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1

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

E-print Network

and deactivation would occur in persons with an at-risk mental state performing a working memory task that entailed=60), identified using the Comprehensive Assessment of At-Risk Mental States, and healthy com- parisonArticle Preserved Working Memory and Altered Brain Activation in Persons at Risk for Psychosis Siti

Adcock, R. Alison

2

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

PubMed Central

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

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

2012-01-01

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

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

PubMed

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 investigated 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

2013-06-15

5

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

6

Alterations in regional homogeneity of spontaneous brain activity in late-life subthreshold depression.  

PubMed

The early detection of major depression in elderly individuals who are at risk of developing the disease is of prime importance when it comes to the prevention of geriatric depression. We used resting-state functional magnetic resonance imaging (fMRI) to examine changes in regional homogeneity (ReHo) of spontaneous activity in late-life subthreshold depression (StD), and we evaluated the sensitivity/specificity performance of these changes. Nineteen elderly individuals with StD and 18 elderly controls underwent a resting-state fMRI scan. The ReHo approach was employed to examine whether StD was related to alterations in resting-state neural activity, in the form of abnormal regional synchronization. Receiver operating characteristic curve analysis and the Fisher stepwise discriminant analysis were used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the StD subjects and normal controls. The results demonstrated that, compared to controls, StD subjects display lower ReHo in the right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), left postcentral gyrus (PCG), and left middle frontal and inferior temporal gyri, as well as higher ReHo in the bilateral insula and right DLPFC. The left PCG and the right DLPFC, OFC, and posterior insula, together reported a predictive accuracy of 91.9%. These results suggest that the regional activity coherence was changed in the resting brain of StD subjects, and that these alterations may serve as potential markers for the early detection of StD in late-life depression. PMID:23301035

Ma, Zhenling; Li, Rui; Yu, Jing; He, Yong; Li, Juan

2013-01-01

7

Alterations in Regional Homogeneity of Spontaneous Brain Activity in Late-Life Subthreshold Depression  

PubMed Central

The early detection of major depression in elderly individuals who are at risk of developing the disease is of prime importance when it comes to the prevention of geriatric depression. We used resting-state functional magnetic resonance imaging (fMRI) to examine changes in regional homogeneity (ReHo) of spontaneous activity in late-life subthreshold depression (StD), and we evaluated the sensitivity/specificity performance of these changes. Nineteen elderly individuals with StD and 18 elderly controls underwent a resting-state fMRI scan. The ReHo approach was employed to examine whether StD was related to alterations in resting-state neural activity, in the form of abnormal regional synchronization. Receiver operating characteristic curve analysis and the Fisher stepwise discriminant analysis were used to evaluate the sensitivity/specificity characteristics of the ReHo index in discriminating between the StD subjects and normal controls. The results demonstrated that, compared to controls, StD subjects display lower ReHo in the right orbitofrontal cortex (OFC), left dorsolateral prefrontal cortex (DLPFC), left postcentral gyrus (PCG), and left middle frontal and inferior temporal gyri, as well as higher ReHo in the bilateral insula and right DLPFC. The left PCG and the right DLPFC, OFC, and posterior insula, together reported a predictive accuracy of 91.9%. These results suggest that the regional activity coherence was changed in the resting brain of StD subjects, and that these alterations may serve as potential markers for the early detection of StD in late-life depression. PMID:23301035

Yu, Jing; He, Yong; Li, Juan

2013-01-01

8

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

PubMed Central

It is well known that the dopamine (DA) system plays an essential role in the organization and regulation of brain activational processes. Various environmental stimuli that induce locomotor activation also increase DA transmission, while DA antagonists decrease spontaneous locomotion. Our previous work supports close relationships between locomotor activation and brain and body temperature increases induced by salient environmental challenges or occurring during motivated behavior. While this correlation was also true for psychomotor stimulant drugs such as meth-amphetamine and MDMA, more complex relationships or even inverted correlations were found for other drugs that are known to increase DA transmission (i.e., heroin and cocaine). In the present study we examined brain (NAcc), muscle and skin temperatures together with conventional locomotion during selective interruption of DA transmission induced by a mixture of D1 and D2 antagonists (SCH23390 and eticlopride at 0.2 mg/kg, sc) and its selective activation by apomorphine (APO 0.05 and 0.25 mg/kg, iv). While full DA receptor blockade decreased spontaneous locomotion, it significantly increased brain, muscle and skin temperatures, suggesting metabolic brain activation under conditions of vasodilatation (or weakening of normal vascular tone). In contrast, APO strongly decreased skin temperature but tended to decrease brain and muscle temperatures despite strong hyperlocomotion and stereotypy. The brain temperature response to APO was strongly dependent on basal brain temperature, with hypothermia at high basal temperatures and weak hyperthermia at low temperatures. While supporting the role of DA in locomotor activation, these data suggest more complex relationships between drug-induced alterations in DA transmission, behavioral activation and metabolic brain activation. PMID:17196751

Brown, P. Leon; Bae, David; Kiyatkin, Eugene A.

2007-01-01

9

Alterations in enterocyte mitochondrial respiratory function and enzyme activities in gastrointestinal dysfunction following brain injury  

PubMed Central

AIM: To determine the alterations in rat enterocyte mitochondrial respiratory function and enzyme activities following traumatic brain injury (TBI). METHODS: Fifty-six male SD rats were randomly divided into seven groups (8 rats in each group): a control group (rats with sham operation) and traumatic brain injury groups at 6, 12, 24 h, days 2, 3, and 7 after operation. TBI models were induced by Feendy’s free-falling method. Mitochondrial respiratory function (respiratory control ratio and ADP/O ratio) was measured with a Clark oxygen electrode. The activities of respiratory chain complex?I-IV and related enzymes were determined by spectrophotometry. RESULTS: Compared with the control group, the mitochondrial respiratory control ratio (RCR) declined at 6 h and remained at a low level until day 7 after TBI (control, 5.42 ± 0.46; 6 h, 5.20 ± 0.18; 12 h, 4.55 ± 0.35; 24 h, 3.75 ± 0.22; 2 d, 4.12 ± 0.53; 3 d, 3.45 ± 0.41; 7 d, 5.23 ± 0.24, P < 0.01). The value of phosphate-to-oxygen (P/O) significantly decreased at 12, 24 h, day 2 and day 3, respectively (12 h, 3.30 ± 0.10; 24 h, 2.61 ± 0.21; 2 d, 2.95 ± 0.18; 3 d, 2.76 ± 0.09, P < 0.01) compared with the control group (3.46 ± 0.12). Two troughs of mitochondrial respiratory function were seen at 24 h and day 3 after TBI. The activities of mitochondrial complex?I?(6 h: 110 ± 10, 12 h: 115 ± 12, 24 h: 85 ± 9, day 2: 80 ± 15, day 3: 65 ± 16, P < 0.01) and complex II (6 h: 105 ± 8, 12 h: 110 ± 92, 24 h: 80 ± 10, day 2: 76 ± 8, day 3: 68 ± 12, P < 0.01) were increased at 6 h and 12 h following TBI, and then significantly decreased at 24 h, day 2 and day 3, respectively. However, there were no differences in complex?I?and II activities between the control and TBI groups. Furthermore, pyruvate dehydrogenase (PDH) activity was significantly decreased at 6 h and continued up to 7 d after TBI compared with the control group (6 h: 90 ± 8, 12 h: 85 ± 10, 24 h: 65 ± 12, day 2: 60 ± 9, day 3: 55 ± 6, day 7: 88 ± 11, P < 0.01). The changes in ?-ketoglutaric dehydrogenase (KGDH) activity were similar to PDH, except that the decrease in KGDH activity began at 12 h after TBI (12 h: 90 ± 12, 24 h: 80 ± 9, day 2: 76 ± 15, day 3: 68 ± 7, day 7: 90 ± 13, P < 0.01). No significant change in malate dehydrogenase (MDH) activity was observed. CONCLUSION: Rat enterocyte mitochondrial respiratory function and enzyme activities are inhibited following TBI. Mitochondrial dysfunction may play an important role in TBI-induced gastrointestinal dysfunction. PMID:25071356

Zhu, Ke-Jun; Huang, Hong; Chu, Hui; Yu, Hang; Zhang, Shi-Ming

2014-01-01

10

Bovine Growth Hormone Transgenic Mice Display Alterations in Locomotor Activity and Brain Monoamine Neurochemistry  

Microsoft Academic Search

Recent clinical and experimental data indicate a role for GH in mechanisms related to anhedonia\\/hedonia, psychic energy, and re- ward. In the present study we have investigated whether bovine GH (bGH) transgenic mice and nontransgenic controls differ in sponta- neous locomotor activity, a behavioral response related to brain do- pamine (DA) and reward mechanisms, as well as in locomotor activity

BO SODERPALM; MIA ERICSON; MOHAMMAD BOHLOOLY-Y; JORGEN A. ENGEL; JAN TORNELL

1999-01-01

11

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

12

Arsenic alters behavioral parameters and brain ectonucleotidases activities in zebrafish (Danio rerio).  

PubMed

Arsenic (As) exposure has been associated with serious chronic health risk to humans including cancer and neurological disturbances. However, there are limited studies about the mechanisms behind its toxicity. In this study, adult zebrafish were exposed to several concentrations of As (0.05, 5, and 15 mg As/L; Na(2)HAsO(4) as As(V)) during 96 h to evaluate the zebrafish locomotor activity, anxiety, and brain extracellular nucleotide hydrolysis. We showed that 5 mg/L As is able to promote significant decrease in the locomotor activity as evaluated by the number of line crossings. In addition, animals treated with 5mg/L As presented an increase in time spent in the lower zone of the tank test, suggesting an anxiogenic effect. Considering that behavioral parameters, such as anxiety and locomotion, might be modulated by the purinergic system, we also evaluated the ectonucleotidase activities in zebrafish brain after a 96-h As exposure. A significant decrease in ATP, ADP, and AMP hydrolysis was observed at 0.05, 5, and 15 mg/L when compared to control group. These findings demonstrated that As might affect behavioral parameters and the ectonucleotidase activities in zebrafish, suggesting this enzyme pathway is a target for neurotoxic effects induced by As. PMID:22265774

Baldissarelli, Luis Antonio; Capiotti, Katiucia Marques; Bogo, Mauricio Reis; Ghisleni, Gabriele; Bonan, Carla Denise

2012-05-01

13

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

PubMed

Where there is no viable alternative, studies of neuronal activity are conducted on animals. The use of animals, particularly for invasive studies of the brain, raises a number of ethical issues. Practical or normative ethics are enforced by legislation, in relation to the dominant welfare guidelines developed in the United Kingdom and elsewhere. Guidelines have typically been devised to cover all areas of biomedical research using animals in general, and thus lack any specific focus on neuroscience studies at the level of the ethics, although details of the specific welfare recommendations are different for invasive studies of the brain. Ethically, there is no necessary distinction between neuroscience and other biomedical research in that the brain is a final common path for suffering, irrespective of whether this involves any direct experience of pain. One exception arises in the case of in vitro studies, which are normally considered as an acceptable replacement for in vivo studies. However, to the extent sentience is possible, maintaining central nervous system tissue outside the body naturally raises ethical questions. Perhaps the most intractable challenge to the ethical use of animals in order to model neuronal disorder is presented by the logical impasse in the argument that the animal is similar enough to justify the validity of the experimental model, but sufficiently different in sentience and capacity for suffering, for the necessary experimental procedures to be permissible. PMID:25205325

Cassaday, Helen J

2014-09-10

14

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

15

A History Of Iron Deficiency Anemia During Infancy Alters Brain Monoamine Activity Later In Juvenile Monkeys  

PubMed Central

Both during and after a period of iron deficiency (ID), iron-dependent neural processes are affected, which raises the potential concern that the anemia commonly experienced by many growing infants could have a protracted effect on the developing brain. To further investigate the effects of ID on the immature brain, 49 infant rhesus monkeys were evaluated across the first year of life. The mothers, and subsequently the infants after weaning, were maintained on a standardized diet containing 180 mg/kg of iron and were not provided other iron-rich foods as treats or supplements. As the infants grew, they were all screened with hematological tests, which documented that 16 (33.3%) became markedly ID between 4-to-8 months of age. During this anemic period and subsequently at one year of age, cerebrospinal fluid (CSF) specimens were collected to compare monoamine activity in the ID and iron-sufficient infants. Monoamine neurotransmitters and metabolite levels were normal at 4 and 8 months of age, but by one year the formerly anemic monkeys had significantly lower dopamine and significantly higher norepinephrine levels. These findings indicate that ID can affect the developmental trajectory of these two important neurotransmitter systems, which are associated with emotionality and behavioral performance, and further that the impact in the young monkey was most evident during the period of recovery. PMID:19194962

Coe, Christopher L.; Lubach, Gabriele R.; Bianco, Laura; Beard, John L.

2009-01-01

16

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

17

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

PubMed

We investigated the neurophysiological correlate of altered regional cerebral glucose metabolism observed in children with epileptic encephalopathy with continuous spike-waves during sleep (CSWS) by using a multimodal approach combining time-sensitive magnetic source imaging (MSI) and positron emission tomography with [(18)F]-fluorodeoxyglucose (FDG-PET). Six patients (4 boys and 2 girls, age range: 4-8 years, 3 patients with Landau-Kleffner syndrome (LKS), 3 patients with atypical rolandic epilepsy (ARE)) were investigated by FDG-PET and MSI at the acute phase of CSWS. In all patients, the onset(s) of spike-waves discharges were associated with significant focal hypermetabolism. The propagation of epileptic discharges to other brain areas was associated with focal hypermetabolism (five patients), hypometabolism (one patient) or the absence of any significant metabolic change (one patient). Interestingly, most of the hypometabolic areas were not involved in the epileptic network per se. This study shows that focal hypermetabolism observed at the acute phase of CSWS are related to the onset or propagation sites of spike-wave discharges. Spike-wave discharges propagation can be associated to other types of metabolic changes, suggesting the occurrence of various neurophysiological mechanisms at the cellular level. Most of the hypometabolic areas are not involved in the epileptic network as such and are probably related to a mechanism of remote inhibition. These findings highlight the critical value of combining FDG-PET with time-sensitive functional neuroimaging approaches such as MSI to assess CSWS epileptic network when surgery is considered as a therapeutic approach. PMID:23561286

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

2013-08-01

18

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

PubMed Central

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

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

2014-01-01

19

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

PubMed

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

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

2014-01-30

20

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

PubMed

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

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

2013-08-15

21

Sertraline alters multidrug resistance phosphoglycoprotein activity in the mouse placenta and fetal blood-brain barrier.  

PubMed

Phosphoglycoprotein (P-gp) is highly expressed in the placental syncytiotrophoblast and prevents xenobiotics from entering the fetus. In tumor cells, P-gp-mediated substrate efflux is inhibited by selective serotonin reuptake inhibitors (SSRIs). However, nothing is known regarding the effects of SSRIs on P-gp function in the placenta or fetal tissues. We hypothesized that the SSRI sertraline would decrease P-gp-mediated drug efflux at the placenta and fetal blood-brain barrier (BBB)-increasing P-gp substrate transfer from the mother to the fetus and fetal brain. In contrast to our hypothesis, this study presents the novel findings that sertraline (4 hours exposure) increases placental P-gp-mediated efflux (P < .001), resulting in decreased drug transfer to the fetus. Meanwhile, sertraline decreases fetal (P < .001) and maternal (P < .05) BBB P-gp-mediated efflux, resulting in increased drug transfer into the fetal and maternal brain from the circulation. This suggests that P-gp regulation by sertraline is tissue specific. These findings have important clinical implications with respect to fetal protection during maternal drug therapy in pregnancy. PMID:22510699

Bhuiyan, Manzerul; Petropoulos, Sophie; Gibb, William; Matthews, Stephen G

2012-04-01

22

HIV-1 induces cytoskeletal alterations and Rac1 activation during monocyte-blood–brain barrier interactions: modulatory role of CCR5  

PubMed Central

Background Most HIV strains that enter the brain are macrophage-tropic and use the CCR5 receptor to bind and infect target cells. Because the cytoskeleton is a network of protein filaments involved in cellular movement and migration, we investigated whether CCR5 and the cytoskeleton are involved in endothelial-mononuclear phagocytes interactions, adhesion, and HIV-1 infection. Results Using a cytoskeleton phospho-antibody microarray, we showed that after co-culture with human brain microvascular endothelial cells (HBMEC), HIV-1 infected monocytes increased expression and activation of cytoskeleton-associated proteins, including Rac1/cdc42 and cortactin, compared to non-infected monocytes co-cultured with HBMEC. Analysis of brain tissues from HIV-1-infected patients validated these findings, and showed transcriptional upregulation of Rac1 and cortactin, as well as increased activation of Rac1 in brain tissues of HIV-1-infected humans, compared to seronegative individuals and subjects with HIV-1-encephalitis. Confocal imaging showed that brain cells expressing phosphorylated Rac1 were mostly macrophages and blood vessels. CCR5 antagonists TAK-799 and maraviroc prevented HIV-induced upregulation and phosphorylation of cytoskeleton-associated proteins, prevented HIV-1 infection of macrophages, and diminished viral-induced adhesion of monocytes to HBMEC. Ingenuity pathway analysis suggests that during monocyte-endothelial interactions, HIV-1 alters protein expression and phosphorylation associated with integrin signaling, cellular morphology and cell movement, cellular assembly and organization, and post-translational modifications in monocytes. CCR5 antagonists prevented these HIV-1-induced alterations. Conclusions HIV-1 activates cytoskeletal proteins during monocyte-endothelial interactions and increase transcription and activation of Rac1 in brain tissues. In addition to preventing macrophage infection, CCR5 antagonists could diminish viral-induced alteration and phosphorylation of cytoskeletal proteins, monocyte adhesion to the brain endothelium and viral entry into the central nervous system. PMID:24571616

2014-01-01

23

ORIGINAL INVESTIGATION Human ecstasy (MDMA) polydrug users have altered brain  

E-print Network

ORIGINAL INVESTIGATION Human ecstasy (MDMA) polydrug users have altered brain activation during-Verlag Berlin Heidelberg 2012 Abstract Rationale Ecstasy (3,4-methylenedioxymethamphetamine [MDMA]) polydrug ecstasy use with semantic memory per- formance and brain activation in ecstasy polydrug users. Methods

Park, Sohee

24

Altered regulation of protein kinase a activity in the medial prefrontal cortex of normal and brain-injured animals actively engaged in a working memory task.  

PubMed

Cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) signaling is required for short- and long-term memory. In contrast, enhanced PKA activity has been shown to impair working memory, a prefrontal cortex (PFC)-dependent, transient form of memory critical for cognition and goal-directed behaviors. Working memory can be impaired after traumatic brain injury (TBI) in the absence of overt damage to the PFC. The cellular and molecular mechanisms that contribute to this deficit are largely unknown. In the present study, we examined whether altered PKA signaling in the PFC as a result of TBI is a contributing mechanism. We measured PKA activity in medial PFC (mPFC) tissue homogenates prepared from sham and 14-day postinjury rats. PKA activity was measured both when animals were inactive and when actively engaged in a spatial working memory task. Our results demonstrate, for the first time, that PKA activity in the mPFC is actively suppressed in uninjured animals performing a working memory task. By comparison, both basal and working memory-related PKA activity was elevated in TBI animals. Inhibition of PKA activity by intra-mPFC administration of Rp-cAMPS into TBI animals had no influence on working memory performance 30?min postinfusion, but significantly improved working memory when tested 24?h later. This improvement was associated with reduced glutamic acid decarboxylase 67 messenger RNA levels. Taken together, these results suggest that TBI-associated working memory dysfunction may result, in part, from enhanced PKA activity, possibly leading to altered expression of plasticity-related genes in the mPFC. PMID:25027811

Kobori, Nobuhide; Moore, Anthony N; Dash, Pramod K

2015-01-15

25

Altered global brain signal in schizophrenia  

PubMed Central

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

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

2014-01-01

26

Altered arginine metabolism in Alzheimer's disease brains.  

PubMed

L-arginine is a semi-essential amino acid with a number of bioactive metabolites. Accumulating evidence suggests the implication of altered arginine metabolism in the pathogenesis of Alzheimer's disease (AD). The present study systematically compared the metabolic profile of L-arginine in the superior frontal gyrus, hippocampus, and cerebellum from AD (mean age 80 years) and normal (mean age 80 or 60 years) cases. The activity and protein expression of nitric oxide synthase and arginase were altered with AD and age in a region-specific manner. There were also AD- and age-related changes in the tissue concentrations of L-arginine and its downstream metabolites (L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine, glutamate, ?-aminobutyric acid, and glutamine) in a metabolite- or region-specific manner. These findings demonstrate that arginine metabolism is dramatically altered in diverse regions of AD brains, thus meriting further investigation to understand its role in the pathogenesis and/or progression of the disease. PMID:24746363

Liu, Ping; Fleete, Michael S; Jing, Yu; Collie, Nicola D; Curtis, Maurice A; Waldvogel, Henry J; Faull, Richard L M; Abraham, Wickliffe C; Zhang, Hu

2014-09-01

27

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

28

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

PubMed

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

2012-10-15

29

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

PubMed

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

30

Altered Baseline Brain Activity with 72 h of Simulated Microgravity – Initial Evidence from Resting-State fMRI  

PubMed Central

To provide the basis and reference to further insights into the neural activity of the human brain in a microgravity environment, we discuss the amplitude changes of low-frequency brain activity fluctuations using a simulated microgravity model. Twelve male participants between 24 and 31 years old received resting-state fMRI scans in both a normal condition and after 72 hours in a ?6° head down tilt (HDT). A paired sample t-test was used to test the amplitude differences of low-frequency brain activity fluctuations between these two conditions. With 72 hours in a ?6° HDT, the participants showed a decreased amplitude of low-frequency fluctuations in the left thalamus compared with the normal condition (a combined threshold of P<0.005 and a minimum cluster size of 351 mm3 (13 voxels), which corresponded with the corrected threshold of P<0.05 determined by AlphaSim). Our findings indicate that a gravity change-induced redistribution of body fluid may disrupt the function of the left thalamus in the resting state, which may contribute to reduced motor control abilities and multiple executive functions in astronauts in a microgravity environment. PMID:23285086

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

2012-01-01

31

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

32

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

PubMed Central

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

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

2010-01-01

33

The un-rested resting brain: Sleep-deprivation alters activity within the default-mode network  

PubMed Central

The sleep-deprived brain has principally been characterized by examining dysfunction during cognitive-task performance. However, far less attention has been afforded the possibility that sleep deprivation may be as, if not more, accurately characterized on the basis of abnormal resting-state brain activity. Here we report that one night of sleep deprivation significantly disrupts the canonical signature of task-related deactivation, resulting in a double dissociation within anterior as well as posterior midline regions of the default network. Indeed, deactivation within these regions alone discriminated sleep-deprived from sleep-control subjects with a 93% degree of sensitivity and 92% specificity. In addition, the relative balance of deactivation within these default nodes significantly correlated with the amount of prior sleep in the control group (and not extended time awake in the deprivation group). Therefore, the stability and balance of task-related deactivation in key default-mode regions may be dependent on prior sleep, such that a lack thereof disrupts this signature pattern of brain activity; findings that may offer explanatory insights into conditions associated with sleep loss at both a clinical as well as societal level. PMID:19702469

Gujar, Ninad; Yoo, Seung-Schik; Hu, Peter; Walker, Matthew P.

2010-01-01

34

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

35

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

36

Copper deficiency in neonatal mice alters brain catecholamine levels  

SciTech Connect

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

Bailey, W.R.; Prohaska, J.R. (Univ. of Minnesota, Duluth (United States))

1991-03-15

37

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

38

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

PubMed

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

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

2015-01-01

39

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

PubMed Central

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

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

2013-01-01

40

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

41

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

42

Working Memory Brain Activation Following Severe Traumatic Brain Injury  

Microsoft Academic Search

Functional magnetic resonance imaging (fMRI) has shown that brain activation during performance of working memory (WM) tasks under high memory loads is altered in adults with severe traumatic brain injury (TBI) relative to uninjured subjects (Perlstein et al., 2004; Scheibel et al., 2003). Our study attempted to equate TBI patients and orthopedically injured (OI) subjects on performance of an N-Back

Mary R. Newsome; Randall S. Scheibel; Joel L. Steinberg; Maya Troyanskaya; Rajkumar G. Sharma; Ronald A. Rauch; Xioaqi Li; Harvey S. Levin

2007-01-01

43

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

44

Violent Video Games Alter Brain Function in Young Men  

MedlinePLUS

... RSNA Annual Meeting November 30, 2011 Violent Video Games Alter Brain Function in Young Men CHICAGO—A ... analysis of long-term effects of violent video game play on the brain has found changes in ...

45

Functional connectivity and alterations in baseline brain state in humans  

PubMed Central

This work examines the influence of changes in baseline activity on the intrinsic functional connectivity fMRI (fc-fMRI) in humans. Baseline brain activity was altered by inducing anesthesia (sevoflurane end-tidal concentration 1%) in human volunteers and fc-fMRI maps between the pre-anesthetized and anesthetized conditions were compared across different brain networks. We particularly focused on low-level sensory areas (primary somatosensory, visual, auditory cortices), the thalamus, and pain (insula), memory (hippocampus) circuits, and the default mode network (DMN), the latter three to examine higher order brain regions. The results indicate that, while fc-fMRI patterns did not significantly differ (p<0.005; 20-voxel cluster threshold) in sensory cortex and in the DMN between the pre- and anesthetized conditions, fc-fMRI in high-order cognitive regions (i.e. memory and pain circuits) was significantly altered by anesthesia. These findings provide further evidence that fc-fMRI reflects intrinsic brain properties, while also demonstrating that 0.5 MAC sevoflurane anesthesia preferentially modulates higher-order connections. PMID:19631277

Martuzzi, Roberto; Ramani, Ramachandran; Qiu, Maolin; Rajeevan, Nallakkandi; Constable, R. Todd

2009-01-01

46

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

47

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

48

Acute brain death alters left ventricular myocardial gene expression  

Microsoft Academic Search

Objectives: The depressed myocardial function observed in brain dead organ donors has been attributed to massive sympathetic discharge and catecholamine cardiotoxicity. Because elevated catecholamines are associated with altered myocardial gene expression, we investigated whether acute brain death from increased intracranial pressure alters the expression of myocardial gene products important in contractility. Methods: A balloon expansion model was used to increase

Thomas Yeh; Andrew S. Wechsler; Laura J. Graham; Kathryn E. Loesser; Domenic A. Sica; Luke Wolfe; Emma R. Jakoi

1999-01-01

49

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

50

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

51

Alterations in antioxidant status, protein concentration, acetylcholinesterase, Na+, K+-ATPase, and Mg2+-ATPase activities in rat brain after forced swimming.  

PubMed

The aim of this study was to investigate whether exercise stress (short [2 h] or prolonged [5 h] forced swimming in rats) could modulate brain total antioxidant status (TAS), tissue protein concentration, and the activities of acetylcholinesterase (AChE), Na +, K +-ATPase, and Mg 2+-ATPase. Protein concentration, TAS and enzyme activities in homogenized rat brain were determined spectrophotometrically. Protein concentration was decreased by 15 % (p < 0.01) and by 30 % (p < 0.001) after 2 h and 5 h of forced swimming, respectively. TAS was decreased by 20 - 25 % after 2 h or 5 h of exercise. AChE was inhibited by 30 % (p < 0.001) and 45 % (p < 0.001) after 2 h and 5 h of forced swimming, respectively. In contrast, Na +, K +-ATPase and Mg 2+-ATPase were stimulated by 80 % (p < 0.001) and 40 % (p < 0.001), respectively, after 2 h of swimming and by 100 % (p < 0.001) and 60 % (p < 0.001), respectively, after 5 h of exercise. Control values in nontreated rats were unaltered (p > 0.05). In conclusion, short or prolonged forced swimming induces oxidative stress in rats, probably resulting in a reduction in brain protein concentration and AChE activity. In addition, a Na +, K +-ATPase and Mg 2+-ATPase activation was observed under the above mentioned experimental conditions. This stress condition may modulate brain intracellular Mg 2+ concentration, neural excitability, metabolic energy production, and neurotransmission. PMID:16388437

Tsakiris, T; Angelogianni, P; Tesseromatis, C; Tsakiris, S; Tsopanakis, C

2006-01-01

52

Do brain tissue transplants alter personal identity? Inadequacies of some \\  

Microsoft Academic Search

Currently, brain tissue transplantations are being developed as a clinical-therapeutic tool in neurodegenerative diseases such as Parkinson's or Alzheimer's disease. From an ethical point of view, distinguishing between the preservation and an alteration of personal identity seems to be central to determining the scope for further application of brain tissue transplantation therapy. The purpose of this article is to review

G Northoff

1996-01-01

53

Brain death and bioelectrical brain activity  

Microsoft Academic Search

The effect of mechanical vibration and light stimulation on the ongoing and evoked bioelectrical activity was studied in two cases with clinically defined brain death and two other patients with severe head injury, one of them with an isoelectric EEG. The importance of such stimulation sequences for the definition of brain death is discussed, with particular emphasis on mechanical vibration.

G. Pfurtscheller; G. Schwarz; W. List

1985-01-01

54

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

55

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

56

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

PubMed

Hyaluronan (HA), a large anionic polysaccharide (glycosaminoglycan), is a major constituent of the extracellular matrix of the adult brain. To address its function, we examined the neurophysiology of knock-out mice deficient in hyaluronan synthase (Has) genes. Here we report that these Has mutant mice are prone to epileptic seizures, and that in Has3(-/-) mice, this phenotype is likely derived from a reduction in the size of the brain extracellular space (ECS). Among the three Has knock-out models, namely Has3(-/-), Has1(-/-), and Has2(CKO), the seizures were most prevalent in Has3(-/-) mice, which also showed the greatest HA reduction in the hippocampus. Electrophysiology in Has3(-/-) brain slices demonstrated spontaneous epileptiform activity in CA1 pyramidal neurons, while histological analysis revealed an increase in cell packing in the CA1 stratum pyramidale. Imaging of the diffusion of a fluorescent marker revealed that the transit of molecules through the ECS of this layer was reduced. Quantitative analysis of ECS by the real-time iontophoretic method demonstrated that ECS volume was selectively reduced in the stratum pyramidale by ? 40% in Has3(-/-) mice. Finally, osmotic manipulation experiments in brain slices from Has3(-/-) and wild-type mice provided evidence for a causal link between ECS volume and epileptiform activity. Our results provide the first direct evidence for the physiological role of HA in the regulation of ECS volume, and suggest that HA-based preservation of ECS volume may offer a novel avenue for development of antiepileptogenic treatments. PMID:24790187

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

2014-04-30

57

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

PubMed

The high comorbidity between major depressive disorder (MDD) and nicotine dependence (ND) is well recognized. Patients with comorbid MDD and ND often have increased suicidal risk and poor outcomes. A dysfunctional dopaminergic brain reward system might be a neurobiological link between MDD and ND. Aripiprazole has been considered as a dopamine stabilizer and was the first atypical antipsychotic agent approved by the US Food and Drug Administration as an adjunctive to the treatment of unipolar MDD. Bupropion is well known as a dual norepinephrine and dopamine reuptake inhibitor, and has been shown to be effective in smoking cessation. One reason bupropion is useful in treating ND is that it enhances the level of dopamine in the brain. Aripiprazole might act as a dopamine agonist similar to the way that bupropion does because of its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. Several recent studies have applied the unique pharmacodynamic characteristics of aripiprazole to treat patients with ND. Based on neuroimaging findings, aripiprazole can reduce substance cravings by altering brain activity, particularly in the brain regions of the anterior cingulate cortex. Therefore, we hypothesize that adjunctive aripiprazole with antidepressant may be an effective treatment for patients with MDD and ND comorbidity. A new drug invention that combines an antidepressant with an adequate dose of aripiprazole thus should be considered. The neurobiological basis for this combination to treat patients with MDD and ND comorbidity deserves further study. PMID:25109873

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

2014-09-01

58

Cranial Irradiation Alters the Brain’s Microenvironment and Permits CCR2+ Macrophage Infiltration  

PubMed Central

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 (CCR2RFP/+CX3CR1GFP/+) 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

59

Brain structural and functional alterations in patients with unilateral hearing loss.  

