mild stress protocol (CMS). After CMS Wistar, both stressed animals as controls received twice ICV injection of minocycline (160 ?g) or vehicle. The oxidative stress and energy metabolism parameters were assessed in the prefrontal cortex (PF), hippocampus (HIP), amygdala (AMY) and nucleus accumbens (Nac). Our findings showed that stress induced an increase on protein carbonyl in the PF, AMY and NAc, and mynocicline injection reversed this alteration. The TBARS was increased by stress in the PF, HIP and NAc, however, minocycline reversed the alteration in the PF and HIP. The Complex I was incrased in AMY by stress, and minocycline reversed this effect, however reduced Complex I activity in the NAc; Complex II reduced in PF and AMY by stress or minocycline; the Complex II-III increased in the HIP in stress plus minocycline treatment and in the NAc with minocycline; in the PF and HIP there were a reduced in Complex IV with stress and minocycline. The creatine kinase was reduced in AMY and NAc with stress and minocycline. In conclusion, minocycline presented neuroprotector effects by reducing oxidative damage and regulating energy metabolism in specific brain areas. PMID:25112549

Réus, Gislaine Z; Abelaira, Helena M; Maciel, Amanda L; Dos Santos, Maria Augusta B; Carlessi, Anelise S; Steckert, Amanda V; Ferreira, Gabriela K; De Prá, Samira D; Streck, Emilio L; Macêdo, Danielle S; Quevedo, João

2015-04-01

182

Alterations in brain temperatures as a possible cause of migraine headache.  

PubMed

Migraine is a debilitating disease with a recurring generally unilateral headache and concomitant symptoms of nausea, vomiting and photo- and/or phonophobia that affects some 11-18% of the population. Most of the mechanisms previously put forward to explain the attacks have been questioned or give an explanation only some of the symptoms. Moreover, the best drugs for treatment are still the 20-year-old triptans, which have serious limitations as regards both efficacy and tolerability. As the dura and some cranial vessels are the only intracranial structures capable of pain sensations, a vascular theory of migraine emerged, but has been debated. Recent theories identified the hyperexcitability of structures involved in pain transmission, such as the trigeminal system or the cortex, or an abnormal modulatory function of the brainstem. However, there is ongoing scientific debate concerning these theories, neither of which is fully capable of explaining the occurrence of a migraine attack. The present article puts forward a hypothesis of the possibility of abnormal temperature regulation in certain regions or the overall brain in migraineurs, the attack being a defense mechanism to prevent neuronal damage. Few examinations have been made of temperature regulation in the human brain. It lacks the carotid rete, a vascular heat exchanger that serves in many animals to provide constant brain temperature. The human brain contains a high density of neurons with a considerable energy demand that is converted to heat. The human brain has a higher temperature than other parts of the body and needs continuous cooling. Recent studies revealed unexpectedly great variations in temperature of various structures of the brain and considerable changes in response to functional activation. There is various evidence in support of the hypothesis that accumulated heat in some structure or the overall brain may be behind the symptoms observed, such as a platelet abnormality, a decreased serotonin content, and dural "inflammation" including vasodilation and brainstem activation. The hypothesis postulates that a migraine attack serves to restore the brain temperature. Abnormally low temperatures in the brain can also result in headache. Surprisingly, no systematic examination of brain temperature changes in migraineurs has been published. Certain case reports support the present hypothesis. Various noninvasive technologies (e.g. MR) capable of monitoring brain temperature are available. If a systematic examination of local brain temperature revealed abnormalities in structures presumed to be involved in migraine, that would increase our understanding of the disease and trigger the development of improved treatment. PMID:24581675

Horváth, Csilla

2014-05-01

183

Different mechanisms account for ERK activation in distinct brain regions following global ischemia and reperfusion  

PubMed Central

Oxidative stress after cerebral ischemia and reperfusion activates extracellular signal-regulated kinases (ERK) in brain. However, the mechanism of this activation has not been elucidated. We have previously reported that in an in vitro model of oxidative stress in immature cortical neuronal cultures, the inhibition of ERK phosphatase activity contributes to ERK1/2 activation and subsequent neuronal toxicity. This study examined whether ERK activation was associated with altered activity of ERK phosphatases in a rat cardiac arrest model. Rats in experimental groups were subjected to asphyxial cardiac arrest for 8 min and then resuscitated for 30 min. Significant ERK activation was detected in both cortex and hippocampus following ischemia/reperfusion by immunoblotting. ERK phosphatase activity was reversibly inhibited in cerebral cortex but not affected in hippocampus following ischemia/reperfusion. MEK1/2 was activated in both cerebral cortex and hippocampus following ischemia/reperfusion. Using a specific inhibitor of protein phosphatase 2A (PP2A), okadaic acid (OA), we have identified PP2A to be the major ERK phosphatase that is responsible for regulating ERK activation in ischemic brain tissues. Orthovanadate inhibited ERK phosphatase activity in brain tissues, suggesting that tyrosine phosphatases and dual specificity phosphatases may also contribute to the ERK phosphatase activity in brain tissues. Together, these data implicate ERK phosphatase in the regulation of ERK activation in distinct brain regions following global ischemia. PMID:17207579

Ho, Yeung; Logue, Eric; Callaway, Clifton W; DeFranco, Donald B

2007-01-01

184

HIV and SIV Induce Alterations in CNS CaMKII Expression and Activation  

PubMed Central

The molecular mechanisms underlying learning and memory impairment in patients with HIV-associated neurological disease have remained unclear. Calcium/calmodulin-dependent kinase II (CaMKII) has key roles in synaptic potentiation and memory storage in neurons and also may have immunomodulatory functions. To determine whether HIV and simian immunodeficiency virus (SIV) induce alterations in CaMKII expression and/or activation (autophosphorylation) in the brain, we measured CaMKII alterations by quantitative immunoblotting in both an in vitro HIV/neuronal culture model and in vivo in an SIV-infected macaque model of HIV-associated neurological damage. Using primary rat hippocampal neuronal cultures treated with culture supernatants harvested from HIV-1–infected human monocyte-derived macrophages (HIV/MDM), we found that CaMKII activation declined after exposure of neurons to HIV/MDM. Consistent with our in vitro measurements, a significant decrease in CaMKII activation was present in both the hippocampus and frontal cortex of SIV-infected macaques compared with uninfected animals. In SIV-infected animals, total CaMKII expression in the hippocampus correlated well with levels of synaptophysin. Furthermore, CaMKII expression in both the hippocampus and frontal cortex was inversely correlated with viral load in the brain. These findings suggest that alterations in CaMKII may compromise synaptic function in the early phases of chronic neurodegenerative processes induced by HIV. PMID:20382699

Gupta, Ravi G.; Kelly, Kathleen M.; Helke, Kris L.; Queen, Suzanne E.; Karper, Jami M.; Dorsey, Jamie L.; Brice, Angela K.; Adams, Robert J.; Tarwater, Patrick M.; Kolson, Dennis L.; Mankowski, Joseph L.

2010-01-01

185

Correspondence of the brain's functional architecture during activation and rest.  

PubMed

Neural connections, providing the substrate for functional networks, exist whether or not they are functionally active at any given moment. However, it is not known to what extent brain regions are continuously interacting when the brain is "at rest." In this work, we identify the major explicit activation networks by carrying out an image-based activation network analysis of thousands of separate activation maps derived from the BrainMap database of functional imaging studies, involving nearly 30,000 human subjects. Independently, we extract the major covarying networks in the resting brain, as imaged with functional magnetic resonance imaging in 36 subjects at rest. The sets of major brain networks, and their decompositions into subnetworks, show close correspondence between the independent analyses of resting and activation brain dynamics. We conclude that the full repertoire of functional networks utilized by the brain in action is continuously and dynamically "active" even when at "rest." PMID:19620724

Smith, Stephen M; Fox, Peter T; Miller, Karla L; Glahn, David C; Fox, P Mickle; Mackay, Clare E; Filippini, Nicola; Watkins, Kate E; Toro, Roberto; Laird, Angela R; Beckmann, Christian F

2009-08-01

186

A Meta-Analysis of Changes in Brain Activity in Clinical Depression  

PubMed Central

Insights into neurobiological mechanisms of depression are increasingly being sought via brain imaging studies. Our aim was to quantitatively summarize overlap and divergence in regions of altered brain activation associated with depression under emotionally valenced compared to cognitively demanding task conditions, and with reference to intrinsic functional connectivity. We hypothesized differences reflective of task demands. A co-ordinate-based meta-analysis technique, activation likelihood estimation, was used to analyze relevant imaging literature. These studies compared brain activity in depressed adults relative to healthy controls during three conditions: (i) emotionally valenced (cognitively easy) tasks (n?=?29); (ii) cognitively demanding tasks (n?=?15); and (iii) resting conditions (n?=?21). The meta-analyses identified five, eight, and seven significant clusters of altered brain activity under emotion, cognition, and resting conditions, respectively, in depressed individuals compared to healthy controls. Regions of overlap and divergence between pairs of the three separate meta-analyses were quantified. There were no significant regions of overlap between emotion and cognition meta-analyses, but several divergent clusters were found. Cognitively demanding conditions were associated with greater activation of right medial frontal and insula regions while bilateral amygdala was more significantly altered during emotion (cognitively undemanding) conditions; consistent with task demands. Overlap was present in left amygdala and right subcallosal cingulate between emotion and resting meta-analyses, with no significant divergence. Our meta-analyses highlight alteration of common brain regions, during cognitively undemanding emotional tasks and resting conditions but divergence of regions between emotional and cognitively demanding tasks. Regions altered reflect current biological and system-level models of depression and highlight the relationship with task condition and difficulty. PMID:25642179

Palmer, Susan M.; Crewther, Sheila G.; Carey, Leeanne M.

2015-01-01

187

Altered myoelectric activity in the experimental blind loop syndrome.  

PubMed Central

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) surgical removal of the loop reduced the alterations in motor function. This study suggests that the altered myoelectric activity in this model of bacterial overgrowth was due, in part, to the abnormal bacterial flora and supports the concept that alterations in motility may contribute to the diarrhea that is characteristic of the blind loop syndrome. PMID:6350361

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

1983-01-01

188

Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density  

PubMed Central

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

Guillermo, Rosamond B.; Yang, Panzao; Vickers, Mark H.; McJarrow, Paul; Guan, Jian

2015-01-01

189

Irritable bowel syndrome in female patients is associated with alterations in structural brain networks.  

PubMed

Alterations in gray matter (GM) density/volume and cortical thickness (CT) have been demonstrated in small and heterogeneous samples of subjects with differing chronic pain syndromes, including irritable bowel syndrome (IBS). Aggregating across 7 structural neuroimaging studies conducted at University of California, Los Angeles, Los Angeles, CA, USA, between August 2006 and April 2011, we examined group differences in regional GM volume in 201 predominantly premenopausal female subjects (82 IBS, mean age: 32±10 SD, 119 healthy controls [HCs], 30±10 SD). Applying graph theoretical methods and controlling for total brain volume, global and regional properties of large-scale structural brain networks were compared between the group with IBS and the HC group. Relative to HCs, the IBS group had lower volumes in the bilateral superior frontal gyrus, bilateral insula, bilateral amygdala, bilateral hippocampus, bilateral middle orbital frontal gyrus, left cingulate, left gyrus rectus, brainstem, and left putamen. Higher volume was found in the left postcentral gyrus. Group differences were no longer significant for most regions when controlling for the Early Trauma Inventory global score, with the exception of the right amygdala and the left postcentral gyrus. No group differences were found for measures of global and local network organization. Compared to HCs, in patients with IBS, the right cingulate gyrus and right thalamus were identified as being significantly more critical for information flow. Regions involved in endogenous pain modulation and central sensory amplification were identified as network hubs in IBS. Overall, evidence for central alterations in patients with IBS was found in the form of regional GM volume differences and altered global and regional properties of brain volumetric networks. PMID:24076048

Labus, Jennifer S; Dinov, Ivo D; Jiang, Zhiguo; Ashe-McNalley, Cody; Zamanyan, Alen; Shi, Yonggang; Hong, Jui-Yang; Gupta, Arpana; Tillisch, Kirsten; Ebrat, Bahar; Hobel, Sam; Gutman, Boris A; Joshi, Shantanu; Thompson, Paul M; Toga, Arthur W; Mayer, Emeran A

2014-01-01

190

Sodium valproate induced alterations in monoamine levels in different regions of the rat brain.  

PubMed

Sodium valproate is a well established anticonvulsant drug but its exact mode of action is not yet clear. With a view to find out whether the mechanism of action of sodium valproate is mediated by alteration in monoamine levels, apart from GABA, in brain, sodium valproate (200 mg/kg body wt) was administered i.p. to male adult Wistar rats for 45 days. The levels of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) were assayed in different brain regions using high performance liquid chromatographic (HPLC) method. It was noted that at the end of the experimental period there was no change in body or brain weight nor were there any neurological deficits as a result of sodium valproate administration. However, after administration of sodium valproate there was a significant increase in norepinephrine levels in hippocampus (P < 0.01) and brainstem (P < 0.01) while a significant decrease was noted in hypothalamus (P < 0.001). Dopamine levels were significantly increased in motor cortex (P < 0.01), hippocampus (P < 0.01) and hypothalamus (P < 0.001). Serotonin levels were significantly increased in striatum-accumbens and brain stem (P < 0.001). However a marginal increase was also observed in motor cortex and hippocampus. 5-HT levels were significantly decreased in hypothalamus (P < 0.001) and cerebellum (P < 0.01). The present findings suggest the possibility that the anticonvulsant effect of sodium valproate could be due to alterations in monoamine levels apart from its action on GABA, which would indicate also the efficacy of this drug in different types of seizures. PMID:8130737

Baf, M H; Subhash, M N; Lakshmana, K M; Rao, B S

1994-01-01

191

Altered expression of claudin family proteins in Alzheimer’s disease and vascular dementia brains  

PubMed Central

Abstract Claudins (Cls) are a multigene family of transmembrane proteins with different tissue distribution, which have an essential role in the formation and sealing capacity of tight junctions (TJs). At the level of the blood–brain barrier (BBB), TJs are the main molecular structures which separate the neuronal milieu from the circulatory space, by a restriction of the paracellular flow of water, ions and larger molecules into the brain. Different studies suggested recently significant BBB alterations in both vascular and degenerative dementia types. In a previous study we found in Alzheimer’s disease (AD) and vascular dementia (VaD) brains an altered expression of occludin, a molecular partner of Cls in the TJs structure. Therefore in this study, using an immunohistochemical approach, we investigated the expression of Cl family proteins (Cl-2, Cl-5 and Cl-11) in frontal cortex of aged control, AD and VaD brains. To estimate the number of Cl-expressing cells, we applied a random systematic sampling and the unbiased optical fractionator method. We found selected neurons, astrocytes, oligodendrocytes and endothelial cells expressing Cl-2, Cl-5 and Cl-11 at detectable levels in all cases studied. We report a significant increase in ratio of neurons expressing Cl-2, Cl-5 and Cl-11 in both AD and VaD as compared to aged controls. The ratio of astrocytes expressing Cl-2 and Cl-11 was significantly higher in AD and VaD as compared to aged controls. The ratio of oligodendrocytes expressing Cl-11 was significantly higher in AD and the ratio of oligodendrocytes expressing Cl-2 was significantly higher in VaD as compared to aged controls. Within the cerebral cortex, Cls were selectively expressed by pyramidal neurons, which are the ones responsible for cognitive processes and affected by AD pathology. Our findings suggest a new function of Cl family proteins which might be linked to response to cellular stress. PMID:20041969

Romanitan, Mihaela O; Popescu, Bogdan O; Spulber, ?tefan; B?jenaru, Ovidiu; Popescu, Lauren?iu M; Winblad, Bengt; Bogdanovic, Nenad

2010-01-01

192

Alterations of NMDA receptor binding in various brain regions among 6-hydroxydopamine-induced Parkinsonian rats.  

PubMed

The N-methyl-d-aspartate (NMDA) system closely interacts with the dopaminergic system and is strongly implicated in the pathophysiological mechanisms and therapeutic paradigms of Parkinson's disease. This study aims to systematically investigate the changes of NMDA receptors in a wide range of brain structures 3 weeks after unilateral medial forebrain bundle lesion by 6-hydroxydopamine (6-OHDA). NMDA receptor distributions and alterations in the post-mortem rat brain were detected by [(3)H] MK-801 binding autoradiography. In the 6-OHDA-induced Parkinsonian rat model, nigrostriatal dopaminergic neuron loss significantly mediated the decreased [(3)H] MK-801 binding, predominantly in the hippocampus (-22.4%, p < 0.001), caudate putamen (-14.1%, p < 0.01), accumbens nucleus (-13.8%, p < 0.05), cingulate cortex (-13.4%, p < 0.001), posteromedial cortical amygdala (-14.5%, p < 0.01) and piriform cortex (-9%, p < 0.05) compared to the controls, while there was a profound reduction of tyrosine hydroxylase (TH) immunohistochemistry in the substantia nigra pars compacta. Alterations in [(3)H] MK-801 in the specific brain regions related to cognitive functions may indicate that cognitive dysfunctions caused by 6-OHDA lesion were via the NMDA system. The downregulation of NMDA receptor binding in the present study provides indirect evidence for plasticity in the NMDA system in the rat brain. The present study improves our understanding of the critical roles of the NMDA receptors in treating neurodegenerative disorders, and implicates NMDA receptors as a novel therapeutic target in the treatment of Parkinson's disease. PMID:24102195

Wang, Qing; Li, Jin; Wei, Xiaobo; Liao, Jinchi; Xu, Yunqi; Lu, Tingting; Qin, Bing; Xie, Junqiang; Deng, Chao; Huang, Xufeng

2014-06-01

193

Stress-induced alterations in large-scale functional networks of the rodent brain.  

PubMed

Stress-related psychopathology is associated with altered functioning of large-scale brain networks. Animal research into chronic stress, one of the most prominent environmental risk factors for development of psychopathology, has revealed molecular and cellular mechanisms potentially contributing to human mental disease. However, so far, these studies have not addressed the system-level changes in extended brain networks, thought to critically contribute to mental disorders. We here tested the effects of chronic stress exposure (10 days immobilization) on the structural integrity and functional connectivity patterns in the brain, using high-resolution structural MRI, diffusion kurtosis imaging, and resting-state functional MRI, while confirming the expected changes in neuronal dendritic morphology using Golgi-staining. Stress effectiveness was confirmed by a significantly lower body weight and increased adrenal weight. In line with previous research, stressed animals displayed neuronal dendritic hypertrophy in the amygdala and hypotrophy in the hippocampal and medial prefrontal cortex. Using independent component analysis of resting-state fMRI data, we identified ten functional connectivity networks in the rodent brain. Chronic stress appeared to increase connectivity within the somatosensory, visual, and default mode networks. Moreover, chronic stress exposure was associated with an increased volume and diffusivity of the lateral ventricles, whereas no other volumetric changes were observed. This study shows that chronic stress exposure in rodents induces alterations in functional network connectivity strength which partly resemble those observed in stress-related psychopathology. Moreover, these functional consequences of stress seem to be more prominent than the effects on gross volumetric change, indicating their significance for future research. PMID:25462693

Henckens, Marloes J A G; van der Marel, Kajo; van der Toorn, Annette; Pillai, Anup G; Fernández, Guillén; Dijkhuizen, Rick M; Joëls, Marian

2015-01-15

194

TRANSLATION OF BRAIN ACTIVITY INTO SLEEP  

PubMed Central

Cytokines including tumor necrosis factor alpha (TNF) play a role in sleep regulation in health and disease. Hypothalamic and cerebral cortical levels of TNF mRNA or TNF protein have diurnal variations with higher levels associated with greater sleep propensity. Sleep loss is associated with enhanced brain TNF. Central or systemic TNF injections enhance sleep. Inhibition of TNF using the soluble TNF receptor, or anti-TNF antibodies, or a TNF siRNA reduces spontaneous sleep. Mice lacking the TNF 55 kD receptor have less spontaneous sleep. Injection of TNF into sleep regulatory circuits, e.g. the hypothalamus, promotes sleep. In normal humans, plasma levels of TNF co-vary with EEG slow wave activity (SWA) and in multiple disease states plasma TNF increases in parallel with sleep propensity. Downstream mechanisms of TNF-enhanced sleep include nitric oxide, adenosine, prostaglandins and activation of nuclear factor kappa B. Neuronal use induces cortical neurons to express TNF and if applied directly to cortical columns TNF induces a functional sleep-like state within the column. TNF mechanistically has several synaptic functions. TNF-sleep data led to the idea that sleep is a fundamental property of neuronal/glial networks such as cortical columns and is dependent upon past activity within such assemblies. This view of brain organization of sleep has profound implications for sleep function that are briefly reviewed herein. PMID:24795496

Krueger, James M.

2012-01-01

195

Altered spontaneous activity in antisocial personality disorder revealed by regional homogeneity.  

PubMed

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. PMID:23804035

Tang, Yan; Liu, Wangyong; Chen, Jingang; Liao, Jian; Hu, Dewen; Wang, Wei

2013-08-01

196

Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks.  

PubMed

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

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

197

Fibromyalgia is characterized by altered frontal and cerebellar structural covariance brain networks  

PubMed Central

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

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

198

Brain Region–Specific Alterations in the Gene Expression of Cytokines, Immune Cell Markers and Cholinergic System Components during Peripheral Endotoxin–Induced Inflammation  

PubMed Central

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)-1?, 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

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

199

Altered Neural Activity and Emotions Following Right Middle Cerebral Artery Stroke  

PubMed Central

Background and Purpose Stroke of the right MCA is common. Such strokes often have consequences for emotional experience, but these can be subtle. In such cases diagnosis is difficult because emotional awareness (limiting reporting of emotional changes) may be affected. The present study sought to clarify the mechanisms of altered emotion experience after right MCA stroke. It was predicted that after right MCA stroke the anterior cingulate cortex (ACC), a brain region concerned with emotional awareness, would show reduced neural activity. Methods Brain activity during presentation of emotional stimuli was measured in six patients with stable stroke, and in 12 age and gender matched non-lesion comparisons using positron emission tomography and the [15O]H2O autoradiographic method. Results MCA stroke was associated with weaker pleasant experience and decreased activity ipsilaterally in the ACC. Other regions involved in emotional processing including thalamus, dorsal and medial prefrontal cortex showed reduced activity ipsilaterally. Dorsal and medial prefrontal cortex, association visual cortex and cerebellum showed reduced activity contralaterally. Experience from unpleasant stimuli was unaltered and was associated with decreased activity only in the left midbrain. Conclusions Right MCA stroke may reduce experience of pleasant emotions by altering brain activity in limbic and paralimbic regions distant from the area of direct damage, in addition to changes due to direct tissue damage to insula and basal ganglia. The knowledge acquired in this study begins to explain the mechanisms underlying emotional changes following right MCA stroke. Recognizing these changes may improve diagnoses, management and rehabilitation of right MCA stroke victims. PMID:20656512

Paradiso, Sergio; Anderson, Beth M.; Boles Ponto, Laura L.; Tranel, Daniel; Robinson, Robert G.

2010-01-01

200

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...

201

ALUMINUM ALTERS CALCIUM TRANSPORT IN PLASMA MEMBRANE AND ENDOPLASMIC RETICULUM FROM RAT BRAIN  

EPA Science Inventory

Calcium is actively transported into intracellular organelles and out of the cytoplasm by Ca2+/Mg2+-ATPases located in the endoplasmic reticulum and plasma membranes. he effects of aluminum on calcium transport were examined in the adult rat brain. 5Ca-uptake was examined in micr...

202

Anger Style, Psychopathology, and Regional Brain Activity  

PubMed Central

Depression and anxiety often involve high levels of trait anger and disturbances in anger expression. Reported anger experience and outward anger expression have recently been associated with left-biased asymmetry of frontal cortical activity, assumed to reflect approach motivation. However, different styles of anger expression could presumably involve different brain mechanisms and/or interact with psychopathology to produce various patterns of brain asymmetry. The present study explored these issues by comparing resting regional electroencephalographic activity in participants high in trait anger who differed in anger expression style (high anger-in, high anger-out, both) and participants low in trait anger, with depression and anxiety systematically assessed. Trait anger, not anger-in or anger-out, predicted left-biased asymmetry at medial frontal EEG sites. The anger-in group reported higher levels of anxious apprehension than did the anger-out group. Furthermore, anxious apprehension moderated the relationship between trait anger, anger-in, and asymmetry in favor of the left hemisphere. Results suggest that motivational direction is not always the driving force behind the relationship of anger and left frontal asymmetry. Findings also support a distinction between anxious apprehension and anxious arousal. PMID:18837620

Stewart, Jennifer L.; Levin, Rebecca L.; Sass, Sarah M.; Heller, Wendy; Miller, Gregory A.

