Keeping brains young with making music.

PubMed

Rogenmoser, Lars; Kernbach, Julius; Schlaug, Gottfried; Gaser, Christian

2018-01-01

Music-making is a widespread leisure and professional activity that has garnered interest over the years due to its effect on brain and cognitive development and its potential as a rehabilitative and restorative therapy of brain dysfunctions. We investigated whether music-making has a potential age-protecting effect on the brain. For this, we studied anatomical magnetic resonance images obtained from three matched groups of subjects who differed in their lifetime dose of music-making activities (i.e., professional musicians, amateur musicians, and non-musicians). For each subject, we calculated a so-called BrainAGE score which corresponds to the discrepancy (in years) between chronological age and the "age of the brain", with negative values reflecting an age-decelerating brain and positive values an age-accelerating brain, respectively. The index of "brain age" was estimated using a machine-learning algorithm that was trained in a large independent sample to identify anatomical correlates of brain-aging. Compared to non-musicians, musicians overall had lower BrainAGE scores, with amateur musicians having the lowest scores suggesting that music-making has an age-decelerating effect on the brain. Unlike the amateur musicians, the professional musicians showed a positive correlation between their BrainAGE scores and years of music-making, possibly indicating that engaging more intensely in just one otherwise enriching activity might not be as beneficial than if the activity is one of several that an amateur musician engages in. Intense music-making activities at a professional level could also lead to stress-related interferences and a less enriched environment than that of amateur musicians, possibly somewhat diminishing the otherwise positive effect of music-making.

Brain MRI lesions and atrophy are associated with employment status in patients with multiple sclerosis.

PubMed

Tauhid, Shahamat; Chu, Renxin; Sasane, Rahul; Glanz, Bonnie I; Neema, Mohit; Miller, Jennifer R; Kim, Gloria; Signorovitch, James E; Healy, Brian C; Chitnis, Tanuja; Weiner, Howard L; Bakshi, Rohit

2015-11-01

Multiple sclerosis (MS) commonly affects occupational function. We investigated the link between brain MRI and employment status. Patients with MS (n = 100) completed a Work Productivity and Activity Impairment (WPAI) (general health version) survey measuring employment status, absenteeism, presenteeism, and overall work and daily activity impairment. Patients "working for pay" were considered employed; "temporarily not working but looking for work," "not working or looking for work due to age," and "not working or looking for work due to disability" were considered not employed. Brain MRI T1 hypointense (T1LV) and T2 hyperintense (T2LV) lesion volumes were quantified. To assess lesional destructive capability, we calculated each subject's ratio of T1LV to T2LV (T1/T2). Normalized brain parenchymal volume (BPV) assessed brain atrophy. The mean (SD) age was 45.5 (9.7) years; disease duration was 12.1 (8.1) years; 75 % were women, 76 % were relapsing-remitting, and 76 % were employed. T1LV, T1/T2, Expanded Disability Status Scale (EDSS) scores, and activity impairment were lower and BPV was higher in the employed vs. not employed group (Wilcoxon tests, p < 0.05). Age, disease duration, MS clinical subtype, and T2LV did not differ between groups (p > 0.05). In multivariable logistic regression modeling, adjusting for age, sex, and disease duration, higher T1LV predicted a lower chance of employment (p < 0.05). Pearson correlations showed that EDSS was associated with activity impairment (p < 0.05). Disease duration, age, and MRI measures were not correlated with activity impairment or other WPAI outcomes (p > 0.05). We report a link between brain atrophy and lesions, particularly lesions with destructive potential, to MS employment status.

Dynamics of the brain: Mathematical models and non-invasive experimental studies

NASA Astrophysics Data System (ADS)

Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

2013-10-01

Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

Contributions of glycogen to astrocytic energetics during brain activation.

PubMed

Dienel, Gerald A; Cruz, Nancy F

2015-02-01

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 μmol/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.

Contributions of Glycogen to Astrocytic Energetics during Brain Activation

PubMed Central

Dienel, Gerald A.; Cruz, Nancy F.

2014-01-01

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

How atypical is atypical language dominance?

PubMed

Knecht, S; Jansen, A; Frank, A; van Randenborgh, J; Sommer, J; Kanowski, M; Heinze, H J

2003-04-01

Atypical, right-hemisphere language dominance is poorly understood. It is often observed in patients with brain reorganization due to lesions early in life. It can also be encountered in seemingly normal individuals. We compared the patterns of neural language activation in 7 individuals with left- and 7 with right-hemisphere language dominance, none of whom had any evidence of brain lesions. We speculated that incongruencies in the activation patterns in atypical, right-hemisphere language dominance could indicate a reorganized neural language system after undetected early brain damage. Functional magnetic resonance imaging analysis of brain activation during phonetic word generation demonstrated (1). no increased activation in the subdominant hemisphere in right compared to left language dominance, (2). a similar variability in the pattern of activation in both groups, and (3). a mirror reverse pattern of activation in right- compared to left-hemisphere dominant subjects. These findings support the view that in individuals with an unrevealing medical history right-hemispheric dominance constitutes a natural rather than an abortive variant of language lateralization.

A pilot study examining functional brain activity 6 months after memory retraining in MS: the MEMREHAB trial.