PubMed

Alterations of brain structure and functional connectivity have been described in patients with hearing impairments due to distinct pathogenesis; however, the influence of unilateral hearing loss (UHL) on brain morphology and regional brain activity is still not completely understood. In this study, we aim to investigate regional brain structural and functional alterations in patients with UHL. T1-weighted volumetric images and task-free fMRIs were acquired from 14 patients with right-sided UHL (pure tone average ? 40 dB HL) and 19 healthy controls. Hearing ability was assessed by pure tone audiometry. Voxel-based morphometry (VBM) was performed to detect brain regions with changed gray matter volume or white matter volume in UHL. The amplitude of low-frequency fluctuation (ALFF) was calculated to analyze brain activity at the baseline and was compared between two groups. Compared with controls, UHL patients showed decreased gray matter volume in bilateral posterior cingulate gyrus and precuneus, left superior/middle/inferior temporal gyrus, and right parahippocampal gyrus and lingual gyrus. Meanwhile, patients showed significantly decreased ALFF in bilateral precuneus, left inferior parietal lobule, and right inferior frontal gyrus and insula and increased ALFF in right inferior and middle temporal gyrus. These findings suggest that chronic UHL could induce brain morphological changes and is associated with aberrant baseline brain activity. PMID:25093284

Yang, Ming; Chen, Hua-Jun; Liu, Bin; Huang, Zhi-Chun; Feng, Yuan; Li, Jing; Chen, Jing-Ya; Zhang, Ling-Ling; Ji, Hui; Feng, Xu; Zhu, Xin; Teng, Gao-Jun

2014-10-01

60

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

61

Structural brain alterations associated with dyslexia predate reading onset.  

PubMed

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

2011-08-01

62

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

63

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

64

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.

65

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

66

Brain alterations within the first 100 days of HIV infection  

PubMed Central

Objective Brain involvement is a serious complication of HIV infection. The earliest changes in the brain, which represents an anatomic site for viral persistence, are largely unknown. Methods This investigation used quantitative Magnetic Resonance methodologies, including high resolution and diffusion tensor (DTI) imaging, to evaluate the brain in 15 HIV and 20 seronegative subjects. All HIV subjects were antibody nonreactive with assay-estimated infection duration of less than 100 days. Results Brain volumetric analysis revealed reduced parenchyma with enlargement of the third ventricle and brainstem. DTI quantified loss of white matter integrity in the corpus callosum and diffusion alterations in caudate. Cognitive differences were indicated in psychomotor speed and visual recall. There were no differences between antiretroviral-initiated and naïve HIV subgroups. Interpretation These findings, quantified within 100 days of infection, shed light on the earliest brain changes in HIV infection. Onset of neural injury may date to initial viral invasion and the transient early period of unchecked viremia and marked immunosuppression of the seroconversion period. PMID:25642430

Ragin, Ann B; Wu, Ying; Gao, Yi; Keating, Sheila; Du, Hongyan; Sammet, Christina; Kettering, Casey S; Epstein, Leon G

2015-01-01

67

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

68

Addiction Related Alteration in Resting-state Brain Connectivity  

PubMed Central

It is widely accepted that addictive drug use is related to abnormal functional organization in the user’s brain. The present study aimed to identify this type of abnormality within the brain networks implicated in addiction by resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI). With fMRI data acquired during resting state from 14 chronic heroin users (12 of whom were being treated with methadone) and 13 non-addicted controls, we investigated the addiction related alteration in functional connectivity between the regions in the circuits implicated in addiction with seed-based correlation analysis. Compared with controls, chronic heroin users showed increased functional connectivity between nucleus accumbens and ventral/rostral anterior cingulate cortex (ACC), and orbital frontal cortex (OFC), between amygdala and OFC; and reduced functional connectivity between prefrontal cortex and OFC, and ACC. These observations of altered resting-state functional connectivity suggested abnormal functional organization in the addicted brain and may provide additional evidence supporting the theory of addiction that emphasizes enhanced salience value of a drug and its related cues but weakened cognitive control in the addictive state. PMID:19703568

Ma, Ning; Liu, Ying; Li, Nan; Wang, Chang-Xin; Zhang, Hao; Jiang, Xiao-Feng; Xu, Hu-Sheng; Fu, Xian-Ming; Hu, Xiaoping; Zhang, Da-Ren

2009-01-01

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

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

71

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

72

Gene expression alterations in bipolar disorder postmortem brains  

PubMed Central

Objectives Bipolar disorder (BD) is a mental illness of unknown neuropathology and has several genetic associations. Antipsychotics are effective for the treatment of acute mania, psychosis, or mixed states in BD individuals. We aimed to identify gene transcripts differentially expressed in postmortem brains from BD individuals in both the antipsychotics-exposed (exposed) and non-exposed groups and controls. Methods We quantified the abundance of gene transcripts in postmortem brains (brains) of seven exposed, seven non-exposed, and 12 controls with the Affymetrix U133P2 GeneChip microarrays and technologies. We applied a q-value of ? 0.005 to identify statistically significant transcripts with mean abundance differences between non-exposed and controls (and/or exposed). Results We identified 2,191 unique genes with significantly altered expression levels in non-exposed brains compared to those in the control and exposed groups. The expression levels of these genes were not significantly different between exposed and controls, suggesting a normalization effect of antipsychotics on the expression of these genes. Gene Ontology (GO) enrichment analysis showed significant (Bonferroni p ? 0.05) clustering of subgroups of the 2,191 genes under a broad number of GO terms, noticeably the protein products of genes enriched are critical to the function of synapses, including intracellular protein trafficking, synaptic vesicle biogenesis, transport, releasing and recycling, as well as organization and stabilization of the node of Ranvier. Conclusions These results support a hypothesis of synaptic and intercellular communication impairment in BD. The apparent normalization of expression patterns with exposure to antipsychotic medication may represent a physiological process that relates both to etiology and improvement patterns of the disorder. PMID:23360497

Chen, Haiming; Wang, Nulang; Zhao, Xin; Ross, Christopher A; O’Shea, K Sue; McInnis, Melvin G

2012-01-01

73

Retardation of fetal brain cell growth during maternal starvation: circulating factors versus altered cellular response.  

PubMed

Maternal starvation inhibits fetal brain development during late gestation in the rat. To determine whether intrinsic or extrinsic factors might be the principal contributor to altered growth, brain cells from 20 day fetuses were cultured in a 96 well plate with MEM and 10% adult rat serum. Tissue growth was monitored by spectrophotometric measurement of the mitochondrial reduction of a chromagen 3-(4,5 dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT). After 1, 4 or 6 days incubation, MTT activity in non confluent cultures was shown to be directly related to tissue mass. When fetal brain cell cultures were incubated with 1% and 10% concentrations of adult rat serum, an 11-fold increase in MTT activity paralleled a 15-fold increase in tritiated thymidine incorporation. The impact of maternal starvation on fetal brain cell growth was examined by measuring MTT activity in fetal brain cells from fed and starved mothers. When cultures were incubated for 6 days with graded concentrations of fed adult serum (1.25-10%), the MTT response was slightly but consistently lower in cells from starved when compared with cells from fed mothers. By contrast, a marked difference in MTT activity which was paralleled by a lower DNA content became apparent when fetal rat brain cells were incubated with starved adult serum. Fetal serum and adult male serum were found to support growth equally well, while incubation of fetal brain cells with maternal sera resulted in lower MTT values than with the corresponding fetal sera. When cells were incubated with fetal sera pooled from starved mothers, MTT activity was decreased by 42 to 45%.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1603259

Gu, D S; Shambaugh, G E; Metzger, B E; Unterman, T G; Radosevich, J A

1992-06-01

74

Alterations in regional brain metabolism in genetic and pharmacological models of reduced NMDA receptor function.  

PubMed

A mouse line has been developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor [Cell 98 (1999) 427]. These NR1 hypomorphic mice represent an experimental model of reduced NMDA receptor function that may be relevant to the pathophysiology of schizophrenia. To further characterize the neurobiological phenotype resulting from developmental NMDA receptor hypofunction, regional brain metabolic activity was assessed by autoradiographic analysis of 14C-2-deoxyglucose (2-DG) uptake. In addition, ligand binding to NMDA, AMPA, and kainate receptors was measured by quantitative autoradiography. MK-801 binding to NMDA receptors was reduced markedly throughout the brain of the NR1 hypomorphic mice. However, no alteration in 3H-AMPA or 3H-kainate binding was apparent in any region examined. Neuroanatomically specific alterations in regional 2-DG uptake were observed in the NR1 hypomorphic animals. Reduced relative 2-DG uptake was observed in the medial prefrontal and anterior cingulate cortices. Altered patterns of 2-DG uptake were also found in neocortical regions, with selective reductions of uptake in layer 6 in frontal regions of somatosensory and motor cortices. These data indicate alterations in cortical circuitry in the NR1 hypomorphic animals and are consistent with functional imaging studies in chronic schizophrenia patients which typically show reduced frontal cortical metabolic activity. Reduced relative 2-DG uptake was also found in the caudate, accumbens, hippocampus, and select thalamic regions in the NR1-deficient mice. However, in many other brain regions no alteration in 2-DG uptake was observed. The alterations in 2-DG uptake in the NR1 hypomorphic mice were distinctly different compared to those observed after acute challenge with the selective NMDA antagonist MK-801 in wild-type mice. The altered patterns of brain 2-DG uptake in the NR1 hypomorphic mice found in the present work, together with the altered behavioral phenotypes previously described, suggest that the mice may provide a valuable model to study novel therapeutic strategies to counteract the neurobiological consequences of chronic developmental NMDA receptor hypofunction. PMID:12270494

Duncan, Gary; Miyamoto, Seiya; Gu, Hongbin; Lieberman, Jeffrey; Koller, Beverly; Snouwaert, John

2002-10-01

75

Growth, Adipose, Brain, and Skin Alterations Resulting from Targeted Disruption of the Mouse Peroxisome Proliferator-Activated Receptor b(d)  

Microsoft Academic Search

To determine the physiological roles of peroxisome proliferator-activated receptor b (PPARb), null mice were constructed by targeted disruption of the ligand binding domain of the murine PPARb gene. Homozygous PPARb-null term fetuses were smaller than controls, and this phenotype persisted postnatally. Gonadal adi- pose stores were smaller, and constitutive mRNA levels of CD36 were higher, in PPARb-null mice than in

JEFFREY M. PETERS; SUSANNA S. T. LEE; WEN LI; JERROLD M. WARD; OKSANA GAVRILOVA; CARRIE EVERETT; MARC L. REITMAN; LYNN D. HUDSON; FRANK J. GONZALEZ

2000-01-01

76

The biguanide metformin alters phosphoproteomic profiling in mouse brain.  

PubMed

Metformin, a potent antihyperglycemic agent is recommended as the first-line oral therapy for type 2 diabetes (T2D). Recently, metformin has been reported to be beneficial to neurodegenerative disease models. However, the putative mechanisms underlying the neuroprotective effects of metformin in disease models are unknown. Thus, we applied LC-MS/MS-based pattern analysis and two-dimensional electrophoresis (2DE)-based proteomic approach to understand the global phosphoproteomic alteration in the brain of metformin-administrated mice. Collectively, LC-MS/MS-based pattern analysis reveals that 41 phosphoproteins were upregulated and 22 phosphoproteins were downregulated in the brain of metformin-administrated mice. In addition, 5 differentially expressed phosphoproteins were identified upon metformin administration by 2DE coupled with mass spectrometry. The phosphorylation status of metabolic enzymes was decreased while that of mitochondrial proteins was increased by metformin. Interestingly, phosphorylated ?-synuclein was significantly decreased by metformin administration. Taken together, our results might provide potential pathways to understand the pharmacological effect of metformin on neuroprotection. PMID:25067825

Khang, Rin; Park, ChiHu; Shin, Joo-Ho

2014-09-01

77

Alteration of blood-brain barrier function by methamphetamine and cocaine  

Microsoft Academic Search

The integrity of the blood-brain barrier (BBB) plays an important role in maintaining a safe neural microenvironment in the\\u000a brain. Loss of BBB integrity has been recognized as a major cause of profound brain alterations. Psychoactive drugs such as\\u000a methamphetamine (METH) or cocaine are well-known drugs of abuse that can alter the permeability of the BBB via various mechanisms.\\u000a In

J. B. Dietrich

2009-01-01

78

Right Brain Activities to Improve Analytical Thinking.  

ERIC Educational Resources Information Center

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

Lynch, Marion E.

79

Ketogenic diet alters dopaminergic activity in the mouse cortex.  

PubMed

The present study was conducted to determine if the ketogenic diet altered basal levels of monoamine neurotransmitters in mice. The catecholamines dopamine (DA) and norephinephrine (NE) and the indolamine serotonin (5HT) were quantified postmortem in six different brain regions of adult mice fed a ketogenic diet for 3 weeks. The dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) and the serotonin metabolite 5-hydroxyindole acetic acid (5HIAA) were also measured. Tissue punches were collected bilaterally from the motor cortex, somatosensory cortex, nucleus accumbens, anterior caudate-putamen, posterior caudate-putamen and the midbrain. Dopaminergic activity, as measured by the dopamine metabolites to dopamine content ratio - ([DOPAC]+[HVA])/[DA] - was significantly increased in the motor and somatosensory cortex regions of mice fed the ketogenic diet when compared to those same areas in brains of mice fed a normal diet. These results indicate that the ketogenic diet alters the activity of the meso-cortical dopaminergic system, which may contribute to the diet's therapeutic effect in reducing epileptic seizure activity. PMID:24769322

Church, William H; Adams, Ryan E; Wyss, Livia S

2014-06-13

80

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

81

Decoding patterns of human brain activity.  

PubMed

Considerable information about mental states can be decoded from noninvasive measures of human brain activity. Analyses of brain activity patterns can reveal what a person is seeing, perceiving, attending to, or remembering. Moreover, multidimensional models can be used to investigate how the brain encodes complex visual scenes or abstract semantic information. Such feats of "brain reading" or "mind reading," though impressive, raise important conceptual, methodological, and ethical issues. What does successful decoding reveal about the cognitive functions performed by a brain region? How should brain signals be spatially selected and mathematically combined to ensure that decoding reflects inherent computations of the brain rather than those performed by the decoder? We highlight recent advances and describe how multivoxel pattern analysis can provide a window into mind-brain relationships with unprecedented specificity, when carefully applied. However, as brain-reading technology advances, issues of neuroethics and mental privacy will be important to consider. PMID:21943172

Tong, Frank; Pratte, Michael S

2012-01-01

82

Traumatic Brain Injury-Induced Alterations in Peripheral Immunity  

PubMed Central

Background The complex alterations that occur in peripheral immunity after traumatic brain injury (TBI) have been poorly characterized to date. The purpose of this study was to determine the temporal changes in the peripheral immune response after TBI in a murine model of closed head injury. Methods C57Bl/6 mice underwent closed head injury via a weight drop technique (n=5) vs. sham injury (n=3) per time point. Blood, spleen, and thymus were collected and immune phenotype, cytokine expression, and antibody production were determined via flow cytometry and multiplex immunoassays at 1, 3, 7, 14, 30, and 60 days post injury. Results TBI results in acute and chronic changes in both the innate and adaptive immune response. TBI resulted in a striking loss of thymocytes as early as 3 days post-injury (2.1×107 TBI vs. 5.6×107 sham, p=0.001). Similarly, blood monocyte counts were markedly diminished as early as 24 hours post-TBI (372/dl TBI vs. 1359/dl sham, p=0.002) and remained suppressed throughout the first month post-injury. At 60 days post-injury monocytes were polarized towards an anti-inflammatory (M2) phenotype. TBI also resulted in diminished IL-12 expression from day 14 post-injury throughout the remainder of the observation period. Conclusion TBI results in temporal changes in both the peripheral and central immune systems culminating in an overall immune suppressed phenotype and anti-inflammatory milieu. Level of Evidence Level 1 prospective randomized controlled animal experiment. PMID:24158195

Schwulst, Steven J.; Trahanas, Diane M.; Saber, Rana; Perlman, Harris

2013-01-01

83

Ontogenetic serotoninergic lesioning alters histaminergic activity in rats in adulthood.  

PubMed

The aim of this study was to determine histamine content in the brain and the effect of histamine receptor antagonists on behavior of adult rats lesioned as neonates with the serotonin (5-HT) neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). At 3 days after birth Wistar rats were pretreated with desipramine (20 mg/kg ip) before bilateral icv administration of 5,7-DHT (37.5 ?g base on each side) or saline-ascorbic (0.1%) vehicle (control). At 10 week levels of 5-HT and its metabolite 5-hydroxyindole acetic acid (5-HIAA) were determined in frontal cortex, striatum, and hippocampus by an HPLC/ED technique. In the hypothalamus, frontal cortex, hippocampus and medulla oblongata, the level of histamine was analyzed by an immunoenzymatic method. Behavioral observations (locomotion, exploratory-, oral-, and stereotyped activity) were performed, and effects of DA receptor agonists (SKF 38393, apomorphine) and histamine receptor antagonists S(+)chlorpheniramine (H(1)), cimetidine (H(2)), and thioperamide (H(3)) were determined. We confirmed that 5,7-DHT profoundly reduced contents of 5-HT and 5-HIAA in the brain in adulthood. Histamine content was also reduced in all examined brain regions. Moreover, in 5,7-DHT-lesioned rats the locomotor and oral activity responses to thioperamide were altered, and apomorphine-induced stereotype was intensified. From the above, we conclude that an intact central serotoninergic system modulates histamine H(3) receptor antagonist effects on the dopaminergic neurons in rats. PMID:20838952

Jo?ko, Jadwiga; Drab, Jacek; Jochem, Jerzy; Nowak, Przemys?aw; Szkilnik, Ryszard; Korossy-Mruk, Eva; Boro?, Dariusz; Kostrzewa, Richard M; Brus, Halina; Brus, Ryszard

2011-08-01

84

Alteration of blood brain barrier permeability by T-2 toxin: Role of MMP-9 and inflammatory cytokines.  

PubMed

T-2 toxin is a cytotoxic fungal secondary metabolite produced by different species of Fusarium such as F. sporotichioides, F. poae, F. equiseti, F. acuminatum etc. This class of mycotoxins causes a number of pathologies including nervous disorders, cardiovascular alterations, immunodepression and hemostatic derangements. In the present study, mechanism of T-2 toxin induced alteration of blood-brain barrier (BBB) permeability was assessed in terms of oxidative stress, gene expression of MMP-9, MMP-2 and their inhibitors TIMP-1 and TIMP-2, activation of inflammatory cytokines in both brain and peripheral tissue spleen. Gel zymography was used to show the activity of MMP-9 and MMP-2. The percutaneous exposure of 1 LD50 T2 toxin caused a reversible alteration in BBB permeability as observed by extravasation of Evans blue dye. Maximum dye level was observed on day 3 and reduced by day 7. A significant GSH depletion was observed on days 1 and 3. Brain ROS and lipid peroxidation levels increased significantly on 1 and 3 days and decreased by day 7. The SOD levels in brain showed significantly higher activity on 3 days (4-fold) and 7 days (5-fold) of toxin exposure compared to control. A similar trend was observed with catalase enzyme levels. The gene expression analysis of cNOS and iNOS showed varying levels of expression on different time points of post exposure. MMP-9 expression was significantly high on days 3 and 7 in brain with corresponding alteration in TIMP-1. MMP-2 and TIMP-2 showed no effect. Gene expression analysis of the inflammatory cytokines, IL-1?, IL-1?, IL-6 and TNF-? showed elevated levels on day 7 in brain. As spleen plays an important role in inflammatory response we analyzed MMP-9, MMP-2 and inflammatory cytokines in spleen. The MMP-9 was activated on day 7. MMP-2 activity was found to be elevated on 3 and 7 days and TIMP-2 mRNA level increased on 1 and 3 days in spleen. Inflammatory cytokines, IL-1 ?, IL-1?, IL-6 and TNF-? showed elevated levels on days 1 and 3 in spleen indicating an early effect in spleen than in brain. In summary, the results of the study showed that the T-2 induced alteration in BBB permeability is mediated through oxidative stress, activation of MMP-9, and proinflammatory cytokines in brain as well as contribution from peripheral tissue spleen. PMID:21112371

Ravindran, Jayaraj; Agrawal, Mona; Gupta, Nimesh; Rao, P V Lakshmana

2011-02-01

85

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

86

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...

87

Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a,  

E-print Network

Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a, , Marco L. Loggia a connec- tivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific connectivity a b s t r a c t Recent functional brain connectivity studies have contributed to our understanding

Napadow, Vitaly

88

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

89

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

90

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

91

Sustained deep-tissue pain alters functional brain connectivity  

PubMed Central

Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically-relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, fronto-parietal control and default mode networks; SMN, SLN, DAN, FCN and DMN) was evaluated with functional-connectivity MRI, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable with no significant changes of subjects’ pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala, was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to inter-individual differences in pain sensitivity. PMID:23718988

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

2013-01-01

92

Protein kinase a in postmortem brain of depressed suicide victims: altered expression of specific regulatory and catalytic subunits  

Microsoft Academic Search

Background We recently reported reduced [3H]cyclic adenosine monophosphate binding and catalytic activity of protein kinase A in prefrontal cortex of depressed suicide victims. Here we examined the molecular basis of these alterations and whether these findings can be replicated in another cohort.Methods Prefrontal cortex from depressed suicide victims and nonpsychiatric controls were obtained from the Lenhossek Human Brain Program, Budapest

Yogesh Dwivedi; Hooriyah S Rizavi; Pradeep K Shukla; Jennifer Lyons; Gabor Faludi; Miklos Palkovits; Andrea Sarosi; Robert R Conley; Rosalinda C Roberts; Carol A Tamminga; Ghanshyam N Pandey

2004-01-01

93

Methamphetamine exposure during brain development alters the brain acetylcholine system in adolescent mice  

PubMed Central

Children exposed to methamphetamine during brain development as a result of maternal drug use have long-term hippocampus-dependent cognitive impairments, but the mechanisms underlying these impairments are not understood. The acetylcholine system plays an important role in cognitive function and potential methamphetamine-induced acetylcholine alterations may be related to methamphetamine-induced cognitive impairments. In this study, we investigated the potential long-term effects of methamphetamine exposure during hippocampal development on the acetylcholine system in adolescence mice on postnatal day 30 and in adult mice on postnatal day 90. Methamphetamine exposure increased the density of acetylcholine neurons in regions of the basal forebrain and the area occupied by acetylcholine axons in the hippocampus in adolescent female mice. In contrast, methamphetamine exposure did not affect the density of GABA cells or total neurons in the basal forebrain. Methamphetamine exposure also increased the number of muscarinic acetylcholine receptors in the hippocampus of adolescent male and female mice. Our results demonstrate for the first time that methamphetamine exposure during hippocampal development affects the acetylcholine system in adolescent mice and that these changes are more profound in females than males. PMID:21824143

Siegel, Jessica A.; Park, Byung S.; Raber, Jacob

2013-01-01

94

Injury timing alters metabolic, inflammatory and functional outcomes following repeated mild traumatic brain injury.  

PubMed

Repeated head injuries are a major public health concern both for athletes, and members of the police and armed forces. There is ample experimental and clinical evidence that there is a period of enhanced vulnerability to subsequent injury following head trauma. Injuries that occur close together in time produce greater cognitive, histological, and behavioral impairments than do injuries separated by a longer period. Traumatic brain injuries alter cerebral glucose metabolism and the resolution of altered glucose metabolism may signal the end of the period of greater vulnerability. Here, we injured mice either once or twice separated by three or 20days. Repeated injuries that were separated by three days were associated with greater axonal degeneration, enhanced inflammatory responses, and poorer performance in a spatial learning and memory task. A single injury induced a transient but marked increase in local cerebral glucose utilization in the injured hippocampus and sensorimotor cortex, whereas a second injury, three days after the first, failed to induce an increase in glucose utilization at the same time point. In contrast, when the second injury occurred substantially later (20days after the first injury), an increase in glucose utilization occurred that paralleled the increase observed following a single injury. The increased glucose utilization observed after a single injury appears to be an adaptive component of recovery, while mice with 2 injuries separated by three days were not able to mount this response, thus this second injury may have produced a significant energetic crisis such that energetic demands outstripped the ability of the damaged cells to utilize energy. These data strongly reinforce the idea that too rapid return to activity after a traumatic brain injury can induce permanent damage and disability, and that monitoring cerebral energy utilization may be a tool to determine when it is safe to return to the activity that caused the initial injury. PMID:24983210

Weil, Zachary M; Gaier, Kristopher R; Karelina, Kate

2014-10-01

95

Global Brain Gene Expression Analysis Links Glutamatergic and GABAergic Alterations to Suicide and Major Depression  

PubMed Central

Background Most studies investigating the neurobiology of depression and suicide have focused on the serotonergic system. While it seems clear that serotonergic alterations play a role in the pathogenesis of these major public health problems, dysfunction in additional neurotransmitter systems and other molecular alterations may also be implicated. Microarray expression studies are excellent screening tools to generate hypotheses about additional molecular processes that may be at play. In this study we investigated brain regions that are known to be implicated in the neurobiology of suicide and major depression are likely to represent valid global molecular alterations. Methodology/Principal Findings We performed gene expression analysis using the HG-U133AB chipset in 17 cortical and subcortical brain regions from suicides with and without major depression and controls. Total mRNA for microarray analysis was obtained from 663 brain samples isolated from 39 male subjects, including 26 suicide cases and 13 controls diagnosed by means of psychological autopsies. Independent brain samples from 34 subjects and animal studies were used to control for the potential confounding effects of comorbidity with alcohol. Using a Gene Ontology analysis as our starting point, we identified molecular pathways that may be involved in depression and suicide, and performed follow-up analyses on these possible targets. Methodology included gene expression measures from microarrays, Gene Score Resampling for global ontological profiling, and semi-quantitative RT-PCR. We observed the highest number of suicide specific alterations in prefrontal cortical areas and hippocampus. Our results revealed alterations of synaptic neurotransmission and intracellular signaling. Among these, Glutamatergic (GLU) and GABAergic related genes were globally altered. Semi-quantitative RT-PCR results investigating expression of GLU and GABA receptor subunit genes were consistent with microarray data. Conclusions/Significance The observed results represent the first overview of global expression changes in brains of suicide victims with and without major depression and suggest a global brain alteration of GLU and GABA receptor subunit genes in these conditions. PMID:19668376

Sequeira, Adolfo; Mamdani, Firoza; Ernst, Carl; Vawter, Marquis P.; Bunney, William E.; Lebel, Veronique; Rehal, Sonia; Klempan, Tim; Gratton, Alain; Benkelfat, Chawki; Rouleau, Guy A.; Mechawar, Naguib; Turecki, Gustavo

2009-01-01

96

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

97

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

98

Active targeting of brain tumors using nanocarriers.  

PubMed

The delivery of drugs to brain tumors is limited by the presence of the blood-brain barrier (BBB) separating the blood from the cerebral parenchyma. An understanding of the specific mechanisms of the brain capillary endothelium has led to the development of various strategies to enhance the penetration of drugs into the brain tissue. Active targeting is a non-invasive approach, which consists in transporting drugs to target organs using site-specific ligands. Drug-loaded nanocarriers capable of recognizing brain capillary endothelial cells and cerebral tumoral cells have shown promising potential in oncology. Endogenous and chimeric ligands binding to carriers or receptors of the BBB have been directly or indirectly conjugated to nanocarriers. This review indexes the main targeted colloidal systems used for drug delivery to the brain. Their pharmacological behavior and their therapeutic effect are discussed. PMID:17716726

Béduneau, Arnaud; Saulnier, Patrick; Benoit, Jean-Pierre

2007-11-01

99

Is Being Plastic Fantastic? Mechanisms of Altered Plasticity after Developmental Traumatic Brain Injury  

PubMed Central

Traumatic brain injury (TBI) is predominantly a clinical problem of young persons, resulting in chronic cognitive and behavioral deficits. Specifically, the physiological response to a diffuse biomechanical injury in a maturing brain can clearly alter normal neuroplasticity. To properly evaluate and investigate developmental TBI requires an understanding of normal principles of cerebral maturation, as well as a consideration of experience-dependent changes. Changes in neuroplasticity may occur through many age-specific processes, and our understanding of these responses at a basic neuroscience level is only beginning. In this article, we will particularly discuss mechanisms of TBI-induced altered developmental plasticity such as altered neurotransmission, distinct molecular responses, cell death, perturbations in neuronal connectivity, experience-dependent ‘good plasticity’ enhancements and chronic ‘bad plasticity’ sequelae. From this summary, we can conclude that ‘young is not always better’ and that the developing brain manifests several crucial vulnerabilities to TBI. PMID:16943660

Giza, Christopher C.; Prins, Mayumi L.

2014-01-01

100

Brain structure alterations associated with weight changes in young females with anorexia nervosa: a case series.  

PubMed

Structural brain changes associated with starvation and clinical measurements were explored in four females with anorexia nervosa with different clinical course, at baseline and 1-year follow-up, after receiving intensive inpatient treatment at a specialized eating disorder unit. Global volume alterations were associated with weight changes. Regional volume alterations were also associated with weight changes, with the largest changes occurring in the nucleus accumbens, amygdala, pallidum, and putamen. Largest changes in cortical thickness occurred in the frontal and temporal lobes. The results are preliminary; however, they show that fluctuations in weight are associated with brain volume alterations, especially gray matter. We suggest that these parts of the brain are vulnerable to starvation and malnutrition, and could be a part of the pathophysiology of AN. PMID:24460514

Fuglset, Tone Seim; Endestad, Tor; Landrø, Nils Inge; Rø, Øyvind

2015-04-01

101

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

PubMed

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

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

2011-09-30

102

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

103

Spontaneous brain activity in combat related PTSD.  

PubMed

Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder, especially in combat veterans. Existing functional neuroimaging studies have provided important insights into the neural mechanisms of PTSD using various experimental paradigms involving trauma recollection or other forms of emotion provocation. However it is not clear whether the abnormal brain activity is specific to the mental processes related to the experimental tasks or reflects general patterns across different brain states. Thus, studying intrinsic spontaneous brain activity without the influence of external tasks may provide valuable alternative perspectives to further understand the neural characteristics of PTSD. The present study evaluated the magnitudes of spontaneous brain activity of male US veterans with or without PTSD, with the two groups matched on age, gender, and ethnicity. Amplitudes of low frequency fluctuation (ALFF), a data driven analysis method, were calculated on each voxel of the resting state fMRI data to measure the magnitudes of spontaneous brain activity. Results revealed that PTSD subjects showed increased spontaneous activity in the amygdala, ventral anterior cingulate cortex, insula, and orbital frontal cortex, as well as decreased spontaneous activity in the precuneus, dorsal lateral prefrontal cortex and thalamus. Within the PTSD group, larger magnitudes of spontaneous activity in the thalamus, precuneus and dorsal lateral prefrontal cortex were associated with lower re-experiencing symptoms. Comparing our results with previous functional neuroimaging findings, increased activity of the amygdala and anterior insula and decreased activity of the thalamus are consistent patterns across emotion provocation states and the resting state. PMID:23643995

Yan, Xiaodan; Brown, Adam D; Lazar, Mariana; Cressman, Victoria L; Henn-Haase, Clare; Neylan, Thomas C; Shalev, Arieh; Wolkowitz, Owen M; Hamilton, Steven P; Yehuda, Rachel; Sodickson, Daniel K; Weiner, Michael W; Marmar, Charles R

2013-06-28

104

Altered small-world brain networks in schizophrenia patients during working memory performance.  