2010-01-01

203

Brain Activity with Reading Sentences and Emoticons  

NASA Astrophysics Data System (ADS)

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.

Yuasa, Masahide; Saito, Keiichi; Mukawa, Naoki

204

NeuroimagingDecoding mental states from brain activity in humans  

Microsoft Academic Search

Recent advances in human neuroimaging have shown that it is possible to accurately decode a person's conscious experience based only on non-invasive measurements of their brain activity. Such 'brain reading' has mostly been studied in the domain of visual perception, where it helps reveal the way in which individual experiences are encoded in the human brain. The same approach can

Geraint Rees; John-Dylan Haynes

2006-01-01

205

Localized Brain Volume and White Matter Integrity Alterations in Adolescent Anorexia Nervosa  

PubMed Central

Objective The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to adults. Method We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls. Results Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups. Conclusions This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder. PMID:24074473

Frank, Guido K.W.; Shott, Megan E.; Hagman, Jennifer O.; Yang, Tony T.

2014-01-01

206

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

PubMed

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. © 2015 International Parkinson and Movement Disorder Society. PMID:25820811

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

2015-04-15

207

Causal interaction following the alteration of target region activation during motor imagery training using real-time fMRI  

PubMed Central

Motor imagery training is an effective approach for motor skill learning and motor function rehabilitation. As a novel method of motor imagery training, real-time fMRI (rtfMRI) enables individuals to acquire self-control of localized brain activation, achieving desired changes in behavior. The regulation of target region activation by rtfMRI often alters the activation of related brain regions. However, the interaction between the target region and these related regions is unclear. The Granger causality model (GCM) is a data-driven method that can explore the causal interaction between brain regions. In this study, we employed rtfMRI to train subjects to regulate the activation of the ipsilateral dorsal premotor area (dPMA) during motor imagery training, and we calculated the causal interaction of the dPMA with other motor-related regions based on the GCM. The results demonstrated that as the activity of the dPMA changed during rtfMRI training, the interaction of the target region with other related regions became significantly altered, and behavioral performance was improved after training. The altered interaction primarily exhibited as an increased unidirectional interaction from the dPMA to the other regions. These findings support the dominant role of the dPMA in motor skill learning via rtfMRI training and may indicate how activation of the target region interacts with the activation of other related regions. PMID:24379775

Zhao, Xiaojie; Zhang, Hang; Song, Sutao; Ye, Qing; Guo, Jia; Yao, Li

2013-01-01

208

Ionic transporter activity in astrocytes, microglia, and oligodendrocytes during brain ischemia  

PubMed Central

Glial cells constitute a large percentage of cells in the nervous system. During recent years, a large number of studies have critically attributed to glia a new role which no longer reflects the long-held view that glia constitute solely a silent and passive supportive scaffolding for brain cells. Indeed, it has been hypothesized that glia, partnering neurons, have a much more actively participating role in brain function. Alteration of intraglial ionic homeostasis in response to ischemic injury has a crucial role in inducing and maintaining glial responses in the ischemic brain. Therefore, glial transporters as potential candidates in stroke intervention are becoming promising targets to enhance an effective and additional therapy for brain ischemia. In this review, we will describe in detail the role played by ionic transporters in influencing astrocyte, microglia, and oligodendrocyte activity and the implications that these transporters have in the progression of ischemic lesion. PMID:23549380

Annunziato, Lucio; Boscia, Francesca; Pignataro, Giuseppe

2013-01-01

209

Specific and Evolving Resting-State Network Alterations in Post-Concussion Syndrome Following Mild Traumatic Brain Injury  

PubMed Central

Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the DSM-IV criteria) at 6 months post-injury compared with 38 mild traumatic brain injury patients with no post-concussion syndrome and 34 healthy controls. All patients underwent magnetic resonance imaging examinations at the subacute (1–3 weeks) and late (6 months) phases after injury. Group-wise differences in functional brain networks were analyzed using graph theory measures. Patterns of long-range functional networks alterations were found in all mild traumatic brain injury patients. Mild traumatic brain injury patients with post-concussion syndrome had greater alterations than patients without post-concussion syndrome. In patients with post-concussion syndrome, changes specifically affected temporal and thalamic regions predominantly at the subacute stage and frontal regions at the late phase. Our results suggest that the post-concussion syndrome is associated with specific abnormalities in functional brain network that may contribute to explain deficits typically observed in PCS patients. PMID:23755237

Messé, Arnaud; Caplain, Sophie; Pélégrini-Issac, Mélanie; Blancho, Sophie; Lévy, Richard; Aghakhani, Nozar; Montreuil, Michèle; Benali, Habib; Lehéricy, Stéphane

2013-01-01

210

BRIEF REPORTS Evidence That Brain MAO A Activity Does Not  

E-print Network

difference in brain MAO A activity between the high (n 26) and low (n 12) MAO A genotypes. Conclusions that this polymorphism by itself does not contribute to differences in brain MAO A activity in healthy adult male- cantly different transcriptional activities in human nonneuronal cell lines. Because of the importance

Goldstein, Rita

211

Altered brain morphometry in carpal tunnel syndrome is associated with median nerve pathology???  

PubMed Central

Objective Carpal tunnel syndrome (CTS) is a common median nerve entrapment neuropathy characterized by pain, paresthesias, diminished peripheral nerve conduction velocity (NCV) and maladaptive functional brain neuroplasticity. We evaluated structural reorganization in brain gray matter (GM) and white matter (WM) and whether such plasticity is linked to altered median nerve function in CTS. Methods We performed NCV testing, T1-weighted structural MRI, and diffusion tensor imaging (DTI) in 28 CTS and 28 age-matched healthy controls (HC). Voxel-based morphometry (VBM) contrasted regional GM volume for CTS versus HC. Significant clusters were correlated with clinical metrics and served as seeds to define associated WM tracts using DTI data and probabilistic tractography. Within these WM tracts, fractional anisotropy (FA), axial (AD) and radial (RD) diffusivity were evaluated for group differences and correlations with clinical metrics. Results For CTS subjects, GM volume was significantly reduced in contralesional S1 (hand-area), pulvinar and frontal pole. GM volume in contralesional S1 correlated with median NCV. NCV was also correlated with RD and was negatively correlated with FA within U-fiber cortico-cortical association tracts identified from the contralesional S1 VBM seed. Conclusions Our study identified clear morphometric changes in the CTS brain. This central morphometric change is likely secondary to peripheral nerve pathology and altered somatosensory afference. Enhanced axonal coherence and myelination within cortico-cortical tracts connecting primary somatosensory and motor areas may accompany peripheral nerve deafferentation. As structural plasticity was correlated with NCV and not symptomatology, the former may be a better determinant of appropriate clinical intervention for CTS, including surgery. PMID:23799199

Maeda, Yumi; Kettner, Norman; Sheehan, James; Kim, Jieun; Cina, Stephen; Malatesta, Cristina; Gerber, Jessica; McManus, Claire; Mezzacappa, Pia; Morse, Leslie R.; Audette, Joseph; Napadow, Vitaly

2013-01-01

212

Brain Alterations and Clinical Symptoms of Dementia in Diabetes: A?/Tau-Dependent and Independent Mechanisms  

PubMed Central

Emerging evidence suggests that diabetes affects cognitive function and increases the incidence of dementia. However, the mechanisms by which diabetes modifies cognitive function still remains unclear. Morphologically, diabetes is associated with neuronal loss in the frontal and temporal lobes including the hippocampus, and aberrant functional connectivity of the posterior cingulate cortex and medial frontal/temporal gyrus. Clinically, diabetic patients show decreased executive function, information processing, planning, visuospatial construction, and visual memory. Therefore, in comparison with the characteristics of AD brain structure and cognition, diabetes seems to affect cognitive function through not only simple AD pathological feature-dependent mechanisms but also independent mechanisms. As an A?/tau-independent mechanism, diabetes compromises cerebrovascular function, increases subcortical infarction, and might alter the blood–brain barrier. Diabetes also affects glucose metabolism, insulin signaling, and mitochondrial function in the brain. Diabetes also modifies metabolism of A? and tau and causes A?/tau-dependent pathological changes. Moreover, there is evidence that suggests an interaction between A?/tau-dependent and independent mechanisms. Therefore, diabetes modifies cognitive function through A?/tau-dependent and independent mechanisms. Interaction between these two mechanisms forms a vicious cycle. PMID:25250014

Sato, Naoyuki; Morishita, Ryuichi

2014-01-01

213

Structural Alterations of the Social Brain: A Comparison between Schizophrenia and Autism  

PubMed Central

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

Radeloff, Daniel; Ciaramidaro, Angela; Siniatchkin, Michael; Hainz, Daniela; Schlitt, Sabine; Weber, Bernhard; Poustka, Fritz; Bölte, Sven; Walter, Henrik; Freitag, Christine Margarete

2014-01-01

214

Brain alterations in adult ADHD: effects of gender, treatment and comorbid depression.  

PubMed

Children with attention-deficit/hyperactivity disorder (ADHD) have smaller volumes of total brain matter and subcortical regions, but it is unclear whether these represent delayed maturation or persist into adulthood. We performed a structural MRI study in 119 adult ADHD patients and 107 controls and investigated total gray and white matter and volumes of accumbens, caudate, globus pallidus, putamen, thalamus, amygdala and hippocampus. Additionally, we investigated effects of gender, stimulant treatment and history of major depression (MDD). There was no main effect of ADHD on the volumetric measures, nor was any effect observed in a secondary voxel-based morphometry (VBM) analysis of the entire brain. However, in the volumetric analysis a significant gender by diagnosis interaction was found for caudate volume. Male patients showed reduced right caudate volume compared to male controls, and caudate volume correlated with hyperactive/impulsive symptoms. Furthermore, patients using stimulant treatment had a smaller right hippocampus volume compared to medication-naïve patients and controls. ADHD patients with previous MDD showed smaller hippocampus volume compared to ADHD patients with no MDD. While these data were obtained in a cross-sectional sample and need to be replicated in a longitudinal study, the findings suggest that developmental brain differences in ADHD largely normalize in adulthood. Reduced caudate volume in male patients may point to distinct neurobiological deficits underlying ADHD in the two genders. Smaller hippocampus volume in ADHD patients with previous MDD is consistent with neurobiological alterations observed in MDD. PMID:24345721

Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Kan, Cornelis C; Buitelaar, Jan; Franke, Barbara

2014-03-01

215

Motor stereotypies and volumetric brain alterations in children with Autistic Disorder  

PubMed Central

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

Goldman, Sylvie; O’Brien, Liam M.; Filipek, Pauline A.; Rapin, Isabelle; Herbert, Martha R.

2013-01-01

216

Brain Structural Alterations in Obsessive-Compulsive Disorder Patients with Autogenous and Reactive Obsessions  

PubMed Central

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. PMID:24098688

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

217

Altered brain response for semantic knowledge in Alzheimer’s disease  

PubMed Central

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 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

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.

2011-01-01

218

Brain injury does not alter the intrinsic differentiation potential of adult neuroblasts.  

PubMed

Neuroblasts produced by the neural stem cells of the adult subventricular zone (SVZ) migrate into damaged brain areas after stroke or other brain injuries, and previous data have suggested that they generate regionally appropriate new neurons. To classify the types of neurons produced subsequent to ischemic injury, we combined BrdU or virus labeling with multiple neuronal markers to characterize new cells at different times after the induction of stroke. We show that SVZ neuroblasts give rise almost exclusively to calretinin-expressing cells in the damaged striatum, resulting in the accumulation of these cells during long term recovery after stroke. The vast majority of SVZ neuroblasts as well as newly born young and mature neurons in the damaged striatum constitutively express the transcription factor Sp8, but do not express transcription factors characteristic of medium-sized spiny neurons, the primary striatal projection neurons lost after stroke. Our results suggest that adult neuroblasts do not alter their intrinsic differentiation potential after brain injury. PMID:19386903

Liu, Fang; You, Yan; Li, Xiaosu; Ma, Tong; Nie, Yanzhen; Wei, Bin; Li, Tiejun; Lin, Huanbing; Yang, Zhengang

2009-04-22

219

Characterizing structural association alterations within brain networks in normal aging using Gaussian Bayesian networks  

PubMed Central

Recent multivariate neuroimaging studies have revealed aging-related alterations in brain structural networks. However, the sensory/motor networks such as the auditory, visual and motor networks, have obtained much less attention in normal aging research. In this study, we used Gaussian Bayesian networks (BN), an approach investigating possible inter-regional directed relationship, to characterize aging effects on structural associations between core brain regions within each of these structural sensory/motor networks using volumetric MRI data. We then further examined the discriminability of BN models for the young (N = 109; mean age =22.73 years, range 20–28) and old (N = 82; mean age =74.37 years, range 60–90) groups. The results of the BN modeling demonstrated that structural associations exist between two homotopic brain regions from the left and right hemispheres in each of the three networks. In particular, compared with the young group, the old group had significant connection reductions in each of the three networks and lesser connection numbers in the visual network. Moreover, it was found that the aging-related BN models could distinguish the young and old individuals with 90.05, 73.82, and 88.48% accuracy for the auditory, visual, and motor networks, respectively. Our findings suggest that BN models can be used to investigate the normal aging process with reliable statistical power. Moreover, these differences in structural inter-regional interactions may help elucidate the neuronal mechanism of anatomical changes in normal aging. PMID:25324771

Guo, Xiaojuan; Wang, Yan; Chen, Kewei; Wu, Xia; Zhang, Jiacai; Li, Ke; Jin, Zhen; Yao, Li

2014-01-01

220

Alterations in the Nrf2-Keap1 signaling pathway and its downstream target genes in rat brain under stress.  

PubMed

Knowledge of the antioxidant defense in the stress-responding structures of the CNS is of crucial importance, since oxidative damage is a phenomenon accompanying many stress-related disorders. Regulation of antioxidative and anti-inflammatory defense through Nrf2 (nuclear factor 2 eritroid related factor 2) pathway has emerged as a promising approach for neuroprotection. In this study, we used chronic social isolation of male Wistar rats to induce depressive-like behavior. We hypothesized that Nrf2-Keap1 pathway is compromised in the limbic brain after prolonged stress. Since subcellular trafficking of Nrf2 and its inhibitor Keap1 (Kelch ECH associating protein 1) is essential for the activation of Nrf2, we determined their protein level in cytosolic and nuclear compartments of hippocampus and prefrontal cortex (PFC). We also determined mRNA levels of Nrf2-regulated genes involved in the production and utilization of glutathione, glutamate cysteine ligase (Gclm), glutathione S-transferase (Gsta3) and glutathione reductase (Gsr). Our results showed that chronic isolation induced anxiety and depressive-like behavior, decreased Nrf2 and in parallel increased Keap1 and nuclear factor kappa B (NF?B) in the hippocampus, which were not accompanied by expression profiles of Nrf2-regulated genes. Chronically stressed rats challenged with acute stress failed to induce any response of examined genes in either of brain structures, even though Nrf2/Keap1 was altered, while in naïve animals Nrf2 activity corresponded with an expression of Nrf2-regulated genes. Our results reveal maladaptive character of chronic stress at Nrf2/Keap1 level followed by pro-inflammatory conditions, and suggest a possible role of these alterations in pathogenesis of depressive/anxiety disorders. PMID:25598205

Djordjevic, Jelena; Djordjevic, Ana; Adzic, Miroslav; Mitic, Milos; Lukic, Iva; Radojcic, Marija B

2015-03-30

221

Dopamine D2 receptor activity modulates Akt signaling and alters GABAergic neuron development and motor behavior in zebrafish larvae.  

PubMed

An imbalance in dopamine-mediated neurotransmission is a hallmark physiological feature of neuropsychiatric disorders, such as schizophrenia. Recent evidence demonstrates that dopamine D(2) receptors, which are the main target of antipsychotics, modulate the activity of the protein kinase Akt, which is known to be downregulated in the brain of patients with schizophrenia. Akt has an important role in the regulation of cellular processes that are critical for neurodevelopment, including gene transcription, cell proliferation, and neuronal migration. Thus, it is possible that during brain development, altered Akt-dependent dopamine signaling itself may lead to defects in neural circuit formation. Here, we used a zebrafish model to assess the direct impact of altered dopamine signaling on brain development and larval motor behavior. We demonstrate that D(2) receptor activation acutely suppresses Akt activity by decreasing the level of pAkt(Thr308) in the larval zebrafish brain. This D(2)-dependent reduction in Akt activity negatively regulates larval movement and is distinct from a D(1)-dependent pathway with opposing affects on motor behavior. In addition, we show that D(2)-dependent suppression of Akt activity causes a late onset change in GSK3b activity, a known downstream target of Akt signaling. Finally, altered D(2) receptor signaling, or direct inhibition of Akt activity, causes a significant decrease in the size of the GABAergic neuron population throughout most of the brain. Our observations suggest that D(2) receptor signaling suppresses Akt-GSK3b activity, which regulates GABAergic neuron development and motor behavior. PMID:21471388

Souza, Bruno Rezende; Romano-Silva, Marco Aurelio; Tropepe, Vincent

2011-04-01

222

D-Lactate altered mitochondrial energy production in rat brain and heart but not liver  

PubMed Central

Background Substantially elevated blood D-lactate (DLA) concentrations are associated with neurocardiac toxicity in humans and animals. The neurological symptoms are similar to inherited or acquired abnormalities of pyruvate metabolism. We hypothesized that DLA interferes with mitochondrial utilization of L-lactate and pyruvate in brain and heart. Methods Respiration rates in rat brain, heart and liver mitochondria were measured using DLA, LLA and pyruvate independently and in combination. Results In brain mitochondria, state 3 respiration was 53% and 75% lower with DLA as substrate when compared with LLA and pyruvate, respectively (p < 0.05). Similarly in heart mitochondria, state 3 respiration was 39% and 86% lower with DLA as substrate when compared with LLA or pyruvate, respectively (p < 0.05). However, state 3 respiration rates were similar between DLA, LLA and pyruvate in liver mitochondria. Combined incubation of DLA with LLA or pyruvate markedly impaired state 3 respiration rates in brain and heart mitochondria (p < 0.05) but not in liver mitochondria. DLA dehydrogenase activities were 61% and 51% lower in brain and heart mitochondria compared to liver, respectively, whereas LLA dehydrogenase activities were similar across all three tissues. An LDH inhibitor blocked state 3 respiration with LLA as substrate in all three tissues. A monocarboxylate transporter inhibitor blocked respiration with all three substrates. Conclusions DLA was a poor respiratory substrate in brain and heart mitochondria and inhibited LLA and pyruvate usage in these tissues. Further studies are warranted to evaluate whether these findings support, in part, the possible neurological and cardiac toxicity caused by high DLA levels. PMID:22296683

2012-01-01

223

Diffuse axonal injury in brain trauma: insights from alterations in neurofilaments  

PubMed Central

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

Siedler, Declan G.; Chuah, Meng Inn; Kirkcaldie, Matthew T. K.; Vickers, James C.; King, Anna E.

2014-01-01

224

[The information theory of brain systemic activity].  

PubMed

Information equivalents of initial requirements and their satisfaction are shown to induce formation of discrete information systemoquanta of psychic activity on morphofunctional structures of the action result acceptor in the course of build-up of cerebral archtectonics of the functional systems governing the behaviour and psychic activity. Consecutive stages of induction of information systemoquanta of action result acceptors are described. Predominant motivations are supposed to play the leading role in the psychic activity through their involvement in the induction of information systemoquanta and their retrieval from memory. The role of emotions in the subjective information estimation of systemic cerebral activity is considered. It is argued that parameters of achievement of adaptive results by a subject are imprinted on acceptor structures via reverse afferentation in the form of specific information images. Enrichment of action results acceptors with information and extraction of information systemoquanta by prevailing motivations are believed to make up the basis of consciousness and thinking. The hypothesis of holographic organization of acceptors of the results of systemic brain action is considered. PMID:22312900

Sudakov, K V

2011-01-01

225

A study on small-world brain functional networks altered by postherpetic neuralgia.  

PubMed

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. PMID:24512793

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

226

Brain fatty acid synthase activates PPAR? to maintain energy homeostasis  

PubMed Central

Central nervous system control of energy balance affects susceptibility to obesity and diabetes, but how fatty acids, malonyl-CoA, and other metabolites act at this site to alter metabolism is poorly understood. Pharmacological inhibition of fatty acid synthase (FAS), rate limiting for de novo lipogenesis, decreases appetite independently of leptin but also promotes weight loss through activities unrelated to FAS inhibition. Here we report that the conditional genetic inactivation of FAS in pancreatic ? cells and hypothalamus produced lean, hypophagic mice with increased physical activity and impaired hypothalamic PPAR? signaling. Administration of a PPAR? agonist into the hypothalamus increased PPAR? target genes and normalized food intake. Inactivation of ? cell FAS enzyme activity had no effect on islet function in culture or in vivo. These results suggest a critical role for brain FAS in the regulation of not only feeding, but also physical activity, effects that appear to be mediated through the provision of ligands generated by FAS to PPAR?. Thus, 2 diametrically opposed proteins, FAS (induced by feeding) and PPAR? (induced by starvation), unexpectedly form an integrative sensory module in the central nervous system to orchestrate energy balance. PMID:17694178

Chakravarthy, Manu V.; Zhu, Yimin; López, Miguel; Yin, Li; Wozniak, David F.; Coleman, Trey; Hu, Zhiyuan; Wolfgang, Michael; Vidal-Puig, Antonio; Lane, M. Daniel; Semenkovich, Clay F.

2007-01-01

227

Cerebral microvessel perfusion and pathologic alteration of the brain during drowsiness and coma, caused by brain tumor (A laboratory study in rats)  

PubMed Central

Background Deterioration of consciousness and coma, in cerebral compression, is traditionally thought to be caused by compression, shift, hemorrhage, or herniation of the brainstem. This study was done to evaluate the vascular perfusion and pathologic alteration in the entire brain during drowsiness and coma. Methods Brain tumors were developed in three newborn rat litters by inoculation of Kirsten Sarcoma Virus (a murine erythroblastosis virus) in the brains. Within several weeks brain tumors developed. When animals became drowsy or comatose, their brains were perfused with microbarium, India ink, or paraformaldehyde solution. In two animals, the brain vasculature was casted by plastic materials. Brains were fixed for magnification radiography, or were prepared for histological examination Results The brains of control animals showed an abundance of microvessels and penetrating capillaries, located perpendicular to the cortex and deep within the brain. The latter can not be detected even in the best routine cerebral angiography in man. Microvessels were obstructed, in a patchy and dispersed fashion, in drowsiness especially in ipsilateral hemisphere. Obstruction of microvessls was present not only in the brainstem but also was present in the rest of the brain and in cerebellum of comatose animals; larger vessels appeared markedly narrowed. The study also revealed evidence of diffuse infarcts, cellular ischemia, swelling, and periventricular damage throughout the brain. Conclusions During drowsiness and coma, caused by cerebral compression, cerebral capillaries progressively obstruct not only in the brain stem, but also throughout the brain; considerably more severe during coma than drowsiness. These likely causes diffuse neurological disabilities and behavioral changes often seen after recovery from coma caused by cerebral compression. PMID:17368521

Hekmatpanah, Javad

2007-01-01

228

Alterations in function and expression of ABC transporters at blood-brain barrier under diabetes and the clinical significances  

PubMed Central

Diabetes is a systematic metabolic disease, which often develops a number of well-recognized vascular complications including brain complications which may partly result from the dysfunction of blood-brain barrier (BBB). BBB is generally considered as a mechanism for protecting the brain from unwanted actions resulting from substances in the blood and maintaining brain homeostasis via monitoring the entry or efflux of compounds. ATP-binding cassette (ABC) family of transporters including P-glycoprotein (P-GP) and breast cancer-related protein (BCRP), widely expressed in the luminal membrane of the microvessel endothelium and in the apical membrane of the choroids plexus epithelium, play important roles in the function of BBB. However, these transporters are easily altered by some diseases. The present article was focused on the alteration in expression and function of both P-GP and BCRP at BBB by diabetes and the clinical significances. PMID:25540622

Liu, Li; Liu, Xiao-Dong

2014-01-01

229

Altering the activation mechanism in Thermomyces lanuginosus lipase.  