PubMed

Impairment of working memory (WM) performance in schizophrenia patients (SZ) is well-established. Compared to healthy controls (HC), SZ patients show aberrant blood oxygen level dependent (BOLD) activations and disrupted functional connectivity during WM performance. In this study, we examined the small-world network metrics computed from functional magnetic resonance imaging (fMRI) data collected as 35 HC and 35 SZ performed a Sternberg Item Recognition Paradigm (SIRP) at three WM load levels. Functional connectivity networks were built by calculating the partial correlation on preprocessed time courses of BOLD signal between task-related brain regions of interest (ROIs) defined by group independent component analysis (ICA). The networks were then thresholded within the small-world regime, resulting in undirected binarized small-world networks at different working memory loads. Our results showed: 1) at the medium WM load level, the networks in SZ showed a lower clustering coefficient and less local efficiency compared with HC; 2) in SZ, most network measures altered significantly as the WM load level increased from low to medium and from medium to high, while the network metrics were relatively stable in HC at different WM loads; and 3) the altered structure at medium WM load in SZ was related to their performance during the task, with longer reaction time related to lower clustering coefficient and lower local efficiency. These findings suggest brain connectivity in patients with SZ was more diffuse and less strongly linked locally in functional network at intermediate level of WM when compared to HC. SZ show distinctly inefficient and variable network structures in response to WM load increase, comparing to stable highly clustered network topologies in HC. PMID:22701611

He, Hao; Sui, Jing; Yu, Qingbao; Turner, Jessica A; Ho, Beng-Choon; Sponheim, Scott R; Manoach, Dara S; Clark, Vincent P; Calhoun, Vince D

2012-01-01

105

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

106

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

107

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

PubMed

Rapid advances in imaging technologies have pushed novel spectroscopic modalities such as Fourier transform infrared spectroscopy (FTIR) and X-ray absorption spectroscopy (XAS) at the sulfur K-edge to the forefront of direct in situ investigation of brain biochemistry. However, few studies have examined the extent to which sample preparation artifacts confound results. Previous investigations using traditional analyses, such as tissue dissection, homogenization, and biochemical assay, conducted extensive research to identify biochemical alterations that occur ex vivo during sample preparation. In particular, altered metabolism and oxidative stress may be caused by animal death. These processes were a concern for studies using biochemical assays, and protocols were developed to minimize their occurrence. In this investigation, a similar approach was taken to identify the biochemical alterations that are detectable by two in situ spectroscopic methods (FTIR, XAS) that occur as a consequence of ischemic conditions created during humane animal killing. FTIR and XAS are well suited to study markers of altered metabolism such as lactate and creatine (FTIR) and markers of oxidative stress such as aggregated proteins (FTIR) and altered thiol redox (XAS). The results are in accordance with previous investigations using biochemical assays and demonstrate that the time between animal death and tissue dissection results in ischemic conditions that alter brain metabolism and initiate oxidative stress. Therefore, future in situ biospectroscopic investigations utilizing FTIR and XAS must take into consideration that brain tissue dissected from a healthy animal does not truly reflect the in vivo condition, but rather reflects a state of mild ischemia. If studies require the levels of metabolites (lactate, creatine) and markers of oxidative stress (thiol redox) to be preserved as close as possible to the in vivo condition, then rapid freezing of brain tissue via decapitation into liquid nitrogen, followed by chiseling the brain out at dry ice temperatures is required. PMID:25350866

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

2015-02-18

108

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

SciTech Connect

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

Nilsson, Tatjana [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden)]. E-mail: Tatjana.Nilsson@ki.se; Bogdanovic, Nenad [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Volkman, Inga [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Winblad, Bengt [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Folkesson, Ronnie [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden); Benedikz, Eirikur [Karolinska Institutet, Neurotec, Section of Experimental Geriatrics, Novum, 141 86 Stockholm (Sweden)

2006-06-02

109

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

110

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

111

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

112

Maternal antibodies from mothers of children with autism alter brain growth and social behavior  

E-print Network

Maternal antibodies from mothers of children with autism alter brain growth and social behavior spectrum disorder (ASD), but not in mothers of typically developing children. This finding has raised. As they matured, IgG-ASD offspring consistently deviated from species-typical social norms by more frequently

Cai, Long

113

Selective Attention to Affective Value Alters How the Brain Processes Olfactory Stimuli  

E-print Network

Selective Attention to Affective Value Alters How the Brain Processes Olfactory Stimuli Edmund T the instruction before odor delivery, and continued after termination of the odor in a short-term memory period for understanding the effects not only of olfactory but also of other sensory stimuli. & INTRODUCTION The primary

Rolls, Edmund T.

114

Variations in Maternal Care Alter GABAA Receptor Subunit Expression in Brain Regions Associated with Fear  

Microsoft Academic Search

Maternal care influences the development of stress reactivity in the offspring. These effects are accompanied by changes in corticotropin-releasing factor (CRF) expression in brain regions that regulate responses to stress. However, such effects appear secondary to those involving systems that normally serve to inhibit CRF expression and release. Thus, maternal care over the first week of life alters GABAA (gamma-aminobutyric

Christian Caldji; Josie Diorio; Michael J Meaney

2003-01-01

115

Altered adrenergic receptor signaling following traumatic brain injury contributes to working memory dysfunction  

Microsoft Academic Search

The prefrontal cortex is highly vulnerable to traumatic brain injury (TBI) and its structural and\\/or functional alterations as a result of TBI can give rise to persistent working memory (WM) dysfunction. Using a rodent model of TBI, we have described profound WM deficits following TBI that are associated with increases in prefrontal catecholamine (both dopamine and norepinephrine) content. In this

N. Kobori; B. Hu; P. K. Dash

2011-01-01

116

BACE1 deficiency causes altered neuronal activity and neurodegeneration  

PubMed Central

SUMMARY BACE1 is required for the release of ?–amyloid (A?) in vivo, and inhibition of BACE1 activity is targeted for reducing A? generation in Alzheimer's patients. In order to further our understanding of the safe use of BACE1 inhibitors in human patients, we aimed to study the physiological functions of BACE1 by characterizing BACE1–null mice. Here we report the finding of spontaneous behavioral seizures in BACE1–null mice. Electroencephalographic recordings revealed abnormal spike-wave discharges in BACE1–null mice, and kainic acid-induced seizures also occurred more frequently in BACE1–null mice compared to their wild-type littermates. Biochemical and morphological studies showed that axonal and surface levels of Nav1.2 were significantly elevated in BACE1–null mice, consistent with the increased fast sodium channel current recorded from BACE1–null hippocampal neurons. Patch-clamp recording also showed altered intrinsic firing properties of isolated BACE1–null hippocampal neurons. Furtherover, population spikes were significantly increased in BACE1–null brain slices, indicating hyperexcitability of BACE1–null neurons. Together, our results suggest that increased sodium channel activity contributes to the epileptic behaviors observed in BACE1–null mice. The knowledge from this study is crucial for the development of BACE1 inhibitors for Alzheimer's therapy and to the applicative study of epilepsy. PMID:20592204

Hu, Xiangyou; Zhou, Xiangdong; He, Wanxia; Yang, Jun; Xiong, Wenchen; Wong, Philip; Wilson, Christopher G.; Yan, Riqiang

2010-01-01

117

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

118

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

119

Brain activation in patients with idiopathic hyperacusis  

Microsoft Academic Search

The neural network associated with idiopathic hyperacusis is still not well known. We studied the brain activation of 3 middle-aged patients with mild to moderate hyperacusis by functional magnetic resonance imaging while they were listening to white noise binaurally. In addition to the temporal lobes, in all patients, sound elicited activation in the frontal lobes (superior, middle, or inferior frontal

Juen-Haur Hwang; Pao-Hsuan Chou; Chang-Wei Wu; Jyh-Horng Chen; Tien-Chen Liu

2009-01-01

120

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

121

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

122

Magnetic resonance elastography reveals altered brain viscoelasticity in experimental autoimmune encephalomyelitis?  

PubMed Central

Cerebral magnetic resonance elastography (MRE) measures the viscoelastic properties of brain tissues in vivo. It was recently shown that brain viscoelasticity is reduced in patients with multiple sclerosis (MS), highlighting the potential of cerebral MRE to detect tissue pathology during neuroinflammation. To further investigate the relationship between inflammation and brain viscoelasticity, we applied MRE to a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). EAE was induced and monitored by MRE in a 7-tesla animal MRI scanner over 4 weeks. At the peak of the disease (day 14 after immunization), we detected a significant decrease in both the storage modulus (G?) and the loss modulus (G?), indicating that both the elasticity and the viscosity of the brain are reduced during acute inflammation. Interestingly, these parameters normalized at a later time point (day 28) corresponding to the clinical recovery phase. Consistent with this, we observed a clear correlation between viscoelastic tissue alteration and the magnitude of perivascular T cell infiltration at both day 14 and day 28. Hence, acute neuroinflammation is associated with reduced mechanical cohesion of brain tissues. Moreover, the reduction of brain viscoelasticity appears to be a reversible process, which is restored when inflammation resolves. For the first time, our study has demonstrated the applicability of cerebral MRE in EAE, and showed that this novel imaging technology is highly sensitive to early tissue alterations resulting from the inflammatory processes. Thus, MRE may serve to monitor early stages of perivascular immune infiltration during neuroinflammation. PMID:24179740

Riek, Kerstin; Millward, Jason M.; Hamann, Isabell; Mueller, Susanne; Pfueller, Caspar F.; Paul, Friedemann; Braun, Jürgen; Infante-Duarte, Carmen; Sack, Ingolf

2012-01-01

123

Heritability of working memory brain activation.  

PubMed

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

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

2011-07-27

124

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

125

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

126

Brain-specific overexpression of trace amine-associated receptor 1 alters monoaminergic neurotransmission and decreases sensitivity to amphetamine.  

PubMed

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

2012-11-01

127

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

ERIC Educational Resources Information Center

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

Lewis, John D.; Elman, Jeffrey L.

2008-01-01

128

Alteration of Protease Levels in Different Brain Areas of Suicide Victims  

Microsoft Academic Search

Numerous recent studies found that proteases play a major role in brain function. In addition to their role in protein turnover, they have modulatory functions and an important role in apoptosis, pathological changes, and other mechanisms. To explore possible differences in brain protein metabolism of suicide victims, we examined the activity of two proteases, cathepsin D and calpain (I and

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

1998-01-01

129

Waterborne manganese exposure alters plasma, brain, and liver metabolites accompanied by changes in stereotypic behaviors  

PubMed Central

Overexposure to waterborne manganese (Mn) is linked with cognitive impairment in children and neurochemical abnormalities in other experimental models. In order to characterize the threshold between Mn-exposure and altered neurochemistry, it is important to identify biomarkers that positively correspond with brain Mn-accumulation. The objective of this study was to identify Mn-induced alterations in plasma, liver, and brain metabolites using liquid/gas chromatography-time of flight-mass spectrometry metabolomic analyses; and to monitor corresponding Mn-induced behavior changes. Weanling Sprague-Dawley rats had access to deionized drinking water either Mn-free or containing 1g Mn/L for six weeks. Behaviors were monitored during the sixth week for a continuous 24h period while in a home cage environment using video surveillance. Mn-exposure significantly increased liver, plasma, and brain Mn concentrations compared to control, specifically targeting the globus pallidus (GP). Mn significantly altered 98 metabolites in the brain, liver, and plasma; notably shifting cholesterol and fatty acid metabolism in the brain (increased oleic and palmitic acid; 12.57 and 15.48 fold change (FC), respectively), and liver (increased oleic acid, 14.51 FC; decreased hydroxybutyric acid, ?14.29 FC). Additionally, Mn-altered plasma metabolites homogentisic acid, chenodeoxycholic acid, and aspartic acid correlated significantly with GP and striatal Mn. Total distance traveled was significantly increased and positively correlated with Mn-exposure, while nocturnal stereotypic and exploratory behaviors were reduced with Mn-exposure and performed largely during the light cycle compared to unexposed rats. These data provide putative biomarkers for Mn-neurotoxicity and suggest that Mn disrupts the circadian cycle in rats. PMID:22056924

Fordahl, Steve; Cooney, Paula; Qiu, Yunping; Xie, Guoxiang; Jia, Wei; Erikson, Keith M.

2011-01-01

130

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

131

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

132

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

PubMed

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

133

Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2  

PubMed Central

Abstract Recently, carriers of a common variant in the autism risk gene, CNTNAP2, were found to have altered functional brain connectivity using functional MRI. Here, we scanned 328 young adults with high-field (4-Tesla) diffusion imaging, to test the hypothesis that carriers of this gene variant would have altered structural brain connectivity. All participants (209 women, 119 men, age: 23.4±2.17 SD years) were scanned with 105-gradient high-angular-resolution diffusion imaging (HARDI) at 4 Tesla. After performing a whole-brain fiber tractography using the full angular resolution of the diffusion scans, 70 cortical surface-based regions of interest were created from each individual's co-registered anatomical data to compute graph metrics for all pairs of cortical regions. In graph theory analyses, subjects homozygous for the risk allele (CC) had lower characteristic path length, greater small-worldness and global efficiency in whole-brain analyses, and lower eccentricity (maximum path length) in 60 of the 70 nodes in regional analyses. These results were not reducible to differences in more commonly studied traits such as fiber density or fractional anisotropy. This is the first study that links graph theory metrics of brain structural connectivity to a common genetic variant linked with autism and will help us understand the neurobiology of the circuits implicated in the risk for autism. PMID:22500773

Dennis, Emily L.; Jahanshad, Neda; Rudie, Jeffrey D.; Brown, Jesse A.; Johnson, Kori; McMahon, Katie L.; de Zubicaray, Greig I.; Montgomery, Grant; Martin, Nicholas G.; Wright, Margaret J.; Bookheimer, Susan Y.; Dapretto, Mirella; Toga, Arthur W.

2011-01-01

134

Listening to the Human Voice Alters Sensorimotor Brain Rhythms  

PubMed Central

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

Lévêque, Yohana; Schön, Daniele

2013-01-01

135

Brain Activity on Navigation in Virtual Environments.  

ERIC Educational Resources Information Center

Assessed the cognitive processing that takes place in virtual environments by measuring electrical brain activity using Fast Fourier Transform analysis. University students performed the same task in a real and a virtual environment, and eye movement measurements showed that all subjects were more attentive when navigating in the virtual world.…

Mikropoulos, Tassos A.

2001-01-01

136

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

137

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.

138

Three dimensional representation of brain electrical activity.  

PubMed

Brain topography mapping is a useful technique for the representation of electrical activity recorded on the scalp. It clarifies spatial and temporal relationships between different cortical areas. In this work we propose a system which includes several enhancements over those previously proposed, such as an optimised interpolation method and a three dimensional reconstruction of maps. This system is available in a personal computer environment. Results clearly show a superiority of the 3D representation over 2D maps obtained with different projections. The performance of this system in terms of speed and precision is comparable to that of dedicated image processing and image synthesis workstations proposed for brain mapping. PMID:7803200

Medina, V; Hassainia, F; Langevin, F; Gaillard, P

1994-01-01

139

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

140

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

141

Total Parenteral Nutrition Alters NPY\\/PYY Receptor Levels in the Rat Brain  

Microsoft Academic Search

Lee, M. C., J. Grant, P. Mannon and T. N. Pappas.Total parenteral nutrition alters NPY\\/PYY receptor levels in the rat brain.PHYSIOL BEHAV 62(6) 1219–1223, 1997.—The regulation of appetite and satiety is complex and may involve peptide mediators such as cholecystokinin (CCK) and neuropeptide Y (NPY). Studies have indicated that calories administered enterally and parenterally impact on feeding, and possibly via

Maggie C Lee; Peter J Mannon; John P Grant; Theodore N Pappas

1997-01-01

142

Compact dynamical model of brain activity.  

PubMed

A compact physiologically based mean-field formulation of brain dynamics is proposed to model observed brain activity and electroencephalographic (EEG) signals. In contrast to existing formulations, which are more detailed and complicated, our model is described by a single second-order delay differential equation that encapsulates salient aspects of the physiology. The model captures essential features of activity mediated by fast corticocortical connections and delayed feedbacks via extracortical pathways and external stimuli. In the linear regime, these features can be simply expressed by three coefficients derived from the properties of these physiological pathways and explicit nonlinear approximations are also derived. This compact model successfully reproduces the main features of experimental EEG's and the predictions of previous models, including resonance peaks in EEG spectra and nonlinear dynamics. As an illustration, key features of the dynamics of epileptic seizures are shown to be reproduced by the model. Due to its compact form, the model will facilitate insight into nonlinear brain dynamics via standard nonlinear techniques and will guide analysis and investigation of more complex models. It is thus a useful tool for analyzing complex brain activity, especially when it exhibits low-dimensional dynamics. PMID:17500726

Kim, J W; Robinson, P A

2007-03-01

143

Compact dynamical model of brain activity  

NASA Astrophysics Data System (ADS)

A compact physiologically based mean-field formulation of brain dynamics is proposed to model observed brain activity and electroencephalographic (EEG) signals. In contrast to existing formulations, which are more detailed and complicated, our model is described by a single second-order delay differential equation that encapsulates salient aspects of the physiology. The model captures essential features of activity mediated by fast corticocortical connections and delayed feedbacks via extracortical pathways and external stimuli. In the linear regime, these features can be simply expressed by three coefficients derived from the properties of these physiological pathways and explicit nonlinear approximations are also derived. This compact model successfully reproduces the main features of experimental EEG’s and the predictions of previous models, including resonance peaks in EEG spectra and nonlinear dynamics. As an illustration, key features of the dynamics of epileptic seizures are shown to be reproduced by the model. Due to its compact form, the model will facilitate insight into nonlinear brain dynamics via standard nonlinear techniques and will guide analysis and investigation of more complex models. It is thus a useful tool for analyzing complex brain activity, especially when it exhibits low-dimensional dynamics.

Kim, J. W.; Robinson, P. A.

2007-03-01

144

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

145

Unlike lithium, anticonvulsants and antidepressants do not alter rat brain myo-inositol.  

PubMed

Lithium is the first-line in bipolar disorder treatment. Lithium's clinical efficacy might be due to its inhibition of myo-inositol turnover in the phosphatidylinositol second messenger system. This study aimed to determine whether this action can extend to antidepressants and anticonvulsants also used to treat bipolar symptoms. Male rats were treated for 2 weeks with an intraperitoneal injection of phenelzine, fluoxetine, desipramine, carbamazepine, lamotrigine, sodium valproate or vehicle. Brains were dissected and myo-inositol concentrations were analyzed using high-field nuclear magnetic resonance spectroscopy at 18.8 T and quantified using Chenomx Profiler software. Brain regions assessed included the prefrontal, temporal and occipital cortical areas as well as the hippocampus. The main finding is that contrary to lithium, the anticonvulsants and antidepressants do not alter brain myo-inositol concentration. This suggests that these agents might work via a mechanism that is not centered on changes in myo-inositol concentration. PMID:17885608

McGrath, Brent M; Greenshaw, Andrew J; McKay, Ryan; Slupsky, Carolyn M; Silverstone, Peter H

2007-10-01

146

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

147

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

148

Temporal organization of ongoing brain activity  

NASA Astrophysics Data System (ADS)

Ongoing brain activity results from the mutual interaction of hundred billions non-linear units and represents a significant part of the overall brain activity. Although its complex dynamics has been widely investigated, a large number of fundamental questions are still open, many of them concerning its temporal structure. Why does a certain population of neurons fires synchronously? Are these synchronized bursts following each other randomly or are they correlated according to some organizing principle? Far from addressing the fundamental problem of its functions, in the present article we focus on the problem of temporal correlations of ongoing cortical activity. We first overview the major features of its temporal structure and review recent experimental results, with particular emphasis on alternative approaches inspired in the theory of stochastic processes; then we introduce a neuronal network model inspired in self organized criticality and compare numerical results with experimental findings.

Lombardi, F.; de Arcangelis, L.

2014-10-01

149

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

150

Estradiol and ER? agonists enhance recognition memory, and DPN, an ER? agonist, alters brain monoamines.  

PubMed

Effects of estradiol benzoate (EB), ER?-selective agonist, propyl pyrazole triol (PPT) and ER?-selective agonists, diarylpropionitrile (DPN) and Compound 19 (C-19) on memory were investigated in OVX rats using object recognition (OR) and placement (OP) memory tasks. Treatments were acute (behavior 4h later) or sub chronic (daily injections for 2 days with behavior 48 h later). Objects were explored in sample trials (T1), and discrimination between sample (old) and new object/location in recognition trials (T2) was examined after 2-4h inter-trial delays. Subjects treated sub chronically with EB, DPN, and C-19, but not PPT, discriminated between old and new objects and objects in old and new locations, suggesting that, at these doses and duration of treatments, estrogenic interactions with ER? contribute to enhancements in recognition memory. Acute injections of DPN, but not PPT, immediately after T1, also enhanced discrimination for both tasks (C19 was not investigated). Effects of EB, DPN and PPT on anxiety and locomotion, measured on elevated plus maze and open field, did not appear to account for the mnemonic enhancements. Monoamines and metabolites were measured following DPN treatment in subjects that did not receive behavioral testing. DPN was associated with alterations in monoamines in several brain areas: indexed by the metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG), or the MHPG/norepinephrine (NE) ratio, NE activity was increased by 60-130% in the prefrontal cortex (PFC) and ventral hippocampus, and NE activity was decreased by 40-80% in the v. diagonal bands and CA1. Levels of the dopamine (DA) metabolite, homovanillic acid (HVA), increased 100% in the PFC and decreased by 50% in the dentate gyrus following DPN treatment. The metabolite of serotonin, 5-hydroxyindole acetic acid (5-HIAA), was increased in the PFC and CA3, by approximately 20%. No monoaminergic changes were noted in striatum or medial septum. Results suggest that ER? mediates sub chronic and acute effects of estrogens on recognition memory and that memory enhancements by DPN may occur, in part, through alterations in monoaminergic containing systems primarily in PFC and hippocampus. PMID:20828630

Jacome, Luis F; Gautreaux, Claris; Inagaki, Tomoko; Mohan, Govini; Alves, Stephen; Lubbers, Laura S; Luine, Victoria

2010-11-01

151

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

152

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

153

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

154

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

PubMed

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

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

2014-01-01

155

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

156

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

157

Cholinergic agonism alters cognitive processing and enhances brain functional connectivity in patients with multiple sclerosis  

Microsoft Academic Search

AbstractThe aim of this study is to define mechanisms underlying the pharmacological effects of brain cholinesterase inhibition on cognitive function in patients with multiple sclerosis (MS). Both a Stroop task and an N-back task were used to probe the changes in brain activity using functional magnetic resonance imaging (fMRI) in a single (investigator)-blind, crossover treatment design studying 15 patients with

S Cader; J Palace; PM Matthews

2009-01-01

158

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

159

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

160

Anxiety and error-related brain activity  

Microsoft Academic Search

Error-related negativity (ERN\\/Ne) is a component of the event-related brain potential (ERP) associated with monitoring action and detecting errors. It is a sharp negative deflection that generally occurs from 50 to 150 ms following response execution and has been associated with anterior cingulate cortex (ACC) activity. An enhanced ERN has been observed in patients with obsessive-compulsive disorder (OCD)—reflecting abnormal ACC

Greg Hajcak; Nicole McDonald; Robert F. Simons

2003-01-01

161

Abdominal surgery activates nesfatin-1 immunoreactive brain nuclei in rats  

PubMed Central

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

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

2011-01-01

162

Iron deficient and manganese supplemented diets alter metals and transporters in the developing rat brain.  

PubMed

Manganese (Mn) neurotoxicity in adults can result in psychological and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. Iron (Fe) deficiency is one of the most prevalent nutritional disorders in the world, affecting approximately 2 billion people, especially pregnant and lactating women, infants, toddlers, and adolescents. Fe deficiency can enhance brain Mn accumulation even in the absence of excess Mn in the environment or the diet. To assess the neurochemical interactions of dietary Fe deficiency and excess Mn during development, neonatal rats were exposed to either a control diet, a low-Fe diet (ID), or a low-Fe diet supplemented with Mn (IDMn) via maternal milk during the lactation period (postnatal days [PN] 4-21). In PN21 pups, both the ID and IDMn diets produced changes in blood parameters characteristic of Fe deficiency: decreased hemoglobin (Hb) and plasma Fe, increased plasma transferrin (Tf), and total iron binding capacity (TIBC). Treated ID and IDMn dams also had decreased Hb throughout lactation and ID dams had decreased plasma Fe and increased Tf and TIBC on PN21. Both ID and IDMn pups had decreased Fe and increased copper brain levels; in addition, IDMn pups also had increased brain levels of several other essential metals including Mn, chromium, zinc, cobalt, aluminum, molybdenum, and vanadium. Concurrent with altered concentrations of metals in the brain, transport proteins divalent metal transporter-1 and transferrin receptor were increased. No significant changes were determined for the neurotransmitters gamma aminobutyric acid and glutamate. The results of this study confirm that there is homeostatic relationship among several essential metals in the brain and not simply between Fe and Mn. PMID:17060373

Garcia, Stephanie J; Gellein, Kristin; Syversen, Tore; Aschner, Michael

2007-01-01

163

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

164

Alterations in Skin and Stratified Epithelia by Constitutively Activated PPARa  

E-print Network

homeostasis. To determine the role of PPARa in skin physiology, transgenic mice were generated usingAlterations in Skin and Stratified Epithelia by Constitutively Activated PPARa Qian Yang1 , Atsushi-activated receptor (PPAR)a is a pleiotropic regulator in many cell types and has recently been implicated in skin

Omiecinski, Curtis

165

Role of brain and peripheral angiotensin II in hypertension and altered arterial baroreflex programmed during fetal life in rat.  

PubMed

Intrauterine programming of hypertension is associated with evidence of increased renin-angiotensin system (RAS) activity. The current study was undertaken to investigate whether arterial baroreflex and blood pressure variability are altered in a model of in utero programming of hypertension secondary to isocaloric protein deprivation and whether activation of the RAS plays a role in this alteration. Pregnant Wistar rats were fed a normal-protein (18%) or low-protein (9%) diet during gestation, which had no effect on litter size, birth weight, or pup survival. Mean arterial blood pressure (MABP; 126 +/- 3 mm Hg 9% versus 108 +/- 4 mm Hg 18%; p < 0.05) and blood pressure variability were significantly greater in the adult offspring of the 9% protein-fed mothers. Arterial baroreflex control of heart rate, generated by graded i.v. infusion of phenylephrine and nitroprusside, was significantly shifted toward higher pressure; i.v. angiotensin-converting enzyme inhibitor normalized MABP and shifted the arterial baroreflex curve of the 9% offspring toward lower pressure without affecting the 18% offspring. For examining whether brain RAS is also involved in programming of hypertension, angiotensin-converting enzyme inhibitor and losartan (specific AT(1) receptor antagonist) were administered intracerebroventricularly; both significantly reduced MABP of the 9% but not the 18% offspring. Autoradiographic receptor binding studies demonstrated an increase in brain AT(1) expression in the subfornical organ and the vascular organ of the lamina terminalis in the 9% offspring. These data demonstrate a major tonic role of brain and peripheral RAS on hypertension associated with antenatal nutrient deprivation. PMID:15071169

Pladys, Patrick; Lahaie, Isabelle; Cambonie, Gilles; Thibault, Gaétan; Lê, Ngoc Loan Oanh; Abran, Daniel; Nuyt, Anne Monique

2004-06-01

166

The Physiochemistry of Capped Nanosilver Predicts Its Biological Activity in Rat Brain Endothelial Cells (REBEC4)  

EPA Science Inventory

The “capping” or coating of nanosilver (nanoAg) extends its potency by limiting its oxidation and aggregation and stabilizing its size and shape. The ability of such coated nanoAg to alter the permeability and activate oxidative stress pathways in rat brain endothelia...

167

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

168

Cypermethrin alters Glial Fibrillary Acidic Protein levels in the rat brain.  

PubMed

Pyrethroids, widely used insecticides, are biologically active in neurons. Whether they act on the non-neuronal brain cells remains an open question. Thus, the aim of this study was to examine whether Cypermethrin intoxication affects astroglial cells in the rat brain. The levels of Glial Fibrillary Acidic Protein (GFAP) in different brain regions were measured by ELISA following oral treatment with 5 or 10% of LD(50) of Cypermethrin per day for 6 days. A significant decrease of GFAP was observed in different brain regions of treated animals. The cerebral cortex showed the most pronounced effect with GFAP levels reduced to 81% of the controls 2 days after treatment and 77% 21 days after treatment. Although we did not find profound changes in the morphology of astrocytes in Cypermethrin treated animals, the decrease in GFAP suggests that astrocytes were affected by low doses of pyrethroids. The possible consequences were discussed. PMID:21783638

Malkiewicz, Katarzyna; Koteras, Marcin; Folkesson, Ronnie; Brzezinski, Jacek; Winblad, Bengt; Szutowski, Miroslaw; Benedikz, Eirikur

2006-01-01

169

Predicting risky choices from brain activity patterns.  

PubMed

Previous research has implicated a large network of brain regions in the processing of risk during decision making. However, it has not yet been determined if activity in these regions is predictive of choices on future risky decisions. Here, we examined functional MRI data from a large sample of healthy subjects performing a naturalistic risk-taking task and used a classification analysis approach to predict whether individuals would choose risky or safe options on upcoming trials. We were able to predict choice category successfully in 71.8% of cases. Searchlight analysis revealed a network of brain regions where activity patterns were reliably predictive of subsequent risk-taking behavior, including a number of regions known to play a role in control processes. Searchlights with significant predictive accuracy were primarily located in regions more active when preparing to avoid a risk than when preparing to engage in one, suggesting that risk taking may be due, in part, to a failure of the control systems necessary to initiate a safe choice. Additional analyses revealed that subject choice can be successfully predicted with minimal decrements in accuracy using highly condensed data, suggesting that information relevant for risky choice behavior is encoded in coarse global patterns of activation as well as within highly local activation within searchlights. PMID:24550270

Helfinstein, Sarah M; Schonberg, Tom; Congdon, Eliza; Karlsgodt, Katherine H; Mumford, Jeanette A; Sabb, Fred W; Cannon, Tyrone D; London, Edythe D; Bilder, Robert M; Poldrack, Russell A

2014-02-18

170

Predicting risky choices from brain activity patterns  

PubMed Central

Previous research has implicated a large network of brain regions in the processing of risk during decision making. However, it has not yet been determined if activity in these regions is predictive of choices on future risky decisions. Here, we examined functional MRI data from a large sample of healthy subjects performing a naturalistic risk-taking task and used a classification analysis approach to predict whether individuals would choose risky or safe options on upcoming trials. We were able to predict choice category successfully in 71.8% of cases. Searchlight analysis revealed a network of brain regions where activity patterns were reliably predictive of subsequent risk-taking behavior, including a number of regions known to play a role in control processes. Searchlights with significant predictive accuracy were primarily located in regions more active when preparing to avoid a risk than when preparing to engage in one, suggesting that risk taking may be due, in part, to a failure of the control systems necessary to initiate a safe choice. Additional analyses revealed that subject choice can be successfully predicted with minimal decrements in accuracy using highly condensed data, suggesting that information relevant for risky choice behavior is encoded in coarse global patterns of activation as well as within highly local activation within searchlights. PMID:24550270

Helfinstein, Sarah M.; Schonberg, Tom; Congdon, Eliza; Karlsgodt, Katherine H.; Mumford, Jeanette A.; Sabb, Fred W.; Cannon, Tyrone D.; London, Edythe D.; Bilder, Robert M.; Poldrack, Russell A.

2014-01-01

171

Altered brain protein expression profiles are associated with molecular neurological dysfunction in the PKU mouse model.  

PubMed

Phenylketonuria (PKU), if not detected and treated in newborns, causes severe neurological dysfunction and cognitive and behavioral deficiencies. Despite the biochemical characterization of PKU, the molecular mechanisms underlying PKU-associated brain dysfunction remain poorly understood. The aim of this study was to gain insights into the pathogenesis of this neurological damage by analyzing protein expression profiles in brain tissue of Black and Tan BRachyury-PahEnu2 mice (a mouse model of PKU). We compared the cerebral protein expression of homozygous PKU mice with that of their heterozygous counterparts using two-dimensional difference gel electrophoresis analysis, and identified 21 differentially expressed proteins, four of which were over-expressed and 17 under-expressed. An in silico bioinformatic approach indicated that protein under-expression was related to neuronal differentiation and dendritic growth, and to such neurological disorders as progressive motor neuropathy and movement disorders. Moreover, functional annotation analyses showed that some identified proteins were involved in oxidative metabolism. To further investigate the proteins involved in the neurological damage, we validated two of the proteins that were most strikingly under-expressed, namely, Syn2 and Dpysl2, which are involved in synaptic function and neurotransmission. We found that Glu2/3 and NR1 receptor subunits were over-expressed in PKU mouse brain. Our results indicate that differential expression of these proteins may be associated with the processes underlying PKU brain dysfunction, namely, decreased synaptic plasticity and impaired neurotransmission. We identified a set of proteins whose expression is affected by hyperphenylalaninemia. We think that phenylketonuria (PKU) brain dysfunction also depends on reduced Syn2 and Dpysl2 levels, increased Glu2/3 and NR1 levels, and decreased Pkm, Ckb, Pgam1 and Eno1 levels. These findings finally confirm that alteration in synaptic function, in transmission and in energy metabolism underlie brain damage provoked by hyperphenylalaninemias. PMID:24548049

Imperlini, Esther; Orrù, Stefania; Corbo, Claudia; Daniele, Aurora; Salvatore, Francesco

2014-06-01

172

Altered brain metabolism of iron as a cause of neurodegenerative diseases?  

PubMed

Iron is the most abundant metal in the human body (Pollitt and Leibel, 1982; Youdim, 1988), and the brain, like the liver, contains a substantially higher concentration of iron than of any other metal (Yehuda and Youdim, 1988). Within the brain, iron shows an uneven distribution, with high levels in the basal ganglia (substantia nigra, putamen, caudate nucleus, and globus pallidus), red nucleus, and dentate nucleus (Spatz, 1922; Hallgren and Sourander, 1958; Hill and Switzer, 1984; Riederer et al., 1989). Iron deposition in the brain is mainly in organic storage forms such as ferritin but not hemosiderin (Hallgren and Sourander, 1958; Octave et al., 1983), with relatively little in a free and reactive form. Although the function of a regionally high brain iron content is unknown, the homeostasis of brain iron is thought to be necessary for normal brain function, especially in learning and memory (Youdim et al., 1989; Yehuda and Youdim, 1989; Pollit and Metallinos-Katsaras, 1990; Youdim, 1990). Thus, a high content of brain iron may be essential, particularly during development, but its presence means that injury to brain cells may release iron ions that can lead to oxidative stress via formation of oxygen free radicals. Such radicals are thought to be involved in lipid peroxidation of the cell membrane, leading to increased membrane fluidity, disturbance of calcium homeostasis, and finally cell death (Youdim et al., 1989; Halliwell, 1992). Iron is an essential participant in many metabolic processes, including (a) DNA, RNA, and protein synthesis, (b) as a cofactor of many heme and nonheme enzymes, (c) the formation of myelin, and (d) the development of the neuronal dendritic tree (Ben-Shachar et al., 1986; Youdim et al., 1991b). A deficiency of iron metabolism would therefore be expected to alter some or all of these processes (Jacobs and Worwood, 1980; Youdim, 1985, 1988). Studies of iron distribution in the human brain have demonstrated that the degree of iron deposition, primarily in the basal ganglia (a predominantly dopamine structure), increases with age (Hallgren and Sourander, 1958) and in certain disorders, most notably the basal ganglia disorders (Seitelberger, 1964). This review will present some of the experimental evidence indicating a role of disturbed iron metabolism as a cause of the neurodegenerative disorder Parkinson's disease and possibly other neurodegenerative disorders such as Alzheimer's disease.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:7519659

Gerlach, M; Ben-Shachar, D; Riederer, P; Youdim, M B

1994-09-01

173

Effects of cranial electrotherapy stimulation on resting state brain activity.  

PubMed

Cranial electrotherapy stimulation (CES) is a U.S. Food and Drug Administration (FDA)-approved treatment for insomnia, depression, and anxiety consisting of pulsed, low-intensity current applied to the earlobes or scalp. Despite empirical evidence of clinical efficacy, its mechanism of action is largely unknown. The goal was to characterize the acute effects of CES on resting state brain activity. Our primary hypothesis was that CES would result in deactivation in cortical and subcortical regions. Eleven healthy controls were administered CES applied to the earlobes at subsensory thresholds while being scanned with functional magnetic resonance imaging in the resting state. We tested 0.5- and 100-Hz stimulation, using blocks of 22 sec "on" alternating with 22 sec of baseline (device was "off"). The primary outcome measure was differences in blood oxygen level dependent data associated with the device being on versus baseline. The secondary outcome measures were the effects of stimulation on connectivity within the default mode, sensorimotor, and fronto-parietal networks. Both 0.5- and 100-Hz stimulation resulted in significant deactivation in midline frontal and parietal regions. 100-Hz stimulation was associated with both increases and decreases in connectivity within the default mode network (DMN). Results suggest that CES causes cortical brain deactivation, with a similar pattern for high- and low-frequency stimulation, and alters connectivity in the DMN. These effects may result from interference from high- or low-frequency noise. Small perturbations of brain oscillations may therefore have significant effects on normal resting state brain activity. These results provide insight into the mechanism of action of CES, and may assist in the future development of optimal parameters for effective treatment. PMID:22741094

Feusner, Jamie D; Madsen, Sarah; Moody, Teena D; Bohon, Cara; Hembacher, Emily; Bookheimer, Susan Y; Bystritsky, Alexander

2012-05-01

174

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

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

Cell Type Specific Analysis of Human Brain Transcriptome Data to Predict Alterations in Cellular Composition.  

PubMed

The central nervous system (CNS) is composed of hundreds of distinct cell types, each expressing different subsets of genes from the genome. High throughput gene expression analysis of the CNS from patients and controls is a common method to screen for potentially pathological molecular mechanisms of psychiatric disease. One mechanism by which gene expression might be seen to vary across samples would be alterations in the cellular composition of the tissue. While the expressions of gene 'markers' for each cell type can provide certain information of cellularity, for many rare cell types markers are not well characterized. Moreover, if only small sets of markers are known, any substantial variation of a marker's expression pattern due to experiment conditions would result in poor sensitivity and specificity. Here, our proposed method combines prior information from mice cell-specific transcriptome profiling experiments with co-expression network analysis, to select large sets of potential cell type-specific gene markers in a systematic and unbiased manner. The method is efficient and robust, and identifies sufficient markers for further cellularity analysis. We then employ the markers to analytically detect changing cellular composition in human brain. Application of our method to temporal human brain microarray data successfully detects changes in cellularity over time that roughly correspond to known epochs of human brain development. Furthermore, application of our method to human brain samples with the neurodevelopmental disorder of autism supports the interpretation that the changes in astrocytes and neurons might contribute to the disorder. PMID:25340014

Xu, Xiaoxiao; Nehorai, Arye; Dougherty, Joseph

2013-07-01

177

Altered microstructure within social-cognitive brain networks during childhood in Williams syndrome.  

PubMed

Williams syndrome (WS) is a neurodevelopmental condition caused by a hemizygous deletion of ?26-28 genes on chromosome 7q11.23. WS is associated with a distinctive pattern of social cognition. Accordingly, neuroimaging studies show that WS is associated with structural alterations of key brain regions involved in social cognition during adulthood. However, very little is currently known regarding the neuroanatomical structure of social cognitive brain networks during childhood in WS. This study used diffusion tensor imaging to investigate the structural integrity of a specific set of white matter pathways (inferior fronto-occipital fasciculus [IFOF] and uncinate fasciculus [UF]) and associated brain regions [fusiform gyrus (FG), amygdala, hippocampus, medial orbitofrontal gyrus (MOG)] known to be involved in social cognition in children with WS and a typically developing (TD) control group. Children with WS exhibited higher fractional anisotropy (FA) and axial diffusivity values and lower radial diffusivity and apparent diffusion coefficient (ADC) values within the IFOF and UF, higher FA values within the FG, amygdala, and hippocampus and lower ADC values within the FG and MOG compared to controls. These findings provide evidence that the WS genetic deletion affects the development of key white matter pathways and brain regions important for social cognition. PMID:23709644

Haas, Brian W; Barnea-Goraly, Naama; Sheau, Kristen E; Yamagata, Bun; Ullas, Shruti; Reiss, Allan L

2014-10-01

178

Low HDL cholesterol, aggression and altered central serotonergic activity  

Microsoft Academic Search

Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore

Laure Buydens-Branchey; Marc Branchey; Jeffrey Hudson; Paul Fergeson

2000-01-01

179

Investigating the physiology of brain activation with MRI  

NASA Astrophysics Data System (ADS)

Functional magnetic resonance imaging (fMRI) has become a powerful tool for investigating the working human brain based on the blood oxygenation level dependent (BOLD) effect on the MR signal. However, despite the widespread use of fMRI techniques for mapping brain activation, the basic physiological mechanisms underlying the observed signal changes are still poorly understood. Arterial spin labeling (ASL) techniques, which measure cerebral blood flow (CBF) and the BOLD effect simultaneously, provide a useful tool for investigating these physiological questions. In this paper, recent results of studies manipulating the baseline CBF both pharmacologically and physiologically will be discussed. These data are consistent with a feed-forward mechanism of neurovascular coupling, and suggest that the CBF change itself may be a more robust reflection of neural activity changes than the BOLD effect. Consistent with these data, a new thermodynamic hypothesis is proposed for the physiological function of CBF regulation: maintenance of the [O2]/[CO2] concentration ratio at the mitochondria in order to preserve the free energy available from oxidative metabolism. A kinetic model based on this hypothesis provides a reasonable quantitative description of the CBF changes associated with neural activity and altered blood gases (CO2 and O2).

Buxton, Richard B.; Uludag, Kamil; Dubowitz, David J.

2004-04-01

180

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 (10days 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

181

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.

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

2015-01-01

182

Altered Causal Connectivity of Resting State Brain Networks in Amnesic MCI  

PubMed Central

Most neuroimaging studies of resting state networks in amnesic mild cognitive impairment (aMCI) have concentrated on functional connectivity (FC) based on instantaneous correlation in a single network. The purpose of the current study was to investigate effective connectivity in aMCI patients based on Granger causality of four important networks at resting state derived from functional magnetic resonance imaging data – default mode network (DMN), hippocampal cortical memory network (HCMN), dorsal attention network (DAN) and fronto-parietal control network (FPCN). Structural and functional MRI data were collected from 16 aMCI patients and 16 age, gender-matched healthy controls. Correlation-purged Granger causality analysis was used, taking gray matter atrophy as covariates, to compare the group difference between aMCI patients and healthy controls. We found that the causal connectivity between networks in aMCI patients was significantly altered with both increases and decreases in the aMCI group as compared to healthy controls. Some alterations were significantly correlated with the disease severity as measured by mini-mental state examination (MMSE), and California verbal learning test (CVLT) scores. When the whole-brain signal averaged over the entire brain was used as a nuisance co-variate, the within-group maps were significantly altered while the between-group difference maps did not. These results suggest that the alterations in causal influences may be one of the possible underlying substrates of cognitive impairments in aMCI. The present study extends and complements previous FC studies and demonstrates the coexistence of causal disconnection and compensation in aMCI patients, and thus might provide insights into biological mechanism of the disease. PMID:24613934

Liang, Peipeng; Li, Zhihao; Deshpande, Gopikrishna; Wang, Zhiqun; Hu, Xiaoping; Li, Kuncheng

2014-01-01

183

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

184

Brain activation during phonological and semantic processing of Chinese characters in deaf signers.  

PubMed

Previous studies found altered brain function in deaf individuals reading alphabetic orthographies. However, it is not known whether similar alterations of brain function are characteristic of non-alphabetic writing systems and whether alterations are specific to certain kinds of lexical tasks. Here we examined differences in brain activation between Chinese congenitally deaf individuals (CD) and hearing controls (HC) during character reading tasks requiring phonological and semantic judgments. For both tasks, we found that CD showed less activation than HC in left inferior frontal gyrus, but greater activation in several right hemisphere regions including inferior frontal gyrus, angular gyrus, and inferior temporal gyrus. Although many group differences were similar across tasks, greater activation in right middle frontal gyrus was more pronounced for the rhyming compared to the meaning task. Finally, within the deaf individuals better performance on the rhyming task was associated with less activation in right inferior parietal lobule and angular gyrus. Our results in Chinese CD are broadly consistent with previous studies in alphabetic languages suggesting greater engagement of inferior frontal gyrus and inferior parietal cortex for reading that is largely independent of task, with the exception of right middle frontal gyrus for phonological processing. The brain behavior correlations potentially indicate that CD that more efficiently use the right hemisphere are better readers. PMID:24795593

Li, Yanyan; Peng, Danling; Liu, Li; Booth, James R; Ding, Guosheng

2014-01-01

185

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...

186

Chronic scream sound exposure alters memory and monoamine levels in female rat brain.  

PubMed

Chronic scream sound alters the cognitive performance of male rats and their brain monoamine levels, these stress-induced alterations are sexually dimorphic. To determine the effects of sound stress on female rats, we examined their serum corticosterone levels and their adrenal, splenic, and thymic weights, their cognitive performance and the levels of monoamine neurotransmitters and their metabolites in the brain. Adult female Sprague-Dawley rats, with and without exposure to scream sound (4h/day for 21 day) were tested for spatial learning and memory using a Morris water maze. Stress decreased serum corticosterone levels, as well as splenic and adrenal weight. It also impaired spatial memory but did not affect the learning ability. Monoamines and metabolites were measured in the prefrontal cortex (PFC), striatum, hypothalamus, and hippocampus. The dopamine (DA) levels in the PFC decreased but the homovanillic acid/DA ratio increased. The decreased DA and the increased 5-hydroxyindoleacetic acid (5-HIAA) levels were observed in the striatum. Only the 5-HIAA level increased in the hypothalamus. In the hippocampus, stress did not affect the levels of monoamines and metabolites. The results suggest that scream sound stress influences most physiologic parameters, memory, and the levels of monoamine neurotransmitter and their metabolites in female rats. PMID:24952268

Hu, Lili; Zhao, Xiaoge; Yang, Juan; Wang, Lumin; Yang, Yang; Song, Tusheng; Huang, Chen

2014-10-01

187

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

188

Melanoma tumors alter proinflammatory cytokine production and monoamine brain function, and induce depressive-like behavior in male mice.  

PubMed

Depression is a commonly observed disorder among cancer patients; however, the mechanisms underlying the relationship between these disorders are not well known. We used an animal model to study the effects of tumor development on depressive-like behavior manifestation, proinflammatory cytokine expression, and central monoaminergic activity. Male OF1 mice were inoculated with B16F10 melanoma tumor cells and subjected to a 21-day behavioral evaluation comprising the novel palatable food (NPF) test and tail suspension test (TST). The mRNA expression levels of proinflammatory cytokines, interleukin (IL)-1? and IL-6, and tumor necrosis factor-alpha (TNF-?), were measured in the hypothalamus and hippocampus and the levels of IL-6 and TNF-? were measured in the blood plasma. We similarly determined the monoamine turnover in various brain areas. The tumors resulted in increasing the immobility in TST and the expression level of IL-6 in the hippocampus. These increases corresponded with a decrease in dopaminergic activity in the striatum and a decrease in serotonin turnover in the prefrontal cortex. Similarly, a high level of tumor development produced increases in the brain expression levels of IL-6 and TNF-? and plasma levels of IL-6. Our findings suggest that these alterations in inflammatory cytokines and monoaminergic system function might be responsible for the manifestation of depressive-like behaviors in tumor-bearing mice. PMID:24995613

Lebeña, Andrea; Vegas, Oscar; Gómez-Lázaro, Eneritz; Arregi, Amaia; Garmendia, Larraitz; Beitia, Garikoitz; Azpiroz, Arantza

2014-10-01

189

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

190

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

191

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

192

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

193

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

194

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

195

Activation of calcineurin underlies altered trafficking of ?2 subunit containing GABAA receptors during prolonged epileptiform activity  

PubMed Central

Fast inhibitory signalling in the mammalian brain is mediated by gamma-aminobutyric acid type A receptors (GABAARs), which are targets for anti-epileptic therapy such as benzodiazepines. GABAARs undergo tightly regulated trafficking processes that are essential for maintenance and physiological modulation of inhibitory strength. The trafficking of GABAARs to and from the membrane is altered during prolonged seizures such as in Status Epilepticus (SE) and has been suggested to contribute to benzodiazepine pharmacoresistance in patients with SE. However, the intracellular signalling mechanisms that cause this modification in GABAAR trafficking remain poorly understood. In this study, we investigate the surface stability of GABAARs during SE utilising the low Mg2+ model in hippocampal rat neurons. Live-cell imaging of super ecliptic pHluorin (SEP)-tagged ?2 subunit containing GABAARs during low Mg2+ conditions reveals that the somatic surface receptor pool undergoes down-regulation dependent on N-methyl-d-aspartate receptor (NMDAR) activity. Analysis of the intracellular Ca2+ signal during low Mg2+ using the Ca2+-indicator Fluo4 shows that this reduction of surface GABAARs correlates well with the timeline of intracellular Ca2+ changes. Furthermore, we show that the activation of the phosphatase calcineurin was required for the decrease in surface GABAARs in neurons undergoing epileptiform activity. These results indicate that somatic modulation of GABAAR trafficking during epileptiform activity in vitro is mediated by calcineurin activation which is linked to changes in intracellular Ca2+ concentrations. These mechanisms could account for benzodiazepine pharmacoresistance and the maintenance of recurrent seizure activity, and reveal potential novel targets for the treatment of SE. This article is part of the Special Issue entitled ‘GABAergic Signaling in Health and Disease’. PMID:25245802

Eckel, Ramona; Szulc, Blanka; Walker, Matthew C.; Kittler, Josef T.

2015-01-01

196

A new stress model, a scream sound, alters learning and monoamine levels in rat brain.  

PubMed

Most existing animal models for stress involve the simultaneous application of physical and psychological stress factors. In the current study, we described and used a novel psychological stress model (scream sound stress). To study the validity of it, we carried out acute and chronic scream sound stress. First, adult Sprague-Dawley (SD) rats were randomly divided into white noise, stress and background groups. The white noise group and stress group were treated with white noise and scream sound for 4h in the morning respectively. Compared with white noise and background groups, exposure to acute scream sound increased corticosterone (CORT) level and decreased latency in Morris water maze (MWM) test. The levels of noradrenaline (NE), dopamine (DA), 5-hydroxytryptamine (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were altered in the striatum, hypothalamus and hippocampus of stress rats. Second, adult SD rats were randomly divided into background and stress groups, which were treated with scream sound for three weeks. Exposure to chronic scream sound suppressed body weight gain, increased corticosterone (CORT) level, influenced the morphology of adrenal gland, improved spleen and thymus indices, and decreased latency in MWM test. NE, DA, DOPAC, HVA and 5-HIAA levels were also altered in the brain of stress rats. Our results suggested that scream sound, as a novel stressor, facilitated learning ability, as well as altered monoamine levels in the rat brain. Moreover, scream sound is easy to apply and can be applied in more animals at the same time. PMID:24096192

Hu, Lili; Yang, Juan; Song, Tusheng; Hou, Ni; Liu, Yong; Zhao, Xiaoge; Zhang, Dianzeng; Wang, Lumin; Wang, Tao; Huang, Chen

2014-01-17

197

Maternal Pravastatin Prevents Altered Fetal Brain Development in a Preeclamptic CD-1 Mouse Model  

PubMed Central

Objective Using an animal model, we have previously shown that preeclampsia results in long-term adverse neuromotor outcomes in the offspring, and this phenotype was prevented by antenatal treatment with pravastatin. This study aims to localize the altered neuromotor programming in this animal model and to evaluate the role of pravastatin in its prevention. Materials and Methods For the preeclampsia model, pregnant CD-1 mice were randomly allocated to injection of adenovirus carrying sFlt-1 or its control virus carrying mFc into the tail vein. Thereafter they received pravastatin (sFlt-1-pra “experimental group”) or water (sFlt-1 “positive control”) until weaning. The mFc group (“negative control”) received water. Offspring at 6 months of age were sacrificed, and whole brains underwent magnetic resonance imaging (MRI). MRIs were performed using an 11.7 Tesla vertical bore MRI scanner. T2 weighted images were acquired to evaluate the volumes of 28 regions of interest, including areas involved in adaptation and motor, spatial and sensory function. Cytochemistry and cell quantification was performed using neuron-specific Nissl stain. One-way ANOVA with multiple comparison testing was used for statistical analysis. Results Compared with control offspring, male sFlt-1 offspring have decreased volumes in the fimbria, periaquaductal gray, stria medullaris, and ventricles and increased volumes in the lateral globus pallidus and neocortex; however, female sFlt-1 offspring showed increased volumes in the ventricles, stria medullaris, and fasciculus retroflexus and decreased volumes in the inferior colliculus, thalamus, and lateral globus pallidus. Neuronal quantification via Nissl staining exhibited decreased cell counts in sFlt-1 offspring neocortex, more pronounced in males. Prenatal pravastatin treatment prevented these changes. Conclusion Preeclampsia alters brain development in sex-specific patterns, and prenatal pravastatin therapy prevents altered neuroanatomic programming in this animal model. PMID:24963809

Carver, Alissa R.; Andrikopoulou, Maria; Lei, Jun; Tamayo, Esther; Gamble, Phyllis; Hou, Zhipeng; Zhang, Jiangyang; Mori, Susumu; Saade, George R.; Costantine, Maged M.; Burd, Irina

2014-01-01

198

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.

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

2014-01-01

199

Dorsal raphe nucleus of brain in the rats flown in space inflight and postflight alteration of structure  

NASA Astrophysics Data System (ADS)

The structure of brain dorsal raphe nucleus (DRN) was studied in the rats flown in space aboard Space Shuttle "Columbia" (STS-58, SLS-2 program) and dissected on day 13 of the mission ("inflight" rats) and in 5-6 hours after finishing 14-day flight ("postflight" rats). The brain of "inflight" rats were excised after decapitation, sectioned sagitally halves of brain were fixed by immersion in 2,5 % glutaraldehyde in 0.1 M cacodylate buffer pH 7.3 at 4°C and kept in the flight at 4°C. After landing the brain frontal 0.5 mm sections from DRN area were osmificated and embedded in araldite at NASA ARC. The brains of "postflight": and control rats were underwent to the same procedure. Electronmicroscopical analysis, computer morphometry and glial cell count were performed at Moscow. In DRN neuropil of "inflight" rats the most part of axo-dendritic synapses were surrounded by glia cell processes and had decreased electron density of pre- and postsynaptic membrane and pronounced diminution of synaptic vesicle amount while dendrites were characterized by decrease in matrix electron density and microtubule quantity that in total indicates the decline of afferent flow reaching DRN neurons in microgravity. In DRN neurons of "inflight" rats all mitochondria were characterized by evenly increased dimensions, decreased matrix electron density, small amount of short and far- between located cristae and enlarged intermembrane and intercristae spaces, that in total points out low level of coupling of oxidation to phosphorilation, decrease in energy supply of neuron. Amount of ribosome in cytoplasm was significantly decreased indicating lower lever of biosynthetic processes. The last is supported by diminished dimensions of neuronal body, nucleus and nucleolus (place of r RNA synthesis), cross section area of that were reduced in DRN neurons of "inflight" rats by 18.8 % (p < 0.01), 11.1 % and 26.6 % (p <0,005) correspondingly. Ultrastructure and dimensions of intracellular structures in DRN of "postflight" rats were not differ significantly fo rm analogous parameters of "inflight" rats. The results of study point out the decrease in mircrogravity in functional activity of DRN - main serotoniner gic center of brain and in combination with the data (Krasnov et. A.; 1998; Krasnov, Dyachkova, 2000) about inflight alteration in locus coeruleus - main noradrenergic center allow to propose the mechanism of decline of growth hormone secretion in mammals during space flight.

Krasnov, I.

200

Inflammation-induced Preterm Birth Alters Neuronal Morphology in the Mouse Fetal Brain  

PubMed Central

Adverse neurological outcome is a major cause of long-term morbidity in ex-preterm children. To investigate the effect of parturition and inflammation on the fetal brain, we utilized two in vivo mouse models of preterm birth. To mimic the most common human scenario of preterm birth, we used a mouse model of intrauterine inflammation by intrauterine infusion of lipopolysaccharide (LPS). To investigate the effect of parturition on the immature fetal brain, in the absence of inflammation, we used a non-infectious model of preterm birth by administering RU486. Pro-inflammatory cytokines (IL-10, IL-1?, IL-6 and TNF-?) in amniotic fluid and inflammatory biomarkers in maternal serum and amniotic fluid were compared between the two models using ELISA. Pro-inflammatory cytokine expression was evaluated in the whole fetal brains from the two models. Primary neuronal cultures from the fetal cortex were established from the different models and controls in order to compare the neuronal morphology. Only the intrauterine inflammation model resulted in an elevation of inflammatory biomarkers in the maternal serum and amniotic fluid. Exposure to inflammation-induced preterm birth, but not non-infectious preterm birth, also resulted in an increase in cytokine mRNA in whole fetal brain and in disrupted fetal neuronal morphology. In particular, Microtubule-associated protein 2 (MAP2) staining was decreased and the number of dendrites was reduced (P < 0.001, ANOVA between groups). These results suggest that inflammation-induced preterm birth and not the process of preterm birth may result in neuroinflammation and alter fetal neuronal morphology. PMID:20155801

Burd, Irina; Bentz, Amy I.; Chai, Jinghua; Gonzalez, Juan; Monnerie, Hubert; Le Roux, Peter D.; Cohen, Akiva S.; Yudkoff, Marc; Elovitz, Michal A.

2010-01-01

201

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

202

Methamphetamine Alters Blood Brain Barrier Protein Expression in Mice, Facilitating Central Nervous System Infection by Neurotropic Cryptococcus neoformans  

PubMed Central

Methamphetamine (METH) is a drug of abuse that is a potent and highly addictive central nervous system (CNS) stimulant. The blood brain barrier (BBB) is a unique interface that in part functions to prevent microbial invasion of the CNS. The effects of METH on brain vasculature have not been studied extensively. We hypothesized that METH alters the BBB integrity, increasing susceptibility to CNS infection. Using a murine model of METH administration, we demonstrated that METH alters BBB integrity and modifies the expression of tight junction and adhesion molecules. Additionally, we showed that BBB disruption accelerates transmigration of the neurotropic fungus Cryptococcus neoformans into the brain parenchyma after systemic infection. Furthermore, METH-treated mice displayed increased mortality as compared to untreated animals. Our findings provide novel evidence of the impact of METH abuse on the integrity of the cells that comprise the BBB and protect the brain from infection. PMID:23532099

Eugenin, Eliseo A.; Greco, Jade M.; Frases, Susana; Nosanchuk, Joshua D.; Martinez, Luis R.

2013-01-01

203

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

204

Ethacrynic acid and furosemide alter Cl, K, and Na distribution between blood, choroid plexus, CSF, and brain.  

PubMed

Can loop diuretics like ethacrynic acid and furosemide, when administered intravenously, significantly alter ion transport and fluid dynamics in CNS? To shed light on this unresolved issue, we tested the ability of these agents to effect redistribution of Na, K and Cl in adult rat brain. Cl penetration into various CNS regions was assessed as the volume of distribution, i.e., uptake, of 36Cl from blood. Ethacrynic acid and furosemide (50 mg/kg IV) reduced by 20-30% the rate of permeation of 36Cl across the blood-CSF barrier, and they elevated [K] and [Cl] in choroid plexus (CP) by 15-25%. The loop diuretic-induced buildup of K and Cl in CP (lateral and 4th ventricle) was likely a reflection of decreased movement of these ions across the apical membrane into CSF. 36Cl activity in parietal cortex and pons-medulla decreased in treatment with furosemide and ethacrynic acid, due to slowing of Cl transport across blood-brain and/or blood-CSF barriers. Our inhibitory findings in intact rats are consistent with those from previous in vitro experiments demonstrating diminution by loop diuretics of Na, K and Cl transport across isolated CP membranes. PMID:1461357

Johanson, C E; Murphy, V A; Dyas, M

1992-11-01

205

Melatonin pretreatment prevented the effect of dexamethasone negative alterations on behavior and hippocampal neurogenesis in the mouse brain.  

PubMed

Glucocorticoids play various physiological functions via the glucocorticoid receptor (GR). Glucocorticoid is associated with the pathophysiology of depression. Dexamethasone (DEX), a synthetic GR agonist, has a greater affinity for GR than the mineralocorticoid receptor (MR) in the hippocampus of pigs and may mimic the effects of GR possession. DEX decreases neurogenesis and induces damage to hippocampal neurons that is associated with depressive-like behavior. Melatonin, a hormone mainly synthesized in the pineal gland, is a potent free radical scavenger and antioxidant. Melatonin alters noradrenergic transmission in depressed patients. It may be interesting to further explore the mechanism of melatonin that is associated with the role of stress as a key factor to precipitate depression and as a factor altering neurogenesis. In this study, we assessed the capability of melatonin to protect the hippocampus of mouse brains to counteract the effects of chronic DEX treatment for 21 days on depressive-like behavior and neurogenesis. Our results revealed that chronic administration of DEX induced depressive-like behavior and that this could be reversed by pretreatment with melatonin. Moreover, the number of 5-bromo-2-deoxyuridine (BrdU)-immunopositive cells and doublecortin (DCX; the neuronal-specific marker) protein levels were significantly reduced in the DEX-treated mice. Pretreatment with melatonin was found to renew BrdU and DCX expression in the dentate gyrus. Furthermore, pretreatment with melatonin prevented DEX-induced reductions in GR and an extracellular-signal-regulated kinase (ERK1/2) in the hippocampal area. Melatonin may protect hippocampal neurons from damage and reverse neurogenesis after chronic DEX by activating brain-derived neurotrophic (BDNF) and ERK1/2 cascades. These results revealed that melatonin pretreatment prevented the reduction of cell proliferation, immature neuron precursor cells, and GR and ERK1/2 expression. This finding indicates that melatonin attenuates the DEX-induced depressive-like behavior, supporting the notion that melatonin possesses anti-stress and neurogenic actions. PMID:24589478

Ruksee, Nootchanart; Tongjaroenbuangam, Walaiporn; Mahanam, Thanutchaporn; Govitrapong, Piyarat

2014-09-01

206

Brain fatty acid synthase activates PPARalpha to maintain energy homeostasis.  

PubMed

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 beta cells and hypothalamus produced lean, hypophagic mice with increased physical activity and impaired hypothalamic PPARalpha signaling. Administration of a PPARalpha agonist into the hypothalamus increased PPARalpha target genes and normalized food intake. Inactivation of beta 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 PPARalpha. Thus, 2 diametrically opposed proteins, FAS (induced by feeding) and PPARalpha (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

2007-09-01

207

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

208

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.