PubMed

It is shown by rational site-directed mutagenesis of the lid region in Thermomyces lanuginosus lipase that it is possible to generate lipase variants with attractive features, e.g., high lipase activity, fast activation at the lipid interface, ability to act on water-soluble substrates, and enhanced calcium independence. The rational design was based on the lid residue composition in Aspergillus niger ferulic acid esterase (FAEA). Five constructs included lipase variants containing the full FAEA lid, a FAEA-like lid, an intermediate lid of FAEA and TlL character, and the entire lid region from Aspergillus terreus lipase (AtL). To investigate an altered activation mechanism for each variant compared to that of TlL, a combination of activity- and spectroscopic-based measurements were applied. The engineered variant with a lid from AtL displayed interfacial activation comparable to that of TlL, whereas variants with FAEA lid character showed interfacial activation independence with pronounced activity toward pNP-acetate and pNP-butyrate below the critical micelle concentration. For variants with lipase and esterase character, lipase activity measurements further indicated a faster activation at the lipid interface. Relative to their activity toward pNP-ester substrates in calcium-rich buffer, all lid variants retained between 15 and 100% activity in buffer containing 5 mM EDTA whereas TlL activity was reduced to less than 2%, demonstrating the lid's central role in governing calcium dependency. For FAEA-like lid variants, accessible hydrophobic surface area measurements showed an approximate 10-fold increase in the level of binding of extrinsic fluorophores to the protein surface relative to that of TlL accompanied by a blue shift in emission indicative of an open lid in aqueous solution. Together, these studies report on the successful alteration of the activation mechanism in TlL by rational design creating novel lipases with new, intriguing functionalities. PMID:24870718

Skjold-Jørgensen, Jakob; Vind, Jesper; Svendsen, Allan; Bjerrum, Morten J

2014-07-01

230

Major Depressive Disorder is Associated with Altered Functional Brain Response During Anticipation and Processing of Heat Pain  

PubMed Central

Context Chronic pain and depression are highly comorbid conditions, yet little is known about the neurobiological basis of pain processing in major depressive disorder (MDD). Objective To examine the neural substrates underlying anticipation and processing of heat pain in a group of unmedicated young adults with current MDD. Design Functional magnetic resonance neuroimaging (fMRI) data were collected during an event-related factorial experimental pain paradigm. Painful and non-painful heat stimuli were applied to the left volar forearm while different color shapes explicitly signaled the intensity of the upcoming stimulus. Setting University brain imaging center. Patients 15 (12 F) young adults with current MDD and 15 (10F) healthy subjects with no history of MDD were recruited and matched for age and level of education. The Structured Clinical Interview for DSM-IV was administered to all participants by a board-certified psychiatrist. Main Outcome measure Between-group differences in blood oxygen level-dependent fMRI signal change to anticipation and processing of painful versus non-painful temperature stimuli. Results MDD compared to healthy controls showed: (1) increased activation in right anterior insular region, dorsal anterior cingulate and right amygdala during anticipation of painful relative to non-painful stimuli, (2) increased activation in right amygdala and decreased activation in periaqueductal gray, rostral anterior cingulate and prefrontal cortices during painful stimulation relative to non-painful stimulation, and (3) in MDD subjects greater activation in the right amygdala during anticipation of pain was associated with greater levels of perceived helplessness. Conclusion These findings suggest that increased emotional reactivity during the anticipation of heat pain may lead to an impaired ability to modulate pain experience in MDD. Future studies should examine the degree to which altered functional brain response during anticipatory processing affects ability to modulate negative affective states in MDD, which is a core characteristic of this disorder. PMID:18981339

Strigo, Irina A.; Simmons, Alan N.; Matthews, Scott C.; Craig, Arthur D. (Bud); Paulus, Martin P.

2009-01-01

231

Artifact suppression and analysis of brain activities with electroencephalography signals  

PubMed Central

Brain-computer interface is a communication system that connects the brain with computer (or other devices) but is not dependent on the normal output of the brain (i.e., peripheral nerve and muscle). Electro-oculogram is a dominant artifact which has a significant negative influence on further analysis of real electroencephalography data. This paper presented a data adaptive technique for artifact suppression and brain wave extraction from electroencephalography signals to detect regional brain activities. Empirical mode decomposition based adaptive thresholding approach was employed here to suppress the electro-oculogram artifact. Fractional Gaussian noise was used to determine the threshold level derived from the analysis data without any training. The purified electroencephalography signal was composed of the brain waves also called rhythmic components which represent the brain activities. The rhythmic components were extracted from each electroencephalography channel using adaptive wiener filter with the original scale. The regional brain activities were mapped on the basis of the spatial distribution of rhythmic components, and the results showed that different regions of the brain are activated in response to different stimuli. This research analyzed the activities of a single rhythmic component, alpha with respect to different motor imaginations. The experimental results showed that the proposed method is very efficient in artifact suppression and identifying individual motor imagery based on the activities of alpha component. PMID:25206446

Rashed-Al-Mahfuz, Md.; Islam, Md. Rabiul; Hirose, Keikichi; Molla, Md. Khademul Islam

2013-01-01

232

Stress-induced depression of motor activity correlates with regional changes in brain norepinephrine but not in dopamine  

Microsoft Academic Search

This experiment examined how inescapable tail shock alters the level of dopamine and norepinephrine within various brain regions of the rat and the relationship of these changes to the depression of motor activity produced by the shock. Following exposure to tail shock that is known to interfere with acquisition of active behavioral tasks, animals were briefly tested for spontaneous motor

J. M. Weiss; W. H. Bailey; L. A. Pohorecky; D. Korzeniowski; G. Grillione

1980-01-01

233

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

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. PMID:25586077

Pandey, Sumeet; Singh, Ashish; Chaudhari, Nirja; Nampoothiri, Laxmipriya P; Kumar, G Naresh

2015-05-01

234

Potential Moderators of Physical Activity on Brain Health  

PubMed Central

Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE), brain derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA), as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function. PMID:23304508

Leckie, Regina L.; Weinstein, Andrea M.; Hodzic, Jennifer C.; Erickson, Kirk I.

2012-01-01

235

Fiber Connectivity Integrated Brain Activation Detection Burak Yoldemir1  

E-print Network

of functional mag- netic resonance imaging (fMRI) data is seriously confounded by the high level of noise. Keywords: activation detection, connectivity, dMRI, fMRI, random walker 1 Introduction Functional magnetic resonance imaging (fMRI) has become the primary modality for studying human brain activity. To map brain

Pulfrey, David L.

236

Binding sites for atrial natriuretic factor (ANF) in brain: alterations in Brattleboro rats  

SciTech Connect

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.

McCarty, R.; Plunkett, L.M.

1986-12-01

237

Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state  

PubMed Central

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

Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

2015-01-01

238

Electroencephalography as a Tool for Assessment of Brain Ischemic Alterations after Open Heart Operations  

PubMed Central

Cardiac surgery is commonly associated with brain ischemia. Few studies addressed brain electric activity changes after on-pump operations. Eyes closed EEG was performed in 22 patients (mean age: 45.2 ± 11.2) before and two weeks after valve replacement. Spouses of patients were invited to participate as controls. Generalized increase of beta power most prominent in beta-1 band was an unambiguous pathological sign of postoperative cortex dysfunction, probably, manifesting due to gamma-activity slowing (“beta buzz” symptom). Generalized postoperative increase of delta-1 mean frequency along with increase of slow-wave activity in right posterior region may be hypothesized to be a consequence of intraoperative ischemia as well. At the same time, significant changes of alpha activity were observed in both patient and control groups, and, therefore, may be considered as physiological. Unexpectedly, controls showed prominent increase of electric activity in left temporal region whereas patients were deficient in left hemisphere activity in comparison with controls at postoperative followup. Further research is needed in order to determine the true neurological meaning of the EEG findings after on-pump operations. PMID:21776370

Golukhova, Elena Z.; Polunina, Anna G.; Lefterova, Natalia P.; Begachev, Alexey V.

2011-01-01

239

Alterations in fiber pathways reveal brain tumor typology: a diffusion tractography study  

PubMed Central

Conventional structural Magnetic Resonance (MR) techniques can accurately identify brain tumors but do not provide exhaustive information about the integrity of the surrounding/embedded white matter (WM). In this study, we used Diffusion-Weighted (DW) MRI tractography to explore tumor-induced alterations of WM architecture without any a priori knowledge about the fiber paths under consideration. We used deterministic multi-fiber tractography to analyze 16 cases of histologically classified brain tumors (meningioma, low-grade glioma, high-grade glioma) to evaluate the integrity of WM bundles in the tumoral region, in relation to the contralateral unaffected hemisphere. Our new tractographic approach yielded measures of WM involvement which were strongly correlated with the histopathological features of the tumor (r = 0.83, p = 0.0001). In particular, the number of affected fiber tracts were significantly (p = 0.0006) different among tumor types. Our method proposes a new application of diffusion tractography for the detection of tumor aggressiveness in those cases in which the lesion does not involve any major/known WM paths and when a priori information about the local fiber anatomy is lacking. PMID:25250209

Ius, Tamara; Skrap, Miran; Fadiga, Luciano

2014-01-01

240

Ultra performance liquid chromatography - mass spectrometry studies of formalin-induced alterations of human brain lipidome.  

PubMed

The development of 'omics' sciences offers new opportunities for the study of neurodegenerative diseases but increases at the same time the sample demand on brain banks that collect and store valuable human post-mortem tissue. Our study aims to evaluate in lipidomics the potential of formalin-fixed tissue compared with the cryopreservation method, considered as the gold standard for biochemical research. Two complementary liquid chromatography/mass spectrometry analytical platforms were used on the basis of hybrid quadrupole time-of-flight and triple quadrupole mass spectrometers. Untargeted fingerprinting, semitargeted profiling of specific lipid classes and targeted monitoring of lipid species were performed in formalin-fixed and cryopreserved samples to provide detailed information at the molecular level on the formalin-induced alterations of the brain tissue. In vitro incubations of lipid standards were also performed to further describe the degradation processes induced by formaldehyde. Phospholipid compounds were found to be extensively hydrolysed, whilst the sphingolipid ones were preserved. N-methylation and N-formylation of amine-containing phospholipids have also been evidenced. These findings show that the potential detrimental effect of formalin on the analytes of interest must be taken into account when analysing formalin-fixed samples. PMID:25303393

Gaudin, Mathieu; Panchal, Maï; Ayciriex, Sophie; Werner, Erwan; Brunelle, Alain; Touboul, David; Boursier-Neyret, Claire; Auzeil, Nicolas; Walther, Bernard; Duyckaerts, Charles; Laprévote, Olivier

2014-10-01

241

Mouse Brain PSA-NCAM Levels Are Altered by Graded-Controlled Cortical Impact Injury  

PubMed Central

Traumatic brain injury (TBI) is a worldwide endemic that results in unacceptably high morbidity and mortality. Secondary injury processes following primary injury are composed of intricate interactions between assorted molecules that ultimately dictate the degree of longer-term neurological deficits. One comparatively unexplored molecule that may contribute to exacerbation of injury or enhancement of recovery is the posttranslationally modified polysialic acid form of neural cell adhesion molecule, PSA-NCAM. This molecule is a critical modulator of central nervous system plasticity and reorganization after injury. In this study, we used controlled cortical impact (CCI) to produce moderate or severe TBI in the mouse. Immunoblotting and immunohistochemical analysis were used to track the early (2, 24, and 48 hour) and late (1 and 3 week) time course and location of changes in the levels of PSA-NCAM after TBI. Variable and heterogeneous short- and long-term increases or decreases in expression were found. In general, alterations in PSA-NCAM levels were seen in the cerebral cortex immediately after injury, and these reductions persisted in brain regions distal to the primary injury site, especially after severe injury. This information provides a starting point to dissect the role of PSA-NCAM in TBI-related pathology and recovery. PMID:22848850

Budinich, Craig S.; Chen, HuaZhen; Lowe, Dennell; Rosenberger, John G.; Bernstock, Joshua D.; McCabe, Joseph T.

2012-01-01

242

Brain activation associated with active and passive lower limb stepping  

PubMed Central

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

Jaeger, Lukas; Marchal-Crespo, Laura; Wolf, Peter; Riener, Robert; Michels, Lars; Kollias, Spyros

2014-01-01

243

Brain activation associated with active and passive lower limb stepping.  

PubMed

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

Jaeger, Lukas; Marchal-Crespo, Laura; Wolf, Peter; Riener, Robert; Michels, Lars; Kollias, Spyros

2014-01-01

244

Hyperdopaminergia and altered locomotor activity in GABAB1-deficient mice.  

PubMed

GABAB1-/- mice, which are devoid of functional GABAB receptors, consistently exhibit marked hyperlocomotion when exposed to a novel environment. Telemetry recordings now revealed that, in a familiar environment, GABAB1-/- mice display an altered pattern of circadian activity but no hyperlocomotion. This indicates that hyperlocomotion is only triggered when GABAB1-/- mice are aroused by novelty. In microdialysis experiments, GABAB1-/- mice exhibited a 2-fold increased extracellular level of dopamine in the striatum. Following D-amphetamine administration, GABAB1-/- mice released less dopamine than wild-type mice, indicative of a reduced cytoplasmic dopamine pool. The hyperdopaminergic state of GABAB1-/- mice is accompanied by molecular changes, including reduced levels of tyrosine hydroxylase mRNA, D1 receptor binding-sites and Ser40 phosphorylation of tyrosine hydroxylase. Tyrosine hydroxylase activity, tissue dopamine content and dopamine metabolism do not appear to be measurably altered. Pharmacological and electrophysiological experiments support that the hyperdopaminergic state of GABAB1-/- mice is not severe enough to inactivate dopamine D2 receptors and to disrupt D2-mediated feedback inhibition of tyrosine hydroxylase activity. The data support that loss of GABAB activity results in a sustained moderate hyperdopaminergic state, which is phenotypically revealed by contextual hyperlocomotor activity. Importantly, the presence of an inhibitory GABA tone on the dopaminergic system mediated by GABAB receptors provides an opportunity for therapeutic intervention. PMID:16606363

Vacher, Claire-Marie; Gassmann, Martin; Desrayaud, Sandrine; Challet, Etienne; Bradaia, Amyaouch; Hoyer, Daniel; Waldmeier, Peter; Kaupmann, Klemens; Pévet, Paul; Bettler, Bernhard

2006-05-01

245

Inhibition of Acetylcholinesterase Modulates NMDA Receptor Antagonist Mediated Alterations in the Developing Brain  

PubMed Central

Exposure to N-methyl-d-aspartate (NMDA) receptor antagonists has been demonstrated to induce neurodegeneration in newborn rats. However, in clinical practice the use of NMDA receptor antagonists as anesthetics and sedatives cannot always be avoided. The present study investigated the effect of the indirect cholinergic agonist physostigmine on neurotrophin expression and the extracellular matrix during NMDA receptor antagonist induced injury to the immature rat brain. The aim was to investigate matrix metalloproteinase (MMP)-2 activity, as well as expression of tissue inhibitor of metalloproteinase (TIMP)-2 and brain-derived neurotrophic factor (BDNF) after co-administration of the non-competitive NMDA receptor antagonist MK801 (dizocilpine) and the acetylcholinesterase (AChE) inhibitor physostigmine. The AChE inhibitor physostigmine ameliorated the MK801-induced reduction of BDNF mRNA and protein levels, reduced MK801-triggered MMP-2 activity and prevented decreased TIMP-2 mRNA expression. Our results indicate that AChE inhibition may prevent newborn rats from MK801-mediated brain damage by enhancing neurotrophin-associated signaling pathways and by modulating the extracellular matrix. PMID:24595240

Bendix, Ivo; Serdar, Meray; Herz, Josephine; von Haefen, Clarissa; Nasser, Fatme; Rohrer, Benjamin; Endesfelder, Stefanie; Felderhoff-Mueser, Ursula; Spies, Claudia D.; Sifringer, Marco

2014-01-01

246

Inhibition of acetylcholinesterase modulates NMDA receptor antagonist mediated alterations in the developing brain.  

PubMed

Exposure to N-methyl-d-aspartate (NMDA) receptor antagonists has been demonstrated to induce neurodegeneration in newborn rats. However, in clinical practice the use of NMDA receptor antagonists as anesthetics and sedatives cannot always be avoided. The present study investigated the effect of the indirect cholinergic agonist physostigmine on neurotrophin expression and the extracellular matrix during NMDA receptor antagonist induced injury to the immature rat brain. The aim was to investigate matrix metalloproteinase (MMP)-2 activity, as well as expression of tissue inhibitor of metalloproteinase (TIMP)-2 and brain-derived neurotrophic factor (BDNF) after co-administration of the non-competitive NMDA receptor antagonist MK801 (dizocilpine) and the acetylcholinesterase (AChE) inhibitor physostigmine. The AChE inhibitor physostigmine ameliorated the MK801-induced reduction of BDNF mRNA and protein levels, reduced MK801-triggered MMP-2 activity and prevented decreased TIMP-2 mRNA expression. Our results indicate that AChE inhibition may prevent newborn rats from MK801-mediated brain damage by enhancing neurotrophin-associated signaling pathways and by modulating the extracellular matrix. PMID:24595240

Bendix, Ivo; Serdar, Meray; Herz, Josephine; von Haefen, Clarissa; Nasser, Fatme; Rohrer, Benjamin; Endesfelder, Stefanie; Felderhoff-Mueser, Ursula; Spies, Claudia D; Sifringer, Marco

2014-01-01

247

Extracellular ?-synuclein alters synaptic transmission in brain neurons by perforating the neuronal plasma membrane.  

PubMed

It has been postulated that the accumulation of extracellular ?-synuclein (?-syn) might alter the neuronal membrane by formation of 'pore-like structures' that will lead to alterations in ionic homeostasis. However, this has never been demonstrated to occur in brain neuronal plasma membranes. In this study, we show that ?-syn oligomers rapidly associate with hippocampal membranes in a punctate fashion, resulting in increased membrane conductance (5 fold over control) and the influx of both calcium and a fluorescent glucose analogue. The enhancement in intracellular calcium (1.7 fold over control) caused a large increase in the frequency of synaptic transmission (2.5 fold over control), calcium transients (3 fold over control), and synaptic vesicle release. Both primary hippocampal and dissociated nigral neurons showed rapid increases in membrane conductance by ?-syn oligomers. In addition, we show here that ?-syn caused synaptotoxic failure associated with a decrease in SV2, a membrane protein of synaptic vesicles associated with neurotransmitter release. In conclusion, extracellular ?-syn oligomers facilitate the perforation of the neuronal plasma membrane, thus explaining, in part, the synaptotoxicity observed in neurodegenerative diseases characterized by its extracellular accumulation. We propose that ?-synuclein (?-syn) oligomers form pore-like structures in the plasma membrane of neurons from central nervous system (CNS). We believe that extracellular ?-syn oligomers facilitate the formation of ?-syn membrane pore-like structures, thus explaining, in part, the synaptotoxicity observed in neurodegenerative diseases characterized by its extracellular accumulation. We think that alterations in ionic homeostasis and synaptic vesicular depletion are key steps that lead to synaptotoxicity promoted by ? -syn membrane pore-like structures. PMID:25669123

Pacheco, Carla R; Morales, Camila N; Ramírez, Alejandra E; Muñoz, Francisco J; Gallegos, Scarlet S; Caviedes, Pablo A; Aguayo, Luis G; Opazo, Carlos M

2015-03-01

248

Differences in Functional Brain Connectivity Alterations Associated with Cerebral Amyloid Deposition in Amnestic Mild Cognitive Impairment  

PubMed Central

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 (A?) deposition (i.e., aMCI+) and aMCI with no or very little A? 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 precuneus. The results indicate that despite the similarity in cross-sectional cognitive features, aMCI? has quite different functional brain connectivity compared to aMCI+. PMID:25745400

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

249

Stimulant and depressant effects of cigarette smoking on brain activity in man  

PubMed Central

Cigarette smoking was found to alter the E.E.G. negativity associated with attention: the 'contingent negative variation' was increased in some smokers and decreased in others. This finding is consistent with the known dual action of nicotine to stimulate or depress neural activity and suggests a means of investigating the effects of other centrally-acting drugs on the human brain. PMID:4788213

Ashton, Heather; Millman, J. E.; Telford, Rosemary; Thompson, J. W.

1973-01-01

250

ASSESSMENT OF CHEMICALLY-INDUCED ALTERATIONS IN BRAIN DEVELOPMENT USING ASSAYS OF NEURON- AND GLIA-LOCALIZED PROTEINS  

EPA Science Inventory

Chemical intervention during prenatal or postnatal ontogeny can result in complex biochemical, morphological and behavioral alterations in brain development (Suzuki, 1980; Miller and O'Callaghan, 1984; Rodier, 1986; Ruppert, 1986). s has been shown at this conference (e.g. by Ham...

251

Alpha- and gamma- tocopherol prevent age-related transcriptional alterations in the heart and brain of mice  

Technology Transfer Automated Retrieval System (TEKTRAN)

To investigate the global effects of vitamin E supplementation on aging, we used high density oligonucleotide arrays to measure transcriptional alterations in the heart and brain (neocortex) of 30-month-old B6C3F1 mice supplemented with alpha- and gamma-tocopherol since middle age (15 months). Gene ...

252

Trypanosoma evansi: adenosine deaminase activity in the brain of infected rats.  

PubMed

The study was undertaken to evaluate changes in the activity of adenosine deaminase (ADA) in brains of rats infected by Trypanosoma evansi. Each rat was intraperitoneally infected with 10(6) trypomastigotes either suspended in fresh (group A; n = 13) and cryopreserved blood (group B; n = 13). Thirteen animals were used as control (group C). ADA activity was estimated in the cerebellum, cerebral cortex, striatum and hippocampus. No differences (P > 0.05) in ADA activity were observed in the cerebellum between infected and non-infected animals. Significant (P < 0.05) reductions in ADA activity occurred in cerebral cortex in acutely (day 4 post-infection; PI) and chronically (day 20 PI) infected rats. ADA activity was significantly (P < 0.05) decreased in the hippocampus in acutely infected rats, but significantly (P < 0.05) increased in the chronically infected rats. Significant (P < 0.05) reductions in ADA activity occurred in the striatum of chronically infected rats. Parasites could be found in peripheral blood and brain tissue through microscopic examination and PCR assay, respectively, in acutely and chronically infected rats. The reduction of ADA activity in the brain was associated with high levels of parasitemia and anemia in acute infections. Alterations in ADA activity of the brain in T. evansi-infected rats may have implications for pathogenesis of the disease. PMID:20655914

Da Silva, Aleksandro S; Bellé, Luziane P; Bitencourt, Paula E R; Perez, Herakles A Garcia; Thomé, Gustavo R; Costa, Marcio M; Oliveira, Camila B; Teixeira, Marta M G; Moretto, Maria B; Mazzanti, Cinthia M; Lopes, Sonia T A; Monteiro, Silvia G

2011-01-01

253

Is meditation associated with altered brain structure? A systematic review and meta-analysis of morphometric neuroimaging in meditation practitioners.  

PubMed

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. PMID:24705269

Fox, Kieran C R; Nijeboer, Savannah; Dixon, Matthew L; Floman, James L; Ellamil, Melissa; Rumak, Samuel P; Sedlmeier, Peter; Christoff, Kalina

2014-06-01

254

Alterations in Prefrontal-Limbic Functional Activation and Connectivity in Chronic Stress-Induced Visceral Hyperalgesia  

PubMed Central

Repeated water avoidance stress (WAS) induces sustained visceral hyperalgesia (VH) in rats measured as enhanced visceromotor response to colorectal distension (CRD). This model incorporates two characteristic features of human irritable bowel syndrome (IBS), VH and a prominent role of stress in the onset and exacerbation of IBS symptoms. Little is known regarding central mechanisms underlying the stress-induced VH. Here, we applied an autoradiographic perfusion method to map regional and network-level neural correlates of VH. Adult male rats were exposed to WAS or sham treatment for 1 hour/day for 10 days. The visceromotor response was measured before and after the treatment. Cerebral blood flow (CBF) mapping was performed by intravenous injection of radiotracer ([14C]-iodoantipyrine) while the rat was receiving a 60-mmHg CRD or no distension. Regional CBF-related tissue radioactivity was quantified in autoradiographic images of brain slices and analyzed in 3-dimensionally reconstructed brains with statistical parametric mapping. Compared to sham rats, stressed rats showed VH in association with greater CRD-evoked activation in the insular cortex, amygdala, and hypothalamus, but reduced activation in the prelimbic area (PrL) of prefrontal cortex. We constrained results of seed correlation analysis by known structural connectivity of the PrL to generate structurally linked functional connectivity (SLFC) of the PrL. Dramatic differences in the SLFC of PrL were noted between stressed and sham rats under distension. In particular, sham rats showed negative correlation between the PrL and amygdala, which was absent in stressed rats. The altered pattern of functional brain activation is in general agreement with that observed in IBS patients in human brain imaging studies, providing further support for the face and construct validity of the WAS model for IBS. The absence of prefrontal cortex-amygdala anticorrelation in stressed rats is consistent with the notion that impaired corticolimbic modulation acts as a central mechanism underlying stress-induced VH. PMID:23527114

Wang, Zhuo; Ocampo, Marco A.; Pang, Raina D.; Bota, Mihail; Bradesi, Sylvie; Mayer, Emeran A.; Holschneider, Daniel P.

2013-01-01

255

Activating memories of depression alters the experience of voluntary action.  