Galvan, Adriana; Devergnas, Annaelle; Wichmann, Thomas

2015-01-01

209

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

210

Regulation of the brain isoprenoids farnesyl- and geranylgeranylpyrophosphate is altered in male Alzheimer patients  

PubMed Central

Post-translational modification of small GTPases by farnesyl- (FPP) and geranylgeranylpyrophosphate (GGPP) has generated much attention due to their potential contribution to cancer, cardiovascular and neurodegenerative diseases. Prenylated proteins have been identified in numerous cell functions and elevated levels of FPP and GGPP have been previously proposed to occur in Alzheimer disease (AD) but have never been quantified. In the present study, we determined if the mevalonate derived compounds FPP and GGPP are increased in brain grey and white matter of male AD patients as compared with control samples. This study demonstrates for the first time that FPP and GGPP levels are significantly elevated in human AD grey and white matter but not cholesterol, indicating a potentially disease-specific targeting of isoprenoid regulation independent of HMG-CoA-reductase. Further suggesting a selective disruption of FPP and GGPP homeostasis in AD, we show that inhibition of HMG-CoA reductase in vivo significantly reduced FPP, GGPP and cholesterol abundance in mice with the largest effect on the isoprenoids. A tentative conclusion is that if indeed regulation of FPP and GGPP is altered in AD brain such changes may stimulate protein prenylation and contribute to AD neuropathophysiology. PMID:19464372

Eckert, Gunter P.; Hooff, Gero P.; Strandjord, Dana M.; Igbavboa, Urule; Volmer, Dietrich A.; Müller, Walter E.; Wood, W. Gibson

2009-01-01

211

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

212

Prenatal cocaine exposure alters progenitor cell markers in the subventricular zone of the adult rat brain  

PubMed Central

Long-term consequences of early developmental exposure to drugs of abuse may have deleterious effects on the proliferative plasticity of the brain. The purpose of this study was to examine the long-term effects of prenatal exposure to cocaine, using the IV route of administration and doses that mimic the peak arterial levels of cocaine use in humans, on the proliferative cell types of the subventricular zones (SVZ) in the adult (180 days-old) rat brain. Employing immunocytochemistry, the expression of GFAP+ (type B cells) and nestin+(GFAP?) (Type C and A cells) staining was quantified in the subcallosal area of the SVZ. GFAP+ expression was significantly different between the prenatal cocaine treated group and the vehicle (saline) control group. The prenatal cocaine treated group possessed significantly lower GFAP+ expression relative to the vehicle control group, suggesting that prenatal cocaine exposure significantly reduced the expression of type B neural stem cells of the SVZ. In addition, there was a significant sex difference in nestin+ expression with females showing approximately 8–13% higher nestin+ expression compared to the males. More importantly, a significant prenatal treatment condition (prenatal cocaine, control) by sex interaction in nestin+ expression was confirmed, indicating different effects of cocaine based on sex of the animal. Specifically, prenatal cocaine exposure eliminated the basal difference between the sexes. Collectively, the present findings suggest that prenatal exposure to cocaine, when delivered via a protocol designed to capture prominent features of recreational usage, can selectively alter the major proliferative cell types in the subcallosal area of the SVZ in an adult rat brain, and does so differently for males and females. PMID:22119286

Patel, Dhyanesh Arvind; Booze, Rosemarie M.; Mactutus, Charles F.

2013-01-01

213

Activation of a mobile robot through a brain computer interface  

Microsoft Academic Search

This work presents the development of a brain computer interface as an alternative communication channel to be used in Robotics. It encompasses the implementation of an electroencephalograph (EEG), as well as the development of all computational methods and necessary techniques to identify mental activities. The developed brain computer interface (BCI) is applied to activate the movements of a 120lb mobile

Alexandre Ormiga Galvão Barbosa; David Ronald Achanccaray; Marco A. Meggiolaro

2010-01-01

214

Alterations in Brain-Derived Neurotrophic Factor in the Mouse Hippocampus Following Acute but Not Repeated Benzodiazepine Treatment  

PubMed Central

Benzodiazepines (BZs) are safe drugs for treating anxiety, sleep, and seizure disorders, but their use also results in unwanted effects including memory impairment, abuse, and dependence. The present study aimed to reveal the molecular mechanisms that may contribute to the effects of BZs in the hippocampus (HIP), an area involved in drug-related plasticity, by investigating the regulation of immediate early genes following BZ administration. Previous studies have demonstrated that both brain derived neurotrophic factor (BDNF) and c-Fos contribute to memory- and abuse-related processes that occur within the HIP, and their expression is altered in response to BZ exposure. In the current study, mice received acute or repeated administration of BZs and HIP tissue was analyzed for alterations in BDNF and c-Fos expression. Although no significant changes in BDNF or c-Fos were observed in response to twice-daily intraperitoneal (i.p.) injections of diazepam (10 mg/kg + 5 mg/kg) or zolpidem (ZP; 2.5 mg/kg + 2.5 mg/kg), acute i.p. administration of both triazolam (0.03 mg/kg) and ZP (1.0 mg/kg) decreased BDNF protein levels within the HIP relative to vehicle, without any effect on c-Fos. ZP specifically reduced exon IV-containing BDNF transcripts with a concomitant increase in the association of methyl-CpG binding protein 2 (MeCP2) with BDNF promoter IV, suggesting that MeCP2 activity at this promoter may represent a ZP-specific mechanism for reducing BDNF expression. ZP also increased the association of phosphorylated cAMP response element binding protein (pCREB) with BDNF promoter I. Future work should examine the interaction between ZP and DNA as the cause for altered gene expression in the HIP, given that BZs can enter the nucleus and intercalate into DNA directly. PMID:24367698

Licata, Stephanie C.; Shinday, Nina M.; Huizenga, Megan N.; Darnell, Shayna B.; Sangrey, Gavin R.; Rudolph, Uwe; Rowlett, James K.; Sadri-Vakili, Ghazaleh

2013-01-01

215

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

216

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

217

Ethacrynic acid and furosemide alter Cl, K, and Na distribution between blood, choroid plexus, CSF, and brain  

Microsoft Academic Search

Can loop diuretics like ethacrynic acid and furosemide, when administered intravenously, significantly alter ion transport and fluid dynamics in CNS? To shed light on this unresolved issue, we tested the ability of these agents to effect redistribution of Na, K and Cl in adult rat brain. Cl penetration into various CNS regions was assessed as the volume of distribution, i.e.,

Conrad E. Johanson; Vincent A. Murphy; Muriel Dyas I

1992-01-01

218

28 BrainResearch, 348 (1985)28-35 Altered Peripheral and Brainstem Auditory Function in Aged Rats  

E-print Network

28 BrainResearch, 348 (1985)28-35 Elsevier BRE 11137 Altered Peripheral and Brainstem Auditory-- hearing loss-- rat A technique for conducting free-field brainstem auditory evoked potential (BAEP that in addition to changes in peripheral auditory structures, changes in the rostral auditory brainstem ac

Knight, Robert T.

219

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...

220

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-related neu- rophysiologic heterogeneity. (Am J Geriatr Psychiatry 2004; 12:596­605) Received August 20, 2003 for Geriatric Psychiatry #12;Scarmeas et al. Am J Geriatr Psychiatry 12:6, November-December 2004 597 In resting

221

Abnormal Activity-Dependent Brain Lactate and Glutamate+Glutamine Responses in Panic Disorder  

PubMed Central

Background Prior evidence suggests panic disorder (PD) is characterized by neurometabolic abnormalities, including increased brain lactate responses to neural activation. Increased lactate responses could reflect a general upregulation of metabolic responses to neural activation. However, prior studies in PD have not measured activity-dependent changes in brain metabolites other than lactate. Here we examine activity-dependent changes in both lactate and glutamate plus glutamine (glx) in PD. Methods Twenty-one PD patients (13 remitted, 8 symptomatic) and 12 healthy volunteers were studied. A single-voxel, J-difference, magnetic resonance spectroscopy editing sequence was used to measure lactate and glx changes in visual cortex induced by visual stimulation. Results PD patients had significantly greater activity-dependent increases in brain lactate than healthy volunteers. The differences were significant for both remitted and symptomatic PD patients, who did not differ from each other. Activity-dependent changes in glx were significantly smaller in PD patients than in healthy volunteers. The temporal correlation between lactate and glx changes was significantly stronger in control subjects than in PD patients. Conclusions The novel demonstration that glx responses are diminished and temporally decoupled from lactate responses in PD contradicts the model of a general upregulation of activity-dependent brain metabolic responses in PD. The increase in activity-dependent brain lactate accumulation appears to be a trait feature of PD. Given the close relationship between lactate and pH in the brain, the findings are consistent with a model of brain metabolic and pH dysregulation associated with altered function of acid-sensitive fear circuits contributing to trait vulnerability in PD. PMID:23332354

Maddock, Richard J.; Buonocore, Michael H.; Miller, Amber R.; Yoon, Jong H.; Soosman, Steffan K.; Unruh, April M.

2013-01-01

222

Altered Small-World Efficiency of Brain Functional Networks in Acupuncture at ST36: A Functional MRI Study  

PubMed Central

Background Acupuncture in humans can produce clinical effects via the central nervous system. However, the neural substrates of acupuncture’s effects remain largely unknown. Results We utilized functional MRI to investigate the topological efficiency of brain functional networks in eighteen healthy young adults who were scanned before and after acupuncture at the ST36 acupoints (ACUP) and its sham point (SHAM). Whole-brain functional networks were constructed by thresholding temporal correlations matrices of ninety brain regions, followed by a graph theory-based analysis. We showed that brain functional networks exhibited small-world attributes (high local and global efficiency) regardless of the order of acupuncture and stimulus points, a finding compatible with previous studies of brain functional networks. Furthermore, the brain networks had increased local efficiency after ACUP stimulation but there were no significant differences after SHAM, indicating a specificity of acupuncture point in coordinating local information flow over the whole brain. Moreover, significant (P<0.05, corrected by false discovery rate approach) effects of only acupuncture point were detected on nodal degree of the left hippocampus (higher nodal degree at ACUP as compared to SHAM). Using an uncorrected P<0.05, point-related effects were also observed in the anterior cingulate cortex, frontal and occipital regions while stimulation-related effects in various brain regions of frontal, parietal and occipital cortex regions. In addition, we found that several limbic and subcortical brain regions exhibited point- and stimulation-related alterations in their regional homogeneity (P<0.05, uncorrected). Conclusions Our results suggest that acupuncture modulates topological organization of whole-brain functional brain networks and the modulation has point specificity. These findings provide new insights into neuronal mechanism of acupuncture from the perspective of functional integration. Further studies would be interesting to apply network analysis approaches to study the effects of acupuncture treatments on brain disorders. PMID:22761766

Liu, Xian; Duan, Xiaohui; Shang, Xiaojing; Long, Yu; Chen, Zhiguang; Li, Xiaofang; Huang, Yan; He, Yong

2012-01-01

223

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

224

Altered Functional Connectivity within and between Brain Modules in Absence Epilepsy: A Resting-State Functional Magnetic Resonance Imaging Study  

PubMed Central

Functional connectivity has been correlated with a patient's level of consciousness and has been found to be altered in several neuropsychiatric disorders. Absence epilepsy patients, who experience a loss of consciousness, are assumed to suffer from alterations in thalamocortical networks; however, previous studies have not explored the changes at a functional module level. We used resting-state functional magnetic resonance imaging to examine the alteration in functional connectivity that occurs in absence epilepsy patients. By parcellating the brain into 90 brain regions/nodes, we uncovered an altered functional connectivity within and between functional modules. Some brain regions had a greater number of altered connections and therefore behaved as key nodes in the changed network pattern; these regions included the superior frontal gyrus, the amygdala, and the putamen. In particular, the superior frontal gyrus demonstrated both an increased value of connections with other nodes of the frontal default mode network and a decreased value of connections with the limbic system. This divergence is positively correlated with epilepsy duration. These findings provide a new perspective and shed light on how functional connectivity and the balance of within/between module connections may contribute to both the state of consciousness and the development of absence epilepsy. PMID:24191250

Xu, Cui-Ping; Zhang, Shou-Wen; Fang, Tie; Chencan, Qian; Huafu, Chen; Zhu, Hong-Wei; Li, Yong-Jie

2013-01-01

225

Maternal inflammation contributes to brain overgrowth and autism-associated behaviors through altered redox signaling in stem and progenitor cells.  

PubMed

A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species. PMID:25418720

Le Belle, Janel E; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R; López-Aranda, Manuel; Silva, Alcino J; Kornblum, Harley I

2014-11-11

226

Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells  

PubMed Central

Summary A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species. PMID:25418720

Le Belle, Janel E.; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R.; López-Aranda, Manuel; Silva, Alcino J.; Kornblum, Harley I.

2014-01-01

227

VAP-1\\/SSAO Plasma Activity and Brain Expression in Human Hemorrhagic Stroke  

Microsoft Academic Search

Background: Vascular adhesion protein-1 (VAP-1) is a cell surface and circulating enzyme that belongs to the semicarbazide-sensitive amine oxidase (SSAO) family, which oxidatively deaminates primary amines and is implicated in leukocyte extravasation. Our aim was to investigate the alteration of soluble VAP-1\\/SSAO activity in plasma samples after acute intracerebral hemorrhage (ICH) and its presence in human ICH brain tissue. Methods:

Mar Hernandez-Guillamon; Montse Solé; Pilar Delgado; Lidia García-Bonilla; Dolors Giralt; Cristina Boada; Anna Penalba; Sandra García; Alan Flores; Marc Ribó; José Alvarez-Sabin; Arantxa Ortega-Aznar; Mercedes Unzeta; Joan Montaner

2012-01-01

228

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

PubMed

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

229

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

230

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

231

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

232

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

233

Serpin Inhibitors of Urokinase and Thrombin in Normal Rat Brain and the 9L Brain Tumor: Evidence for Elevated Expression of Protease Nexin I-like Inhibitor and a Novel Sodium Dodecyl Sulfate-activated Tumor Antithrombin1  

Microsoft Academic Search

Increasing attention is being paid to alterations of the hemostatic balance in tumors, in general, and brain tumors, in particular. Apparently divergent results, showing excess fibrinolysis (i.e., increased plasminogen activator activity) or its inhibition (i.e., increased inhibitor activity), have been reported. The 9L rat brain tumor is a gliosarcoma and a model used to study treatment paradigms for human gliomas.

J. S. Rao; J. B. Baker; R. A. Morantz; B. Kimler; R. Evans; B. W. Festoff

234

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

235

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

236

PHYSICAL ACTIVITY, INFLAMMATION, AND VOLUME OF THE AGING BRAIN  

PubMed Central

Physical activity influences inflammation, and both affect brain structure and Alzheimer’s disease (AD) risk. We hypothesized that older adults with greater reported physical activity intensity and lower serum levels of the inflammatory marker tumor necrosis factor ? (TNF?) would have larger regional brain volumes on subsequent magnetic resonance imaging (MRI) scans. In 43 cognitively intact older adults (79.3 ± 4.8 years) and 39 patients with AD (81.9 ± 5.1 years at the time of MRI) participating in the Cardiovascular Health Study, we examined year-1 reported physical activity intensity, year-5 blood serum TNF? measures, and year-9 volumetric brain MRI scans. We examined how prior physical activity intensity and TNF? related to subsequent total and regional brain volumes. Physical activity intensity was measured using the modified Minnesota Leisure Time Physical Activities questionnaire at year 1 of the study, when all subjects included here were cognitively intact. Stability of measures was established for exercise intensity over 9 years and TNF? over 3 years in a subset of subjects who had these measurements at multiple time points. When considered together, more intense physical activity intensity and lower serum TNF? were both associated with greater total brain volume on follow-up MRI scans. TNF?, but not physical activity, was associated with regional volumes of the inferior parietal lobule, a region previously associated with inflammation in AD patients. Physical activity and TNF? may independently influence brain structure in older adults. PMID:24836855

BRASKIE, M. N.; BOYLE, C. P.; RAJAGOPALAN, P.; GUTMAN, B. A.; TOGA, A. W.; RAJI, C. A.; TRACY, R. P.; KULLER, L. H.; BECKER, J. T.; LOPEZ, O. L.; THOMPSON, P. M.

2014-01-01

237

Stress in Pregnancy Activates Neurosteroid Production in the Fetal Brain  

Microsoft Academic Search

Neurosteroids such as allopregnanolone are potent agonists at the GABAA receptor and suppress the fetal CNS activity. These steroids are synthesized in the fetal brain either from cholesterol or from circulating precursors derived from the placenta. The concentrations of allopregnanolone are remarkably high in the fetal brain and rise further in response to acute hypoxic stress, induced by constriction of

Jonathan J. Hirst; Tamara Yawno; Phuong Nguyen; David W. Walker

2006-01-01

238

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

E-print Network

identified. These distinct patterns can be separated from each other from a single resting FMRI dataset ``active'' even when at ``rest.'' brain connectivity BrainMap FMRI functional connectivity resting (FMRI) since it was first noted that, even with the subject at rest, the FMRI time series from one part

Miall, Chris

239

Three-Dimensional Electrical Impedance Tomography of Human Brain Activity  

Microsoft Academic Search

Regional cerebral blood flow and blood volume changes that occur during human brain activity will change the local impedance of that cortical area, as blood has a lower impedance than that of brain. Theoretically, such impedance changes could be measured from scalp electrodes and reconstructed into images of the internal impedance of the head. Electrical Impedance Tomography (EIT) is a

Tom Tidswell; Adam Gibson; Richard H. Bayford; David S. Holder

2001-01-01

240

Peers increase adolescent risk taking by enhancing activity in the brain’s reward circuitry  

PubMed Central

The presence of peers increases risk taking among adolescents but not adults. We posited that the presence of peers may promote adolescent risk taking by sensitizing brain regions associated with the anticipation of potential rewards. Using fMRI, we measured brain activity in adolescents, young adults, and adults as they made decisions in a simulated driving task. Participants completed one task block while alone, and one block while their performance was observed by peers in an adjacent room. During peer observation blocks, adolescents selectively demonstrated greater activation in reward-related brain regions, including the ventral striatum and orbitofrontal cortex, and activity in these regions predicted subsequent risk taking. Brain areas associated with cognitive control were less strongly recruited by adolescents than adults, but activity in the cognitive control system did not vary with social context. Results suggest that the presence of peers increases adolescent risk taking by heightening sensitivity to the potential reward value of risky decisions. PMID:21499511

Chein, Jason; Albert, Dustin; O’Brien, Lia; Uckert, Kaitlyn; Steinberg, Laurence

2010-01-01

241

Atypical spatial working memory and task-general brain activity in adolescents with a family history of alcoholism  

PubMed Central

Background Altered behavioral performance and brain activation during spatial working memory (SWM) tasks have been demonstrated in individuals with an alcohol use disorder (AUD). It is possible that alterations in processing during SWM may be present prior to initiation of heavy alcohol use in adolescents with a family history of AUDs (FHP) and therefore represent a premorbid neural phenotype that could increase risk for developing an AUD. The goal of our study was to investigate group differences in brain activation during a SWM task between FHP adolescents and adolescents with no family history of AUDs (FHN), as well as examine the relationship between brain activation and individual differences in family history density (FHD) of AUDs. Methods 18 FHP and 16 gender and age-matched FHN participants completed a SWM and vigilance task while undergoing a functional magnetic resonance imaging (fMRI) scan. Results There were no group differences in task performance. The FHN group demonstrated expected greater activation during the SWM than vigilance condition in the right middle frontal gyrus and dorsolateral prefrontal cortex, whereas the FHP group demonstrated comparable brain activation for both the more demanding and simple task conditions. Additionally, FHD was associated with greater activation of the right superior parietal cortex and less activation of the right cerebellum during the SWM task, but not during the vigilance task. Conclusions Results suggest FHP adolescents demonstrate alterations in activation of prefrontal regions that are related more generally to the maintenance of top-down cognitive control and alterations in parietal and cerebellar regions that are specific to spatial working memory. Alterations in top-down cognitive control may be a general risk factor for FHP adolescents, whereas SWM-specific alterations are seen as a function of family history loading. PMID:23078615

Mackiewicz Seghete, Kristen L.; Cservenka, Anita; Herting, Megan M.; Nagel, Bonnie J.

2012-01-01

242

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

243

Brain-Computer Interfaces (BCI): Restoration of Movement and Thought from Neuroelectric and Metabolic Brain Activity  

Microsoft Academic Search

This chapter provides an overview of the scientific and clinical progress in the development of non-invasive and invasive\\u000a brain-computer interfaces (BCI). BCI uses electric, magnetic or metabolic brain activity for the activation and control of\\u000a external devices and computers. Clinically, until now it has been successfully used as a communication system for totally\\u000a paralyzed patients (“locked-in patients”), in restoration of

Surjo R. Soekadar; Klaus Haagen; Niels Birbaumer

244

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

245

Pam (Peptidylglycine ?-amidating monooxygenase) heterozygosity alters brain copper handling with region specificity  

PubMed Central

Copper (Cu), an essential trace element present throughout the mammalian nervous system, is crucial for normal synaptic function. Neuronal handling of Cu is poorly understood. We studied the localization and expression of Atp7a, the major intracellular Cu transporter in the brain, and its relation to peptidylglycine ?-amidating monooxygenase (PAM), an essential cuproenzyme and regulator of Cu homeostasis in neuroendocrine cells. Based on biochemical fractionation and immunostaining of dissociated neurons, Atp7a was enriched in postsynaptic vesicular fractions. Cu followed a similar pattern, with ~20% of total Cu in synaptosomes. A mouse model heterozygous for the Pam gene (PAM+/?) is selectively Cu deficient in the amygdala. As in cortex and hippocampus, Atp7a and PAM expression overlap in the amygdala, with highest expression in interneurons. Messenger RNA levels of Atox-1 and Atp7a, which deliver Cu to the secretory pathway, were reduced in the amygdala but not the hippocampus in PAM+/? mice, along with GABAB receptor mRNA levels. Consistent with Cu deficiency, dopamine ?-monooxygenase function was impaired as evidenced by elevated dopamine metabolites in the amygdala, but not the hippocampus, of PAM+/? mice. These alterations in Cu delivery to the secretory pathway in the PAM+/? amygdala may contribute to the physiological and behavioral deficits observed. PMID:24032518

Gaier, Eric D; Miller, Megan B; Ralle, Martina; Aryal, Dipendra; Wetsel, William C; Mains, Richard E; Eipper, Betty A

2013-01-01

246

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. Hum Brain Mapp 36:1180-1189, 2015. © 2014 Wiley Periodicals, Inc. 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

247

Spatial heterogeneity analysis of brain activation in fMRI  

PubMed Central

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

248

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

249

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

250

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

251

Alterations in blood-brain barrier function following acute hypertension: comparison of the blood-to-brain transfer of horseradish peroxidase with that of alpha-aminisobutyric acid  

SciTech Connect

The blood-brain barrier (BBB) selectively restricts the blood-to-brain passage of many solutes owing to unique properties of cerebrovascular endothelial cell membranes. To date, experimental study of the BBB has been accomplished primarily through the use of two different methodological approaches. Morphological studies have mostly employed large molecular weight (MW) tracers to detect morphological alterations underlying increased permeability. Physiological studies, employing smaller, more physiologic tracers have successfully described, quantitatively, certain functional aspects of blood-to-brain transfer. The current work attempts to merge these two approaches and to consider barrier function/dysfunction from both a morphological and a functional perspective. Specifically, the study compares in rats, following acute hypertension, the cerebrovascular passage of /sup 14/C-alpha-aminoisobutyric acid (AIB) and that of horseradish peroxidase (HRP). The blood-to-brain passage of AIB and HRP were compared following acute hypertension, with regard to both the distributions of the tracer extravasation patterns and the magnitude of tracer extravasation. The results of this study suggest that traditional morphological barrier studies alone do not reveal all aspects of altered barrier status and that multiple mechanisms underlying increased BBB permeability may operate simultaneously during BBB dysfunction.

Ellison, M.D.B.

1985-01-01

252

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

253

Lipopolysaccharide alters the blood–brain barrier transport of amyloid ? protein: A mechanism for inflammation in the progression of Alzheimer’s disease  

Microsoft Academic Search

Alzheimer’s disease (AD) brains are characterized by accumulation of amyloid ? protein (A?) and neuroinflammation. Increased blood-to-brain influx and decreased brain-to-blood efflux across the blood–brain barrier (BBB) have been proposed as mechanisms for A? accumulation. Epidemiological studies suggest that the nonsteroidal anti-inflammatory drug (NSAID) indomethacin slows the progression of AD. We hypothesized that inflammation alters BBB handling of A?. Mice

Laura B. Jaeger; Shinya Dohgu; Rukhsana Sultana; Jessica L. Lynch; Joshua B. Owen; Michelle A. Erickson; Gul N. Shah; Tulin O. Price; Melissa A. Fleegal-Demotta; D. Allan Butterfiled; William A. Banks

2009-01-01

254

Thalidomide combined with irradiation alters the activity of two proteases.  

PubMed

The aim of the present study was to investigate the effects of thalidomide, a drug known for its anti?angiogenic and antitumor properties, at its cytotoxic dose previously determined as 40 µg/ml (according to four cytotoxic test results). The effect of the drug alone and in combination with radiotherapy using Cobalt 60 (60Co) at 45 Gy on the enzymatic activity of substance?P degrading A disintegrin and metalloproteinase (ADAM)10 and neprilysin (NEP) was investigated in the mouse breast cancer cell lines 4T1 and 4T1 heart metastases post?capsaicin (4THMpc). Thalidomide (40 µg/ml) exerted differing effects on the activities of ADAM10 and NEP enzymes. In 4T1 cells, 40 µg/ml thalidomide alone did not alter ADAM10 enzyme activity. 60Co irradiation at 45 Gy alone caused a 42% inhibition in ADAM10 activity, however, the inhibition increased to 89% when combined therapy was used. By contrast, in the 4THMpc cell line, 40 µg/ml thalidomide alone induced a 66.6% increase in ADAM10 enzyme activity. Radiotherapy alone and thalidomide with 60Co combined therapy caused a 33.3 and 40% inhibition of ADAM10 activity, respectively. In 4T1 cells, thalidomide alone caused a 40.9% increase in NEP activity. Radiation therapy alone or in combination with the drug caused a 40.7% increase in NEP activity. In more aggressive 4THMpc cells, thalidomide alone caused a 26.6% increase in NEP activity. Radiotherapy alone and combined therapy caused a 33.3 and 37% increase in enzyme activity, respectively. To the best of our knowledge, the present study is the first to demonstrate that thalidomide alone or in combination with radiotherapy exhibits significant cytotoxic effects on 4T1 and 4THMpc mouse breast cancer cell lines indicating that this drug affects the enzymatic activity of ADAM10 and NEP in vitro. PMID:25370353

Sim?ek, Ece; Aydemir, Esra; Korcum, Aylin Fidan; Fi?k?n, Kayahan

2015-02-01

255

Maternal caffeine exposure alters neuromotor development and hippocampus acetylcholinesterase activity in rat offspring.  

PubMed

The objective of this study was to evaluate the effects of maternal caffeine intake on the neuromotor development of rat offspring and on acetylcholine degradation and acetylcholinesterase (AChE) expression in the hippocampus of 14-day-old infant rats. Rat dams were treated with caffeine (0.3g/L) throughout gestation and lactation until the pups were 14 days old. The pups were divided into three groups: (1) control, (2) caffeine, and (3) washout caffeine. The washout group received a caffeine solution until the seventh postnatal day (P7). Righting reflex (RR) and negative geotaxis (NG) were assessed to evaluate postural parameters as an index of neuromotor reflexes. An open-field (OF) test was conducted to assess locomotor and exploratory activities as well as anxiety-like behaviors. Caffeine treatment increased both RR and NG latency times. In the OF test, the caffeine group had fewer outer crossings and reduced locomotion compared to control, while the washout group showed increased inner crossings in relation to the other groups and fewer rearings only in comparison to the control group. We found decreased AChE activity in the caffeine group compared to the other groups, with no alteration in AChE transcriptional regulation. Chronic maternal exposure to caffeine promotes important alterations in neuromotor development. These results highlight the ability of maternal caffeine intake to interfere with cholinergic neurotransmission during brain development. PMID:25451122

Souza, Ana Claudia; Souza, Andressa; Medeiros, Liciane Fernandes; De Oliveira, Carla; Scarabelot, Vanessa Leal; Da Silva, Rosane Souza; Bogo, Mauricio Reis; Capiotti, Katiucia Marques; Kist, Luiza Wilges; Bonan, Carla D; Caumo, Wolnei; Torres, Iraci L S

2015-01-21

256

Letm1, the mitochondrial Ca2+/H+ antiporter, is essential for normal glucose metabolism and alters brain function in Wolf–Hirschhorn syndrome  

PubMed Central

Mitochondrial metabolism, respiration, and ATP production necessitate ion transport across the inner mitochondrial membrane. Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1), one of the genes deleted in Wolf–Hirschhorn syndrome, encodes a putative mitochondrial Ca2+/H+ antiporter. Cellular Letm1 knockdown reduced Ca2+mito uptake, H+mito extrusion and impaired mitochondrial ATP generation capacity. Homozygous deletion of Letm1 in mice resulted in embryonic lethality before day 6.5 of embryogenesis and ?50% of the heterozygotes died before day 13.5 of embryogenesis. The surviving heterozygous mice exhibited altered glucose metabolism, impaired control of brain ATP levels, and increased seizure activity. We conclude that loss of Letm1 contributes to the pathology of Wolf–Hirschhorn syndrome in humans and may contribute to seizure phenotypes by reducing glucose oxidation and other specific metabolic alterations. PMID:23716663

Jiang, Dawei; Zhao, Linlin; Clish, Clary B.; Clapham, David E.

2013-01-01

257

Alteration of biophysical activity of pulmonary surfactant by aluminosilicate nanoparticles.  

PubMed

The influence of five different types of aluminosilicate nanoparticles (NPs) on the dynamic surface activity of model pulmonary surfactant (PS) (Survanta) was studied experimentally using oscillating bubble tensiometry. Bentonite, halloysite and montmorillonite (MM) NPs, which are used as fillers of polymer composites, were characterized regarding the size distribution, morphology and surface area. Particle doses applied in the studies were estimated based on the inhalation rate and duration, taking into account the expected aerosol concentration and deposition efficiency after penetration of NPs into the alveolar region. The results indicate that aluminosilicate NPs at concentrations in the pulmonary liquid above 0.1?mg?cm(-3) are capable of promoting alterations of the original dynamic biophysical activity of the PS. This effect is indicated by deviation of the minimum surface tension, stability index and the size of surface tension hysteresis. Such response is dependent on the type of NPs present in the system and is stronger when particle concentration increases. It is suggested that interactions between NPs and the PS must be related to the surfactant adsorption on the suspended particles, while in the case of surface-modified clay NPs the additional washout of surface-active components may be expected. It is speculated that observed changes in surface properties of the surfactant may be associated with undesired health effects following extensive inhalation of aluminosilicate NPs in the workplace. PMID:23363039

Kondej, Dorota; Sosnowski, Tomasz R

2013-02-01

258

Microwave irradiation decreases ATP, increases free [Mg2+], and alters in vivo intracellular reactions in rat brain  

PubMed Central

Rapid inactivation of metabolism is essential for accurately determining the concentrations of metabolic intermediates in the in vivo state. We compared a broad spectrum of energetic intermediate metabolites and neurotransmitters in brains obtained by microwave irradiation to those obtained by freeze blowing, the most rapid method of extracting and freezing rat brain. The concentrations of many intermediates, cytosolic free NAD(P)+/NAD(P)H ratios, as well as neurotransmitters were not affected by the microwave procedure. However, the brain concentrations of ATP were about 30% lower, whereas those of ADP, AMP, and GDP were higher in the microwave-irradiated compared with the freeze-blown brains. In addition, the hydrolysis of approximately 1 ?mol/g of ATP, a major in vivo Mg2+-binding site, was related to approximately five-fold increase in free [Mg2+] (0.53 ± 0.07 mM in freeze blown vs. 2.91 mM ± 0.48 mM in microwaved brains), as determined from the ratio [citrate]/[isocitrate]. Consequently, many intracellular properties, such as the phosphorylation potential and the ?G’ of ATP hydrolysis were significantly altered in microwaved tissue. The determinations of some glycolytic and TCA cycle metabolites, the phosphorylation potential, and the ?G’ of ATP hydrolysis do not represent the in vivo state when using microwave-fixed brain tissue. PMID:23013291

Srivastava, Shireesh; Kashiwaya, Yoshihiro; Chen, Xuesong; Geiger, Jonathan D.; Pawlosky, Robert; Veech, Richard L.

2012-01-01

259

Viable mouse gene ablations that robustly alter brain A? levels are rare  

Microsoft Academic Search

BACKGROUND: Accumulation of amyloid-? (A?) peptide in the brain is thought to play a key pathological role in Alzheimer's disease. Many pharmacological targets have therefore been proposed based upon the biochemistry of A?, but not all are equally tractable for drug discovery. RESULTS: To search for novel targets that affect brain A? without causing toxicity, we screened mouse brain samples

Jeremy H Toyn; Xu-Alan Lin; Mark W Thompson; Valerie Guss; Jere E Meredith Jr; Sethu Sankaranarayanan; Nestor Barrezueta; John Corradi; Antara Majumdar; Daniel L Small; Melissa Hansard; Thomas Lanthorn; Ryan S Westphal; Charles F Albright

2010-01-01

260

Reduced brain functional reserve and altered functional connectivity in patients with multiple sclerosis  

Microsoft Academic Search

Cognitive dysfunction (affecting particularly attention and working memory) occurs early in patients with multiple sclerosis. Previous studies have focused on identifying potentially adaptive functional reorganization through recruitment of new brain regions that could limit expression of these deficits. However, lesion studies remind us that functional specializations in the brain make certain brain regions necessary for a given task. We therefore

Sarah Cader; Alberto Cifelli; Yasir Abu-Omar; Jacqueline Palace; Paul M. Matthews

2006-01-01

261

Early Risk, Attention, and Brain Activation in Adolescents Born Preterm  

ERIC Educational Resources Information Center

The relations among early cumulative medical risk, cumulative environmental risk, attentional control, and brain activation were assessed in 15-16-year-old adolescents who were born preterm. Functional magnetic resonance imaging found frontal, temporal, and parietal cortex activation during an attention task with greater activation of the left…

Carmody, Dennis P.; Bendersky, Margaret; Dunn, Stanley M.; DeMarco, J. Kevin; Hegyi, Thomas; Hiatt, Mark; Lewis, Michael

2006-01-01

262

Aluminium induced structural, metabolic alterations and protective effects of desferrioxamine in the brain tissue of mice: An FTIR study  

NASA Astrophysics Data System (ADS)

In this study, we intended to made a new approach to evaluate aluminium induced metabolic changes in mice brain tissue using Fourier transform infrared spectroscopy. Results demonstrate that FTIR can successfully indicate the molecular changes that occur in all groups. The overall findings demonstrate the alterations on the major biochemical constituents, such as lipids, proteins and nucleic acids of the brain tissues of mice. The significant decrease in the area value of amide A peak and Olefinicdbnd CH stretching band suggests an alteration in the protein profile and lipid levels due to aluminium exposure, respectively. The significant shift in the amide I and amide II protein peaks may indicate the progression of aluminium induced Alzheimer's disease. Further the administration of DFO significantly improved the level of protein and brought back the amide I and II peaks nearer to the control value. Histopathological results also revealed impairment of Aluminium induced alterations in brain tissue. The results of the FTIR study were found to be in agreement with biochemical studies.

Sivakumar, S.; Sivasubramanian, J.; Raja, B.

2012-12-01

263

Brain death management: Keystone of transplantation activity  

Microsoft Academic Search

DURING the 5 past years, harvest of organs from cadaver sources has been decreasing in Lyon University Hospital Center (Lyon CHU) while it remained stable in the whole France Center East Region (R3) (Table 1).Diagnoses of brain death and organ harvest tend to be performed more often in local district hospitals in order to shorten the procedure and avoid transferring

M. Bret; B. Coronel; O. Vinot; J. F. Moskovtchenko

1997-01-01

264

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

265

Maternal exposure to nanoparticulate titanium dioxide during the prenatal period alters gene expression related to brain development in the mouse  

PubMed Central

Background Nanotechnology is developing rapidly throughout the world and the production of novel man-made nanoparticles is increasing, it is therefore of concern that nanomaterials have the potential to affect human health. The purpose of this study was to investigate the effects of maternal exposure to nano-sized anatase titanium dioxide (TiO2) on gene expression in the brain during the developmental period using cDNA microarray analysis combined with Gene Ontology (GO) and Medical Subject Headings (MeSH) terms information. Results Analysis of gene expression using GO terms indicated that expression levels of genes associated with apoptosis were altered in the brain of newborn pups, and those associated with brain development were altered in early age. The genes associated with response to oxidative stress were changed in the brains of 2 and 3 weeks old mice. Changes of the expression of genes associated with neurotransmitters and psychiatric diseases were found using MeSH terms. Conclusion Maternal exposure of mice to TiO2 nanoparticles may affect the expression of genes related to the development and function of the central nervous system. PMID:19640265

Shimizu, Midori; Tainaka, Hitoshi; Oba, Taro; Mizuo, Keisuke; Umezawa, Masakazu; Takeda, Ken

2009-01-01

266

Self-affirmation alters the brain's response to health messages and subsequent behavior change.  

PubMed

Health communications can be an effective way to increase positive health behaviors and decrease negative health behaviors; however, those at highest risk are often most defensive and least open to such messages. For example, increasing physical activity among sedentary individuals affects a wide range of important mental and physical health outcomes, but has proven a challenging task. Affirming core values (i.e., self-affirmation) before message exposure is a psychological technique that can increase the effectiveness of a wide range of interventions in health and other domains; however, the neural mechanisms of affirmation's effects have not been studied. We used functional magnetic resonance imaging (fMRI) to examine neural processes associated with affirmation effects during exposure to potentially threatening health messages. We focused on an a priori defined region of interest (ROI) in ventromedial prefrontal cortex (VMPFC), a brain region selected for its association with self-related processing and positive valuation. Consistent with our hypotheses, those in the self-affirmation condition produced more activity in VMPFC during exposure to health messages and went on to increase their objectively measured activity levels more. These findings suggest that affirmation of core values may exert its effects by allowing at-risk individuals to see the self-relevance and value in otherwise-threatening messages. PMID:25646442

Falk, Emily B; O'Donnell, Matthew Brook; Cascio, Christopher N; Tinney, Francis; Kang, Yoona; Lieberman, Matthew D; Taylor, Shelley E; An, Lawrence; Resnicow, Kenneth; Strecher, Victor J

2015-02-17

267

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

268

A Battery-Powered Activity-Dependent Intracortical Microstimulation IC for Brain-Machine-Brain Interface  

Microsoft Academic Search

This paper describes an activity-dependent intracor- tical microstimulation (ICMS) system-on-chip (SoC) that converts extracellular neural spikes recorded from one brain region to electrical stimuli delivered to another brain region in real time in vivo. The 10.9-mm SoC incorporates two identical 4-channel modules, each comprising an analog recording front-end with total input noise voltage of 3.12 V and noise efficiency factor

Meysam Azin; David J. Guggenmos; Scott Barbay; Randolph J. Nudo; Pedram Mohseni

2011-01-01

269

Personality traits and its association with resting regional brain activity.  

PubMed

The association between personality and resting brain activity was investigated. Personality was assessed using the NEO-Five-factor Inventory (NEO-FFI) and resting brain activity was indexed by eyes closed EEG spectral magnitude from four frequency bands over the entire cortex. Results suggest that there are differences between males and females in the NEO-FFI personality traits. The NEO FFI traits were associated with lower frequency brain activity in both males and females. Mild significant and consistent associations were found between delta and theta activity across all cortical regions with Extraversion and Conscientiousness. There were few associations between personality traits and alpha and beta activity, this was shown in males only. Fewer associations between personality and faster frequency bands such as alpha may be due to the methodological problem of using fixed alpha bands. Multiple regression analyses showed that individual alpha frequencies had a greater contribution to personality traits than fixed band alpha waves. PMID:16019096

Tran, Yvonne; Craig, Ashley; Boord, Peter; Connell, Kathy; Cooper, Nicholas; Gordon, Evian

2006-06-01

270

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

271

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

272

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

273

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

274

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

275

[Need-information organization of brain activity].  

PubMed

Experimental results and literature data point to the leading role of four brain structures in the genesis of emotional states and in the organization of goal directed behaviour. Owing to the functioning of the frontal parts of the neocortex behaviour is oriented to signals with a high probability of their reinforcement, and owing to the hypothalamus--to satisfaction of the dominant need. Unlike the neocortex the hippocampus is necessary for reactions to signals of lowly probable events, which is typical of emotionally exicted brain. The amygdala complx participates in creation of a balance, a dynamic co-existence between completing needs (motivations) and corresponding emotions. As a result, behaviour becomes more plastic and adequate to the given situation. PMID:473899

Simonov, P V

1979-01-01

276

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

277

Acoustic noise alters selective attention processes as indicated by direct current (DC) brain potential changes.  

PubMed

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

278

Alterations in the level of OFQ/N-IR in rat brain regions by cocaine  

PubMed Central

We have previously shown that administration of orphanin FQ/nociceptin (OFQ/N), the endogenous ligand of the opioid receptor-like (ORL-1) receptor, into the lateral ventricles or VTA blocked cocaine sensitization. In the present study, we determined the effect of acute and chronic cocaine treatment on the level of endogenous OFQ/N in rat brain regions. Male Sprague Dawley rats were tested for motor activity in response to saline or cocaine (20 mg/kg) injection once daily for three consecutive days. To determine the effect of single or repeated cocaine administration on the level of OFQ/N, rats were sacrificed one hour following saline or cocaine injection either on day 1 or 3, respectively. Additional groups of rats were treated similarly with saline or cocaine on days 1–3 and sacrificed or tested for locomotor sensitization on day 8. Consistent with previous studies, repeated cocaine administration induced locomotor sensitization to a challenge dose of cocaine (7.5 mg/kg) given on day 8. Measurements of tissue content of OFQ/N-IR using radioimmunoassay indicated that the rat hypothalamus and striatum respectively contained the highest and lowest level of the peptide among the brain regions tested. Acute cocaine decreased the level of OFQ-IR in the rat midbrain and to a lesser extent in the striatum. On the other hand, the level of OFQ/N was higher in rats treated with cocaine on days 1–3 and sacrificed on day 8. These findings suggest that endogenous OFQ/N may be involved in the actions of cocaine and possibly in cocaine-induced motor stimulation and locomotor sensitization. PMID:18572206

Lutfy, Kabirullah; Lam, Hoa; Narayanan, Shridhar

2008-01-01

279

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

280

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

281

Human brain activity with functional NIR optical imager  

NASA Astrophysics Data System (ADS)

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

Luo, Qingming

2001-08-01

282

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...

283

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

284

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

285

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

286

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

287

Influence of altered gravity on brain cellular energy and plasma membrane metabolism of developing lower aquatic vertebrates  

NASA Astrophysics Data System (ADS)

Biochemical analyses of the brain of cichlid fish larvae, exposed for 7 days to increased acceleration of 3g (hyper-g), revealed an increase in energy availability (succinate dehydrogenase activity, SDH), and in mitochondrial energy transformation (creatine kinase, Mi_a-CK), but no changes in an energy consumptive process (high-affinity Ca^2+-ATPase). Brain glucose-6-phosphate dehydrogenase (G6PDH) of developing fish was previously found to be increased after hyper-g exposure. Three respectively 5 hours thereafter dramatic fluctuations in enzyme activity were registered. Analysing the cytosolic or plasma membrane-located brain creatine kinase (BB-CK) of clawed toad larvae after long-term hyper-g exposure a significant increase in enzyme activity was demonstrated, whereas the activity of a high affinity Ca^2+-ATPase remained unaffected.

Slenzka, K.; Appel, R.; Kappel, Th.; Rahmann, H.

288

Brain activity and medical diagnosis: an EEG study  

PubMed Central

Background Despite new brain imaging techniques that have improved the study of the underlying processes of human decision-making, to the best of our knowledge, there have been very few studies that have attempted to investigate brain activity during medical diagnostic processing. We investigated brain electroencephalography (EEG) activity associated with diagnostic decision-making in the realm of veterinary medicine using X-rays as a fundamental auxiliary test. EEG signals were analysed using Principal Components (PCA) and Logistic Regression Analysis Results The principal component analysis revealed three patterns that accounted for 85% of the total variance in the EEG activity recorded while veterinary doctors read a clinical history, examined an X-ray image pertinent to a medical case, and selected among alternative diagnostic hypotheses. Two of these patterns are proposed to be associated with visual processing and the executive control of the task. The other two patterns are proposed to be related to the reasoning process that occurs during diagnostic decision-making. Conclusions PCA analysis was successful in disclosing the different patterns of brain activity associated with hypothesis triggering and handling (pattern P1); identification uncertainty and prevalence assessment (pattern P3), and hypothesis plausibility calculation (pattern P2); Logistic regression analysis was successful in disclosing the brain activity associated with clinical reasoning success, and together with regression analysis showed that clinical practice reorganizes the neural circuits supporting clinical reasoning. PMID:24083668

2013-01-01

289

Males and females differ in brain activation during cognitive tasks  

Microsoft Academic Search

To examine the effect of gender on regional brain activity, we utilized functional magnetic resonance imaging (fMRI) during a motor task and three cognitive tasks; a word generation task, a spatial attention task, and a working memory task in healthy male (n = 23) and female (n = 10) volunteers. Functional data were examined for group differences both in the number of pixels activated,

Emily C. Bell; Morgan C. Willson; Alan H. Wilman; Sanjay Dave; Peter H. Silverstone

2006-01-01

290

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

291

Ageing alters behavioural function and brain arginine metabolism in male Sprague-Dawley rats.  

PubMed

A growing body of evidence suggests the involvement of L-arginine and its metabolites in the ageing and neurodegenerative processes. The present study assessed behavioural performance in 4- (young), 12- (middle-aged) and 24- (aged) month-old male Sprague-Dawley rats, and investigated age-related changes in the activity of two key arginine metabolic enzymes, nitric oxide synthase (NOS) and arginase, and the levels of L-arginine and its downstream metabolites in a number of memory-related brain structures. Aged rats were less anxious and performed poorly in the water maze task relative to the young and middle-aged rats, and both middle-aged and aged rats displayed reduced exploratory activity relative to the young ones. There were significant age-related changes in NOS and arginase activities, and the levels of L-arginine, L-citrulline, L-ornithine, agmatine, putrescine, spermidine, spermine and glutamate, but not ?-aminobutyric acid, in the CA1, CA2/3 and dentate gyrus sub-regions of the hippocampus and the prefrontal, entorhinal, perirhinal, postrhinal and temporal (an auditory cortex) cortices in a region-specific manner. Cluster analyses revealed that the nine related neurochemical variables formed distinct groups, which changed as a function of ageing. Multiple regression analyses revealed a number of significant correlations between the neurochemical and behavioural variables. The present study further supports the involvement of arginine metabolism in the ageing process, and provides further evidence of the effects of animals' behavioural experience on arginine metabolism. PMID:22989918

Gupta, N; Jing, Y; Collie, N D; Zhang, H; Liu, P

2012-12-13

292

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.

293

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

294

Induced hyperammonemia alters neuropsychology, brain MR spectroscopy and magnetization transfer in cirrhosis  

Microsoft Academic Search

Hyperammonemia is a universal finding after gastrointestinal hemorrhage in cirrhosis. We administered an oral amino acid solution mimicking the hemoglobin molecule to examine neuropsychological changes, brain glutamine levels, and brain magnetization transfer ratio (MTR). Forty-eight metabolically stable patients with cirrhosis and no evidence of “overt” hepatic encephalopathy (HE) were randomized to receive 75 g of amino acid solution or placebo;

Sherzad Balata; Steven W. M. Olde Damink; Karen Ferguson; Ian Marshall; Peter C. Hayes; Nicolaas E. P. Deutz; Roger Williams; Joanna Wardlaw; Rajiv Jalan

2003-01-01

295

Altered Structural Brain Connectivity in Healthy Carriers of the Autism Risk Gene, CNTNAP2  

E-print Network

Imaging, UCLA School of Medicine, Los Angeles, CA; 2 Ahmanson Lovelace Brain Mapping Center, UCLA, Los Drive South, Suite 225 Los Angeles, CA 90095-7334 neda.jahanshad@gmail.com Jeffrey D Rudie Ahmanson-Lovelace Dapretto Ahmanson-Lovelace Brain Mapping Center 660 Charles E. Young Drive South Los Angeles, CA 90095

Thompson, Paul

296

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

297

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

298

Altered microRNA expression profiles in post-mortem brain samples from individuals with schizophrenia and bipolar disorder  

PubMed Central

Background MicroRNAs (miRNAs) are potent regulators of gene expression with proposed roles in brain development and function. We hypothesized that miRNA expression profiles are altered in individuals with severe psychiatric disorders. Methods Using real-time quantitative PCR, we compared the expression of 435 miRNAs and 18 snoRNAs in post-mortem brain tissue samples from individuals with schizophrenia, individuals with bipolar disorder, and psychiatrically healthy control subjects (n = 35 each group). Detailed demographic data, sample selection and storage conditions, and drug and substance exposure histories were available for all subjects. Bayesian model averaging was used to simultaneously assess the impact of these covariates as well as the psychiatric phenotype on miRNA expression profiles. Results Of the variables considered, sample storage time, brain pH, alcohol at time of death, and post-mortem interval were found to affect the greatest proportion of miRNAs. 19% of miRNAs analyzed exhibited positive evidence of altered expression due to a diagnosis of schizophrenia or bipolar disorder. Both conditions were associated with reduced miRNA expression levels, with a much more pronounced effect observed for bipolar disorder. Conclusions This study suggests that modest under-expression of several miRNAs may be involved in the complex pathogenesis of major psychosis. PMID:21183010

Moreau, Michael P.; Bruse, Shannon E.; David-Rus, Richard; Buyske, Steven; Brzustowicz, Linda M.

2010-01-01

299

Brain responses to body image stimuli but not food are altered in women with bulimia nervosa  

PubMed Central

Background Research into the neural correlates of bulimia nervosa (BN) psychopathology remains limited. Methods In this functional magnetic resonance imaging study, 21 BN patients and 23 healthy controls (HCs) completed two paradigms: 1) processing of visual food stimuli and 2) comparing their own appearance with that of slim women. Participants also rated food craving and anxiety levels. Results Brain activation patterns in response to food cues did not differ between women with and without BN. However, when evaluating themselves against images of slim women, BN patients engaged the insula more and the fusiform gyrus less, compared to HCs, suggesting increased self-focus among women with BN whilst comparing themselves to a ‘slim ideal’. In these BN patients, exposure to food and body image stimuli increased self-reported levels of anxiety, but not craving. Conclusions Our findings suggest that women with BN differ from HCs in the way they process body image, but not in the way they process food stimuli. PMID:24238299

2013-01-01

300

Multisensory stimuli elicit altered oscillatory brain responses at gamma frequencies in patients with schizophrenia  

PubMed Central

Deficits in auditory and visual unisensory responses are well documented in patients with schizophrenia; however, potential abnormalities elicited from multisensory audio-visual stimuli are less understood. Further, schizophrenia patients have shown abnormal patterns in task-related and task-independent oscillatory brain activity, particularly in the gamma frequency band. We examined oscillatory responses to basic unisensory and multisensory stimuli in schizophrenia patients (N = 46) and healthy controls (N = 57) using magnetoencephalography (MEG). Time-frequency decomposition was performed to determine regions of significant changes in gamma band power by group in response to unisensory and multisensory stimuli relative to baseline levels. Results showed significant behavioral differences between groups in response to unisensory and multisensory stimuli. In addition, time-frequency analysis revealed significant decreases and increases in gamma-band power in schizophrenia patients relative to healthy controls, which emerged both early and late over both sensory and frontal regions in response to unisensory and multisensory stimuli. Unisensory gamma-band power predicted multisensory gamma-band power differently by group. Furthermore, gamma-band power in these regions predicted performance in select measures of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) test battery differently by group. These results reveal a unique pattern of task-related gamma-band power in schizophrenia patients relative to controls that may indicate reduced inhibition in combination with impaired oscillatory mechanisms in patients with schizophrenia. PMID:25414652

Stone, David B.; Coffman, Brian A.; Bustillo, Juan R.; Aine, Cheryl J.; Stephen, Julia M.

2014-01-01

301

Spontaneous brain activity predicts learning ability of foreign sounds.  

PubMed

Can learning capacity of the human brain be predicted from initial spontaneous functional connectivity (FC) between brain areas involved in a task? We combined task-related functional magnetic resonance imaging (fMRI) and resting-state fMRI (rs-fMRI) before and after training with a Hindi dental-retroflex nonnative contrast. Previous fMRI results were replicated, demonstrating that this learning recruited the left insula/frontal operculum and the left superior parietal lobe, among other areas of the brain. Crucially, resting-state FC (rs-FC) between these two areas at pretraining predicted individual differences in learning outcomes after distributed (Experiment 1) and intensive training (Experiment 2). Furthermore, this rs-FC was reduced at posttraining, a change that may also account for learning. Finally, resting-state network analyses showed that the mechanism underlying this reduction of rs-FC was mainly a transfer in intrinsic activity of the left frontal operculum/anterior insula from the left frontoparietal network to the salience network. Thus, rs-FC may contribute to predict learning ability and to understand how learning modifies the functioning of the brain. The discovery of this correspondence between initial spontaneous brain activity in task-related areas and posttraining performance opens new avenues to find predictors of learning capacities in the brain using task-related fMRI and rs-fMRI combined. PMID:23719798

Ventura-Campos, Noelia; Sanjuán, Ana; González, Julio; Palomar-García, María-Ángeles; Rodríguez-Pujadas, Aina; Sebastián-Gallés, Núria; Deco, Gustavo; Ávila, César

2013-05-29

302

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

303

Isoflurane induces dose-dependent alterations in the cortical connectivity profiles and dynamic properties of the brain's functional architecture.  

PubMed

Despite their widespread use, the effect of anesthetic agents on the brain's functional architecture remains poorly understood. This is particularly true of alterations that occur beyond the point of induced unconsciousness. Here, we examined the distributed intrinsic connectivity of macaques across six isoflurane levels using resting-state functional MRI (fMRI) following the loss of consciousness. The results from multiple analysis strategies showed stable functional connectivity (FC) patterns between 1.00% and 1.50% suggesting this as a suitable range for anesthetized nonhuman primate resting-state investigations. Dose-dependent effects were evident at moderate to high dosages showing substantial alteration of the functional topology and a decrease or complete loss of interhemispheric cortical FC strength including that of contralateral homologues. The assessment of dynamic FC patterns revealed that the functional repertoire of brain states is related to anesthesia depth and most strikingly, that the number of state transitions linearly decreases with increased isoflurane dosage. Taken together, the results indicate dose-specific spatial and temporal alterations of FC that occur beyond the typically defined endpoint of consciousness. Future work will be necessary to determine how these findings generalize across anesthetic types and extend to the transition between consciousness and unconsciousness. PMID:25044934

Hutchison, R Matthew; Hutchison, Melina; Manning, Kathryn Y; Menon, Ravi S; Everling, Stefan

2014-12-01

304

Impaired Brain Creatine Kinase Activity in Huntington's Disease  

PubMed Central

Background Huntington's disease (HD) is associated with impaired energy metabolism in the brain. Creatine kinase (CK) catalyzes ATP-dependent phosphorylation of creatine (Cr) into phosphocreatine (PCr), thereby serving as readily available high-capacity spatial and temporal ATP buffering. Objective: Substantial evidence supports a specific role of the Cr/PCr system in neurodegenerative diseases. In the brain, the Cr/PCr ATP-buffering system is established by a concerted operation of the brain-specific cytosolic enzyme BB-CK and ubiquitous mitochondrial uMt-CK. It is not yet established whether the activity of these CK isoenzymes is impaired in HD. Methods We measured PCr, Cr, ATP and ADP in brain extracts of 3 mouse models of HD – R6/2 mice, N171-82Q and HdhQ111 mice – and the activity of CK in cytosolic and mitochondrial brain fractions from the same mice. Results The PCr was significantly increased in mouse HD brain extracts as compared to nontransgenic littermates. We also found an approximately 27% decrease in CK activity in both cytosolic and mitochondrial fractions of R6/2 and N171-82Q mice, and an approximately 25% decrease in the mitochondria from HdhQ111 mice. Moreover, uMt-CK and BB-CK activities were approximately 63% lower in HD human brain samples as compared to nondiseased controls. Conclusion Our findings lend strong support to the role of impaired energy metabolism in HD, and point out the potential importance of impairment of the CK-catalyzed ATP-buffering system in the etiology of HD. PMID:21124007

Zhang, S.F.; Hennessey, T.; Yang, L.; Starkova, N.N.; Beal, M.F.; Starkov, A.A.

2011-01-01

305

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

306

Does bosentan protect diabetic brain alterations in rats? The role of endothelin-1 in the diabetic brain.  

PubMed

Diabetes mellitus (DM) is a major problem all over the world, affecting more people in recent years. Individuals with diabetes are more prone to disease than non-diabetics, especially vascular complications. The aim of this study was to examine the roles of the endothelin (ET)-1 in brain damage formed in a streptozocin (STZ)-induced diabetes model, and the effect of bosentan, which is the non-specific ET1 receptor blocker in the prevention of the diabetes-induced brain damage. To examine the effects of bosentan (50 mg/kg and 100 mg/kg) in this study, the rats were given the drug for 3 months. The rats were divided into four groups: the sham group (n = 10), the diabetic control group (n = 10), the group of diabetic rats given bosentan 50 mg/kg (n = 10) and the group of diabetic rats given bosentan 100 mg/kg (n = 10). Diabetes was induced in the rats by STZ (60 mg/kg i.p.). On day 91, all rats were killed. Brain tissues of the rats were measured by molecular, biochemical and histopathological methods. Antioxidant levels in the therapy groups were observed as quite near to the values in the healthy group. In this study, while the brain eNOS levels in the diabetic groups decreased, the ET1 and iNOS levels were found to be increased. However, in the diabetes group, hippocampus and cerebellum, pericellular oedema and a number of neuronal cytoretraction were increased in neuropiles, whereas these results were decreased in the therapy group. Based on all of these results, ET1 will not be ignored in diabetes-induced cerebral complications. PMID:25200216

Demir, Recep; Cadirci, Elif; Akpinar, Erol; Cayir, Yasemin; Atmaca, Hasan Tarik; Un, Harun; Kunak, Celalettin Semih; Yayla, Muhammed; Bayraktutan, Zafer; Demir, Ilknur

2015-03-01

307

Applications of electroencephalography to characterize brain activity: perspectives in stroke.  

PubMed

A wide array of neuroimaging technologies are now available that offer unprecedented opportunities to study the brain in health and disease. Each technology has associated strengths and weaknesses that need to be considered to maximize their utility, especially when used in combination. One imaging technology, electroencephalography (EEG), has been in use for more than 80 years, but as a result of recent technologic advancements EEG has received renewed interest as an inexpensive, noninvasive and versatile technique to evaluate neural activity in the brain. In part, this is due to new opportunities to combine EEG not only with other imaging modalities, but also with neurostimulation and robotics technologies. When used in combination, noninvasive brain stimulation and EEG can be used to study cause-and-effect relationships between interconnected brain regions providing new avenues to study brain function. Although many of these approaches are still in the developmental phase, there is substantial promise in their ability to deepen our understanding of brain function. The ability to capture the causal relationships between brain function and behavior in individuals with neurologic disorders or injury has important clinical implications for the development of novel biomarkers of recovery and response to therapeutic interventions. The goals of this paper are to provide an overview of the fundamental principles of EEG; discuss past, present, and future applications of EEG in the clinical management of stroke; and introduce the technique of combining EEG with a form of noninvasive brain stimulation, transcranial magnetic stimulation, as a powerful synergistic research paradigm to characterize brain function in both health and disease.Video Abstract available (see Supplemental Digital Content 1, http://links.lww.com/JNPT/A87) for more insights from the authors. PMID:25522236

Borich, Michael R; Brown, Katlyn E; Lakhani, Bimal; Boyd, Lara A

2015-01-01

308

Prefrontal Transcranial Direct Current Stimulation Alters Activation and Connectivity in Cortical and Subcortical Reward Systems: A tDCS-fMRI Study  

PubMed Central

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. PMID:24453107

Weber, Matthew J.; Messing, Samuel B.; Rao, Hengyi; Detre, John A.; Thompson-Schill, Sharon L.

2014-01-01

309

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

PubMed

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique used both experimentally and therapeutically to modulate regional brain function. However, few studies have directly measured the aftereffects of tDCS on brain activity or examined changes in task-related brain activity consequent to prefrontal tDCS. To investigate the neural effects of tDCS, we collected fMRI data from 22 human subjects, both at rest and while performing the Balloon Analog Risk Task (BART), before and after true or sham transcranial direct current stimulation. TDCS decreased resting blood perfusion in orbitofrontal cortex and the right caudate and increased task-related activity in the right dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC) in response to losses but not wins or increasing risk. Network analysis showed that whole-brain connectivity of the right ACC correlated positively with the number of pumps subjects were willing to make on the BART, and that tDCS reduced connectivity between the right ACC and the rest of the brain. Whole-brain connectivity of the right DLPFC also correlated negatively with pumps on the BART, as prior literature would suggest. Our results suggest that tDCS can alter activation and connectivity in regions distal to the electrodes. PMID:24453107

Weber, Matthew J; Messing, Samuel B; Rao, Hengyi; Detre, John A; Thompson-Schill, Sharon L

2014-08-01

310

Stress-induced asymmetric frontal brain activity and aggression risk.  

PubMed

Impersonal stressors, not only interpersonal provocation, can instigate aggression through an associative network linking negative emotions to behavioral activation (L. Berkowitz, 1990). Research has not examined the brain mechanisms that are engaged by different types of stress and serve to promote hostility and aggression. The present study examined whether stress exposure elicits more left than right frontal brain activity implicated in behavioral approach motivation and whether this lateralized brain activity predicts stress-induced aggression and hostile/aggressive tendencies. Results showed that (a) participants in the impersonal (assigned to stress by a computer) and interpersonal (assigned to stress by a provoking confederate) stress conditions both showed more left than right frontal electroencephalogram activity after condition assignment and stress exposure and (b) the 2 stress groups exhibited subsequent increases in aggression relative to the no-stress group. Importantly, left frontal asymmetry in response to stress exposure predicted increases in subsequent aggressive behavior, a finding that did not emerge in the no-stress condition. Thus, both the interpersonal and impersonal stressors impacted state changes in brain activity related to behavioral approach, suggesting that stress reactivity involving approach activation represents risk for behavioral dysregulation. PMID:19222320

Verona, Edelyn; Sadeh, Naomi; Curtin, John J

2009-02-01

311

Rabies virus selectively alters 5-HT1 receptor subtypes in rat brain.  

PubMed

Rabies virus infection in man induces a series of clinical symptoms, some suggesting involvement of the central serotonergic system. The results of the present study show that, 5 days after rabies virus infection in rat, the total reversible high-affinity binding of [3H]5-HT in the hippocampus is not affected, suggesting that 5-HT1A binding is not altered. 5-HT1B sites identified by [125I]cyanopindolol binding are not affected in the cortex 3 and 5 days after the infection. Accordingly, the cellular inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on the [3H]acetylcholine-evoked release, presumably related to 5-HT1B receptor activity, is not modified 3 days after infection. In contrast, [3H]5-HT binding determined in the presence of drugs masking 5-HT1A, 5-HT1B and 5-HT1C receptors, is markedly (50%) reduced 3 days after the viral infection. These results suggest that 5-HT1D-like receptor subtypes may be affected specifically and at an early stage after rabies viral infection. PMID:8491253

Ceccaldi, P E; Fillion, M P; Ermine, A; Tsiang, H; Fillion, G

1993-04-15

312

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

313

Dietary intake alters behavioral recovery and gene expression profiles in the brain of juvenile rats that have experienced a concussion  

PubMed Central

Concussion and mild traumatic brain injury (mTBI) research has made minimal progress diagnosing who will suffer from lingering symptomology or generating effective treatment strategies. Research demonstrates that dietary intake affects many biological systems including brain and neurological health. This study determined if exposure to a high fat diet (HFD) or caloric restriction (CR) altered post-concussion susceptibility or resiliency using a rodent model of pediatric concussion. Rats were maintained on HFD, CR, or standard diet (STD) throughout life (including the prenatal period and weaning). At postnatal day 30, male and female rats experienced a concussion or a sham injury which was followed by 17 days of testing. Prefrontal cortex and hippocampus tissue was collected for molecular profiling. Gene expression changes in BDNF, CREB, DNMT1, FGF-2, IGF1, LEP, PGC-1?, SIRT1, Tau, and TERT were analyzed with respect to injury and diet. Analysis of telomere length (TL) using peripheral skin cells and brain tissue found that TL in skin significantly correlated with TL in brain tissue and TL was affected by dietary intake and injury status. With respect to mTBI outcomes, diet was correlated with recovery as animals on the HFD often displayed poorer performance than animals on the CR diet. Molecular analysis demonstrated that diet induced epigenetic changes that can be associated with differences in individual predisposition and resiliency to post-concussion syndrome.