PubMed

The sense of agency is a profoundly important human experience and is strongly linked to volitional action. The importance of this experience is underscored by the fact that many neurological and psychiatric disorders are partially characterized by an abnormal sense of agency (e.g., schizophrenia, anxiety disorders, depression). Healthy participants perceive the temporal interval between a voluntary action and its effect to be shorter than it actually is, and this illusion has been suggested as an implicit index of agency. Here, we investigated whether activating memories of depression alters perception of this action-effect interval, compared to activating memories of the previous day, or a baseline condition in which specific memories were not activated. Results showed that action-effect interval estimates were significantly longer after remembering a depressing episode than after remembering the previous day, or in the baseline condition. Thus, activating memories of depression alters the experience of voluntary actions and effects. We suggest that interval estimation measures could be useful in clinical settings, to implicitly assess the sense of agency in patients with disorders affecting their sense of control. In this way, obtaining action-effect interval estimates, pre-, during, and post-treatment, could aid in tracking treatment-induced changes in the sense of agency. PMID:23247470

Obhi, Sukhvinder S; Swiderski, Kristina M; Farquhar, Riley

2013-09-01

256

Altered brain function underlying verbal memory encoding and retrieval in psychotic major depression  

PubMed Central

Psychotic major depression (PMD) is associated with deficits in verbal memory as well as other cognitive impairments. This study investigated brain function in individuals with PMD during a verbal declarative memory task. Participants included 16 subjects with PMD, 15 subjects with non-psychotic major depression (NPMD) and 16 healthy controls (HC). Functional magnetic resonance imaging (fMRI) data were acquired while subjects performed verbal memory encoding and retrieval tasks. During the explicit encoding task, subjects semantically categorized words as either “man-made” or “not manmade.” For the retrieval task, subjects identified whether words had been presented during the encoding task. Functional MRI data were processed using SPM5 and a group by condition ANOVA. Clusters of activation showing either a significant main effect of group or an interaction of group by condition were further examined using t-tests to identify group differences. During the encoding task, the PMD group showed lower hippocampus, insula, and prefrontal activation compared to HC. During the retrieval task, the PMD group showed lower recognition accuracy and higher prefrontal and parietal cortex activation compared to both HC and NPMD groups. Verbal retrieval deficits in PMD may be associated with deficient hippocampus function during encoding. Increased brain activation during retrieval may reflect an attempt to compensate for encoding deficits. PMID:23149036

Kelley, Ryan; Garrett, Amy; Cohen, Jeremy; Gomez, Rowena; Lembke, Anna; Keller, Jennifer; Reiss, Allan L.; Schatzberg, Alan

2013-01-01

257

Spontaneous and task-evoked brain activity negatively interact  

PubMed Central

A widely held assumption is that spontaneous and task-evoked brain activity sum linearly, such that the recorded brain response in each single trial is the algebraic sum of the constantly changing ongoing activity and the stereotypical evoked activity. Using functional magnetic resonance imaging (fMRI) signals acquired from normal humans, we show that this assumption is invalid. Across widespread cortices, evoked activity interacts negatively with ongoing activity, such that higher prestimulus baseline results in less activation or more deactivation. As a consequence of this negative interaction, trial-to-trial variability of cortical activity decreases following stimulus onset. We further show that variability reduction follows overlapping but distinct spatial pattern from that of task activation/deactivation and it contains behaviorally relevant information. These results favor an alternative perspective to the traditional dichotomous framework of ongoing and evoked activity – one that views the brain as a nonlinear dynamical system whose trajectory is tighter when performing a task; further, incoming sensory stimuli modulate the brain’s activity in a manner that depends on its initial state. We propose that across-trial variability may provide a new approach to brain mapping in the context of cognitive experiments. PMID:23486941

He, Biyu J.

2013-01-01

258

Optical imaging of neural and hemodynamic brain activity  

NASA Astrophysics Data System (ADS)

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 sleep disturbances could push the vasculature to critical limits, leading to metabolic deficit and the potential for tissue trauma.

Schei, Jennifer Lynn

259

Effects of brief starvation on brain protease activity  

Microsoft Academic Search

Changes in the activity of proteases (cathepsin D and calpains) caused by 48-h food withdrawal were studied in the brain, liver, kidney, spleen, and heart of 3-, 12-, and 24-month-old Fischer rats. Cathepsin D activity was similar in brain, liver, and heart of control animals; in kidney it was 5-fold higher and in spleen about 10-fold higher. With age, activity

Agnes Kenessey; Miriam Banay-Schwartz; Teresita De Guzman; Abel Lajtha

1991-01-01

260

Exposure to vehicle emissions results in altered blood brain barrier permeability and expression of matrix metalloproteinases and tight junction proteins in mice  

PubMed Central

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 ?g/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)-1? 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

2013-01-01

261

Acute focal brain damage alters mitochondrial dynamics and autophagy in axotomized neurons  

PubMed Central

Mitochondria are key organelles for the maintenance of life and death of the cell, and their morphology is controlled by continual and balanced fission and fusion dynamics. A balance between these events is mandatory for normal mitochondrial and neuronal function, and emerging evidence indicates that mitochondria undergo extensive fission at an early stage during programmed cell death in several neurodegenerative diseases. A pathway for selective degradation of damaged mitochondria by autophagy, known as mitophagy, has been described, and is of particular importance to sustain neuronal viability. In the present work, we analyzed the effect of autophagy stimulation on mitochondrial function and dynamics in a model of remote degeneration after focal cerebellar lesion. We provided evidence that lesion of a cerebellar hemisphere causes mitochondria depolarization in axotomized precerebellar neurons associated with PTEN-induced putative kinase 1 accumulation and Parkin translocation to mitochondria, block of mitochondrial fusion by Mfn1 degradation, increase of calcineurin activity and dynamin-related protein 1 translocation to mitochondria, and consequent mitochondrial fission. Here we suggest that the observed neuroprotective effect of rapamycin is the result of a dual role: (1) stimulation of autophagy leading to damaged mitochondria removal and (2) enhancement of mitochondria fission to allow their elimination by mitophagy. The involvement of mitochondrial dynamics and mitophagy in brain injury, especially in the context of remote degeneration after acute focal brain damage, has not yet been investigated, and these findings may offer new target for therapeutic intervention to improve functional outcomes following acute brain damage. PMID:25429622

Cavallucci, V; Bisicchia, E; Cencioni, M T; Ferri, A; Latini, L; Nobili, A; Biamonte, F; Nazio, F; Fanelli, F; Moreno, S; Molinari, M; Viscomi, M T; D'Amelio, M

2014-01-01

262

Research Report Distinct resting-state brain activities in  

E-print Network

Research Report Distinct resting-state brain activities in heroin-dependent individuals Yi Zhanga online 30 May 2011 Previous functional imaging studies on heroin addicts have focused on abnormal brain of heroin-dependent individuals. In the current study, we applied the pattern classification technique

Tian, Jie

263

Nanotools for Neuroscience and Brain Activity Mapping  

E-print Network

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 ...

Alivisatos, A. Paul

264

Epigenetic Alterations in the Brain Associated with HIV-1 Infection and Methamphetamine Dependence  

PubMed Central

HIV involvement of the CNS continues to be a significant problem despite successful use of combination antiretroviral therapy (cART). Drugs of abuse can act in concert with HIV proteins to damage glia and neurons, worsening the neurotoxicity caused by HIV alone. Methamphetamine (METH) is a highly addictive psychostimulant drug, abuse of which has reached epidemic proportions and is associated with high-risk sexual behavior, increased HIV transmission, and development of drug resistance. HIV infection and METH dependence can have synergistic pathological effects, with preferential involvement of frontostriatal circuits. At the molecular level, epigenetic alterations have been reported for both HIV-1 infection and drug abuse, but the neuropathological pathways triggered by their combined effects are less known. We investigated epigenetic changes in the brain associated with HIV and METH. We analyzed postmortem frontal cortex tissue from 27 HIV seropositive individuals, 13 of which had a history of METH dependence, in comparison to 14 cases who never used METH. We detected changes in the expression of DNMT1, at mRNA and protein levels, that resulted in the increase of global DNA methylation. Genome-wide profiling of DNA methylation in a subset of cases, showed differential methylation on genes related to neurodegeneration; dopamine metabolism and transport; and oxidative phosphorylation. We provide evidence for the synergy of HIV and METH dependence on the patterns of DNA methylation on the host brain, which results in a distinctive landscape for the comorbid condition. Importantly, we identified new epigenetic targets that might aid in understanding the aggravated neurodegenerative, cognitive, motor and behavioral symptoms observed in persons living with HIV and addictions. PMID:25054922

Desplats, Paula; Dumaop, Wilmar; Cronin, Peter; Gianella, Sara; Woods, Steven; Letendre, Scott; Smith, David; Masliah, Eliezer; Grant, Igor

2014-01-01

265

Methylmercury induced alterations in the nerve growth factor level in the developing brain.  

PubMed

Pre- and early postnatal stages in the development of the central nervous system (CNS) are very sensitive to the toxic effects of methylmercury. The influence of methylmercury on the level of nerve growth factor (NGF) during the development of CNS was studied. Sprague-Dawley rats were exposed indirectly throughout the fetal and suckling periods until weaning on postnatal day 25 (P 25) via their dams given methylmercury in the diet (3.9 mg/kg diet). In addition, after weaning offsprings were exposed directly to methylmercury via the diet until postnatal day 50 (P 50). The level of NGF was analyzed in cortical areas and in the septum with a sensitive enzyme immunoassay. The pups exposed to MeHg exhibited a 50% elevation in the level of NGF in the hippocampus on P 25 and P 50 compared to control animals. Concomitantly, the level of NGF decreased by 30% in the septum on P 25 and P 50, suggesting that the retrograde transport of NGF from hippocampus to septum could be affected by the exposure of methylmercury. The exact mechanism by which the low level of mercury is affecting the NGF concentration in the developing brain is yet unknown. The increase of NGF in the hippocampus and the decrease of NGF measured in the septum could reflect altered conditions for neurotrophic support in these areas of the brain as a result of the exposure to heavy metal. Thus, this finding might indicate a connection between exposure of heavy metals and neurodegeneration, such as that found in the basal forebrain in Alzheimer's disease. PMID:1769107

Lärkfors, L; Oskarsson, A; Sundberg, J; Ebendal, T

1991-10-21

266

Regional Brain Activation in Response to Rectal Distension in Patients with Irritable Bowel Syndrome and the Effect of a History of Abuse  

Microsoft Academic Search

Previous studies have demonstrated alterations in brain response to rectal distension in patients with irritable bowel syndrome (IBS) compared to controls. Our aim was to compare regional brain activity in response to rectal balloon distension in patients with IBS and healthy controls. We studied six patients with IBS and six healthy controls. Positron emission tomography scans were obtained during rectal

Yehuda Ringel; Douglas A. Drossman; Timothy G. Turkington; Barbara Bradshaw; Thomas C. Hawk; Shrikant Bangdiwala; R. Edward Coleman; William E. Whitehead

2003-01-01

267

[The action of a magnetic field on the bioelectrical activity of the brain in healthy subjects and epilepsy patients].  

PubMed

The influence of reduced geomagnetic field as well as alternative magnetic field action on the brain bioelectric activity was analysed in 18 healthy individuals and in 20 epileptic patients. The alteration of magnetic field elevated functional activity of the brain synchronizing structures and increased either epileptic activity or activation of epileptic focus. The data allow to conclude that the magnetic field effects are mediated by the deep sensory nerve-pathways. The role of the right hemisphere in magnetic field perception and participation of back temporal areas in these processes are considered. PMID:8754342

Karlov, V A; Selitski?, G V; Sorokina, N D

1996-01-01

268

Expression of astrocytic markers aquaporin 4 and connexin 43 is altered in brains of subjects with autism  

PubMed Central

Neuroanatomical studies have revealed extensive structural brain abnormalities in subjects with autism. Recently, studies have provided evidence of neuroglial responses and neuroinflammation in autism. The current study investigated whether two astrocytic markers: aquaporin 4 and connexin 43 are altered in brains from subjects with autism. Postmortem brain tissues from Brodmann's Area 40 (BA40, parietal cortex), Brodmann's Area 9 (BA9, superior frontal cortex), and cerebella of subjects with autism and matched controls were subject to SDS-PAGE and western blotting. Connexin 43 expression was increased significantly in BA9. Aquaporin 4 expression was decreased significantly in cerebellum. These data suggest that changes are apparent in markers for abnormal glial-neuronal communication (connexin 43 and aquaporin 4) in brains of subjects with autism. PMID:18435417

Fatemi, S. Hossein; Folsom, Timothy D.; Reutiman, Teri J.; Lee, Susanne

2009-01-01

269

Effects of a carbohydrate supplement upon resting brain activity.  

PubMed

Glucose is a major energy source for the brain, and along with several monosaccharide derivatives as components of brain gangliosides, they play important roles in neurologic function. However, there is little information available on the role of glucose and other monosaccharides on resting brain activity. This study was designed to evaluate the effects of a single dose of a carbohydrate supplement containing glucose and several of its derivatives on resting brain activity in 20 healthy male college students. The supplement provided an insignificant amount of carbohydrate (3.9 g), protein (0.28 g), fat (0 g), and calories (14 kcal). The amount of glucose in the supplement was 0.5 g (1% the amount of glucose used in adult studies of cognitive functioning and memory). We hypothesized that the glyconutrient supplement would enhance brain activity associated with alertness and attention. The study design was double blind, with subjects randomly assigned to one of two orders, either carbohydrate supplement week one followed by placebo a week later, or the opposite. Electrical brain activity was monitored by 15 electrodes positioned at nine standard international 10-20 system locations, including three bilateral pairs at frontal, parietal, and occipital sites. Thirty minutes following ingestion of a placebo or carbohydrate supplement drink, EEG activity was recorded for 10-mins while subjects focused on a stationary visual target. Spectral power of resting brain activity was computed and analyzed contrasting the placebo and supplement groups. Relative to placebo, the carbohydrate supplement significantly enhanced power in three brain wave frequencies (theta, alpha, and beta) that are known to be associated with attention and arousal. Since changes were observed in the supplement but not placebo group, our study suggests that additional sugars in the glyconutritional supplement facilitate enhancement of brain electrical activity. Whether the apparent enhancement of arousal in baseline recordings is associated with improved task performance remains to be determined. PMID:15759600

Wang, Chenghua; Szabo, Joanne S; Dykman, Roscoe A

2004-01-01

270

Spatial heterogeneity analysis of brain activation in fMRI.  

PubMed

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

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

271

Aberrant brain activation of error processing among adults with attention deficit and hyperactivity disorder.  

PubMed

Individuals with adult attention deficit/hyperactivity disorder (ADHD) have a deficit in their cognitive control. The aim of this study was to reveal the brain correlates of the deficits in response inhibition or error processing in adult ADHD. A total of 29 adults with ADHD and 25 control individuals were recruited. They completed an event-related-design Go/No-go task under functional magnetic resonance imaging scanning. Both the ADHD group and the control group exhibited activation of the frontostriatal network when processing response inhibition. They also exhibited activation of the frontoinsula cortex and anterior cingulate in error processing. Adults with ADHD have a lower brain activation of error processing over the right inferior frontal lobe adjacent to the insula than control individuals. The altered frontoinsula cortex activation may represent the mechanism of error processing deficit among adults with ADHD. PMID:25835273

Chen, Chiao-Yun; Yen, Ju-Yu; Yen, Cheng-Fang; Chen, Cheng-Sheng; Liu, Gin-Chung; Liang, Chih-Yuan; Ko, Chih-Hung

2015-04-01

272

The Bile Acid-Sensitive Ion Channel (BASIC) Is Activated by Alterations of Its Membrane Environment  

PubMed Central

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. PMID:25360526

Schmidt, Axel; Lenzig, Pia; Oslender-Bujotzek, Adrienne; Kusch, Jana; Dias Lucas, Susana; Gründer, Stefan; Wiemuth, Dominik

2014-01-01

273

Brain region-specific altered expression and association of mitochondria-related genes in autism  

PubMed Central

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 DNAJC19, DNM1L, LRPPRC, SLC25A12, SLC25A14, SLC25A24 and TOMM20 were reduced in at least two of the brain regions of autism patients. Conclusions Our study, though preliminary, brings to light some new genes associated with MtD in autism. If MtD is detected in early stages, treatment strategies aimed at reducing its impact may be adopted. PMID:23116158

2012-01-01

274

Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.  

PubMed

The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. PMID:25155242

Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

2014-11-01

275

Systems/Circuits The Autonomic Brain: An Activation Likelihood Estimation  

E-print Network

Systems/Circuits The Autonomic Brain: An Activation Likelihood Estimation Meta-Analysis for Central, Massachusetts General Hospital, Charlestown, Massachusetts 02129 The autonomic nervous system (ANS) is of paramount importance for daily life. Its regulatory action on respiratory, cardiovascular, digestive

Napadow, Vitaly

276

Alcohol Intoxication Effects on Simulated Driving: Exploring Alcohol-Dose Effects on Brain Activation Using Functional MRI  

Microsoft Academic Search

Driving while intoxicated is a major public health problem. We investigated impaired driving using a simulated driving skill game that presents an ‘in-car’ view of a road and a readout of speed. We explored brain activation and behavioral alterations from baseline at two blood alcohol concentrations (BACs). Participants received single-blind individualized doses of beverage alcohol designed to produce blood alcohol

Vince D Calhoun; James J Pekar; Godfrey D Pearlson

2004-01-01

277

Human brain activity with near-infrared spectroscopy  

Microsoft Academic Search

Human brain activity was studied with a real time functional Near-InfraRed Imager (fNIRI). The imager has 16 measurement channels and covers 4 cm by 9 cm detection area. Brain activities in occipital, motor and prefrontal area were studied with the fNIRI. In prefrontal stimulation, language cognition, analogies, forming memory for new associations, emotional thinking, and mental arithmetic were carried out.

Qingming Luo; Britton Chance

1999-01-01

278

Hydrogen Peroxide Stimulates Activity and Alters Behavior in Drosophila melanogaster  

PubMed Central

Circadian rhythms in animals are regulated at the level of individual cells and by systemic signaling to coordinate the activities of multiple tissues. The circadian pacemakers have several physiological outputs, including daily locomotor rhythms. Several redox-active compounds have been found to function in regulation of circadian rhythms in cells, however, how particular compounds might be involved in regulating specific animal behaviors remains largely unknown. Here the effects of hydrogen peroxide on Drosophila movement were analyzed using a recently developed three-dimensional real-time multiple fly tracking assay. Both hydrogen peroxide feeding and direct injection of hydrogen peroxide caused increased adult fly locomotor activity. Continuous treatment with hydrogen peroxide also suppressed daily locomotor rhythms. Conditional over-expression of the hydrogen peroxide-producing enzyme superoxide dismutase (SOD) also increased fly activity and altered the patterns of locomotor activity across days and weeks. The real-time fly tracking system allowed for detailed analysis of the effects of these manipulations on behavior. For example, both hydrogen peroxide feeding and SOD over-expression increased all fly motion parameters, however, hydrogen peroxide feeding caused relatively more erratic movement, whereas SOD over-expression produced relatively faster-moving flies. Taken together, the data demonstrate that hydrogen peroxide has dramatic effects on fly movement and daily locomotor rhythms, and implicate hydrogen peroxide in the normal control of these processes. PMID:19862323

Grover, Dhruv; Ford, Daniel; Brown, Christopher; Hoe, Nicholas; Erdem, Aysen; Tavaré, Simon; Tower, John

2009-01-01

279

A Selective HDAC 1/2 Inhibitor Modulates Chromatin and Gene Expression in Brain and Alters Mouse Behavior in Two Mood-Related Tests  

PubMed Central

Psychiatric diseases, including schizophrenia, bipolar disorder and major depression, are projected to lead global disease burden within the next decade. Pharmacotherapy, the primary – albeit often ineffective – treatment method, has remained largely unchanged over the past 50 years, highlighting the need for novel target discovery and improved mechanism-based treatments. Here, we examined in wild type mice the impact of chronic, systemic treatment with Compound 60 (Cpd-60), a slow-binding, benzamide-based inhibitor of the class I histone deacetylase (HDAC) family members, HDAC1 and HDAC2, in mood-related behavioral assays responsive to clinically effective drugs. Cpd-60 treatment for one week was associated with attenuated locomotor activity following acute amphetamine challenge. Further, treated mice demonstrated decreased immobility in the forced swim test. These changes are consistent with established effects of clinical mood stabilizers and antidepressants, respectively. Whole-genome expression profiling of specific brain regions (prefrontal cortex, nucleus accumbens, hippocampus) from mice treated with Cpd-60 identified gene expression changes, including a small subset of transcripts that significantly overlapped those previously reported in lithium-treated mice. HDAC inhibition in brain was confirmed by increased histone acetylation both globally and, using chromatin immunoprecipitation, at the promoter regions of upregulated transcripts, a finding consistent with in vivo engagement of HDAC targets. In contrast, treatment with suberoylanilide hydroxamic acid (SAHA), a non-selective fast-binding, hydroxamic acid HDAC 1/2/3/6 inhibitor, was sufficient to increase histone acetylation in brain, but did not alter mood-related behaviors and had dissimilar transcriptional regulatory effects compared to Cpd-60. These results provide evidence that selective inhibition of HDAC1 and HDAC2 in brain may provide an epigenetic-based target for developing improved treatments for mood disorders and other brain disorders with altered chromatin-mediated neuroplasticity. PMID:23967191

Schroeder, Frederick A.; Lewis, Michael C.; Fass, Daniel M.; Wagner, Florence F.; Zhang, Yan-Ling; Hennig, Krista M.; Gale, Jennifer; Zhao, Wen-Ning; Reis, Surya; Barker, Douglas D.; Berry-Scott, Erin; Kim, Sung Won; Clore, Elizabeth L.; Hooker, Jacob M.; Holson, Edward B.; Haggarty, Stephen J.; Petryshen, Tracey L.

2013-01-01

280

Brain Activity Patterns Uniquely Supporting Visual Feature Integration after Traumatic Brain Injury  

PubMed Central

Traumatic brain injury (TBI) patients typically respond more slowly and with more variability than controls during tasks of attention requiring speeded reaction time. These behavioral changes are attributable, at least in part, to diffuse axonal injury (DAI), which affects integrated processing in distributed systems. Here we use a multivariate method sensitive to distributed neural activity to compare brain activity patterns of patients with chronic phase moderate to-severe TBI to those of controls during performance on a visual feature integration task assessing complex attentional processes that has previously shown sensitivity to TBI. The TBI patients were carefully screened to be free of large focal lesions that can affect performance and brain activation independently of DAI. The task required subjects to hold either one or three features of a Target in mind while suppressing responses to distracting information. In controls, the multi-feature condition activated a distributed network including limbic, prefrontal, and medial temporal structures. TBI patients engaged this same network in the single-feature and baseline conditions. In multi-feature presentations, TBI patients alone activated additional frontal, parietal, and occipital regions. These results are consistent with neuroimaging studies using tasks assessing different cognitive domains, where increased spread of brain activity changes was associated with TBI. Our results also extend previous findings that brain activity for relatively moderate task demands in TBI patients is similar to that associated with of high task demands in controls. PMID:22180740

Raja Beharelle, Anjali; Tisserand, Danielle; Stuss, Donald T.; McIntosh, Anthony R.; Levine, Brian

2011-01-01

281

Multiple toxic doses of methamphetamine alter neurotensin concentrations in various region of the rat brain  

SciTech Connect

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.

Hanson, G.R.; Merchant, K.; Gibb, J.W.; Letter, A.A.

1986-03-05

282

Altered AMP deaminase activity may extend postmortem glycolysis.  