Mychasiuk, Richelle; Hehar, Harleen; Ma, Irene; Esser, Michael J.

2015-01-01

314

Anoxic versus traumatic brain injury: amount of tissue loss, not etiology, alters cognitive and emotional function.  

PubMed

Research in neuropsychology suggests that the etiology of a neurologic injury determines the neuropathological and neuropsychological changes. This study compared neuropsychological outcome in subjects who had traumatic brain injury (TBI) with subjects who had anoxic brain injury (ABI), who were matched for age, gender, and ventricle-to-brain ratio. There were no group differences for morphologic or neuropsychological measures. Both groups exhibited impaired memory, attention, and executive function, as well as slowed mental processing speed. Intelligence correlated with whole brain volume, and measures of memory correlated with hippocampal atrophy. There was no unique contribution of hippocampal atrophy on neuropsychological outcome between the groups. In the absence of localized lesions, the amount of neural tissue loss, rather than etiology, may be the critical factor in neuropsychological outcome. PMID:15769207

Hopkins, Ramona O; Tate, David F; Bigler, Erin D

2005-03-01

315

Self-Representations: Alterations in Frontotemporal Lobar Degeneration and Correlates in the Brain.  

E-print Network

??Self-representations are multi-faceted and complex. Frontotemporal lobar degeneration (FTLD) is a neurodegenerative disease that selectively atrophies anterior brain regions (e.g., frontal pole, insula, anterior cingulate… (more)

Sturm, Virginia Emily

2009-01-01

316

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

317

Zingiber Officinale Alters 3,4-methylenedioxymethamphetamine-Induced Neurotoxicity in Rat Brain  

PubMed Central

Objective: The spice Zingiber officinale or ginger possesses antioxidant activity and neuroprotective effects. The effects of this traditional herbal medicine on 3,4-methylenedioxymethamphetamine (MDMA) induced neurotoxicity have not yet been studied. The present study considers the effects of Zingiber officinale on MDMA-induced spatial memory impairment and apoptosis in the hippocampus of male rats. Materials and Methods: In this experimental study, 21 adult male Sprague Dawley rats (200-250 g) were classified into three groups (control, MDMA, and MDMA plus ginger). The groups were intraperitoneally administered 10 mg/kg MDMA, 10 mg/kg MDMA plus 100 mg/kg ginger extract, or 1 cc/kg normal saline as the control solution for one week (n=7 per group). Learning memory was assessed by Morris water maze (MWM) after the last administration. Finally, the brains were removed to study the cell number in the cornu ammonis (CA1) hippocampus by light microscope, Bcl-2 by immunoblotting, and Bax expression by reverse transcription polymerase chain reaction (RT-PCR). Data was analyzed using SPSS 16 software and a one-way ANOVA test. Results: Escape latency and traveled distances decreased significantly in the MDMA plus ginger group relative to the MDMA group (p<0.001). Cell number increased in the MDMA plus ginger group in comparison to the MDMA group. Down-regulation of Bcl-2 and up-regulation of Bax were observed in the MDMA plus ginger group in comparison to the MDMA group (p<0.05). Conclusion: Our findings suggest that ginger consumption may lead to an improvement of MDMA-induced neurotoxicity. PMID:23508562

Mehdizadeh, Mehdi; Dabaghian, Fataneh; Nejhadi, Akram; Fallah-huseini, Hassan; Choopani, Samira; Shekarriz, Nima; Molavi, Nima; Basirat, Arghavan; Mohammadzadeh Kazorgah, Farzaneh; Samzadeh-Kermani, Alireza; Soleimani Asl, Sara

2012-01-01

318

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

319

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 only alters the activity of the sensory areas but also reshapes the regional and circuit functional organization of the cognitive control network. PMID:24788317

Zhao, Fu; Wang, Zhenmin; Ge, Jianqiao; Zhang, Kai; Gao, Zhixian; Gao, Jia-Hong; Yang, Yihong; Fan, Jin; Zou, Qihong; Liu, Pinan

2014-01-01

320

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

321

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

322

ALTERATIONS IN CALCIUM ION ACTIVITY BY ELF AND RF ELECTROMAGNETIC FIELDS  

EPA Science Inventory

Alterations in calcium ion activity by ELF and RF electromagnetic fields Introduction Calcium ions play many important roles in biological systems. For example, calcium ion activity can be used as an indicator of second-messenger signal-transduction processe...

323

Brain Activation during Sentence Comprehension among Good and Poor  

E-print Network

comprehension task among good and poor readers in the third (n 5 32) and fifth (n 5 35) grades. Reading ability struggling readers during a higher-level reading comprehension task (Seki et al. 2001 report a smallBrain Activation during Sentence Comprehension among Good and Poor Readers Ann Meyler1 , Timothy A

324

The Design of Integrated Circuits to Observe Brain Activity  

Microsoft Academic Search

The ability to monitor the simultaneous electrical activity of multiple neurons in the brain enables a wide range of scientific and clinical endeavors. Recent efforts to merge miniature multielectrode neural recording arrays with integrated electronics have revealed significant circuit design challenges. Weak neural signals must be amplified and filtered using low-noise circuits placed close to the electrodes themselves, but power

Reid R. Harrison

2008-01-01

325

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

326

Alterations in phospholipidomic profile in the brain of mouse model of depression induced by chronic unpredictable stress.  

PubMed

Depression is a worldwide disability disease associated with high morbidity and has increased dramatically in the last few years. The differential diagnosis and the definition of an individualized therapy for depression are hampered by the absence of specific biomarkers. The aim of this study was to evaluate the phospholipidomic profile of the brain and myocardium in a mouse model of depression induced by chronic unpredictable stress (CUS). The lipidomic profile was evaluated by thin layer and liquid chromatography and mass spectrometry and lipid oxidation was estimated by FOX II assay. Antioxidant enzyme activity and the oxidized/reduced glutathione (GSH/GSSG) ratio were also evaluated. Results showed that chronic stress affects primarily the lipid profile of the brain, inducing an increase in lipid hydroperoxides, which was not detected in the myocardium. A significant decrease in phosphatidylinositol (PI) and in cardiolipin (CL) relative contents and also oxidation of CL and a significant increase of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) were observed in the brain of mice after unpredictable chronic stress conditions. In the myocardium only an increase in PC content was observed. Nevertheless, both organs present a decreased GSH/GSSG ratio when compared to control groups, corroborating the occurrence of oxidative stress. The enzyme activities of catalase (CAT) and superoxide dismutase (SOD) were found to be decreased in the myocardium and increased in the brain, while glutathione reductase (GR) was decreased in the brain. Our results indicate that in a mouse model for studying depression induced by CUS, the modification of the expression of oxidative stress-related enzymes did not prevent lipid oxidation in organs, particularly in the brain. These observations suggest that depression has an impact on the brain lipidome and that further studies are needed to better understand lipids role in depression and to evaluate their potential as future biomarkers. PMID:24814727

Faria, R; Santana, M M; Aveleira, C A; Simões, C; Maciel, E; Melo, T; Santinha, D; Oliveira, M M; Peixoto, F; Domingues, P; Cavadas, C; Domingues, M R M

2014-07-25

327

Alterations in the expression of vascular endothelial growth factor in the rat brain following gamma knife surgery  

PubMed Central

Gamma knife surgery (GKS) is used for the treatment of various brain diseases. However, the mechanisms underlying brain injury following irradiation remain to be elucidated. Given that vascular endothelial growth factor (VEGF) is closely associated with pathological angiogenesis and the permeability of the blood brain barrier (BBB), the present study was designed to analyze temporal alterations in VEGF expression in the cerebral cortex and the effect of VEGF on cerebral edema in rats following GKS. Adult male Wistar rats were subjected to GKS at maximum doses of 60 Gy. Animals were sacrificed between 4 and 24 weeks after GKS. Immunohistochemistry, enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction (RT-PCR) were employed for detecting VEGF expression. The vessel density was measured by CD31+ cell count and vascular structures were examined using electron microscopy. Brain water content and BBB permeability were measured in the present study. VEGF expression in the irradiated cortex progressively increased until 16 weeks after GKS when the maximal expression was reached, and then gradually decreased to the control level 24 weeks after GKS. These findings were confirmed by RT-PCR. A mild decrease in vessel density was observed 4 weeks after GKS, followed by an increase in vessel density between 8 and 20 weeks later. Furthermore, previous studies also demonstrated vascular damage, opening of the BBB and an increase in brain water content occurring simultaneously. To the best of our knowledge, these data demonstrated for the first time dynamic changes in VEGF expression following GKS and also suggest the importance of VEGF expression in pathological angiogenesis and edema formation following GKS. PMID:25176344

CHENG, LEI; MA, LIN; REN, HECHENG; ZHAO, HONGWEI; PANG, YIQIANG; WANG, YONGHENG; WEI, MING

2014-01-01

328

A mutation in the HFE gene is associated with altered brain iron profiles and increased oxidative stress in mice.  

PubMed

Because of the increasing evidence that H63D HFE polymorphism appears in higher frequency in neurodegenerative diseases, we evaluated the neurological consequences of H63D HFE in vivo using mice that carry H67D HFE (homologous to human H63D). Although total brain iron concentration did not change significantly in the H67D mice, brain iron management proteins expressions were altered significantly. The 6-month-old H67D mice had increased HFE and H-ferritin expression. At 12 months, H67D mice had increased H- and L-ferritin but decreased transferrin expression suggesting increased iron storage and decreased iron mobilization. Increased L-ferritin positive microglia in H67D mice suggests that microglia increase iron storage to maintain brain iron homeostasis. The 6-month-old H67D mice had increased levels of GFAP, increased oxidatively modified protein levels, and increased cystine/glutamate antiporter (xCT) and hemeoxygenase-1 (HO-1) expression indicating increased metabolic and oxidative stress. By 12 months, there was no longer increased astrogliosis or oxidative stress. The decrease in oxidative stress at 12 months could be related to an adaptive response by nuclear factor E2-related factor 2 (Nrf2) that regulates antioxidant enzymes expression and is increased in the H67D mice. These findings demonstrate that the H63D HFE impacts brain iron homeostasis, and promotes an environment of oxidative stress and induction of adaptive mechanisms. These data, along with literature reports on humans with HFE mutations provide the evidence to overturn the traditional paradigm that the brain is protected from HFE mutations. The H67D knock-in mouse can be used as a model to evaluate how the H63D HFE mutation contributes to neurodegenerative diseases. PMID:23429074

Nandar, Wint; Neely, Elizabeth B; Unger, Erica; Connor, James R

2013-06-01

329

Brain-region–specific alterations of the trajectories of neuronal volume growth throughout the lifespan in autism  

PubMed Central

Several morphometric studies have revealed smaller than normal neurons in the neocortex of autistic subjects. To test the hypothesis that abnormal neuronal growth is a marker of an autism-associated global encephalopathy, neuronal volumes were estimated in 16 brain regions, including various subcortical structures, Ammon’s horn, archicortex, cerebellum, and brainstem in 14 brains from individuals with autism 4 to 60 years of age and 14 age-matched control brains. This stereological study showed a significantly smaller volume of neuronal soma in 14 of 16 regions in the 4- to 8-year-old autistic brains than in the controls. Arbitrary classification revealed a very severe neuronal volume deficit in 14.3% of significantly altered structures, severe in 50%, moderate in 21.4%, and mild in 14.3% structures. This pattern suggests desynchronized neuronal growth in the interacting neuronal networks involved in the autistic phenotype. The comparative study of the autistic and control subject brains revealed that the number of structures with a significant volume deficit decreased from 14 in the 4- to 8-year-old autistic subjects to 4 in the 36- to 60-year-old. Neuronal volumes in 75% of the structures examined in the older adults with autism are comparable to neuronal volume in age-matched controls. This pattern suggests defects of neuronal growth in early childhood and delayed up-regulation of neuronal growth during adolescence and adulthood reducing neuron soma volume deficit in majority of examined regions. However, significant correction of neuron size but limited clinical improvements suggests that delayed correction does not restore functional deficits. PMID:24612906

2014-01-01

330

Region-specific metabolic alterations in the brain of the APP/PS1 transgenic mice of Alzheimer's disease.  

PubMed

Alzheimer's disease (AD) is the most common neurodegenerative disorder worldwide, but its etiology is still not completely understood. The identification of underlying pathological mechanisms is becoming increasingly important for the discovery of biomarkers and therapies, for which metabolomics presents a great potential. In this work, we studied metabolic alterations in different brain regions of the APP/PS1 mice by using a high-throughput metabolomic approach based on the combination of gas chromatography-mass spectrometry and ultra-high performance liquid chromatography-mass spectrometry. Multivariate statistics showed that metabolomic perturbations are widespread, affecting mainly the hippocampus and the cortex, but are also present in regions not primarily associated with AD such as the striatum, cerebellum and olfactory bulbs. Multiple metabolic pathways could be linked to the development of AD-type disorders in this mouse model, including abnormal purine metabolism, bioenergetic failures, dyshomeostasis of amino acids and disturbances in membrane lipids, among others. Interestingly, region-specific alterations were observed for some of the potential markers identified, associated with abnormal fatty acid composition of phospholipids and sphingomyelins, or differential regulation of neurotransmitter amino acids (e.g. glutamate, glycine, serine, N-acetyl-aspartate), not previously described to our knowledge. Therefore, these findings could provide a new insight into brain pathology in Alzheimer's disease. PMID:25281826

González-Domínguez, Raúl; García-Barrera, Tamara; Vitorica, Javier; Gómez-Ariza, José Luis

2014-12-01

331

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.

332

Active Lessons for Active Brains: Teaching Boys and Other Experiential Learners, Grades 3-10  

ERIC Educational Resources Information Center

If you're tired of repeating yourself to students who aren't listening, try a little less talk and a lot more action. The authors follow the best-selling "Teaching the Male Brain and Teaching the Female Brain" with this ready-to-use collection of mathematics, language arts, science, and classroom management strategies. Designed for active,…

James, Abigail Norfleet; Allison, Sandra Boyd; McKenzie, Caitlin Zimmerman

2011-01-01

333

Differential effects of exercise on brain opioid receptor binding and activation in rats.  

PubMed

Physical exercise stimulates the release of endogenous opioid peptides supposed to be responsible for changes in mood, anxiety, and performance. Exercise alters sensitivity to these effects that modify the efficacy at the opioid receptor. Although there is evidence that relates exercise to neuropeptide expression in the brain, the effects of exercise on opioid receptor binding and signal transduction mechanisms downstream of these receptors have not been explored. Here, we characterized the binding and G protein activation of mu opioid receptor, kappa opioid receptor or delta opioid receptor in several brain regions following acute (7 days) and chronic (30 days) exercise. As regards short- (acute) or long-term effects (chronic) of exercise, overall, higher opioid receptor binding was observed in acute-exercise animals and the opposite was found in the chronic-exercise animals. The binding of [(35) S]GTP?S under basal conditions (absence of agonists) was elevated in sensorimotor cortex and hippocampus, an effect more evident after chronic exercise. Divergence of findings was observed for mu opioid receptor, kappa opioid receptor, and delta opioid receptor receptor activation in our study. Our results support existing evidence of opioid receptor binding and G protein activation occurring differentially in brain regions in response to diverse exercise stimuli. We characterized the binding and G protein activation of mu, kappa, and delta opioid receptors in several brain regions following acute (7 days) and chronic (30 days) exercise. Higher opioid receptor binding was observed in the acute exercise animal group and opposite findings in the chronic exercise group. Higher G protein activation under basal conditions was noted in rats submitted to chronic exercise, as visible in the depicted pseudo-color autoradiograms. PMID:25330347

Arida, Ricardo Mario; Gomes da Silva, Sérgio; de Almeida, Alexandre Aparecido; Cavalheiro, Esper Abrão; Zavala-Tecuapetla, Cecilia; Brand, Serge; Rocha, Luisa

2015-01-01

334

Convergent Findings of Altered Functional and Structural Brain Connectivity in Individuals with High Functioning Autism: A Multimodal MRI Study  

PubMed Central

Brain tissue changes in autism spectrum disorders seem to be rather subtle and widespread than anatomically distinct. Therefore a multimodal, whole brain imaging technique appears to be an appropriate approach to investigate whether alterations in white and gray matter integrity relate to consistent changes in functional resting state connectivity in individuals with high functioning autism (HFA). We applied diffusion tensor imaging (DTI), voxel-based morphometry (VBM) and resting state functional connectivity magnetic resonance imaging (fcMRI) to assess differences in brain structure and function between 12 individuals with HFA (mean age 35.5, SD 11.4, 9 male) and 12 healthy controls (mean age 33.3, SD 9.0, 8 male). Psychological measures of empathy and emotionality were obtained and correlated with the most significant DTI, VBM and fcMRI findings. We found three regions of convergent structural and functional differences between HFA participants and controls. The right temporo-parietal junction area and the left frontal lobe showed decreased fractional anisotropy (FA) values along with decreased functional connectivity and a trend towards decreased gray matter volume. The bilateral superior temporal gyrus displayed significantly decreased functional connectivity that was accompanied by the strongest trend of gray matter volume decrease in the temporal lobe of HFA individuals. FA decrease in the right temporo-parietal region was correlated with psychological measurements of decreased emotionality. In conclusion, our results indicate common sites of structural and functional alterations in higher order association cortex areas and may therefore provide multimodal imaging support to the long-standing hypothesis of autism as a disorder of impaired higher-order multisensory integration. PMID:23825652

Samson, Andrea C.; Kirsch, Valerie; Blautzik, Janusch; Grothe, Michel; Erat, Okan; Hegenloh, Michael; Coates, Ute; Reiser, Maximilian F.; Hennig-Fast, Kristina; Meindl, Thomas

2013-01-01

335

Chronic acetyl-L-carnitine alters brain energy metabolism and increases noradrenaline and serotonin content in healthy mice.  

PubMed

Acetyl-L-carnitine (ALCAR), the short-chain ester of carnitine, is a common dietary supplement readily available in health food stores, claimed to improve energy levels and muscle strength. ALCAR has numerous effects on brain and muscle metabolism, protects against neurotoxic insults and may be an effective treatment for certain forms of depression. However, little is known about the effect of chronic ALCAR supplementation on the brain metabolism of healthy mice. Here, we investigated ALCAR's effect on cerebral energy and neurotransmitter metabolism after supplementing the drinking water of mice with ALCAR for 25 days, providing a daily dose of about 0.5 g/kg. Thereafter the animals were injected with [1-(13)C]glucose, and (13)C incorporation into and levels of various metabolites were quantified in extracts of the hippocampal formation (HF) and cortex using (1)H- and (13)C-nuclear magnetic resonance (NMR) spectroscopy and high performance liquid chromatography (HPLC). Increased glucose levels were detected in both regions together with a decreased amount of [3-(13)C]lactate, but no alterations in incorporation of (13)C derived from [1-(13)C]glucose into the amino acids glutamate, GABA and glutamine. These findings are consistent with decreased metabolism of glucose to lactate but not via the TCA cycle. Higher amounts of the sum of adenosine nucleotides, phosphocreatine and the phosphocreatine/creatine ratio found in the cortex of ALCAR-treated mice are indicative of increased energy levels. Furthermore, ALCAR supplementation increased the levels of the neurotransmitters noradrenaline in the HF and serotonin in cortex, consistent with ALCAR's potential efficacy for depressive symptoms. Other ALCAR-induced changes observed included reduced amounts of GABA in the HF and increased myo-inositol. In conclusion, chronic ALCAR supplementation decreased glucose metabolism to lactate, resulted in increased energy metabolite and altered monoamine neurotransmitter levels in the mouse brain. PMID:22549035

Smeland, Olav B; Meisingset, Tore W; Borges, Karin; Sonnewald, Ursula

2012-07-01

336

Brain white matter microstructure alterations in adolescent rhesus monkeys exposed to early life stress: associations with high cortisol during infancy  

PubMed Central

Background Early adverse experiences, especially those involving disruption of the mother-infant relationship, are detrimental for proper socioemotional development in primates. Humans with histories of childhood maltreatment are at high risk for developing psychopathologies including depression, anxiety, substance abuse, and behavioral disorders. However, the underlying neurodevelopmental alterations are not well understood. Here we used a nonhuman primate animal model of infant maltreatment to study the long-term effects of this early life stress on brain white matter integrity during adolescence, its behavioral correlates, and the relationship with early levels of stress hormones. Methods Diffusion tensor imaging and tract based spatial statistics were used to investigate white matter integrity in 9 maltreated and 10 control animals during adolescence. Basal plasma cortisol levels collected at one month of age (when abuse rates were highest) were correlated with white matter integrity in regions with group differences. Total aggression was also measured and correlated with white matter integrity. Results We found significant reductions in white matter structural integrity (measured as fractional anisotropy) in the corpus callosum, occipital white matter, external medullary lamina, as well as in the brainstem of adolescent rhesus monkeys that experienced maternal infant maltreatment. In most regions showing fractional anisotropy reductions, opposite effects were detected in radial diffusivity, without changes in axial diffusivity, suggesting that the alterations in tract integrity likely involve reduced myelin. Moreover, in most regions showing reduced white matter integrity, this was associated with elevated plasma cortisol levels early in life, which was significantly higher in maltreated than in control infants. Reduced fractional anisotropy in occipital white matter was also associated with increased social aggression. Conclusions These findings highlight the long-term impact of infant maltreatment on brain white matter structural integrity, particularly in tracts involved in visual processing, emotional regulation, and somatosensory and motor integration. They also suggest a relationship between elevations in stress hormones detected in maltreated animals during infancy and long-term brain white matter structural effects. PMID:24289263

2013-01-01

337

Different alcohol exposures induce selective alterations on the expression of dynorphin and nociceptin systems related genes in rat brain.  

PubMed

Molecular mechanisms of adaptive transformations caused by alcohol exposure on opioid dynorphin and nociceptin systems have been investigated in the rat brain. Alcohol was intragastrically administered to rats to resemble human drinking with several hours of exposure: water or alcohol (20% in water) at a dose of 1.5?g/kg three times daily for 1 or 5 days. The development of tolerance and dependence were recorded daily. Brains were dissected 30 minutes (1- and 5-day groups) or 1, 3 or 7 days after the last administration for the three other 5-day groups (groups under withdrawal). Specific alterations in opioid genes expression were ascertained. In the amygdala, an up-regulation of prodynorphin and pronociceptin was observed in the 1-day group; moreover, pronociceptin and the kappa opioid receptor mRNAs in the 5-day group and both peptide precursors in the 1-day withdrawal group were also up-regulated. In the prefrontal cortex, an increase in prodynorhin expression in the 1-day group was detected. These data indicate a relevant role of the dynorphinergic system in the negative hedonic states associated with multiple alcohol exposure. The pattern of alterations observed for the nociceptin system appears to be consistent with its role of functional antagonism towards the actions of ethanol associated with other opioid peptides. Our findings could help to the understanding of how alcohol differentially affects the opioid systems in the brain and also suggest the dynorphin and nociceptin systems as possible targets for the treatment and/or prevention of alcohol dependence. PMID:21507157

D'Addario, Claudio; Caputi, Francesca F; Rimondini, Roberto; Gandolfi, Ottavio; Del Borrello, Elia; Candeletti, Sanzio; Romualdi, Patrizia

2013-05-01

338

Breastfeeding, Brain Activation to Own Infant Cry, and Maternal Sensitivity  

PubMed Central

Background Research points to the importance of breastfeeding for promoting close mother-infant contact and social-emotional development. Recent functional magnetic resonance imaging (fMRI) studies have identified brain regions related to maternal behaviors. However, little research has addressed the neurobiological mechanisms underlying the relationship between breastfeeding and maternal behavior in human mothers. We investigated the associations between breastfeeding, maternal brain response to own infant stimuli, and maternal sensitivity in the early postpartum. Methods Seventeen biological mothers of healthy infants participated in two matched groups according to feeding method – exclusive breastfeeding and exclusive formula-feeding at 2-4 weeks postpartum. fMRI scanning was conducted in the first postpartum month to examine maternal brain activation in response to her own baby's cry versus control baby-cry. Dyadic interactions between mothers and infants at 3-4 months postpartum were videotaped in the home and blindly coded for maternal sensitivity. Results In the first postpartum month, breastfeeding mothers showed greater activations in the superior frontal gyrus, insula, precuneus, striatum, and amygdala while listening to their own baby-cry as compared to formula-feeding mothers. For both breastfeeding and formula-feeding mothers, greater activations in the right superior frontal gyrus and amygdala were associated with higher maternal sensitivity at 3-4 months postpartum. Conclusions Results suggest links between breastfeeding and greater response to infant cues in brain regions implicated in maternal-infant bonding and empathy during the early postpartum. Such brain activations may facilitate greater maternal sensitivity as infants enter their social world. PMID:21501165

Kim, Pilyoung; Feldman, Ruth; Mayes, Linda C.; Eicher, Virginia; Thompson, Nancy; Leckman, James F.; Swain, James E.

2011-01-01

339

Chronic repetitive transcranial magnetic stimulation alters beta-adrenergic and 5-HT2 receptor characteristics in rat brain.  

PubMed

Repetitive transcranial magnetic stimulation (rTMS) has been shown to affect mood in health and disease. Evidence to date has demonstrated an antidepressant potential for low- and high-frequency rTMS treatment. In animal behavioral models of depression magnetic stimulation of the brain induced similar effects to those of electroconvulsive shock (ECS). In this study the effects of repeated rTMS on rat brain noradrenaline, dopamine, serotonin and their metabolites levels, as well as on beta-adrenergic and 5-HT2 receptor characteristics were studied. After 10 days of treatment, beta-adrenergic receptors were significantly up regulated in the frontal cortex, down regulated in the striatum and were unchanged in the hippocampus. 5-HT2 receptors were down regulated in the frontal cortex and were not changed in the other brain areas. No change in benzodiazepine receptors in the frontal cortex and cerebellum were demonstrated. These findings demonstrate specific and selective alterations induced by repeated rTMS, which are distinct from those induced by other antidepressant treatments. TMS therapeutic effects in humans and behavioral and biochemical effects in animal, suggest that TMS has a unique mechanism of action which requires further investigation. PMID:9878693

Ben-Shachar, D; Gazawi, H; Riboyad-Levin, J; Klein, E

1999-01-16

340

Traumatic Brain Injury in Young Rats Leads to Progressive Behavioral Deficits Coincident with Altered Tissue Properties in Adulthood  

PubMed Central

Abstract Traumatic brain injury (TBI) affects many infants and children, and results in enduring motor and cognitive impairments with accompanying changes in white matter tracts, yet few experimental studies in rodent juvenile models of TBI (jTBI) have examined the timeline and nature of these deficits, histologically and functionally. We used a single controlled cortical impact (CCI) injury to the parietal cortex of rats at post-natal day (P) 17 to evaluate behavioral alterations, injury volume, and morphological and molecular changes in gray and white matter, with accompanying measures of electrophysiological function. At 60 days post-injury (dpi), we found that jTBI animals displayed behavioral deficits in foot-fault and rotarod tests, along with a left turn bias throughout their early developmental stages and into adulthood. In addition, anxiety-like behaviors on the zero maze emerged in jTBI animals at 60?dpi. The final lesion constituted only ?3% of brain volume, and morphological tissue changes were evaluated using MRI, as well as immunohistochemistry for neuronal nuclei (NeuN), myelin basic protein (MBP), neurofilament-200 (NF200), and oligodendrocytes (CNPase). White matter morphological changes were associated with a global increase in MBP immunostaining and reduced compound action potential amplitudes at 60?dpi. These results suggest that brain injury early in life can induce long-term white matter dysfunction, occurring in parallel with the delayed development and persistence of behavioral deficits, thus modeling clinical and longitudinal TBI observations. PMID:22697253

Ajao, David O.; Pop, Viorela; Kamper, Joel E.; Adami, Arash; Rudobeck, Emil; Huang, Lei; Vlkolinsky, Roman; Hartman, Richard E.; Ashwal, Stephen; Obenaus, André

2012-01-01

341

Brain waves and brain wiring: the role of endogenous and sensory-driven neural activity in development.  

PubMed

Neural activity is critical for sculpting the intricate circuits of the nervous system from initially imprecise neuronal connections. Disrupting the formation of these precise circuits may underlie many common neurodevelopmental disorders, ranging from subtle learning disorders to pervasive developmental delay. The necessity for sensory-driven activity has been widely recognized as crucial for infant brain development. Recent experiments in neurobiology now point to a similar requirement for endogenous neural activity generated by the nervous system itself before sensory input is available. Here we use the formation of precise neural circuits in the visual system to illustrate the principles of activity-dependent development. Competition between the projections from lateral geniculate nucleus neurons that receive sensory input from the two eyes shapes eye-specific connections from an initially diffuse projection into ocular dominance columns. When the competition is altered during a critical period for these changes, by depriving one eye of vision, the normal ocular dominance column pattern is disrupted. Before ocular dominance column formation, the highly ordered projection from retina to lateral geniculate nucleus develops. These connections form before the retina can respond to light, but at a time when retinal ganglion cells spontaneously generate highly correlated bursts of action potentials. Blockade of this endogenous activity, or biasing the competition in favor of one eye, results in a severe disruption of the pattern of retinogeniculate connections. Similar spontaneous, correlated activity has been identified in many locations in the developing central nervous system and is likely to be used during the formation of precise connections in many other neural systems. Understanding the processes of activity-dependent development could revolutionize our ability to identify, prevent, and treat developmental disorders resulting from disruptions of neural activity that interfere with the formation of precise neural circuits. PMID:10203134

Penn, A A; Shatz, C J

1999-04-01

342

Altered brain protein expression profiles are associated with molecular neurological dysfunction in the PKU mouse model  

PubMed Central

Phenylketonuria (PKU), if not detected and treated in newborns, causes severe neurological dysfunction and cognitive and behavioral deficiencies. Despite the biochemical characterization of PKU, the molecular mechanisms underlying PKU-associated brain dysfunction remain poorly understood. The aim of this study was to gain insights into the pathogenesis of this neurological damage by analyzing protein expression profiles in brain tissue of Black and Tan BRachyury-PahEnu2 mice (a mouse model of PKU). We compared the cerebral protein expression of homozygous PKU mice with that of their heterozygous counterparts using two-dimensional difference gel electrophoresis analysis, and identified 21 differentially expressed proteins, four of which were over-expressed and 17 under-expressed. An in silico bioinformatic approach indicated that protein under-expression was related to neuronal differentiation and dendritic growth, and to such neurological disorders as progressive motor neuropathy and movement disorders. Moreover, functional annotation analyses showed that some identified proteins were involved in oxidative metabolism. To further investigate the proteins involved in the neurological damage, we validated two of the proteins that were most strikingly under-expressed, namely, Syn2 and Dpysl2, which are involved in synaptic function and neurotransmission. We found that Glu2/3 and NR1 receptor subunits were over-expressed in PKU mouse brain. Our results indicate that differential expression of these proteins may be associated with the processes underlying PKU brain dysfunction, namely, decreased synaptic plasticity and impaired neurotransmission. PMID:24548049

Imperlini, Esther; Orrù, Stefania; Corbo, Claudia; Daniele, Aurora; Salvatore, Francesco

2014-01-01

343

Altered arachidonic acid cascade enzymes in postmortem brain from bipolar disorder patients.  

PubMed

Mood stabilizers that are approved for treating bipolar disorder (BD), when given chronically to rats, decrease expression of markers of the brain arachidonic metabolic cascade, and reduce excitotoxicity and neuroinflammation-induced upregulation of these markers. These observations, plus evidence for neuroinflammation and excitotoxicity in BD, suggest that arachidonic acid (AA) cascade markers are upregulated in the BD brain. To test this hypothesis, these markers were measured in postmortem frontal cortex from 10 BD patients and 10 age-matched controls. Mean protein and mRNA levels of AA-selective cytosolic phospholipase A(2) (cPLA(2)) IVA, secretory sPLA(2) IIA, cyclooxygenase (COX)-2 and membrane prostaglandin E synthase (mPGES) were significantly elevated in the BD cortex. Levels of COX-1 and cytosolic PGES (cPGES) were significantly reduced relative to controls, whereas Ca(2+)-independent iPLA(2)VIA, 5-, 12-, and 15-lipoxygenase, thromboxane synthase and cytochrome p450 epoxygenase protein and mRNA levels were not significantly different. These results confirm that the brain AA cascade is disturbed in BD, and that certain enzymes associated with AA release from membrane phospholipid and with its downstream metabolism are upregulated. As mood stabilizers downregulate many of these brain enzymes in animal models, their clinical efficacy may depend on suppressing a pathologically upregulated cascade in BD. An upregulated cascade should be considered as a target for drug development and for neuroimaging in BD. PMID:20038946

Kim, H-W; Rapoport, S I; Rao, J S

2011-04-01

344

PRENATAL EXPOSURE TO CHLORPYRIFOS ALTERS NEUROTROPHIN IMMUNOREACTIVITY AND APOPTOSIS IN RAT BRAIN.  

EPA Science Inventory

In the present study, the effects of the organophosphate pesticide chlorpyrifos [CPF; O,O'diethyl O-3,5,6-trichloro-2-pyridyl) phosphorothionate] on the regional distribution of three neurotrophic factors and on levels of apoptosis in gestational rat brain were characterized. P...

345

Alterations in regional brain metabolism in genetic and pharmacological models of reduced NMDA receptor function  

Microsoft Academic Search

A mouse line has been developed that expresses low levels of the NMDA R1 (NR1) subunit of the NMDA receptor [Cell 98 (1999) 427]. These NR1 hypomorphic mice represent an experimental model of reduced NMDA receptor function that may be relevant to the pathophysiology of schizophrenia. To further characterize the neurobiological phenotype resulting from developmental NMDA receptor hypofunction, regional brain

Gary E Duncan; Seiya Miyamoto; Hongbin Gu; Jeffrey A Lieberman; Beverly H Koller; John N Snouwaert

2002-01-01

346

Chronic ethanol consumption profoundly alters regional brain ceramide and sphingomyelin content in rodents.  

PubMed

Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to -37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at 50 ?m spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol. PMID:25387107

Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N; Baldwin, Katherine; Womack, Virginia; Pagiazitis, John G; O'Rourke, Joseph R; Thanos, Panayotis K; Balaban, Carey; Schultz, J Albert; Volkow, Nora D; Woods, Amina S

2015-02-18

347

High-throughput gene expression profiling of opioid-induced alterations in discrete brain areas.  

PubMed

Whole-genome screening methods are unique approach to search for novel genes and molecular pathways involved in drug action. High-throughput profiling allows the gene expression levels of tens of thousands of transcripts to be measured simultaneously. Here, we describe transcriptional profiling in a specific area of the brain using DNA microarrays and next-generation sequencing. PMID:25293316

Korostynski, Michal; Piechota, Marcin; Golda, Slawomir; Przewlocki, Ryszard

2015-01-01

348

Water diffusion in brain cortex closely tracks underlying neuronal activity  

PubMed Central

Neuronal activity results in a local increase in blood flow. This concept serves as the basis for functional MRI. Still, this approach remains indirect and may fail in situations interfering with the neurovascular coupling mechanisms (drugs, anesthesia). Here we establish that water molecular diffusion is directly modulated by underlying neuronal activity using a rat forepaw stimulation model under different conditions of neuronal stimulation and neurovascular coupling. Under nitroprusside infusion, a neurovascular-coupling inhibitor, the diffusion response and local field potentials were maintained, whereas the hemodynamic response was abolished. As diffusion MRI reflects interactions of water molecules with obstacles (e.g., cell membranes), the observed changes point to a dynamic modulation of the neural tissue structure upon activation, which remains to be investigated. These findings represent a significant shift in concept from the current electrochemical and neurovascular coupling principles used for brain imaging, and open unique avenues to investigate mechanisms underlying brain function. PMID:23801756

Tsurugizawa, Tomokazu; Ciobanu, Luisa; Le Bihan, Denis

2013-01-01

349

Regional Homogeneity of Intrinsic Brain Activity in Happy and Unhappy Individuals  

PubMed Central

Background Why are some people happier than others? This question has intrigued many researchers. However, limited work has addressed this question within a neuroscientific framework. Methods The present study investigated the neural correlates of trait happiness using the resting-state functional magnetic resonance imaging (rs-fMRI) approach. Specifically, regional homogeneity (ReHo) was examined on two groups of young adults: happy and unhappy individuals (N?=?25 per group). Results Decreased ReHo in unhappy relative to happy individuals was observed within prefrontal cortex, medial temporal lobe, superior temporal lobe, and retrosplenial cortex. In contrast, increased ReHo in unhappy relative to happy individuals was observed within the dorsolateral prefrontal cortex, middle cingulate gyrus, putamen, and thalamus. In addition, the ReHo within the left thalamus was negatively correlated with Chinese Happiness Inventory (CHI) score within the happy group. Limitations As an exploratory study, we examined how general trait happiness is reflected in the regional homogeneity of intrinsic brain activity in a relatively small sample. Examining other types of happiness in a larger sample using a multitude of intrinsic brain activity indices are warranted for future work. Conclusions The local synchronization of BOLD signal is altered in unhappy individuals. The regions implicated in this alteration partly overlapped with previously identified default mode network, emotional circuitry, and rewarding system, suggesting that these systems may be involved in happiness. PMID:24454814

Luo, Yangmei; Huang, Xiting; Yang, Zhen; Li, Baolin; Liu, Jie; Wei, Dongtao

2014-01-01

350

Brain activation during anticipation of sound sequences.  

PubMed

Music consists of sound sequences that require integration over time. As we become familiar with music, associations between notes, melodies, and entire symphonic movements become stronger and more complex. These associations can become so tight that, for example, hearing the end of one album track can elicit a robust image of the upcoming track while anticipating it in total silence. Here, we study this predictive "anticipatory imagery" at various stages throughout learning and investigate activity changes in corresponding neural structures using functional magnetic resonance imaging. Anticipatory imagery (in silence) for highly familiar naturalistic music was accompanied by pronounced activity in rostral prefrontal cortex (PFC) and premotor areas. Examining changes in the neural bases of anticipatory imagery during two stages of learning conditional associations between simple melodies, however, demonstrates the importance of fronto-striatal connections, consistent with a role of the basal ganglia in "training" frontal cortex (Pasupathy and Miller, 2005). Another striking change in neural resources during learning was a shift between caudal PFC earlier to rostral PFC later in learning. Our findings regarding musical anticipation and sound sequence learning are highly compatible with studies of motor sequence learning, suggesting common predictive mechanisms in both domains. PMID:19244522

Leaver, Amber M; Van Lare, Jennifer; Zielinski, Brandon; Halpern, Andrea R; Rauschecker, Josef P

2009-02-25

351

Enhanced nociceptive responding in two rat models of depression is associated with alterations in monoamine levels in discrete brain regions.  

PubMed

Altered pain responding in depression is a widely recognized but poorly understood phenomenon. The present study investigated nociceptive responding to acute (thermal and mechanical) and persistent (inflammatory) noxious stimuli in two animal models of depression, the olfactory bulbectomized (OB) and the Wistar-Kyoto (WKY) rat. In addition, this study examined if altered nociceptive behaviour was associated with changes in monoamine levels in discrete brain regions. OB rats exhibited mechanical allodynia (von Frey test) but not thermal hyperalgesia (hot plate and tail-flick tests) when compared to sham-operated counterparts. Formalin-induced nociceptive behaviour was both heightened and prolonged in OB versus sham-operated controls. An inverse correlation was observed between 5-hydroxyindoleacetic acid (5-HIAA) concentration in the hippocampus and amygdaloid cortex and nociceptive behaviour in the formalin test. In comparison, WKY rats exhibited thermal hyperalgesia in the hot plate test, while behaviour in the tail-flick and von Frey tests did not differ between WKY and Sprague-Dawley rats. Furthermore, WKY rats exhibited enhanced formalin-evoked nociceptive responding up to 40 min post administration, an effect inversely correlated with serotonin and 5-HIAA levels in the hypothalamus. In conclusion, these findings demonstrate that altered pain responding observed in clinically depressed patients can be modelled pre-clinically, providing a means of investigating the neurochemical basis of, and possible treatments for, this phenomenon. PMID:20955767

Burke, N N; Hayes, E; Calpin, P; Kerr, D M; Moriarty, O; Finn, D P; Roche, M

2010-12-29

352

Interaction between physostigmine and soman on brain regional cholinesterase activity and /sup 3/H-physostigmine distribution  

SciTech Connect

Physostigmine (Phy) concentrations (as radioactivity) were studied in various brain areas after /sup 3/H-Phy administration as a function of time. Five min after 500 ..mu..g/kg i.m., cortex (CX) and total brain showed similar concentrations (370 ng/g) which were 50-90% higher than those of other brain regions (striatum, hippocampus, and medulla oblongata). Soman did not affect Phy levels in whole brain after pretreatment with Phy (100 or 500 ..mu..g/kg), however, the regional distribution of Phy was altered by soman as was ChE inhibition. A significant increase in Phy concentration was seen in HC (22 and 45% at 5 and 30 min, respectively) and CX (21% at 30 min). ChE activity in total brain was 12, 30, and 24% (5, 15 and 30 min after soman administration) lower than after Phy alone. If the pretreatment dose of Phy was increased to 500 ..mu..g/kg /sup 3/H-Phy, ChE activity was further reduced to 4, 13 and 19%. This might indicate that higher doses of Phy provide more protection of the enzyme from soman than lower doses. The protective role of Phy seen in total brain was not consistent for all brain regions. Soman alone produced a 95% ChE inhibition and there were no differences in its effect between total brain or brain areas. Pretreatment of the rat with Phy produced a protective effect upon ChE activity up to 30 min. However, no protective effect on survival was observed.

Hallak, M.E.; Woodruff, E.; Giacobini, E.

1986-03-05

353

Effects of ionizing radiation on the blood brain barrier permeability to pharmacologically active substances  

SciTech Connect

Ionizing radiation can impair the integrity of the blood brain barrier (BBB). Data on early and late damage after brain irradiation are usually reported separately, yet a gradual transition between these two types has become evident. Signs appearing within 3 weeks after irradiation are considered to be early manifestations. The mechanism of radiation-effected integrity impairment of the BBB is discussed in relation to changes in morphological structures forming the BBB, the endothelium of intracerebral vessels, and in the surrounding astrocytes. Alterations in the function of the BBB are manifested in the endothelium by changes in the ultrastructural location of the activity of phosphatases and by the activation of pinocytotic vesicular transport, and in astrocyte cytoplasm by glycogen deposition. The changes in ultrastructure were critically surveyed with regard to increasing doses of radiation to the brain in the range of 5 Gy to 960 Gy. The qualitative as well as the semiquantitative and quantitative observations on the passage of substances across the damaged BBB were treated separately. Qualitative changes are based mainly on findings of extravasation of vital stains and of labelled proteins. The quantitative studies established differences in radiation-induced changes in the permeability of the BBB depending on the structure and physico-chemical properties of the barrier penetrating tracers. Indirect evaluation of radiation-induced BBB changes is based on studies of pharmacological effects of substances acting on the CNS. In conclusion, radiation impairs significantly the integrity of the BBB following single irradiation of the brain with a dose exceeding 10-15 Gy. The response of the BBB to ionizing radiation is dependent both on the dose to which the brain is exposed and on specific properties of the tracer. 68 references.

Trnovec, T.; Kallay, Z.; Bezek, S. (Institute of Experimental Pharmacology, Bratislava (Yugoslavia))

1990-12-01

354

Joint sparse representation of brain activity patterns in multi-task FMRI data.  

PubMed

A single-task functional magnetic resonance imaging (fMRI) experiment may only partially highlight alterations to functional brain networks affected by a particular disorder. Multivariate analysis across multiple fMRI tasks may increase the sensitivity of fMRI-based diagnosis. Prior research using multi-task analysis in fMRI, such as those that use joint independent component analysis (jICA), has mainly assumed that brain activity patterns evoked by different tasks are independent. This may not be valid in practice. Here, we use sparsity, which is a natural characteristic of fMRI data in the spatial domain, and propose a joint sparse representation analysis (jSRA) method to identify common information across different functional subtraction (contrast) images in data from a multi-task fMRI experiment. Sparse representation methods do not require independence, or that the brain activity patterns be nonoverlapping. We use functional subtraction images within the joint sparse representation analysis to generate joint activation sources and their corresponding sparse modulation profiles. We evaluate the use of sparse representation analysis to capture individual differences with simulated fMRI data and with experimental fMRI data. The experimental fMRI data was acquired from 16 young (age: 19-26) and 16 older (age: 57-73) adults obtained from multiple speech comprehension tasks within subjects, where an independent measure (namely, age in years) can be used to differentiate between groups. Simulation results show that this method yields greater sensitivity, precision, and higher Jaccard indexes (which measures similarity and diversity of the true and estimated brain activation sources) than does the jICA method. Moreover, superiority of the jSRA method in capturing individual differences was successfully demonstrated using experimental fMRI data. PMID:25073167

Ramezani, M; Marble, K; Trang, H; Johnsrude, I S; Abolmaesumi, P

2015-01-01

355

Decomposition of spontaneous brain activity into distinct fMRI co-activation patterns  

PubMed Central

Recent fMRI studies have shown that analysis of the human brain's spontaneous activity may provide a powerful approach to reveal its functional organization. Dedicated methods have been proposed to investigate co-variation of signals from different brain regions, with the goal of revealing neuronal networks (NNs) that may serve specialized functions. However, these analysis methods generally do not take into account a potential non-stationary (variable) interaction between brain regions, and as a result have limited effectiveness. To address this, we propose a novel analysis method that uses clustering analysis to sort and selectively average fMRI activity time frames to produce a set of co-activation patterns. Compared to the established networks extracted with conventional analysis methods, these co-activation patterns demonstrate novel network features with apparent relevance to the brain's functional organization. PMID:24550788

Liu, Xiao; Chang, Catie; Duyn, Jeff H.

2013-01-01

356

Fast transient networks in spontaneous human brain activity.  

PubMed

To provide an effective substrate for cognitive processes, functional brain networks should be able to reorganize and coordinate on a sub-second temporal scale. We used magnetoencephalography recordings of spontaneous activity to characterize whole-brain functional connectivity dynamics at high temporal resolution. Using a novel approach that identifies the points in time at which unique patterns of activity recur, we reveal transient (100-200 ms) brain states with spatial topographies similar to those of well-known resting state networks. By assessing temporal changes in the occurrence of these states, we demonstrate that within-network functional connectivity is underpinned by coordinated neuronal dynamics that fluctuate much more rapidly than has previously been shown. We further evaluate cross-network interactions, and show that anticorrelation between the default mode network and parietal regions of the dorsal attention network is consistent with an inability of the system to transition directly between two transient brain states. DOI: http://dx.doi.org/10.7554/eLife.01867.001. PMID:24668169

Baker, Adam P; Brookes, Matthew J; Rezek, Iead A; Smith, Stephen M; Behrens, Timothy; Probert Smith, Penny J; Woolrich, Mark

2014-01-01

357

Contributions of glycogen to astrocytic energetics during brain activation.  

PubMed

Glycogen is the major store of glucose in brain and is mainly in astrocytes. Brain glycogen levels in unstimulated, carefully-handled rats are 10-12 ?mol/g, and assuming that astrocytes account for half the brain mass, astrocytic glycogen content is twice as high. Glycogen turnover is slow under basal conditions, but it is mobilized during activation. There is no net increase in incorporation of label from glucose during activation, whereas label release from pre-labeled glycogen exceeds net glycogen consumption, which increases during stronger stimuli. Because glycogen level is restored by non-oxidative metabolism, astrocytes can influence the global ratio of oxygen to glucose utilization. Compensatory increases in utilization of blood glucose during inhibition of glycogen phosphorylase are large and approximate glycogenolysis rates during sensory stimulation. In contrast, glycogenolysis rates during hypoglycemia are low due to continued glucose delivery and oxidation of endogenous substrates; rates that preserve neuronal function in the absence of glucose are also low, probably due to metabolite oxidation. Modeling studies predict that glycogenolysis maintains a high level of glucose-6-phosphate in astrocytes to maintain feedback inhibition of hexokinase, thereby diverting glucose for use by neurons. The fate of glycogen carbon in vivo is not known, but lactate efflux from brain best accounts for the major metabolic characteristics during activation of living brain. Substantial shuttling coupled with oxidation of glycogen-derived lactate is inconsistent with available evidence. Glycogen has important roles in astrocytic energetics, including glucose sparing, control of extracellular K(+) level, oxidative stress management, and memory consolidation; it is a multi-functional compound. PMID:24515302

Dienel, Gerald A; Cruz, Nancy F

2015-02-01

358

A Manganese-Enhanced Diet Alters Brain Metals and Transporters in the Developing Rat  

Microsoft Academic Search

Manganese (Mn) neurotoxicity in adults can result in psycho- logical and neurological disturbances similar to Parkinson's disease, including extrapyramidal motor system defects and altered behaviors. However, virtually nothing is known regarding excess Mn accumulation during central nervous system develop- ment. Developing rats were exposed to a diet high in Mn via maternal milk during lactation (PN4-21). The high Mn diet

Stephanie J. Garcia; Kristin Gellein; Tore Syversen; Michael Aschner

2006-01-01

359

ALTERATIONS IN BRAIN PROTEIN KINASE C ISOFORMS FOLLOWING DEVELOPMENTAL EXPOSURE TO POLYCHLORINATED BIPHENYL MIXTURE.  

EPA Science Inventory

PCBs have been shown to alter several neurochemical end-points and are implicated in the etiology of some neurological diseases. Recent in vivo studies from our laboratory indicated that developmental exposure to a commercial PCB mixture, Aroclor 1254, caused perturbations in cal...

360

Altered neuronal activity relationships between the pedunculopontine nucleus and motor cortex in a rodent model of Parkinson's disease  

PubMed Central

The pedunculopontine nucleus (PPN) is a new deep brain stimulation (DBS) target for Parkinson's disease (PD), but little is known about PPN firing pattern alterations in PD. The anesthetized rat is a useful model for investigating the effects of dopamine loss on the transmission of oscillatory cortical activity through basal ganglia structures. After dopamine loss, synchronous oscillatory activity emerges in the subthalamic nucleus and substantia nigra pars reticulata in phase with cortical slow oscillations. To investigate the impact of dopamine cell lesion-induced changes in basal ganglia output on activity in the PPN, this study examines PPN spike timing with reference to motor cortex (MCx) local field potential (LFP) activity in urethane- and ketamine-anesthetized rats. Seven – ten days after unilateral 6-hydroxydopamine lesion of the medial forebrain bundle, spectral power in PPN spike trains and coherence between PPN spiking and PPN LFP activity increased in the ?1 Hz range in urethane-anesthetized rats. PPN spike timing also changed from firing predominantly in-phase with MCx slow oscillations in the intact urethane-anesthetized rat to firing predominantly antiphase to MCx oscillations in the hemi-parkinsonian rat. These changes were not observed in the ketamine-anesthetized preparation. These observations suggest that dopamine loss alters PPN spike timing by increasing inhibitory oscillatory input to the PPN from basal ganglia output nuclei, a phenomenon that may be relevant to motor dysfunction and PPN DBS efficacy in PD patients. PMID:18601924

Aravamuthan, Bhooma R.; Bergstrom, Debra A.; French, Robin A.; Taylor, Joseph J.; Parr-Brownlie, Louise C.; Walters, Judith R.

2014-01-01

361

Aromatase activity in the ovary and brain of the eastern mosquitofish (Gambusia holbrooki) exposed to paper mill effluent.  

PubMed Central

Studies have shown that female mosquitofish living downstream of a paper mill located on the Fenholloway River, Florida, have masculinized secondary sex characteristics, including altered anal fin development and reproductive behavior. Masculinization can be caused by exposure to androgens in the water or from an alteration in aromatase activity in the fish. We hypothesized that aromatase activity would be inhibited by a component(s) of the paper mill effluent. Aromatase inhibition could masculinize the hormonal profile and, subsequently, secondary sex characteristics of the exposed females. Therefore, we predicted that ovarian and brain aromatase activity would be lower in the female mosquitofish from the Fenholloway River compared with the reference site, the Econfina River. Adult females were collected and standard length, body mass, anal fin length, and segment number were measured. Ovarian and brain aromatase activity were determined using a tritiated water assay. Fenholloway females had masculinized anal fin development as indicated by an increase in the number of segments in the longest anal fin ray (p < 0.0001), yet the length of the ray did not differ between sites (p = 0.95). Fenholloway females exhibited higher ovarian (p = 0.0039) and brain (p = 0.0003) aromatase activity compared with reference site fish. These data do not support aromatase inhibition as the mechanism for masculinization, suggesting that the masculinization of the Fenholloway female mosquitofish is due to androgenic contaminants. Future studies should examine the relationship between aromatase enzyme activity and exposure to environmental androgens. PMID:12060840

Orlando, Edward F; Davis, William P; Guillette, Louis J

2002-01-01

362

Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons  

PubMed Central

Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300–400 ?m from the stimulation, but not when inhibition was non-selectively weakened with the GABAA blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity. PMID:22347168

Shlosberg, Dan; Buskila, Yossi; Abu-Ghanem, Yasmin; Amitai, Yael

2012-01-01

363

Spatiotemporal alterations of cortical network activity by selective loss of NOS-expressing interneurons.  

PubMed

Deciphering the role of GABAergic neurons in large neuronal networks such as the neocortex forms a particularly complex task as they comprise a highly diverse population. The neuronal isoform of the enzyme nitric oxide synthase (nNOS) is expressed in the neocortex by specific subsets of GABAergic neurons. These neurons can be identified in live brain slices by the nitric oxide (NO) fluorescent indicator diaminofluorescein-2 diacetate (DAF-2DA). However, this indicator was found to be highly toxic to the stained neurons. We used this feature to induce acute phototoxic damage to NO-producing neurons in cortical slices, and measured subsequent alterations in parameters of cellular and network activity. Neocortical slices were briefly incubated in DAF-2DA and then illuminated through the 4× objective. Histochemistry for NADPH-diaphorase (NADPH-d), a marker for nNOS activity, revealed elimination of staining in the illuminated areas following treatment. Whole cell recordings from several neuronal types before, during, and after illumination confirmed the selective damage to non-fast-spiking (FS) interneurons. Treated slices displayed mild disinhibition. The reversal potential of compound synaptic events on pyramidal neurons became more positive, and their decay time constant was elongated, substantiating the removal of an inhibitory conductance. The horizontal decay of local field potentials (LFPs) was significantly reduced at distances of 300-400 ?m from the stimulation, but not when inhibition was non-selectively weakened with the GABA(A) blocker picrotoxin. Finally, whereas the depression of LFPs along short trains of 40 Hz stimuli was linearly reduced with distance or initial amplitude in control slices, this ordered relationship was disrupted in DAF-treated slices. These results reveal that NO-producing interneurons in the neocortex convey lateral inhibition to neighboring columns, and shape the spatiotemporal dynamics of the network's activity. PMID:22347168

Shlosberg, Dan; Buskila, Yossi; Abu-Ghanem, Yasmin; Amitai, Yael

2012-01-01

364

Worry tendencies predict brain activation during aversive imagery.  

PubMed

Because of its abstract nature, worrying might function as an avoidance response in order to cognitively disengage from fearful imagery. The present functional magnetic resonance imaging study investigated neural correlates of aversive imagery and their association with worry tendencies, as measured by the Penn State Worry Questionnaire (PSWQ). Nineteen healthy women first viewed, and subsequently imagined pictures from two categories, 'threat' and 'happiness'. Worry tendencies were negatively correlated with brain activation in the anterior cingulate cortex, the prefrontal cortex (dorsolateral, dorsomedial, ventrolateral), the parietal cortex and the insula. These negative correlations between PSWQ scores and localized brain activation were specific for aversive imagery. Moreover, activation in the above mentioned regions was positively associated with the experienced vividness of both pleasant and unpleasant mental pictures. As the identified brain regions are involved in emotion regulation, vivid imagery and memory retrieval, a lowered activity in high PSWQ scorers might be associated with cognitive disengagement from aversive imagery as well as insufficient refresh rates of mental pictures. Our preliminary findings encourage future imagery studies on generalized anxiety disorder patients, as one of the main symptoms of this disorder is excessive worrying. PMID:19545612

Schienle, Anne; Schäfer, Axel; Pignanelli, Roman; Vaitl, Dieter

2009-09-25

365

Hormonal contraceptives masculinize brain activation patterns in the absence of behavioral changes in two numerical tasks.  

PubMed

The aim of the present study was to identify, whether and how oral hormonal contraceptives (OCs) alter women's number processing. Behavioral performance and brain activation patterns (BOLD-response) of 14 OC-users were evaluated during two distinct numerical tasks (number comparison, number bisection) and compared to 16 men (high testosterone), and 16 naturally cycling women, once during their follicular (low hormone levels) and once during their luteal cycle phase (high progesterone). For both tasks, reliable sex differences and menstrual cycle dependent modulation have previously been described. If progestogenic effects of the synthetic progestins contained in OC play a predominant role, OC-users should be comparable to luteal women. If androgenic effects of the synthetic steroids exert the progestogenic actions, OC-users should be comparable to men. Likewise, if neither of the above are the case, the reduction of endogenous steroids by OCs should make OC-users comparable to follicular women. Our findings suggest that OC-users resemble follicular women in their behavioral performance, but show male-like brain activation patterns during both tasks. Analysis of brain-behavior relationships suggests that OC-users differ from naturally cycling women in the way they recruit their neural resources to deal with challenges of the tasks. We conclude that OCs, which are used by 100 million women worldwide, may have profound effects on cognition that have not been recognized so far. PMID:24231554

Pletzer, Belinda; Kronbichler, Martin; Nuerk, Hans-Christoph; Kerschbaum, Hubert

2014-01-16

366

Anomalous Light Phenomena vs. Bioelectric Brain Activity  

NASA Astrophysics Data System (ADS)

We present a research proposal concerning the instrumented investigation of anomalous light phenomena that are apparently correlated with particular mind states, such as prayer, meditation or psi. Previous research by these authors demonstrate that such light phenomena can be monitored and measured quite efficiently in areas of the world where they are reported in a recurrent way. Instruments such as optical equipment for photography and spectroscopy, VLF spectrometers, magnetometers, radar and IR viewers were deployed and used massively in several areas of the world. Results allowed us to develop physical models concerning the structural and time-variable behaviour of light phenomena, and their kinematics. Recent insights and witnesses have suggested to us that a sort of "synchronous connection" seems to exist between plasma-like phenomena and particular mind states of experiencers who seem to trigger a light manifestation which is very similar to the one previously investigated. The main goal of these authors is now aimed at the search for a concrete "entanglement-like effect" between the experiencer's mind and the light phenomena, in such a way that both aspects are intended to be monitored and measured simultaneously using appropriate instrumentation. The goal of this research project is twofold: a) to verify quantitatively the existence of one very particular kind of mind-matter interaction and to study in real time its physical and biophysical manifestations; b) to repeat the same kind of experiment using the same test-subject in different locations and under various conditions of geomagnetic activity.

Teodorani, M.; Nobili, G.

367

Alterations in Serotonin Activity and Psychiatric Symptoms After Recovery From Bulimia Nervosa  

Microsoft Academic Search

Background: Women with bulimia nervosa (BN) have disturbances of mood and behavior and alterations of monoamine activity when they are bingeing and purg- ing. It is not known whether these alterations are sec- ondary to pathological eating behavior or traits that could contribute to the pathogenesis of BN. Methods: To avoid the confounding effects of patho- logical eating behavior, we

Walter H. Kaye; Catherine G. Greeno; Howard Moss; John Fernstrom; Madelyn Fernstrom; Lisa R. Lilenfeld; Theodore E. Weltzin; J. John Mann

1998-01-01

368

Alterations in mouse brain lipidome after disruption of CST gene: a lipidomics study.  

PubMed

To investigate the effects of a critical enzyme, cerebroside sulfotransferase (CST), involving sulfatide biosynthesis on lipid (particularly sphingolipid) homeostasis, herein, we determined the lipidomes of brain cortex and spinal cord from CST null and heterozygous (CST(-/-) and CST(+/-), respectively) mice in comparison to their wild-type littermates by multi-dimensional mass spectrometry-based shotgun lipidomics. As anticipated, we demonstrated the absence of sulfatide in the tissues from CST(-/-) mice and found that significant reduction of sulfatide mass levels was also present, but in an age-dependent manner, in CST(+/-) mice. Unexpectedly, we revealed that the profiles of sulfatide species in CST(+/-) mice were significantly different from that of littermate controls with an increase in the composition of species containing saturated and hydroxylated fatty acyl chains. Contrary to the changes of sulfatide levels, shotgun lipidomics analysis did not detect significant changes of the mass levels of other lipid classes examined. Taken together, shotgun lipidomics analysis demonstrated anticipated sulfatide mass deficiency in CST defect mouse brain and revealed novel brain lipidome homeostasis in these mice. These results might provide new insights into the role of CST in myelin function. PMID:24395133

Wang, Chunyan; Wang, Miao; Zhou, Yunhua; Dupree, Jeffrey L; Han, Xianlin

2014-08-01

369

Differential changes of metabolic brain activity and interregional functional coupling in prefronto-limbic pathways during different stress conditions: functional imaging in freely behaving rodent pups  

PubMed Central

The trumpet-tailed rat or degu (Octodon degus) is an established model to investigate the consequences of early stress on the development of emotional brain circuits and behavior. The aim of this study was to identify brain circuits, that respond to different stress conditions and to test if acute stress alters functional coupling of brain activity among prefrontal and limbic regions. Using functional imaging (2-Fluoro-deoxyglucose method) in 8-day-old male degu pups the following stress conditions were compared: (A) pups together with parents and siblings (control), (B) separation of the litter from the parents, (C) individual separation from parents and siblings, and (D) individual separation and presentation of maternal calls. Condition (B) significantly downregulated brain activity in the prefrontal cortex, hippocampus, nucleus accumbens (NAcc), and sensory areas compared to controls. Activity decrease was even more pronounced during condition (C), where, in contrast to all other regions, activity in the PAG was increased. Interestingly, brain activity in stress-associated brain regions such as the amygdala and habenula was not affected. In condition (D) maternal vocalizations “reactivated” brain activity in the cingulate and precentral medial cortex, NAcc, and striatum and in sensory areas. In contrast, reduced activity was measured in the prelimbic and infralimbic cortex (IL) and in the hippocampus and amygdala. Correlation analysis revealed complex, region- and situation-specific changes of interregional functional coupling among prefrontal and limbic brain regions during stress exposure. We show here for the first time that early life stress results in a widespread reduction of brain activity in the infant brain and changes interregional functional coupling. Moreover, maternal vocalizations can partly buffer stress-induced decrease in brain activity in some regions and evoked very different functional coupling patterns compared to the three other conditions. PMID:22590453

Bock, Jörg; Riedel, Anett; Braun, Katharina

2012-01-01

370

Multichannel EEG Brain Activity Pattern Analysis in Time-Frequency Domain with Nonnegative Matrix  

E-print Network

(NMF) post-processing section in brain computer interface (BCI) training paradigm is presented: EEG, time-frequency signal analysis, brain computer interface, empirical mode decomposition electrical brain activity to control devices or computers in form of brain computer interfaces (BCI

Cichocki, Andrzej

371