PubMed

Postmortem energy metabolism drives hydrogen accumulation in muscle and results in a fairly constant ultimate pH. Extended glycolysis results in adverse pork quality and may be possible with greater adenonucleotide availability postmortem. We hypothesized that slowing adenonucleotide removal by reducing AMP deaminase activity would extend glycolysis and lower the ultimate pH of muscle. Longissimus muscle samples were incorporated into an in vitro system that mimics postmortem glycolysis with or without pentostatin, an AMP deaminase inhibitor. Pentostatin lowered ultimate pH and increased lactate and glucose 6-phosphate with time. Based on these results and that AMPK ?3(R200Q) mutated pigs (RN(-)) produce low ultimate pH pork, we hypothesized AMP deaminase abundance and activity would be lower in RN(-) muscle than wild-type. RN(-) muscle contained lower AMP deaminase abundance and activity. These data show that altering adenonucleotide availability postmortem can extend postmortem pH decline and suggest that AMP deaminase activity may, in part, contribute to the low ultimate pH observed in RN(-) pork. PMID:25498483

England, E M; Matarneh, S K; Scheffler, T L; Wachet, C; Gerrard, D E

2015-04-01

283

The impact of microglial activation on blood-brain barrier in brain diseases  

PubMed Central

The blood-brain barrier (BBB), constituted by an extensive network of endothelial cells (ECs) together with neurons and glial cells, including microglia, forms the neurovascular unit (NVU). The crosstalk between these cells guarantees a proper environment for brain function. In this context, changes in the endothelium-microglia interactions are associated with a variety of inflammation-related diseases in brain, where BBB permeability is compromised. Increasing evidences indicate that activated microglia modulate expression of tight junctions, which are essential for BBB integrity and function. On the other hand, the endothelium can regulate the state of microglial activation. Here, we review recent advances that provide insights into interactions between the microglia and the vascular system in brain diseases such as infectious/inflammatory diseases, epilepsy, ischemic stroke and neurodegenerative disorders. PMID:25404894

da Fonseca, Anna Carolina Carvalho; Matias, Diana; Garcia, Celina; Amaral, Rackele; Geraldo, Luiz Henrique; Freitas, Catarina; Lima, Flavia Regina Souza

2014-01-01

284

Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells  

PubMed Central

Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an animal model of depression) as a priming factor could affect microglial cells and might lead to depressive-like disturbances in adult male rat offspring. We investigated the behavioral changes (sucrose preference test, Porsolt test), the expression of C1q and CD40 mRNA and the level of microglia (Iba1 positive) in 3-month-old control and prenatally stressed male offspring rats. In addition, we characterized the morphological and biochemical parameters of potentially harmful (NO, iNOS, IL-1?, IL-18, IL-6, TNF-?, CCL2, CXCL12, CCR2, CXCR4) and beneficial (insulin-like growth factor-1 (IGF-1), brain derived neurotrophic factor (BDNF)) phenotypes in cultures of microglia obtained from the cortices of 1–2 days old control and prenatally stressed pups. The adult prenatally stressed rats showed behavioral (anhedonic- and depression-like) disturbances, enhanced expression of microglial activation markers and an increased number of Iba1-immunopositive cells in the hippocampus and frontal cortex. The morphology of glia was altered in cultures from prenatally stressed rats, as demonstrated by immunofluorescence microscopy. Moreover, in these cultures, we observed enhanced expression of CD40 and MHC II and release of pro-inflammatory cytokines, including IL-1?, IL-18, TNF-? and IL-6. Prenatal stress significantly up-regulated levels of the chemokines CCL2, CXCL12 and altered expression of their receptors, CCR2 and CXCR4 while IGF-1 production was suppressed in cultures of microglia from prenatally stressed rats. Our results suggest that prenatal stress may lead to excessive microglia activation and contribute to the behavioral changes observed in depression in adulthood.

?lusarczyk, Joanna; Trojan, Ewa; G?ombik, Katarzyna; Budziszewska, Bogus?awa; Kubera, Marta; Laso?, W?adys?aw; Popio?ek-Barczyk, Katarzyna; Mika, Joanna; W?dzony, Krzysztof; Basta-Kaim, Agnieszka

2015-01-01

285

Age-dependent alterations of corticostriatal activity in the YAC128 mouse model of Huntington disease.  

PubMed

Huntington disease is a genetic neurodegenerative disorder that produces motor, neuropsychiatric, and cognitive deficits and is caused by an abnormal expansion of the CAG tract in the huntingtin (htt) gene. In humans, mutated htt induces a preferential loss of medium spiny neurons in the striatum and, to a lesser extent, a loss of cortical neurons as the disease progresses. The mechanisms causing these degenerative changes remain unclear, but they may involve synaptic dysregulation. We examined the activity of the corticostriatal pathway using a combination of electrophysiological and optical imaging approaches in brain slices and acutely dissociated neurons from the YAC128 mouse model of Huntington disease. The results demonstrated biphasic age-dependent changes in corticostriatal function. At 1 month, before the behavioral phenotype develops, synaptic currents and glutamate release were increased. At 7 and 12 months, after the development of the behavioral phenotype, evoked synaptic currents were reduced. Glutamate release was decreased by 7 months and was markedly reduced by 12 months. These age-dependent alterations in corticostriatal activity were paralleled by a decrease in dopamine D(2) receptor modulation of the presynaptic terminal. Together, these findings point to dynamic alterations at the corticostriatal pathway and emphasize that therapies directed toward preventing or alleviating symptoms need to be specifically designed depending on the stage of disease progression. PMID:19244517

Joshi, Prasad R; Wu, Nan-Ping; André, Véronique M; Cummings, Damian M; Cepeda, Carlos; Joyce, John A; Carroll, Jeffrey B; Leavitt, Blair R; Hayden, Michael R; Levine, Michael S; Bamford, Nigel S

2009-02-25

286

The influence of carbon dioxide on brain activity and metabolism in conscious humans.  

PubMed

A better understanding of carbon dioxide (CO(2)) effect on brain activity may have a profound impact on clinical studies using CO(2) manipulation to assess cerebrovascular reserve and on the use of hypercapnia as a means to calibrate functional magnetic resonance imaging (fMRI) signal. This study investigates how an increase in blood CO(2), via inhalation of 5% CO(2), may alter brain activity in humans. Dynamic measurement of brain metabolism revealed that mild hypercapnia resulted in a suppression of cerebral metabolic rate of oxygen (CMRO(2)) by 13.4% ± 2.3% (N=14) and, furthermore, the CMRO(2) change was proportional to the subject's end-tidal CO(2) (Et-CO(2)) change. When using functional connectivity MRI (fcMRI) to assess the changes in resting-state neural activity, it was found that hypercapnia resulted in a reduction in all fcMRI indices assessed including cluster volume, cross-correlation coefficient, and amplitude of the fcMRI signal in the default-mode network (DMN). The extent of the reduction was more pronounced than similar indices obtained in visual-evoked fMRI, suggesting a selective suppression effect on resting-state neural activity. Scalp electroencephalogram (EEG) studies comparing hypercapnia with normocapnia conditions showed a relative increase in low frequency power in the EEG spectra, suggesting that the brain is entering a low arousal state on CO(2) inhalation. PMID:20842164

Xu, Feng; Uh, Jinsoo; Brier, Matthew R; Hart, John; Yezhuvath, Uma S; Gu, Hong; Yang, Yihong; Lu, Hanzhang

2011-01-01

287

Comparison of laterality index of upper and lower limb movement using brain activated fMRI  

NASA Astrophysics Data System (ADS)

Asymmetry of bilateral cerebral function, i.e. laterality, is an important phenomenon in many brain actions such as motor functions. This asymmetry maybe altered in some clinical conditions such as Multiple Sclerosis (MS). The aim of this study was to delineate the laterality differences for upper and lower limbs in healthy subjects to compare this pattern with subjects suffering from MS in advance. Hence 9 Male healthy subjects underwent fMRI assessment, while they were asked to move their limbs in a predetermined pattern. The results showed that hands movement activates the brain with a significant lateralization in pre-motor cortex in comparison with lower limb. Also, dominant hands activate brain more lateralized than the non-dominant hand. In addition, Left basal ganglia were observed to be activated regardless of the hand used, While, These patterns of Brain activation was not detected in lower limbs. We hypothesize that this difference might be attributed to this point that hand is usually responsible for precise and fine voluntary movements, whereas lower limb joints are mainly responsible for locomotion, a function integrating voluntary and automatic bilateral movements.

Harirchian, Mohammad Hossein; Oghabian, Mohammad Ali; Rezvanizadeh, Alireza; Bolandzadeh, Niousha

2008-03-01

288

Smoking and the developing brain: altered white matter microstructure in attention-deficit/hyperactivity disorder and healthy controls.  

PubMed

Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated with increased smoking and widespread WM abnormalities, suggesting that the developing ADHD brain might be especially vulnerable to effects of smoking. This study aims to investigate the effect of smoking on (WM) microstructure in adolescents and young adults with and without ADHD. Diffusion tensor imaging was performed in an extensively phenotyped sample of nonsmokers (n = 95, 50.5% ADHD), irregular smokers (n = 41, 58.5% ADHD), and regular smokers (n = 50, 82.5% ADHD), aged 14-24 years. A whole-brain voxelwise approach investigated associations of smoking, ADHD and their interaction, with WM microstructure as measured by fractional anisotropy (FA) and mean diffusivity (MD). Widespread alterations in FA and MD were found for regular smokers compared to irregular and nonsmokers, mainly located in the corpus callosum and WM tracts surrounding the basal ganglia. Several regions overlapped with regions of altered FA for ADHD versus controls, albeit in different directions. Irregular and nonsmokers did not differ, and ADHD and smoking did not interact. Results implicate that smoking and ADHD have independent effects on WM microstructure, and possibly do not share underlying mechanisms. Two mechanisms may play a role in the current results. First, smoking may cause alterations in WM microstructure in the maturing brain. Second, pre-existing WM microstructure differences possibly reflect a risk factor for development of a smoking addiction. PMID:25484258

van Ewijk, Hanneke; Groenman, Annabeth P; Zwiers, Marcel P; Heslenfeld, Dirk J; Faraone, Stephen V; Hartman, Catharina A; Luman, Marjolein; Greven, Corina U; Hoekstra, Pieter J; Franke, Barbara; Buitelaar, Jan; Oosterlaan, Jaap

2015-03-01

289

Cortisol’s effects on hippocampal activation in depressed patients are related to alterations in memory formation  

PubMed Central

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 one hour 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. PMID:21220074

Abercrombie, Heather C.; Jahn, Allison L.; Davidson, Richard J.; Kern, Simone; Kirschbaum, Clemens; Halverson, Jerry

2010-01-01

290

Numerical Models of Human Circulatory System under Altered Gravity: Brain Circulation  

NASA Technical Reports Server (NTRS)

A computational fluid dynamics (CFD) approach is presented to model the blood flow through the human circulatory system under altered gravity conditions. Models required for CFD simulation relevant to major hemodynamic issues are introduced such as non-Newtonian flow models governed by red blood cells, a model for arterial wall motion due to fluid-wall interactions, a vascular bed model for outflow boundary conditions, and a model for auto-regulation mechanism. The three-dimensional unsteady incompressible Navier-Stokes equations coupled with these models are solved iteratively using the pseudocompressibility method and dual time stepping. Moving wall boundary conditions from the first-order fluid-wall interaction model are used to study the influence of arterial wall distensibility on flow patterns and wall shear stresses during the heart pulse. A vascular bed modeling utilizing the analogy with electric circuits is coupled with an auto-regulation algorithm for multiple outflow boundaries. For the treatment of complex geometry, a chimera overset grid technique is adopted to obtain connectivity between arterial branches. For code validation, computed results are compared with experimental data for steady and unsteady non-Newtonian flows. Good agreement is obtained for both cases. In sin-type Gravity Benchmark Problems, gravity source terms are added to the Navier-Stokes equations to study the effect of gravitational variation on the human circulatory system. This computational approach is then applied to localized blood flows through a realistic carotid bifurcation and two Circle of Willis models, one using an idealized geometry and the other model using an anatomical data set. A three- dimensional anatomical Circle of Willis configuration is reconstructed from human-specific magnetic resonance images using an image segmentation method. The blood flow through these Circle of Willis models is simulated to provide means for studying gravitational effects on the brain circulation under auto-regulation.

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

2003-01-01

291

In vivo recordings of brain activity using organic transistors  

PubMed Central

In vivo electrophysiological recordings of neuronal circuits are necessary for diagnostic purposes and for brain-machine interfaces. Organic electronic devices constitute a promising candidate because of their mechanical flexibility and biocompatibility. Here we demonstrate the engineering of an organic electrochemical transistor embedded in an ultrathin organic film designed to record electrophysiological signals on the surface of the brain. The device, tested in vivo on epileptiform discharges, displayed superior signal-to-noise ratio due to local amplification compared with surface electrodes. The organic transistor was able to record on the surface low-amplitude brain activities, which were poorly resolved with surface electrodes. This study introduces a new class of biocompatible, highly flexible devices for recording brain activity with superior signal-to-noise ratio that hold great promise for medical applications. PMID:23481383

Khodagholy, Dion; Doublet, Thomas; Quilichini, Pascale; Gurfinkel, Moshe; Leleux, Pierre; Ghestem, Antoine; Ismailova, Esma; Hervé, Thierry; Sanaur, Sébastien; Bernard, Christophe; Malliaras, George G.

2013-01-01

292

Neurobehavioral changes in response to alterations in gene expression profiles in the brains of mice exposed to low and high levels of mercury vapor during postnatal development.  

PubMed

This study examined the relationship between neurobehavioral changes and alterations in gene expression profiles in the brains of mice exposed to different levels of Hg(0) during postnatal development. Neonatal mice were repeatedly exposed to mercury vapor (Hg(0)) at a concentration of 0.057 mg/m(3) (low level), which was close to the current threshold value (TLV), and 0.197 mg/m(3) (high level) for 24 hr until the 20(th) day postpartum. Behavioral responses were evaluated based on changes in locomotor activity in the open field test (OPF), learning ability in the passive avoidance response test (PA), and spatial learning ability in the Morris water maze (MM) at 12 weeks of age. No significant differences were observed in the three behavioral measurements between mice exposed to the low level of Hg(0) and control mice. On the other hand, total locomotive activity in mice exposed to the high level of Hg(0) was significantly decreased and central locomotion was reduced in the OPF task. Mercury concentrations were approximately 0.4 ?g/g and 1.9 ?g/g in the brains of mice exposed to the low and high levels of Hg(0), respectively. Genomic analysis revealed that the expression of 2 genes was up-regulated and 18 genes was down-regulated in the low-level exposure group, while the expression of 3 genes was up-regulated and 70 genes was down-regulated in the high-level exposure group. Similar alterations in the expression of seven genes, six down-regulated genes and one up-regulated gene, were observed in both groups. The results indicate that an increase in the number of altered genes in the brain may be involved in the emergence of neurobehavioral effects, which may be associated with the concentration of mercury in the brain. Moreover, some of the commonly altered genes following exposure to both concentrations of Hg(0) with and without neurobehavioral effects may be candidates as sensitive biomarker genes for assessing behavioral effects in the early stages of development. PMID:25056781

Yoshida, Minoru; Honda, Akiko; Watanabe, Chiho; Satoh, Masahiko; Yasutake, Akira

2014-08-01

293

Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Alter the Gut-Brain Communication.  

PubMed

This study investigated the anatomical integrity of vagal innervation of the gastrointestinal tract following vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) operations. The retrograde tracer fast blue (FB) was injected into the stomach to label vagal neurons originating from nodose ganglion (NG) and dorsal motor nucleus of the vagus (DMV). Microglia activation was determined by quantifying changes in the fluorescent staining of hindbrain sections against an ionizing calcium adapter binding molecule 1 (Iba1). Reorganization of vagal afferents in the hindbrain was studied by fluorescent staining against isolectin 4 (IB4). The density of Iba1- and IB4-immunoreactivity was analyzed using Nikon Elements software. There was no difference in the number of FB-labeled neurons located in NG and DMV between VSG and VSG-sham rats. RYGB, but not RYGB-sham rats, showed a dramatic reduction in number of FB-labeled neurons located in the NG and DMV. VSG increased, while the RYGB operation decreased, the density of vagal afferents in the nucleus tractus solitarius (NTS). The RYGB operation, but not the VSG procedure, significantly activated microglia in the NTS and DMV. Results of this study show that the RYGB, but not the VSG procedure, triggers microglia activation in vagal structures and remodels gut-brain communication. PMID:25722893

Ballsmider, L A; Vaughn, A C; David, M; Hajnal, A; Di Lorenzo, P M; Czaja, K

2015-01-01

294

Alterations in the basal ganglia in patients with brain tumours may be due to excessive iron deposition  

PubMed Central

The accumulation of iron in the brain is a common physiological process. However, alterations in the deposition of iron or other paramagnetic substances are associated with various diseases. In the present study, the deposition of paramagnetic substances in patients with brain tumours was evaluated using T2 relaxometry. A total of 23 patients with untreated tumours or with recurrent tumours following treatment, together with a group of 19 age-matched healthy controls, were examined using T2 relaxometry at 3T. The relaxation times in the basal ganglia, thalamus and white matter were evaluated. Significantly lower T2 relaxation times were identified in the basal ganglia and thalamus of the patients with tumours, as compared with those of the controls (P<0.05). No statistically significant difference was identified between patients with untreated or recurrent brain tumours. The reduction in T2 relaxation times in the brain tumour patients was possibly caused by the accumulation of iron, since iron homeostasis is known to be altered in patients with tumours. We propose that increased iron deposition is a consequence of a higher risk of oxidative stress caused by an increased iron concentration in the plasma or cerebrospinal fluid. PMID:25435931

HERYNEK, VÍT; WAGNEROVÁ, DITA; MALUCELLI, ALBERTO; VYMAZAL, JOSEF; SAMEŠ, MARTIN; HÁJEK, MILAN

2015-01-01

295

Brain modularity controls the critical behavior of spontaneous activity  

NASA Astrophysics Data System (ADS)

The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure.

Russo, R.; Herrmann, H. J.; de Arcangelis, L.

2014-03-01

296

Brain modularity controls the critical behavior of spontaneous activity.  

PubMed

The human brain exhibits a complex structure made of scale-free highly connected modules loosely interconnected by weaker links to form a small-world network. These features appear in healthy patients whereas neurological diseases often modify this structure. An important open question concerns the role of brain modularity in sustaining the critical behaviour of spontaneous activity. Here we analyse the neuronal activity of a model, successful in reproducing on non-modular networks the scaling behaviour observed in experimental data, on a modular network implementing the main statistical features measured in human brain. We show that on a modular network, regardless the strength of the synaptic connections or the modular size and number, activity is never fully scale-free. Neuronal avalanches can invade different modules which results in an activity depression, hindering further avalanche propagation. Critical behaviour is solely recovered if inter-module connections are added, modifying the modular into a more random structure. PMID:24621482

Russo, R; Herrmann, H J; de Arcangelis, L

2014-01-01

297

Fluctuations in Neuronal Activity: Clues to Brain Function  

NASA Astrophysics Data System (ADS)

Recordings from neuronal preparations, either in vitro or in the intact brain, are characterized by fluctuations, what is commonly considered as "noise". Due to the current recording and analysis methods, it is not feasible to separate what we term noise, from the "meaningful" neuronal activity. We propose that fluctuations serve to maintain brain activity in an optimal state for cognitive processing, not allowing it to fall into long-term periodic behaviour. We have studied fluctuations in magnetoencephalographic (MEG) recordings from normal subjects and epileptic patients, in electroencephalographic (EEG) recordings from children with impact injury, as well as in intracerebral electrophysiological recordings in freely moving rats. Specifically, we have determined phase locking patterns between brain areas from these recordings, which display fluctuations at different scales. We submit the idea that the variability in phase synchronization affords a more complete search of all possible phase differences in a hypothetical phase-locking state space that contributes to brain information processing. In brain pathologies, like epileptiform activity here studied, different levels of fluctuations in phase synchrony may favour the generation of stable synchronized states that characterize epileptic seizures. While the border between noise and high-dimensional dynamics is fuzzy, the scrutiny of neuronal fluctuations at different levels will provide important insights to the unravelling of the relation between brain and behaviour.

Pérez Velazquez, José L.; Guevara, Ramón; Belkas, Jason; Wennberg, Richard; Senjanoviè, Goran; García Dominguez, Luis

2005-08-01

298

Synchronous brain activity across individuals underlies shared psychological perspectives.  

PubMed

For successful communication, we need to understand the external world consistently with others. This task requires sufficiently similar cognitive schemas or psychological perspectives that act as filters to guide the selection, interpretation and storage of sensory information, perceptual objects and events. Here we show that when individuals adopt a similar psychological perspective during natural viewing, their brain activity becomes synchronized in specific brain regions. We measured brain activity with functional magnetic resonance imaging (fMRI) from 33 healthy participants who viewed a 10-min movie twice, assuming once a 'social' (detective) and once a 'non-social' (interior decorator) perspective to the movie events. Pearson's correlation coefficient was used to derive multisubject voxelwise similarity measures (inter-subject correlations; ISCs) of functional MRI data. We used k-nearest-neighbor and support vector machine classifiers as well as a Mantel test on the ISC matrices to reveal brain areas wherein ISC predicted the participants' current perspective. ISC was stronger in several brain regions--most robustly in the parahippocampal gyrus, posterior parietal cortex and lateral occipital cortex--when the participants viewed the movie with similar rather than different perspectives. Synchronization was not explained by differences in visual sampling of the movies, as estimated by eye gaze. We propose that synchronous brain activity across individuals adopting similar psychological perspectives could be an important neural mechanism supporting shared understanding of the environment. PMID:24936687

Lahnakoski, Juha M; Glerean, Enrico; Jääskeläinen, Iiro P; Hyönä, Jukka; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

2014-10-15

299

Synchronous brain activity across individuals underlies shared psychological perspectives  

PubMed Central

For successful communication, we need to understand the external world consistently with others. This task requires sufficiently similar cognitive schemas or psychological perspectives that act as filters to guide the selection, interpretation and storage of sensory information, perceptual objects and events. Here we show that when individuals adopt a similar psychological perspective during natural viewing, their brain activity becomes synchronized in specific brain regions. We measured brain activity with functional magnetic resonance imaging (fMRI) from 33 healthy participants who viewed a 10-min movie twice, assuming once a ‘social’ (detective) and once a ‘non-social’ (interior decorator) perspective to the movie events. Pearson's correlation coefficient was used to derive multisubject voxelwise similarity measures (inter-subject correlations; ISCs) of functional MRI data. We used k-nearest-neighbor and support vector machine classifiers as well as a Mantel test on the ISC matrices to reveal brain areas wherein ISC predicted the participants' current perspective. ISC was stronger in several brain regions—most robustly in the parahippocampal gyrus, posterior parietal cortex and lateral occipital cortex—when the participants viewed the movie with similar rather than different perspectives. Synchronization was not explained by differences in visual sampling of the movies, as estimated by eye gaze. We propose that synchronous brain activity across individuals adopting similar psychological perspectives could be an important neural mechanism supporting shared understanding of the environment. PMID:24936687

Lahnakoski, Juha M.; Glerean, Enrico; Jääskeläinen, Iiro P.; Hyönä, Jukka; Hari, Riitta; Sams, Mikko; Nummenmaa, Lauri

2014-01-01

300

Chronic ethanol alters network activity and endocannabinoid signaling in the prefrontal cortex  

PubMed Central

Chronic use of alcohol is associated with structural and functional alterations in brain areas that subserve cognitive processes. Of particular importance is the prefrontal cortex (PFC) that is involved in higher order behaviors such as decision making, risk assessment and judgment. Understanding the mechanisms that underlie alcohol's effects on PFC function is important for developing strategies to overcome the cognitive deficits that may predispose individuals to relapse. Our previous studies showed that acutely applied ethanol inhibits network activity in slices of prefrontal cortex and that exogenous and endogenous cannabinoids modulate up-state dynamics. In the present study, we examined the effects of repeated alcohol exposure on cannabinoid regulation of up-states in slice cultures of the prefrontal cortex. Compared to controls, up-state duration, but not amplitude was enhanced when measured 4 days after a 10 day ethanol exposure (44 mM ethanol; equivalent to 0.2% blood ethanol). Administration of the CB1 agonist WIN 55,212-2 enhanced the amplitude of up-states in control cultures but not in those treated previously with ethanol. This lack of effect occurred in the absence of any noticeable change in CB1 receptor protein expression. Chronic ethanol treatment and withdrawal also blunted WIN's inhibition of electrically evoked GABA IPSCs in layer II/III pyramidal neurons but not those in layer V/VI. WIN inhibited the amplitude of spontaneous GABA IPSCs in both layers and the magnitude of this effect was not altered by ethanol treatment. However, in layer V/VI neurons, WIN's effect on sIPSC frequency was greater in ethanol treated cultures. WIN also inhibited electrically evoked NMDA EPSCs in both layer II/III and V/VI neurons but this action was unaffected by ethanol treatment and withdrawal. Overall, these results suggest that ethanol's down-regulation of cannabinoid signaling results in altered network activity in the prefrontal cortex. PMID:25100953

Pava, Matthew J.; Woodward, John J.

2014-01-01

301

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

PubMed Central

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

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

2012-01-01

302

Calpain activity in adult and aged human brain regions  

Microsoft Academic Search

We assayed calpain activity in 27 human brain regions from adult (43–65 years of age) and aged (66–83 years of age) postmortem tissue samples. Calpain I (µM Ca-requiring) activity was 10% or less of the total activity; it was below detectable levels in a number of areas, and so data are are expressed as total (µM+mM Ca-dependent) calpain activity. The

Miriam Banay-Schwartz; Teresita DeGuzman; Miklos Palkovits; Abel Lajtha

1994-01-01

303

Organic matter alteration at active and relict sedimentary oxidation fronts  

SciTech Connect

Sedimentary oxidation fronts, generated by downward diffusion of O{sub 2} into previously reducing sediments, provide an opportunity to study the effects of O{sub 2} exposure on organic matter preservation, where other factors are invariant. Oxidation fronts have now been identified in a number of environments, including turbidities found on the Madeira abyssal plain (NE Atlantic) and in sapropels from the Mediterranean. A multifaceted study is being carried out on a series of relict fronts in turbidities of varied origin and composition, recovered from the Madeira abyssal plain on ODP Leg 157. A similar study is being made on an active front in the most recent, S1 sapropel, from the central Mediterranean. In both cases, the relatively organic-rich turbidities and sapropels are intercalated with typical, organic-poor pelagic marts. Analyses include major and minor inorganic elements, stable and N isotopes, palynomorphs, surface areas and a comprehensive suite of biochemicals. Although the extent of alteration varies, striking changes in organic content and composition occur across many of the oxidation fronts, and the oxidized horizons resemble the interclated marls. A common trend is that organic C contents drop from {open_quotes}monolayer equivalent{close_quotes} sorptive loadings in the unoxidized horizons (typical of continental mar in sediments) to submonolayer loadings, typical of the pelagic marls. Shifts are also observed in redox-sensitive trace metals and in stable C and N isotopic compositions, although the patterns and extent are not uniform. The results clearly indicate that in these pelagic settings, where O{sub 2} exposure is typically long, organic material deposited and then preserved for extended periods under anomalous reducing conditions, can be extensively altered on relatively short-term exposure to O{sub 2} Implications of these findings will be discussed.

Cowie, G.L.; Calvert, S.E. [Univ. of British Columbia, Vancouver (Canada); Hedges, J.I. [Univ. of Washington, Seattle, WA (United States)] [and others

1996-12-31

304

Organic matter alteration at active and relict sedimentary oxidation fronts  

SciTech Connect

Sedimentary oxidation fronts, generated by downward diffusion of O[sub 2] into previously reducing sediments, provide an opportunity to study the effects of O[sub 2] exposure on organic matter preservation, where other factors are invariant. Oxidation fronts have now been identified in a number of environments, including turbidities found on the Madeira abyssal plain (NE Atlantic) and in sapropels from the Mediterranean. A multifaceted study is being carried out on a series of relict fronts in turbidities of varied origin and composition, recovered from the Madeira abyssal plain on ODP Leg 157. A similar study is being made on an active front in the most recent, S1 sapropel, from the central Mediterranean. In both cases, the relatively organic-rich turbidities and sapropels are intercalated with typical, organic-poor pelagic marts. Analyses include major and minor inorganic elements, stable and N isotopes, palynomorphs, surface areas and a comprehensive suite of biochemicals. Although the extent of alteration varies, striking changes in organic content and composition occur across many of the oxidation fronts, and the oxidized horizons resemble the interclated marls. A common trend is that organic C contents drop from [open quotes]monolayer equivalent[close quotes] sorptive loadings in the unoxidized horizons (typical of continental mar in sediments) to submonolayer loadings, typical of the pelagic marls. Shifts are also observed in redox-sensitive trace metals and in stable C and N isotopic compositions, although the patterns and extent are not uniform. The results clearly indicate that in these pelagic settings, where O[sub 2] exposure is typically long, organic material deposited and then preserved for extended periods under anomalous reducing conditions, can be extensively altered on relatively short-term exposure to O[sub 2] Implications of these findings will be discussed.

Cowie, G.L.; Calvert, S.E. (Univ. of British Columbia, Vancouver (Canada)); Hedges, J.I. (Univ. of Washington, Seattle, WA (United States)) (and others)

1996-01-01

305

Systemic nitroglycerin activates peptidergic and catecholaminergic pathways in rat brain  

Microsoft Academic Search

In this study, we carried out an immunohistochemical evaluation of the neurochemical characteristics of neurons that are activated (i.e., express Fos protein) in response to systemic administration of nitroglycerin. In the brain stem, a significant percentage of activated neurons contained noradrenaline as a neurotransmitter, whereas only a few of them contained serotonin. In the paraventricular and supraoptic nuclei of the

Cristina Tassorelli; Shirley A. Joseph

1996-01-01

306

Brain acetycholinesterase activity in botulism-intoxicated mallards  

USGS Publications Warehouse

Brain acetylcholinesterase (AChE) activity in captive-reared mallards (Anas platyrhynchos) that died of botulism was compared with euthanized controls. AChE levels for both groups were within the range reported for normal mallards, and there was no significant difference in mean AChE activity between birds that ingested botulism toxin and died and those that did not.

Rocke, T.E.; Samuel, M.D.

1991-01-01

307

Measurement of brain activity by near-infrared light  

Microsoft Academic Search

We review our most recent results on near-IR studies of human brain activity, which have been evolving in two directions: detection of neuronal signals and measurements of functional hemo- dynamics. We discuss results obtained so far, describing in detail the techniques we developed for detecting neuronal activity, and present- ing results of a study that, as we believe, confirms the

Enrico Gratton; Vladislav Toronov; Ursula Wolf; Martin Wolf; Andrew Webb

2005-01-01

308

A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis  

PubMed Central

To explore brain involvement in chronic fatigue syndrome (CFS), the statistical parametric mapping of brain MR images has been extended to voxel-based regressions against clinical scores. Using SPM5 we performed voxel-based morphometry (VBM) and analysed T1- and T2-weighted spin-echo MR signal levels in 25 CFS subjects and 25 normal controls (NC). Clinical scores included CFS fatigue duration, a score based on the 10 most common CFS symptoms, the Bell score, the hospital anxiety and depression scale (HADS) anxiety and depression, and hemodynamic parameters from 24-h blood pressure monitoring. We also performed group?×?hemodynamic score interaction regressions to detect locations where MR regressions were opposite for CFS and NC, thereby indicating abnormality in the CFS group. In the midbrain, white matter volume was observed to decrease with increasing fatigue duration. For T1-weighted MR and white matter volume, group?×?hemodynamic score interactions were detected in the brainstem [strongest in midbrain grey matter (GM)], deep prefrontal white matter (WM), the caudal basal pons and hypothalamus. A strong correlation in CFS between brainstem GM volume and pulse pressure suggested impaired cerebrovascular autoregulation. It can be argued that at least some of these changes could arise from astrocyte dysfunction. These results are consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system (ANS). © 2011 The Authors. NMR in Biomedicine published by John Wiley & Sons, Ltd. PMID:21560176

Barnden, Leighton R; Crouch, Benjamin; Kwiatek, Richard; Burnet, Richard; Mernone, Anacleto; Chryssidis, Steve; Scroop, Garry; Del Fante, Peter

2011-01-01

309

Acoustic Noise Alters Selective Attention Processes as Indicated by Direct Current (DC) Brain Potential Changes  

PubMed Central

Acoustic environmental noise, even of low to moderate intensity, is known to adversely affect information processing in animals and humans via attention mechanisms. In particular, facilitation and inhibition of information processing are basic functions of selective attention. Such mechanisms can be investigated by analyzing brain potentials under conditions of externally directed attention (intake of environmental information) versus internally directed attention (rejection of environmental stimuli and focusing on memory/planning processes). This study investigated brain direct current (DC) potential shifts—which are discussed to represent different states of cortical activation—of tasks that require intake and rejection of environmental information under noise. It was hypothesized that without background noise rejection tasks would show more positive DC potential changes compared to intake tasks and that under noise both kinds of tasks would show positive DC shifts as an expression of cortical inhibition caused by noise. DC potential shifts during intake and rejection tasks were analyzed at 16 standard locations in 45 persons during irrelevant speech or white noise vs. control condition. Without noise, rejection tasks were associated with more positive DC potential changes compared to intake tasks. During background noise, however, this difference disappeared and both kinds of tasks led to positive DC shifts. Results suggest—besides some limitations—that noise modulates selective attention mechanisms by switching to an environmental information processing and noise rejection mode, which could represent a suggested “attention shift”. Implications for fMRI studies as well as for public health in learning and performance environments including susceptible persons are discussed. PMID:25264675

Trimmel, Karin; Schätzer, Julia; Trimmel, Michael

2014-01-01

310

Alteration of the Expression of Pesticide-Metabolizing Enzymes in Pregnant Mice: Potential Role in the Increased Vulnerability of the Developing Brain  

PubMed Central

Studies on therapeutic drug disposition in humans have shown significant alterations as the result of pregnancy. However, it is not known whether pesticide metabolic capacity changes throughout pregnancy, which could affect exposure of the developing brain. We sought to determine the effect of pregnancy on the expression of hepatic enzymes involved in the metabolism of pesticides. Livers were collected from virgin and pregnant C57BL/6 mice at gestational days (GD)7, GD11, GD14, GD17, and postpartum days (PD)1, PD15, and PD30. Relative mRNA expression of several enzymes involved in the metabolism of pesticides, including hepatic cytochromes (Cyp) P450s, carboxylesterases (Ces), and paraoxonase 1 (Pon1), were assessed in mice during gestation and the postpartum period. Compared with virgin mice, alterations in the expression occurred at multiple time points, with the largest changes observed on GD14. At this time point, the expression of most of the Cyps involved in pesticide metabolism in the liver (Cyp1a2, Cyp2d22, Cyp2c37, Cyp2c50, Cyp2c54, and Cyp3a11) were downregulated by 30% or more. Expression of various Ces isoforms and Pon1 were also decreased along with Pon1 activity. These data demonstrate significant alterations in the expression of key enzymes that detoxify pesticides during pregnancy, which could alter exposure of developing animals to these chemicals. PMID:23223497

Fortin, Marie C.; Aleksunes, Lauren M.

2013-01-01

311

Progressive Brain Damage, Synaptic Reorganization and NMDA Activation in a Model of Epileptogenic Cortical Dysplasia  

PubMed Central

Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity. PMID:24587109

Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

2014-01-01

312

Mild Blast Events Alter Anxiety, Memory, and Neural Activity Patterns in the Anterior Cingulate Cortex  

PubMed Central

There is a general interest in understanding of whether and how exposure to emotionally traumatizing events can alter memory function and anxiety behaviors. Here we have developed a novel laboratory-version of mild blast exposure comprised of high decibel bomb explosion sound coupled with strong air blast to mice. This model allows us to isolate the effects of emotionally fearful components from those of traumatic brain injury or bodily injury typical associated with bomb blasts. We demonstrate that this mild blast exposure is capable of impairing object recognition memory, increasing anxiety in elevated O-maze test, and resulting contextual generalization. Our in vivo neural ensemble recording reveal that such mild blast exposures produced diverse firing changes in the anterior cingulate cortex, a region processing emotional memory and inhibitory control. Moreover, we show that these real-time neural ensemble patterns underwent post-event reverberations, indicating rapid consolidation of those fearful experiences. Identification of blast-induced neural activity changes in the frontal brain may allow us to better understand how mild blast experiences result in abnormal changes in memory functions and excessive fear generalization related to post-traumatic stress disorder. PMID:23741416

Xie, Kun; Kuang, Hui; Tsien, Joe Z.

2013-01-01

313

Alterations in human EEG activity caused by extremely low frequency electromagnetic fields.  

PubMed

This study has investigated whether extremely low frequency (ELF) electromagnetic fields (EMFs) can alter human brain activity. Linearly polarised magnetic flux density of 20 muT (rms) was generated using a standard double Helmholtz coils and applied to the human head over a sequence of 1 minute stimulations followed by one minute without stimulation in the following order of frequencies 50, 16.66, 13, 10, 8.33 and 4 Hz. We collected recordings on 33 human volunteers under double-blind counter-balanced conditions. Each stimulation lasted for two minutes followed by one minute post-stimulation EEG recording. The same procedure was repeated for the EMF control sessions, where the order of control and exposure sessions was determined randomly according to the subject's ID number. The rest period between two conditions (exposure and control) was 30 minutes. The results indicate that there was a significant increase in Alpha1, Alpha2, and Beta1 at the frontal brain region, and a significant decrease in Alpha2 band in parietal and occipital region due to EMF exposure. PMID:17945759

Cvetkovic, D; Jovanov, E; Cosic, I

2006-01-01

314

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

PubMed Central

Fetal brain development involves the development of the neuro-vegetative (autonomic) control that is mediated by the autonomic nervous system (ANS). Disturbances of the fetal brain development have implications for diseases in later postnatal life. In that context, the fetal functional brain age can be altered. Universal principles of developmental biology applied to patterns of autonomic control may allow a functional age assessment. The work aims at the development of a fetal autonomic brain age score (fABAS) based on heart rate patterns. We analysed n?=?113 recordings in quiet sleep, n?=?286 in active sleep, and n?=?29 in active awakeness from normals. We estimated fABAS from magnetocardiographic recordings (21.4–40.3 weeks of gestation) preclassified in quiet sleep (n?=?113, 63 females) and active sleep (n?=?286, 145 females) state by cross-validated multivariate linear regression models in a cross-sectional study. According to universal system developmental principles, we included indices that address increasing fluctuation range, increasing complexity, and pattern formation (skewness, power spectral ratio VLF/LF, pNN5). The resulting models constituted fABAS. fABAS explained 66/63% (coefficient of determination R2 of training and validation set) of the variance by age in quiet, while 51/50% in active sleep. By means of a logistic regression model using fluctuation range and fetal age, quiet and active sleep were automatically reclassified (94.3/93.1% correct classifications). We did not find relevant gender differences. We conclude that functional brain age can be assessed based on universal developmental indices obtained from autonomic control patterns. fABAS reflect normal complex functional brain maturation. The presented normative data are supplemented by an explorative study of 19 fetuses compromised by intrauterine growth restriction. We observed a shift in the state distribution towards active awakeness. The lower WGA dependent fABAS values found in active sleep may reflect alterations in the universal developmental indices, namely fluctuation amplitude, complexity, and pattern formation that constitute fABAS. PMID:24058564

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

2013-01-01

315

PERINATAL EXPOSURE TO POLYCHLORINATED BIPHENYLS AROCLOR 1016 OR 1254 DID NOT ALTER BRAIN CATECHOLAMINES NOR DELAYED ALTERNATION PERFORMANCE IN LONG EVANS RATS  

EPA Science Inventory

Several reports have indicated that polychlorinated biphenyls (PCB) altered development of biogenic amine systems in the brain, impaired behavioral performances and disrupted maturation of the thyroid axis. The current study examines whether these developmental effects of PCB ar...

316

Silicon Shrinkwrap Melts Smoothly Onto Cat Brain to Monitor Activity in Real Time  

E-print Network

Silicon Shrinkwrap Melts Smoothly Onto Cat Brain to Monitor Activity in Real Time By Jeremy Hsu Activity in Real Time Silk-Silicon Implantable Electronics Conform to Tissues, Then Melt Away Brain Scans, brains, cat brains, electrical activity, electrodes, implants, mesh, silicon, silk, surface electrodes

Rogers, John A.

317

[Brain metabolism alterations in patients with anorexia nervosa observed in 1H-MRS  

Microsoft Academic Search

The causes of metabolic brain changes in patients with anorexia nervosa are still not fully explained. The purpose of this study was to use the 1H-MRS method in investigating metabolic changes in the brain of patients with anorexia nervosa. We studied 10 patients for visible alternations in brain metabolism and compared the results to healthy controls. 1H-MRS was acquired by

P. Grzelak; W. Gajewicz; A. Wyszogrodzka-Kucharska; A. Rotkiewicz; L. Stefanczyk; B. M. Goraj; J. Rabe-Jablonska

2005-01-01

318

Resting Cerebral Blood Flow Alterations in Chronic Traumatic Brain Injury: An Arterial Spin Labeling Perfusion fMRI Study  

PubMed Central

Abstract Non-invasive measurement of resting state cerebral blood flow (CBF) may reflect alterations of brain structure and function after traumatic brain injury (TBI). However, previous imaging studies of resting state brain in chronic TBI have been limited by several factors, including measurement in relative rather than absolute units, use of crude spatial registration methods, exclusion of subjects with substantial focal lesions, and exposure to ionizing radiation, which limits repeated assessments. This study aimed to overcome those obstacles by measuring absolute CBF with an arterial spin labeling perfusion fMRI technique, and using an image preprocessing protocol that is optimized for brains with mixed diffuse and focal injuries characteristic of moderate and severe TBI. Resting state CBF was quantified in 27 individuals with moderate to severe TBI in the chronic stage, and 22 demographically matched healthy controls. In addition to global CBF reductions in the TBI subjects, more prominent regional hypoperfusion was found in the posterior cingulate cortices, the thalami, and multiple locations in the frontal cortices. Diffuse injury, as assessed by tensor-based morphometry, was mainly associated with reduced CBF in the posterior cingulate cortices and the thalami, where the greatest volume losses were detected. Hypoperfusion in superior and middle frontal cortices, in contrast, was associated with focal lesions. These results suggest that structural lesions, both focal and diffuse, are the main contributors to the absolute CBF alterations seen in chronic TBI, and that CBF may serve as a tool to assess functioning neuronal volume. We also speculate that resting reductions in posterior cingulate perfusion may reflect alterations in the default-mode network, and may contribute to the attentional deficits common in TBI. PMID:20528163

Whyte, John; Patel, Sunil; Avants, Brian; Europa, Eduardo; Wang, Jiongjiong; Slattery, John; Gee, James C.; Coslett, H. Branch; Detre, John A.

2010-01-01

319

Altered Serotonin 2A Receptor Activity in Women Who Have Recovered From Bulimia Nervosa  

Microsoft Academic Search

Objective: The authors' goal was to confirm that brain seroto- nin (5-HT) alterations are present in patients who have recov- ered from bulimia nervosa. Positron emission tomography im- aging with (18F)altanserin was used to characterize binding of the 5-HT2A receptor, which might contribute to altered feeding, mood, or impulse control. Method: Nine women who had recovered from bulimia ner- vosa

Walter H. Kaye; Guido K. Frank; Carolyn C. Meltzer; Julie C. Price; Claire W. McConaha; Penelope J. Crossan; B. S. Kelly; L. Klump

2001-01-01

320

Altered expression of metabotropic glutamate receptor 1 alpha after acute diffuse brain injury  

PubMed Central

The diffuse brain injury model was conducted in Sprague-Dawley rats, according to Marmarou's free-fall attack. The water content in brain tissue, expression of metabotropic glutamate receptor 1? mRNA and protein were significantly increased after injury, reached a peak at 24 hours, and then gradually decreased. After treatment with the competitive antagonist of metabotropic glutamate receptor 1?, (RS)-1-aminoindan-1, 5-dicarboxylic acid, the water content of brain tissues decreased between 12–72 hours after injury, and neurological behaviors improved at 2 weeks. These experimental findings suggest that the 1-aminoindan-1, 5-dicarboxylic acid may result in marked neuroprotection against diffuse brain injury.

Cao, Fei; Chen, Mantao; Li, Gu; Ye, Ke; Huang, Xin; Zheng, Xiujue

2012-01-01

321

Dynamics of event-related causality in brain electrical activity.  

PubMed

A new method (Event-Related Causality, ERC) is proposed for the investigation of functional interactions between brain regions during cognitive processing. ERC estimates the direction, intensity, spectral content, and temporal course of brain activity propagation within a cortical network. ERC is based upon the short-time directed transfer function (SDTF), which is measured in short EEG epochs during multiple trials of a cognitive task, as well as the direct directed transfer function (dDTF), which distinguishes direct interactions between brain regions from indirect interactions via brain regions. ERC uses new statistical methods for comparing estimates of causal interactions during prestimulus "baseline" epochs and during poststimulus "activated" epochs in order to estimate event-related increases and decreases in the functional interactions between cortical network components during cognitive tasks. The utility of the ERC approach is demonstrated through its application to human electrocorticographic recordings (ECoG) of a simple language task. ERC analyses of these ECoG recordings reveal frequency-dependent interactions, particularly in high gamma (>60 Hz) frequencies, between brain regions known to participate in the recorded language task, and the temporal evolution of these interactions is consistent with the putative processing stages of this task. The method may be a useful tool for investigating the dynamics of causal interactions between various brain regions during cognitive task performance. PMID:17712784

Korzeniewska, Anna; Crainiceanu, Ciprian M; Ku?, Rafa?; Franaszczuk, Piotr J; Crone, Nathan E

2008-10-01

322

Altered brain mechanisms of emotion processing in pre-manifest Huntington's disease.  

PubMed

Huntington's disease is an inherited neurodegenerative disease that causes motor, cognitive and psychiatric impairment, including an early decline in ability to recognize emotional states in others. The pathophysiology underlying the earliest manifestations of the disease is not fully understood; the objective of our study was to clarify this. We used functional magnetic resonance imaging to investigate changes in brain mechanisms of emotion recognition in pre-manifest carriers of the abnormal Huntington's disease gene (subjects with pre-manifest Huntington's disease): 16 subjects with pre-manifest Huntington's disease and 14 control subjects underwent 1.5 tesla magnetic resonance scanning while viewing pictures of facial expressions from the Ekman and Friesen series. Disgust, anger and happiness were chosen as emotions of interest. Disgust is the emotion in which recognition deficits have most commonly been detected in Huntington's disease; anger is the emotion in which impaired recognition was detected in the largest behavioural study of emotion recognition in pre-manifest Huntington's disease to date; and happiness is a positive emotion to contrast with disgust and anger. Ekman facial expressions were also used to quantify emotion recognition accuracy outside the scanner and structural magnetic resonance imaging with voxel-based morphometry was used to assess the relationship between emotion recognition accuracy and regional grey matter volume. Emotion processing in pre-manifest Huntington's disease was associated with reduced neural activity for all three emotions in partially separable functional networks. Furthermore, the Huntington's disease-associated modulation of disgust and happiness processing was negatively correlated with genetic markers of pre-manifest disease progression in distributed, largely extrastriatal networks. The modulated disgust network included insulae, cingulate cortices, pre- and postcentral gyri, precunei, cunei, bilateral putamena, right pallidum, right thalamus, cerebellum, middle frontal, middle occipital, right superior and left inferior temporal gyri, and left superior parietal lobule. The modulated happiness network included postcentral gyri, left caudate, right cingulate cortex, right superior and inferior parietal lobules, and right superior frontal, middle temporal, middle occipital and precentral gyri. These effects were not driven merely by striatal dysfunction. We did not find equivalent associations between brain structure and emotion recognition, and the pre-manifest Huntington's disease cohort did not have a behavioural deficit in out-of-scanner emotion recognition relative to controls. In addition, we found increased neural activity in the pre-manifest subjects in response to all three emotions in frontal regions, predominantly in the middle frontal gyri. Overall, these findings suggest that pathophysiological effects of Huntington's disease may precede the development of overt clinical symptoms and detectable cerebral atrophy. PMID:22505631

Novak, Marianne J U; Warren, Jason D; Henley, Susie M D; Draganski, Bogdan; Frackowiak, Richard S; Tabrizi, Sarah J

2012-04-01

323

Effects of Chronic Active Cannabis Use on Visuomotor Integration, in Relation to Brain Activation and Cortisol Levels  

PubMed Central

Cannabis is the most abused illegal substance in the United States. Alterations in brain function and motor behavior have been reported in chronic cannabis users, but the results have been variable. The current study aimed to determine whether chronic active cannabis use in humans may alter psychomotor function, brain activation, and hypothalamic-pituitary-axis (HPA) function in men and women. 30 cannabis users (16 men and 14 women, 18 to 45 years old) and 30 non-drug user controls (16 men and 14 women, 19 to 44 years old) were evaluated with neuropsychological tests designed to assess motor behavior and functional MRI (fMRI), using a 3 Tesla scanner, during a visually paced finger-sequencing task, cued by a flashing checkerboard (at 2 or 4 Hz). Salivary cortisol was measured to assess HPA function. Male, but not female, cannabis users had significantly slower performance on psychomotor speed tests. As a group, cannabis users had greater activation in BA 6 than controls, while controls had greater activation in the visual area BA 17 than cannabis users. Cannabis users also had higher salivary cortisol levels than controls (p = 0.002). Chronic active cannabis use is associated with slower and less efficient psychomotor function, especially in the male users, as indicated by a shift from regions involved with automated visually guided responses to more executive or attentional control areas. These brain activities may be attenuated by the higher cortisol levels in the cannabis users which in turn may lead to less efficient visual-motor function. PMID:22159107

King, G.R.; Ernst, T.; Deng, W.; Stenger, A.; Gonzales, R.M.K; Nakama, H.; Chang, L.

2012-01-01

324

Cannabinoid receptor type-2 stimulation, blockade, and deletion alters the vascular inflammatory responses to traumatic brain injury.  

PubMed

BackgroundImmunomodulatory therapies have been identified as interventions for secondary injury after traumatic brain injury (TBI). The cannabinoid receptor type-2 (CB2R) is proposed to play an important, endogenous role in regulating inflammation. The effects of CB2R stimulation, blockade, and deletion on the neurovascular inflammatory responses to TBI were assessed.MethodsWild-type C57BL/6 or CB2R knockout mice were randomly assigned to controlled cortical impact (CCI) injury or to craniotomy control groups. The effects of treatment with synthetic, selective CB2R agonists (0-1966 and JWH-133), a selective CB2R antagonist, or vehicle solution administered to CCI groups were assessed at 1-day after injury. Changes in TNF-¿, intracellular adhesion molecule (ICAM-1), inducible nitric oxide synthase (iNOS), macrophage/microglial ionized calcium-binding adaptor molecule, and blood-brain-barrier (BBB) permeability were assessed using ELISA, quantitative RT-PCR, immunohistochemistry, and fluorometric analysis of sodium fluorescein uptake. CB2R knockouts and wild-type mice with CCI injury were treated with a CB2R agonist or vehicle treatment.ResultsTNF-¿ mRNA increased at 6 hours and 1 to 3 days after CCI; a CB2R antagonist and genetic knockout of the CB2R exacerbated TNF-¿ mRNA expression. Treatment with a CB2R agonist attenuated TNF-¿ protein levels indicating post-transcriptional mechanisms. Intracellular adhesion molecule (ICAM-1) mRNA was increased at 6 hours, and at 1 to 2 days after CCI, reduced in mice treated with a CB2R agonist, and increased in CB2R knockout mice with CCI. Sodium fluorescein uptake was increased in CB2R knockouts after CCI, with and without a CB2R agonist. iNOS mRNA expression peaked early (6 hours) and remained increased from 1 to 3 days after injury. Treatment with a CB2R agonist attenuated increases in iNOS mRNA expression, while genetic deletion of the CB2R resulted in substantial increases in iNOS expression. Double label immunohistochemistry confirmed that iNOS was expressed by macrophage/microglia in the injured cortex.ConclusionFindings demonstrate that the endogenous cannabinoid system and CB2R play an important role in regulating inflammation and neurovascular responses in the traumatically injured brain. CB2R stimulation with two agonists (0-1966 and JWH-133) dampened post-traumatic inflammation, while blockade or deletion of the CB2R worsened inflammation. Findings support previous evidence that modulating the CB2R alters infiltrating macrophages and activated resident microglia. Further investigation into the role of the CB2R on specific immune cell populations in the injured brain is warranted. PMID:25416141

Amenta, Peter S; Jallo, Jack I; Tuma, Ronald F; Hooper, Douglas C; Elliott, Melanie B

2014-11-22

325

Low brain allopregnanolone levels mediate flattened circadian activity associated with memory impairments in aged rats  

PubMed Central

Background Sleep and cognitive impairments are two of the most prevalent neuropsychiatric disorders in the aged population. Age-related memory dysfunctions can result from alterations in sleep/wake circadian rhythm. However, the underlying mechanism of these alterations is unknown. Here, we demonstrate the role of alterations in brain steroid levels in age-related sleep-dependent memory impairment in rats. Methods Sleep/wake circadian activity and spatial memory performance were evaluated in adult, middle-aged, and aged rats, and steroid levels were measured in brain structures involved in mediating sleep-dependent memory processes using gas chromatography/mass spectrometry. The causal relationship between circadian activity and allopregnanolone levels was assessed using an inhibitor of allopregnanolone synthesis (indomethacin). Results Similar to observations in humans, a subpopulation of middle-aged and aged rats show flattened amplitude of circadian activity associated with impaired spatial long-term memory performance. Sleep-dependent memory dysfunction was associated with a low level of allopregnanolone in the hypothalamus, pedunculopontine nucleus, and ventral striatum. Inhibition of allopregnanolone synthesis in young rats decreased allopregnanolone in the hypothalamus and produced flattened amplitude of circadian activity similar to aged rats. Conclusions These findings identify brainstem and basal forebrain allopregnanolone as an essential endogenous substrate involved in mediating sleep-dependent memory function in young and aged rats. Allopregnanolone may play a critical role in preserving individuals from age-induced alterations in sleep and memory processes and may represent a novel target for attenuating age-related declines in sleep and memory. PMID:20471631

George, Olivier; Vallée, Monique; Vitiello, Sergio; Le Moal, Michel; Piazza, Pier-Vincenzo; Mayo, Willy

2010-01-01

326

Proteomic analysis of mouse models of Niemann-Pick C disease reveals alterations in the steady-state levels of lysosomal proteins within the brain  

PubMed Central

Niemann-Pick C disease (NPC) is a neurodegenerative lysosomal disorder characterized by storage of cholesterol and other lipids caused by defects in NPC1, a transmembrane protein involved in cholesterol export from the lysosome, or NPC2, an intralysosomal cholesterol transport protein. Alterations in lysosomal activities have been implicated in NPC pathogenesis therefore the aim of this study was to conduct a proteomic analysis of lysosomal proteins in mice deficient in either NPC1 or NPC2 to identify secondary changes that might be associated with disease. Lysosomal proteins containing the specific mannose 6-phosphate modification were purified from wild-type and Npc1?/? and Npc2?/? mutant mouse brains at different stages of disease progression and identified by bottom-up LC-MS/MS and quantified by spectral counting. Levels of a number of lysosomal proteins involved in lipid catabolism including prosaposin and the two subunits of ?-hexosaminidase were increased in both forms of NPC, possibly representing a compensatory cellular response to the accumulation of glycosphingolipids. Several other lysosomal proteins were significantly altered, including proteases and glycosidases. Changes in lysosomal protein levels corresponded with similar alterations in activities and transcript levels. Understanding the rationale for such changes may provide insights into the pathophysiology of NPC. PMID:23070805

Sleat, David E.; Wiseman, Jennifer A.; Sohar, Istvan; El –Banna, Mukarram; Zheng, Haiyan; Moore, Dirk F.; Lobel, Peter

2013-01-01

327

Mapping Functional Brain Activation Using [14C]-Iodoantipyrine in Male Serotonin Transporter Knockout Mice  

PubMed Central

Background Serotonin transporter knockout mice have been a powerful tool in understanding the role played by the serotonin transporter in modulating physiological function and behavior. However, little work has examined brain function in this mouse model. We tested the hypothesis that male knockout mice show exaggerated limbic activation during exposure to an emotional stressor, similar to human subjects with genetically reduced transcription of the serotonin transporter. Methodology/Principal Findings Functional brain mapping using [14C]-iodoantipyrine was performed during recall of a fear conditioned tone. Regional cerebral blood flow was analyzed by statistical parametric mapping from autoradiographs of the three-dimensionally reconstructed brains. During recall, knockout mice compared to wild-type mice showed increased freezing, increased regional cerebral blood flow of the amygdala, insula, and barrel field somatosensory cortex, decreased regional cerebral blood flow of the ventral hippocampus, and conditioning-dependent alterations in regional cerebral blood flow in the medial prefrontal cortex (prelimbic, infralimbic, and cingulate). Anxiety tests relying on sensorimotor exploration showed a small (open field) or paradoxical effect (marble burying) of loss of the serotonin transporter on anxiety behavior, which may reflect known abnormalities in the knockout animal's sensory system. Experiments evaluating whisker function showed that knockout mice displayed impaired whisker sensation in the spontaneous gap crossing task and appetitive gap cross training. Conclusions This study is the first to demonstrate altered functional activation in the serotonin transporter knockout mice of critical nodes of the fear conditioning circuit. Alterations in whisker sensation and functional activation of barrel field somatosensory cortex extend earlier reports of barrel field abnormalities, which may confound behavioral measures relying on sensorimotor exploration. PMID:21886833

Pang, Raina D.; Wang, Zhuo; Klosinski, Lauren P.; Guo, Yumei; Herman, David H.; Celikel, Tansu; Dong, Hong Wei; Holschneider, Daniel P.

2011-01-01

328

Developmental vitamin D deficiency alters brain protein expression in the adult rat: Implications for neuropsychiatric disorders  

Microsoft Academic Search

An increased risk for multiple sclerosis and schizophrenia is observed at increasing latitude and in patients born in winter or spring. To explore a possible link between maternal vitamin D deficiency and these brain disorders, we examined the impact of prenatal hypovitaminosis D on protein expression in the adult rat brain. Vitamin D-deficient female rats were mated with vita- min

Lionel Almeras; Darryl Eyles; Philippe Benech; Daniel Laffite; Claude Villard; Angela Patatian; Jose Boucraut; Alan Mackay-Sim; John McGrath; François Féron

2007-01-01

329

The antidepressant tranylcypromine alters cellular proliferation and migration in the adult goldfish brain.  

PubMed

The goldfish (Carassius auratus) is a widely studied vertebrate model organism for studying cell proliferation in the adult brain, and provide the experimental advantage of growing their body and brain throughout their ?30-year life time. Cell proliferation occurs in the teleost brain in widespread proliferation zones. Increased cell proliferation in the brain has been linked to the actions of certain antidepressants, including tranylcypromine (TCP), which is used in the treatment of depression. We hypothesized that proliferation zones in the adult goldfish brain can be used to determine the antidepressant effects on cellular proliferation. Here, we report that bromodeoxyuridine (BrdU) labeling over a 24-hr period can be used to rapidly identify the proliferation zones throughout the goldfish brain, including the telencephalon, diencephalon, optic tectal lobes, cerebellum, and facial and vagal lobes. In the first 24 hr of BrdU administration, TCP caused an approximate and significant doubling of labeled cells in the combined brain regions examined, as detected by BrdU immunohistochemistry. TCP caused the greatest increase in cell proliferation in the cerebellum. The normal migratory paths of the proliferating cells within the cerebellum were not affected by TCP treatment. These results indicate that the goldfish provide significant advantages as a vertebrate model for rapidly investigating the effects of antidepressant drugs on cellular proliferation and migration in the normal and injured brain. PMID:24816924

Romanczyk, Tara B; Jacobowitz, David M; Pollard, Harvey B; Wu, Xingjia; Anders, Juanita J

2014-10-01

330

Changes in Connectivity after Visual Cortical Brain Damage Underlie Altered Visual Function  

ERIC Educational Resources Information Center

The full extent of the brain's ability to compensate for damage or changed experience is yet to be established. One question particularly important for evaluating and understanding rehabilitation following brain damage is whether recovery involves new and aberrant neural connections or whether any change in function is due to the functional…

Bridge, Holly; Thomas, Owen; Jbabdi, Saad; Cowey, Alan

2008-01-01

331

Can human activities alter the drowning fate of barrier islands?  

NASA Astrophysics Data System (ADS)

Low-lying coastal barriers face an uncertain future over the coming century and beyond as sea levels rise, with many projections suggesting end-of-century rates of sea-level rise as high or higher than 1 cm/yr. Geologically, such rates of sea-level rise have been experienced several thousand years ago and we can use our understanding of geological processes and sedimentary evidence to help unravel the dynamics of natural barriers experiencing sea-level rise. Along many modern coastal barriers, however, anthropic change, such as beach nourishment, dune construction, and emplacement of hard structures, plays a dominant role in coastline dynamics. A fundamental question to be addressed is whether human activities intended to preserve infrastructure and beach recreation may make wholesale collapse, or 'drowning,' of barrier systems more likely. Here we present a numerical modeling tool that couples natural processes and the human responses to these changes (and the subsequent of human responses on natural processes). Recent theoretical model development suggests that barriers are intrinsically morphodynamic features, responding to sea-level rise in complex ways through the interactions of marine processes and barrier overwash. Undeveloped coastal barriers would therefore respond to an accelerated sea-level rise in complex, less predictable manners than suggested by existing long-term models. We have developed a model that examines non-equilibrium cross-shore evolution of barrier systems at decadal to centennial temporal scales, focusing on the interactions between processes of shoreface evolution and overwash deposition. Model responses demonstrate two means of barrier collapse during sea-level rise: 'height drowning', which occurs when overwash fluxes are insufficient to maintain the landward migration rate required to keep in pace with sea-level rise, and 'width drowning', which occurs when the shoreface response is insufficient to maintain the barrier geometry during landward migration. The model also demonstrates the potential for discontinuous shoreline retreat, with alternating periods of barrier stability and rapid migration, even for constant rates of sea-level rise. Anthropic activities can strongly interact with these behaviors. In particular, considering only cross-shore processes, beach nourishment activities widen the beach and can affect shoreface fluxes, and dune building, which curtails the overwash process, can potentially enhance barrier drowning by reducing overwash fluxes. Furthermore, coastal protection activities of adjacent communities or even individual property holders can be uncoordinated or coordinated, with their effects coupled along the coast through coastal reorientation and gradients in alongshore sediment transport. In the coordinated framework, owners act in concert to alter the barrier based upon community benefits, whereas in the non-coordinated framework owners alter only their own property. Another important role in management is the perception of future sea-level-rise-associated losses—communities manage their coast differently depending on their adopted forecast for sea-level rise. We find that coordinated behavior coupled with natural processes can substantially affect the drowning scenarios from the individual decision-making process.

Lorenzo-Trueba, J.; Ashton, A. D.; Jin, D.; Hoagland, P.; Kite-Powell, H.

2012-12-01

332

Brain cellular and mitochondrial respiration in media of altered pH  

Microsoft Academic Search

This study was designed to investigate the effects of altered pH on cellular aerobic energy metabolism in the immature and adult rat cerebral cortex. Cerebral cortical slice respiration was measured polarographically in acid and alkaline media. In separate experiments, the extracellular pH was changed by altering the HCO3- concentration or the intracellular pH and extracellular pH were changed by altering

D. Holtzman; J. E. Olson; H. Nguyen; J. Hsu; N. Lewiston

1987-01-01

333

Real-world carbon nanoparticle exposures induce brain and gonadal alterations in zebrafish (Danio rerio) as determined by biospectroscopy techniques.  

PubMed

Carbon-based nanoparticles (CNPs) have emerged as novel man-made materials with diverse applications, which may present significant risks to organisms. To bridge the gap in our knowledge of nanotoxicology, a number of in vitro or in vivo studies have been carried out. However, toxicity data remains limited. Herein, we employed a biospectroscopy approach to assess CNP-induced effects in zebrafish (Danio rerio). Zebrafish were exposed to Fullerene (C60), long or short multi-walled carbon nanotubes (MWCNTs), or single-walled carbon nanotubes (SWCNTs) for 21 days at two concentrations: 0.1 mg L(-1) or 0.001 mg L(-1). Following exposure, the brain, gills, gonads and liver from zebrafish were interrogated by attenuated total reflection Fourier-transform infrared (ATR-FTIR) or Raman spectroscopy. Computational analysis was then applied to the acquired infrared (IR) spectra, and distinct biochemical segregations between the exposed tissues vs. control were observed with spectral biomarkers of alterations identified. In addition, lipid-to-protein ratios in all four tissues were calculated by the IR spectra; unsaturated lipid levels in brain and gonad were assessed by Raman spectroscopy. Marked lipid alterations were observed. These findings show that biospectroscopy approaches have the potential to detect CNP-induced biochemical alterations in zebrafish. PMID:25745670

Li, Junyi; Ying, Guang-Guo; Jones, Kevin C; Martin, Francis L

2015-03-30

334

Inferring deep-brain activity from cortical activity using functional near-infrared spectroscopy  

PubMed Central

Functional near-infrared spectroscopy (fNIRS) is an increasingly popular technology for studying brain function because it is non-invasive, non-irradiating and relatively inexpensive. Further, fNIRS potentially allows measurement of hemodynamic activity with high temporal resolution (milliseconds) and in naturalistic settings. However, in comparison with other imaging modalities, namely fMRI, fNIRS has a significant drawback: limited sensitivity to hemodynamic changes in deep-brain regions. To overcome this limitation, we developed a computational method to infer deep-brain activity using fNIRS measurements of cortical activity. Using simultaneous fNIRS and fMRI, we measured brain activity in 17 participants as they completed three cognitive tasks. A support vector regression (SVR) learning algorithm was used to predict activity in twelve deep-brain regions using information from surface fNIRS measurements. We compared these predictions against actual fMRI-measured activity using Pearson’s correlation to quantify prediction performance. To provide a benchmark for comparison, we also used fMRI measurements of cortical activity to infer deep-brain activity. When using fMRI-measured activity from the entire cortex, we were able to predict deep-brain activity in the fusiform cortex with an average correlation coefficient of 0.80 and in all deep-brain regions with an average correlation coefficient of 0.67. The top 15% of predictions using fNIRS signal achieved an accuracy of 0.7. To our knowledge, this study is the first to investigate the feasibility of using cortical activity to infer deep-brain activity. This new method has the potential to extend fNIRS applications in cognitive and clinical neuroscience research. PMID:25798327

Liu, Ning; Cui, Xu; Bryant, Daniel M.; Glover, Gary H.; Reiss, Allan L.

2015-01-01

335

Alterations in cerebrospinal fluid glycerophospholipids and phospholipase A2 activity in Alzheimer's disease[S  

PubMed Central

Our aim is to study selected cerebrospinal fluid (CSF) glycerophospholipids (GP) that are important in brain pathophysiology. We recruited cognitively healthy (CH), minimally cognitively impaired (MCI), and late onset Alzheimer's disease (LOAD) study participants and collected their CSF. After fractionation into nanometer particles (NP) and supernatant fluids (SF), we studied the lipid composition of these compartments. LC-MS/MS studies reveal that both CSF fractions from CH subjects have N-acyl phosphatidylethanolamine, 1-radyl-2-acyl-sn-glycerophosphoethanolamine (PE), 1-radyl-2-acyl-sn-glycerophosphocholine (PC), 1,2-diacyl-sn-glycerophosphoserine (PS), platelet-activating factor-like lipids, and lysophosphatidylcholine (LPC). In the NP fraction, GPs are enriched with a mixture of saturated, monounsaturated, and polyunsaturated fatty acid species, while PE and PS in the SF fractions are enriched with PUFA-containing molecular species. PC, PE, and PS levels in CSF fractions decrease progressively in participants from CH to MCI, and then to LOAD. Whereas most PC species decrease equally in LOAD, plasmalogen species account for most of the decrease in PE. A significant increase in the LPC-to-PC ratio and PLA2 activity accompanies the GP decrease in LOAD. These studies reveal that CSF supernatant fluid and nanometer particles have different GP composition, and that PLA2 activity accounts for altered GPs in these fractions as neurodegeneration progresses. PMID:23868911

Fonteh, Alfred N.; Chiang, Jiarong; Cipolla, Matthew; Hale, Jack; Diallo, Fatimatou; Chirino, Alejandra; Arakaki, Xianghong; Harrington, Michael G.

2013-01-01

336

Overexpression of cerebral and hepatic cytochrome P450s alters behavioral activity of rat offspring following prenatal exposure to lindane  

SciTech Connect

Oral administration of different doses (0.0625, 0.125 or 0.25 mg/kg corresponding to 1/1400th, 1/700th or 1/350th of LD{sub 50}) of lindane to the pregnant Wistar rats from gestation days 5 to 21 were found to produce a dose-dependent increase in the activity of cytochrome P450 (CYP)-dependent 7-ethoxyresorufin-O-deethylase (EROD), 7-pentoxyresorufin-O-dealkylase (PROD) and N-nitrosodimethylamine demethylase (NDMA-d) in brain and liver of offspring postnatally at 3 weeks. The increase in the activity of CYP monooxygenases was found to be associated with the increase in the mRNA and protein expression of xenobiotic metabolizing CYP1A, 2B and 2E1 isoenzymes in the brain and liver of offspring. Dose-dependent alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 3 weeks have suggested that increase in CYP activity may possibly lead to the formation of metabolites to the levels that may be sufficient to alter the behavioral activity of the offspring. Interestingly, the inductive effect on cerebral and hepatic CYPs was found to persist postnatally up to 6 weeks in the offspring at the relatively higher doses (0.125 and 0.25 mg/kg) of lindane and up to 9 weeks at the highest dose (0.25 mg/kg), though the magnitude of induction was less than that observed at 3 weeks. Alterations in the parameters of spontaneous locomotor activity in the offspring postnatally at 6 and 9 weeks, though significant only in the offspring at 3 and 6-week of age, have further indicated that due to the reduced activity of the CYPs during the ontogeny, lindane and its metabolites may not be effectively cleared from the brain. The data suggest that low dose prenatal exposure to the pesticide has the potential to produce overexpression of xenobiotic metabolizing CYPs in brain and liver of the offspring which may account for the behavioral changes observed in the offspring.

Johri, Ashu; Yadav, Sanjay; Dhawan, Alok [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India); Parmar, Devendra [Developmental Toxicology Division, Industrial Toxicology Research Centre, P. O. Box 80, M. G. Marg, Lucknow-226 001, U. P. (India)], E-mail: parmar_devendra@hotmail.com

2007-12-15

337

Clinical Significance of Basal Ganglia Alterations at Brain MRI and 1 H MRS in Cirrhosis and Role in the Pathogenesis of Hepatic Encephalopathy  

Microsoft Academic Search

In hepatic encephalopathy, a progressive and diffuse impairment in brain function is associated with gradual alterations that can be detected by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H MRS). In some patients, a variety of movement disorders suggestive of extrapyramidal impairment points toward basal ganglia (BG) alterations. Accordingly, (i) hyperintensities at MRI predominant in the pallidum, an

Laurent Spahr; Pierre R. Burkhard; Hannelore Grötzsch; Antoine Hadengue

2002-01-01

338

Not just the brain: methamphetamine disrupts blood-spinal cord barrier and induces acute glial activation and structural damage of spinal cord cells.  

PubMed

Acute methamphetamine (METH) intoxication induces metabolic brain activation as well as multiple physiological and behavioral responses that could result in life-threatening health complications. Previously, we showed that METH (9 mg/kg) used in freely moving rats induces robust leakage of blood-brain barrier, acute glial activation, vasogenic edema, and structural abnormalities of brain cells. These changes were tightly correlated with drug-induced brain hyperthermia and were greatly potentiated when METH was used at warm ambient temperatures (29°C), inducing more robust and prolonged hyperthermia. Extending this line of research, here we show that METH also strongly increases the permeability of the blood-spinal cord barrier as evidenced by entry of Evans blue and albumin immunoreactivity in T9-12 segments of the spinal cord. Similar to the blood-brain barrier, leakage of bloodspinal cord barrier was associated with acute glial activation, alterations of ionic homeostasis, water tissue accumulation (edema), and structural abnormalities of spinal cord cells. Similar to that in the brain, all neurochemical alterations correlated tightly with drug-induced elevations in brain temperature and they were enhanced when the drug was used at 29°C and brain hyperthermia reached pathological levels (>40°C). We discuss common features and differences in neural responses between the brain and spinal cord, two inseparable parts of the central nervous system affected by METH exposure. PMID:25687701

Kiyatkin, Eugene A; Sharma, Hari S

2015-01-01

339

Dietary docosahexaenoic acid supplementation alters select physiological endocannabinoid-system metabolites in brain and plasma  

PubMed Central

The endocannabinoid metabolome consists of a growing, (patho)physiologically important family of fatty-acid derived signaling lipids. Diet is a major source of fatty acid substrate for mammalian endocannabinoid biosynthesis. The principal long-chain PUFA found in mammalian brain, docosahexaenoic acid (DHA), supports neurological function, retinal development, and overall health. The extent to which dietary DHA supplementation influences endocannabinoid-related metabolites in brain, within the context of the circulating endocannabinoid profile, is currently unknown. We report the first lipidomic analysis of acute 2-week DHA dietary supplementation effects on the physiological state of 15 fatty-acid, N-acylethanolamine, and glycerol-ester endocannabinoid metabolome constituents in murine plasma and brain. The DHA-rich diet markedly elevated DHA, eicosapentaenoic acid, 2-eicosapentanoylglycerol (EPG), and docosahexanoylethanolamine in both compartments. Dietary DHA enhancement generally affected the synthesis of the N-acyl-ethanolamine and glycerol-ester metabolites to favor the docosahexaenoic and eicosapentaenoic vs. arachidonoyl and oleoyl homologs in both brain and plasma. The greater overall responsiveness of the endocannabinoid metabolome in plasma versus brain may reflect a more circumscribed homeostatic response range of brain lipids to dietary DHA supplementation. The ability of short-term DHA enhancement to modulate select constituents of the physiological brain and plasma endocannabinoid metabolomes carries metabolic and therapeutic implications. PMID:20071693

Wood, JodiAnne T.; Williams, John S.; Pandarinathan, Lakshmipathi; Janero, David R.; Lammi-Keefe, Carol J.; Makriyannis, Alexandros

2010-01-01

340

Hippocampal Inactivation with TTX Impairs Long-Term Spatial Memory Retrieval and Modifies Brain Metabolic Activity  

PubMed Central

Functional inactivation techniques enable studying the hippocampal involvement in each phase of spatial memory formation in the rat. In this study, we applied tetrodotoxin unilaterally or bilaterally into the dorsal hippocampus to evaluate the role of this brain structure in retrieval of memories acquired 28 days before in the Morris water maze. We combined hippocampal inactivation with the assessment of brain metabolism using cytochrome oxidase histochemistry. Several brain regions were considered, including the hippocampus and other related structures. Results showed that both unilateral and bilateral hippocampal inactivation impaired spatial memory retrieval. Hence, whereas subjects with bilateral hippocampal inactivation showed a circular swim pattern at the side walls of the pool, unilateral inactivation favoured swimming in the quadrants adjacent to the target one. Analysis of cytochrome oxidase activity disclosed regional differences according to the degree of hippocampal functional blockade. In comparison to control group, animals with bilateral inactivation showed increased CO activity in CA1 and CA3 areas of the hippocampus during retrieval, while the activity of the dentate gyrus substantially decreased. However, unilateral inactivated animals showed decreased CO activity in Ammon's horn and the dentate gyrus. This study demonstrated that retrieval recruits differentially the hippocampal subregions and the balance between them is altered with hippocampal functional lesions. PMID:23724089

Conejo, Nélida María; Cimadevilla, José Manuel; González-Pardo, Héctor; Méndez-Couz, Marta; Arias, Jorge Luis

2013-01-01

341

Imaging brain activation in nicotine-sensitized rats.  

PubMed

Our purpose was to determine if sensitization to nicotine could be assessed using functional magnetic resonance imaging (fMRI) with BOLD contrast. Sensitization describes a phenomenon whereby subsequent doses of a drug produce greater responses than the initial dose. Robust locomotor sensitization was demonstrated in adult male Sprague-Dawley rats by the daily administration of nicotine 0.4 mg/kg over 5 days. In parallel experiments, brain activity was monitored using fMRI in animals receiving their first dose (acute) or fifth dose of nicotine (sensitized) and appropriate saline controls. Compared to the acute nicotine animals, brain activity in the sensitized animals demonstrated prolonged BOLD activation in response to nicotine in the hippocampus, nucleus accumbens, prefrontal cortex, ventral pallidum and ventral tegmentum, and more intense peak activation in the hippocampus, prefrontal cortex and ventral tegmentum. In addition, sensitization was associated with a relative decrease in activation in the anterior cingulate gyrus. Furthermore, despite the rich endowment of nicotinic receptors in the visual cortex there was no change in activation with sensitization, thus establishing the specificity of the observed pattern of regional activation and inhibition. Taken together, the current studies support the premise that nicotine sensitization is accompanied by changes in brain activation including a sensitized BOLD response in the extended limbic system that may subserve the process of dependence. PMID:18279841

Li, Zhixin; DiFranza, Joseph R; Wellman, Robert J; Kulkarni, Praveen; King, Jean A

2008-03-14

342

Chronic neck pain alters muscle activation patterns to sudden movements.  

PubMed

The aim of this study was to assess the activation of the sternocleidomastoid (SCM) and splenius capitis (SC) muscles in response to unanticipated, full body perturbations in individuals with chronic neck pain (NP) and age-matched healthy controls (HC). Individuals with NP had a history of NP for 8.9 ± 7.8 years, rated the intensity of NP as 4.2 ± 2.0 (score out of 10), and scored 15.3 ± 6.5 on the Neck Disability Index. Participants stood on a moveable platform during which 32 randomized postural perturbations (eight repetitions of four perturbation types: 8 cm forward slide (FS), 8 cm backward slides, 10° forward tilt, and 10° backward tilt) with varying inter-perturbation time intervals were performed over a period of 5 min. Bilateral surface electromyography (EMG) from the SCM and SC was recorded, and the onset time and the average rectified value of the EMG signal was determined for epochs of 100 ms; starting 100 ms prior to and 500 ms after the perturbation onset. Individuals with NP, as compared to HC, demonstrated delayed onset times and reduced EMG amplitude of the SCM and SC muscles in response to all postural perturbations. Such findings were most pronounced following the FS postural perturbation (healthy vs. NP for SCM 83.3 ± 8.0 vs. 86.3 ± 4.4 and SC 75.6 ± 3.5 vs. 89.3 ± 4.2), which was also associated with the greatest change (expressed in % relative to baseline) in EMG amplitude (healthy vs. NP for SCM 206.6 ± 50.4 vs. 115.9 ± 15.7 and SC 83.4 ± 19.2 vs. 69.2 ± 10.9) across all postural perturbations types. Individuals with NP display altered neural control of the neck musculature in response to rapid, unanticipated full body postural perturbations. Although the relative timing of neck musculature activity in individuals with NP appears to be intact, simultaneous co-activation of the neck musculature emerges for unanticipated anterior-posterior postural perturbations. PMID:24632836

Boudreau, Shellie A; Falla, Deborah

2014-06-01

343

On a Mathematical Model of Brain Activities  

SciTech Connect

The procedure of recognition can be described as follows: There is a set of complex signals stored in the memory. Choosing one of these signals may be interpreted as generating a hypothesis concerning an 'expexted view of the world'. Then the brain compares a signal arising from our senses with the signal chosen from the memory leading to a change of the state of both signals. Furthermore, measurements of that procedure like EEG or MEG are based on the fact that recognition of signals causes a certain loss of excited neurons, i.e. the neurons change their state from 'excited' to 'nonexcited'. For that reason a statistical model of the recognition process should reflect both--the change of the signals and the loss of excited neurons. A first attempt to explain the process of recognition in terms of quantum statistics was given. In the present note it is not possible to present this approach in detail. In lieu we will sketch roughly a few of the basic ideas and structures of the proposed model of the recognition process (Section). Further, we introduce the basic spaces and justify the choice of spaces used in this approach. A more elaborate presentation including all proofs will be given in a series of some forthcoming papers. In this series also the procedures of creation of signals from the memory, amplification, accumulation and transformation of input signals, and measurements like EEG and MEG will be treated in detail.

Fichtner, K.-H. [Friedrich Schiller Unversity Jena, Institute of Applied Mathematics, E.-Abbe-Platz 2, 07743 Jena (Germany); Fichtner, L. [Friedrich Schiller Unversity Jena, Institute of Psychology, Am Steiger 3, 07743 Jena (Germany); Freudenberg, W. [Brandenb. Techn. University Cottbus, Dep. of Mathematics, PO box 10 13 44, 03013 Cottbus (Germany); Ohya, M. [Tokyo University of Science, Department of Information Science, Noda City, Chiba 278-8510 (Japan)

2007-12-03

344

On a Mathematical Model of Brain Activities  

NASA Astrophysics Data System (ADS)

The procedure of recognition can be described as follows: There is a set of complex signals stored in the memory. Choosing one of these signals may be interpreted as generating a hypothesis concerning an "expexted view of the world". Then the brain compares a signal arising from our senses with the signal chosen from the memory leading to a change of the state of both signals. Furthermore, measurements of that procedure like EEG or MEG are based on the fact that recognition of signals causes a certain loss of excited neurons, i.e. the neurons change their state from "excited" to "nonexcited". For that reason a statistical model of the recognition process should reflect both—the change of the signals and the loss of excited neurons. A first attempt to explain the process of recognition in terms of quantum statistics was given in [1]. In the present note it is not possible to present this approach in detail. In lieu we will sketch roughly a few of the basic ideas and structures of the proposed model of the recognition process (Section). Further, we introduce the basic spaces and justify the choice of spaces used in this approach. A more elaborate presentation including all proofs will be given in a series of some forthcoming papers [2, 3]. In this series also the procedures of creation of signals from the memory, amplification, accumulation and transformation of input signals, and measurements like EEG and MEG will be treated in detail.

Fichtner, K.-H.; Fichtner, L.; Freudenberg, W.; Ohya, M.

2007-12-01

345

Brain, Liver, and Serum Salusin-alpha and -beta Alterations in Sprague-Dawley Rats with or without Metabolic Syndrome  

PubMed Central

Background This metabolic syndrome (MetS) study was designed to investigate changes in expression of the neuropeptides salusin-? (Sal-?) and salusin-? (Sal-?) in brain and liver tissue in response to obesity and related changes induced by high-fructose diet and explored how these changes were reflected in the circulating levels of Sal-? and Sal-?, as well as revealing how the lipid profile and concentrations of glucose and uric acid were altered. Material/Methods The study included 14 Sprague-Dawley rats. The control group was fed ad libitum on standard rat pellets, while the intervention group was given water with 10% fructose in addition to the standard rat pellet for 3 months. Sal-? and Sal-? concentrations in the serum and tissue supernatants were measured by ELISA, and immunohistochemical staining was used to demonstrate expression of the hormones in brain and liver. Results Sal-? and Sal-? levels in both the serum and the brain and liver tissue supernatants were lower in the MetS group than the control group. Sal-? and Sal-? were shown by immunohistochemistry to be produced in the brain epithelium, the supraoptic nucleus of the hypothalamus, and the liver hepatocytes. Conclusions The decrease in Sal-? and Sal-? might be involved in the etiopathology of the metabolic syndrome induced by fructose. PMID:25070707

Citil, Cihan; Konar, Vahit; Aydin, Suleyman; Yilmaz, Musa; Albayrak, Serdal; Ozercan, Ibrahim Hanifi; Ozkan, Yusuf

2014-01-01

346

LIPID ABNORMALITIES IN SUCCINATE SEMIALDEHYDE DEHYDROGENASE (Aldh5a1?/?) DEFICIENT MOUSE BRAIN PROVIDE ADDITIONAL EVIDENCE FOR MYELIN ALTERATIONS  

PubMed Central

Earlier work from our laboratory provided evidence for myelin abnormalities (decreased quantities of proteins associated with myelin compaction, decreased sheath thickness) in cortex and hippocampus of Aldh5a1?/? mice, which have a complete ablation of the succinate semialdehyde dehydrogenase protein [1]. In the current report, we have extended these findings via comprehensive analysis of brain phospholipid fractions, including quantitation of fatty acids in individual phospholipid subclasses and estimation of hexose-ceramide in Aldh5a1?/? brain. In comparison to wild-type littermates (Aldh5a1+/+), we detected a 20% reduction in the ethanolamine glycerophospholipid content of Aldh5a1?/? mice, while other brain phospholipids (choline glycerophospholipid, phosphatidylserine and phosphatidylinositol) were within normal limits. Analysis of individual fatty acids in each of these fractions revealed consistent alterations in n-3 fatty acids, primarily increased 22:6n-3 levels (docosahexaenoic acid; DHA). In the phosphatidyl serine fraction there were marked increases in the proportions of polyunsaturated fatty acids with corresponding decreases of monounsaturated fatty acids. Interestingly, the levels of hexose-ceramide (glucosyl- and galactosylceramide, principal myelin cerebrosides) were decreased in Aldh5a1?/? brain tissue (one-tailed t test, p=0.0449). The current results suggest that lipid and myelin abnormalities in this animal may contribute to the pathophysiology. PMID:17300923

Barcelo-Coblijn, G.; Murphy, E. J.; Mills, K.; Winchester, B.; Jakobs, C.; Snead, O.C.; Gibson, KM

2007-01-01

347

Active tactile exploration enabled by a brain-machine-brain interface  

PubMed Central

Brain-machine interfaces (BMIs)1,2 use neuronal activity recorded from the brain to establish direct communication with external actuators, such as prosthetic arms. While BMIs aim to restore the normal sensorimotor functions of the limbs, so far they have lacked tactile sensation. Here we demonstrate the operation of a brain-machine-brain interface (BMBI) that both controls the exploratory reaching movements of an actuator and enables the signalling of artificial tactile feedback through intracortical microstimulation (ICMS) of the primary somatosensory cortex (S1). Monkeys performed an active-exploration task in which an actuator (a computer cursor or a virtual-reality hand) was moved using a BMBI that derived motor commands from neuronal ensemble activity recorded in primary motor cortex (M1). ICMS feedback occurred whenever the actuator touched virtual objects. Temporal patterns of ICMS encoded the artificial tactile properties of each object. Neuronal recordings and ICMS epochs were temporally multiplexed to avoid interference. Two monkeys operated this BMBI to search and discriminate one out of three visually undistinguishable objects, using the virtual hand to identify the unique artificial texture (AT) associated with each. These results suggest that clinical motor neuroprostheses might benefit from the addition of ICMS feedback to generate artificial somatic perceptions associated with mechanical, robotic, or even virtual prostheses. PMID:21976021

O’Doherty, Joseph E.; Lebedev, Mikhail A.; Ifft, Peter J.; Zhuang, Katie Z.; Shokur, Solaiman; Bleuler, Hannes; Nicolelis, Miguel A. L.

2011-01-01

348

Composition and On Demand Deployment of Distributed Brain Activity Analysis Application on Global Grids  

E-print Network

1 Composition and On Demand Deployment of Distributed Brain Activity Analysis Application on Global are brain science and high-energy physics. The analysis of brain activity data gathered from the MEG and analyze brain functions and requires access to large-scale computational resources. The potential platform

Abramson, David

349

2D-1H proton magnetic resonance spectroscopic imaging study on brain metabolite alterations in patients with diabetic hypertension.  

PubMed

The aim of the present study was to investigate the possible metabolic alterations in the frontal cortex and parietal white matter in patients with diabetic hypertension (DHT) using proton magnetic resonance (MR) spectroscopic imaging. A total of 33 DHT patients and 30 healthy control subjects aged between 45 and 75 were included in the present study. All subjects were right?handed. The spectroscopy data were collected using a GE Healthcare 1.5T MR scanner. The multi?voxels were located in the semioval center (repetition time/echo time=1,500 ms/35 ms). The area of interest was 8x10x2 cm in volume and contained the two sides of the frontal cortex and the parietal white matter. The spectra data were processed using SAGE software. The ratios of brain metabolite concentrations, particularly for N?acetylaspartate (NAA)/creatine (Cr) and Choline (Cho)/Cr were calculated and analyzed. Statistical analyses were performed using SPSS 17.0. The NAA/Cr ratio of the bilateral prefrontal cortex of the DHT group was significantly lower than that of the control group (left t=?7.854, P=0.000 and right t=?5.787, P=0.000), The Cho/Cr ratio was also much lower than the control group (left t=2.422, P=0.024 and right t=2.920, P=0.007). NAA/Cr ratio of the left parietal white matter of the DHT group was extremely lower than that of the control group (t=?4.199, P=0.000). Therefore, DHT may result in metabolic disorders in the frontal cortex and parietal white matter but the metabolic alterations are different in various regions of the brain. The alteration in cerebral metabolism is associated with diabetes and hypertension. The ratios of NAA/Cr and Cho/Cr are potential metabolic markers for the brain damage induced by DHT. PMID:25652580

Cao, Zhen; Ye, Bi-Di; Shen, Zhi-Wei; Cheng, Xiao-Fang; Yang, Zhong-Xian; Liu, Yan-Yan; Wu, Ren-Hua; Geng, Kuan; Xiao, Ye-Yu

2015-06-01

350

BRAIN CHOLINESTERASE ACTIVITY OF BOBWHITE ACUTELY EXPOSED TO CHLORPYRIFOS  

EPA Science Inventory

Northern bobwhite, Colinus virginianus, were orally dosed with the organophosphorus insecticide chlorpyrifos to examine effects on brain cholinesterase (AChE) activity. wo-week-old quail were acutely exposed and euthanized at selected times following gavage-dosing, ranging from 1...

351

Working Memory Training: Improving Intelligence--Changing Brain Activity  

ERIC Educational Resources Information Center

The main objectives of the study were: to investigate whether training on working memory (WM) could improve fluid intelligence, and to investigate the effects WM training had on neuroelectric (electroencephalography--EEG) and hemodynamic (near-infrared spectroscopy--NIRS) patterns of brain activity. In a parallel group experimental design,…

Jausovec, Norbert; Jausovec, Ksenija

2012-01-01

352

Measurement of brain activity using optical and electrical method  

Microsoft Academic Search

There are patients that cannot produce bioelectric signals such as patients with advanced stages of Amyotrophic Lateral Sclerosis or that have suffered severe spinal cord injury, are unable to use assistive devices such as the exoskeleton HAL. This paper proposes a non-invasive brain activity scanning method for collecting the patient's movement intentions by developing a hybrid sensor that can measure

Atsushi Saito; Alexsandr Ianov; Yoshiyuki Sankai

2009-01-01

353

Influence of endocrine active compounds on the developing rodent brain  

Microsoft Academic Search

Changes in the volumes of sexually dimorphic brain nuclei are often used as a biomarker for developmental disruption by endocrine-active compounds (EACs). However, these gross, morphological analyses do not reliably predict disruption of cell phenotype or neuronal function. Therefore, an experimental approach that simultaneously assesses anatomical, physiological and behavioral endpoints is required when developing risk assessment models for EAC exposure.

Heather B. Patisaul; Eva K. Polston

2008-01-01

354

Acute Exposure to Perchlorethylene alters Rat Visual Evoked Potentials in Relation to Brain Concentration  

EPA Science Inventory

These experiments sought to establish a dose-effect relationship between the concentration of perchloroethylene (PCE) in brain tissue and concurrent changes in visual function. A physiologically-based pharmacokinetic (PBPK) model was implemented to predict concentrations of PCE ...

355

Describing brain activity of persons with AD and depressive symptoms.  

PubMed

The purpose of this retrospective pilot study was to characterize depression of AD using electrophysiological changes in the brain activity of persons with AD and depressive symptoms. Participants had a mean age of 70.12±12.68. Participants manifested an increase in absolute/relative theta activity (p=.000) over entire brain when compared to normative population-based database. Electrophysiological changes did not differ by age or gender except for increased absolute theta activity in the right lateral frontal areas (t-test=-2.31 to -2.39, p=.04) in females. An increased theta activity suggests that depressive symptoms may be part of AD symptomatology, not a co-morbid feature. PMID:25457693

Holston, Ezra C

2014-12-01

356

Chemotherapy altered brain functional connectivity in women with breast cancer: a pilot study.  

PubMed

Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, 1 month after, and 1 year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity 1 month after chemotherapy that partially returned to baseline at 1 year in the dorsal attention network. Decreased connectivity was seen in the default mode network at 1 month and 1 year following chemotherapy. In addition, increased subjective memory complaints were noted at 1 month and 1 year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

Dumas, Julie A; Makarewicz, Jenna; Schaubhut, Geoffrey J; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A

2013-12-01

357

Chemotherapy Altered Brain Functional Connectivity in Women with Breast Cancer: A Pilot Study  

PubMed Central

Adjuvant chemotherapy is associated with improvements in long-term cancer survival. However, reports of cognitive impairment following treatment emphasize the importance of understanding the long-term effects of chemotherapy on brain functioning. Cognitive deficits found in chemotherapy patients suggest a change in brain functioning that affects specific cognitive domains such as attentional processing and executive functioning. This study examined the processes potentially underlying these changes in cognition by examining brain functional connectivity pre- and post-chemotherapy in women with breast cancer. Functional connectivity examines the temporal correlation between spatially remote brain regions in an effort to understand how brain networks support specific cognitive functions. Nine women diagnosed with breast cancer completed a functional magnetic resonance imaging (fMRI) session before chemotherapy, one month after, and one year after the completion of chemotherapy. Seed-based functional connectivity analyses were completed using seeds in the intraparietal sulcus (IPS) to examine connectivity in the dorsal anterior attention network and in the posterior cingulate cortex (PCC) to examine connectivity in the default mode network. Results showed decreased functional connectivity one month after chemotherapy that partially returned to baseline at one year in the dorsal attention network. Decreased connectivity was seen in the default mode network at one month and one year following chemotherapy. In addition, increased subjective memory complaints were noted at one month and one year post-chemotherapy. These findings suggest a detrimental effect of chemotherapy on brain functional connectivity that is potentially related to subjective cognitive assessment. PMID:23852814

Dumas, Julie A.; Makarewicz, Jenna; Schaubhut, Geoffrey J.; Devins, Robert; Albert, Kimberly; Dittus, Kim; Newhouse, Paul A.

2013-01-01

358

Temporal- and Location-Specific Alterations of the GABA Recycling System in Mecp2 KO Mouse Brains  

PubMed Central

Rett syndrome (RTT), associated with mutations in methyl-CpG-binding protein 2 (Mecp2), is linked to diverse neurological symptoms such as seizures, motor disabilities, and cognitive impairments. An altered GABAergic system has been proposed as one of many underlying pathologies of progressive neurodegeneration in several RTT studies. This study for the first time investigated the temporal- and location-specific alterations in the expression of ?-amino butyric acid (GABA) transporter 1 (GAT-1), vesicular GABA transporter (vGAT), and glutamic acid decarboxylase 67kD (GAD67) in wild type (WT) and knockout (KO) mice in the Mecp2tm1.1Bird/y mouse model of RTT. Immunohistochemistry (IHC) co-labeling of GAT-1 with vGAT identified GABAergic synapses that were quantitated for mid-sagittal sections in the frontal cortex (FC), hippocampal dentate gyrus (DG), and striatum (Str). An age-dependent increase in the expression of synaptic GABA transporters, GAT-1, and vGAT, was observed in the FC and DG in WT brains. Mecp2 KO mice showed a significant alteration in this temporal profile that was location-specific, only in the FC. GAD67-positive cell densities also showed an age-dependent increase in the FC, but a decrease in the DG in WT mice. However, these densities were not significantly altered in the KO mice in the regions examined in this study. Therefore, the significant location-specific downregulation of synaptic GABA transporters in Mecp2 KO brains with unaltered densities of GAD67-positive interneurons may highlight the location-specific synaptic pathophysiology in this model of RTT. PMID:24737935

Kang, Seok K; Kim, Shin Tae; Johnston, Michael V; Kadam, Shilpa D

2014-01-01

359

Alterations in brain neurotrophic and glial factors following early age chronic methylphenidate and cocaine administration.  

PubMed

Attention deficit hyperactivity disorder (ADHD) overdiagnosis and a pharmacological attempt to increase cognitive performance, are the major causes for the frequent (ab)use of psychostimulants in non-ADHD individuals. Methylphenidate is a non-addictive psychostimulant, although its mode of action resembles that of cocaine, a well-known addictive and abused drug. Neuronal- and glial-derived growth factors play a major role in the development, maintenance and survival of neurons in the central nervous system. We hypothesized that methylphenidate and cocaine treatment affect the expression of such growth factors. Beginning on postnatal day (PND) 14, male Sprague Dawley rats were treated chronically with either cocaine or methylphenidate. The rats were examined behaviorally and biochemically at several time points (PND 35, 56, 70 and 90). On PND 56, rats treated with cocaine or methylphenidate from PND 14 through PND 35 exhibited increased hippocampal glial-cell derived neurotrophic factor (GDNF) mRNA levels, after 21 withdrawal days, compared to the saline-treated rats. We found a significant association between cocaine and methylphenidate treatments and age progression in the prefrontal protein expression of brain derived neurotrophic factor (BDNF). Neither treatments affected the behavioral parameters, although acute cocaine administration was associated with increased locomotor activity. It is possible that the increased hippocampal GDNF mRNA levels, may be relevant to the reduced rate of drug seeking behavior in ADHD adolescence that were maintained from childhood on methylphenidate. BDNF protein level increase with age, as well as following stimulant treatments at early age may be relevant to the neurobiology and pharmacotherapy of ADHD. PMID:25576963

Simchon-Tenenbaum, Yaarit; Weizman, Abraham; Rehavi, Moshe

2015-04-01

360

Brain  

MedlinePLUS

... will return after updating. Resources Archived Modules Updates Brain Cerebrum The cerebrum is the part of the ... the outside of the brain and spinal cord. Brain Stem The brain stem is the part of ...

361

Brain Electrical Activity Changes and Cognitive Development.  

ERIC Educational Resources Information Center

This study investigated the relationship of cognitive developmental changes to physiological and anatomical changes by measuring both types of data within the same subjects. Cortical electrical activity was measured in 24 males between 10 and 12 years of age. Event-related potentials (ERPs) were recorded from midline scalp electrodes during a…

Hartley, Deborah; Thomas, David G.

362

Altered Regional and Circuit Resting-State Activity Associated with Unilateral Hearing Loss  

PubMed Central

The deprivation of sensory input after hearing damage results in functional reorganization of the brain including cross-modal plasticity in the sensory cortex and changes in cognitive processing. However, it remains unclear whether partial deprivation from unilateral auditory loss (UHL) would similarly affect the neural circuitry of cognitive processes in addition to the functional organization of sensory cortex. Here, we used resting-state functional magnetic resonance imaging to investigate intrinsic activity in 34 participants with UHL from acoustic neuroma in comparison with 22 matched normal controls. In sensory regions, we found decreased regional homogeneity (ReHo) in the bilateral calcarine cortices in UHL. However, there was an increase of ReHo in the right anterior insular cortex (rAI), the key node of cognitive control network (CCN) and multimodal sensory integration, as well as in the left parahippocampal cortex (lPHC), a key node in the default mode network (DMN). Moreover, seed-based resting–state functional connectivity analysis showed an enhanced relationship between rAI and several key regions of the DMN. Meanwhile, lPHC showed more negative relationship with components in the CCN and greater positive relationship in the DMN. Such reorganizations of functional connectivity within the DMN and between the DMN and CCN were confirmed by a graph theory analysis. These results suggest that unilateral sensory input damage not o