PubMed

Dobryakova, Ekaterina; Wylie, Glenn R; DeLuca, John; Chiaravalloti, Nancy D

2014-09-01

Cognitive impairment in individuals with multiple sclerosis (MS) is now well recognized. One of the most common cognitive deficits is found in memory functioning, largely due to impaired acquisition. We examined functional brain activity 6 months after memory retraining in individuals with MS. The current report presents long term follow-up results from a randomized clinical trial on a memory rehabilitation protocol known as the modified Story Memory Technique. Behavioral memory performance and brain activity of all participants were evaluated at baseline, immediately after treatment, and 6 months after treatment. Results revealed that previously observed increases in patterns of cerebral activation during learning immediately after memory training were maintained 6 months post training.

Two-dimensional zymography differentiates gelatinase isoforms in stimulated microglial cells and in brain tissues of acute brain injuries.

PubMed

Chen, Shanyan; Meng, Fanjun; Chen, Zhenzhou; Tomlinson, Brittany N; Wesley, Jennifer M; Sun, Grace Y; Whaley-Connell, Adam T; Sowers, James R; Cui, Jiankun; Gu, Zezong

2015-01-01

Excessive activation of gelatinases (MMP-2/-9) is a key cause of detrimental outcomes in neurodegenerative diseases. A single-dimension zymography has been widely used to determine gelatinase expression and activity, but this method is inadequate in resolving complex enzyme isoforms, because gelatinase expression and activity could be modified at transcriptional and posttranslational levels. In this study, we investigated gelatinase isoforms under in vitro and in vivo conditions using two-dimensional (2D) gelatin zymography electrophoresis, a protocol allowing separation of proteins based on isoelectric points (pI) and molecular weights. We observed organomercuric chemical 4-aminophenylmercuric acetate-induced activation of MMP-2 isoforms with variant pI values in the conditioned medium of human fibrosarcoma HT1080 cells. Studies with murine BV-2 microglial cells indicated a series of proform MMP-9 spots separated by variant pI values due to stimulation with lipopolysaccharide (LPS). The MMP-9 pI values were shifted after treatment with alkaline phosphatase, suggesting presence of phosphorylated isoforms due to the proinflammatory stimulation. Similar MMP-9 isoforms with variant pI values in the same molecular weight were also found in mouse brains after ischemic and traumatic brain injuries. In contrast, there was no detectable pI differentiation of MMP-9 in the brains of chronic Zucker obese rats. These results demonstrated effective use of 2D zymography to separate modified MMP isoforms with variant pI values and to detect posttranslational modifications under different pathological conditions.

Rapid intranasal delivery of chloramphenicol acetyltransferase in the active form to different brain regions as a model for enzyme therapy in the CNS.

PubMed

Appu, Abhilash P; Arun, Peethambaran; Krishnan, Jishnu K S; Moffett, John R; Namboodiri, Aryan M A

2016-02-01

The blood brain barrier (BBB) is critical for maintaining central nervous system (CNS) homeostasis by restricting entry of potentially toxic substances. However, the BBB is a major obstacle in the treatment of neurotoxicity and neurological disorders due to the restrictive nature of the barrier to many medications. Intranasal delivery of active enzymes to the brain has therapeutic potential for the treatment of numerous CNS enzyme deficiency disorders and CNS toxicity caused by chemical threat agents. The aim of this work is to provide a sensitive model system for analyzing the rapid delivery of active enzymes into various regions of the brain with therapeutic bioavailability. We tested intranasal delivery of chloramphenicol acetyltransferase (CAT), a relatively large (75kD) enzyme, in its active form into different regions of the brain. CAT was delivered intranasally to anaesthetized rats and enzyme activity was measured in different regions using a highly specific High Performance Thin Layer Chromatography (HP-TLC)-radiometry coupled assay. Active enzyme reached all examined areas of the brain within 15min (the earliest time point tested). In addition, the yield of enzyme activity in the brain was almost doubled in the brains of rats pre-treated with matrix metalloproteinase-9 (MMP-9). Intranasal administration of active enzymes in conjunction with MMP-9 to the CNS is both rapid and effective. The present results suggest that intranasal enzyme therapy is a promising method for counteracting CNS chemical threat poisoning, as well as for treating CNS enzyme deficiency disorders. Published by Elsevier B.V.

Fueling and imaging brain activation

PubMed Central

Dienel, Gerald A

2012-01-01

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

The Prorenin and (Pro)renin Receptor: New Players in the Brain Renin-Angiotensin System?

PubMed Central

Li, Wencheng; Peng, Hua; Seth, Dale M.; Feng, Yumei

2012-01-01

It is well known that the brain renin-angiotensin (RAS) system plays an essential role in the development of hypertension, mainly through the modulation of autonomic activities and vasopressin release. However, how the brain synthesizes angiotensin (Ang) II has been a debate for decades, largely due to the low renin activity. This paper first describes the expression of the vasoconstrictive arm of RAS components in the brain as well as their physiological and pathophysiological significance. It then focus on the (pro)renin receptor (PRR), a newly discovered component of the RAS which has a high level in the brain. We review the role of prorenin and PRR in peripheral organs and emphasize the involvement of brain PRR in the pathogenesis of hypertension. Some future perspectives in PRR research are heighted with respect to novel therapeutic target for the treatment of hypertension and other cardiovascular diseases. PMID:23316344

In vivo relationship between monoamine oxidase type B and alcohol dehydrogenase: effects of ethanol and phenylethylamine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aliyu, S.U.; Upahi, L.

The role of acute ethanol and phenylethylamine on the brain and platelet monoamine oxidase activities, hepatic cytosolic alcohol dehydrogenase, redox state and motor behavior were studied in male rats. Ethanol on its own decreased the redox couple ratio, as well as, alcohol dehydrogenase activity in the liver while at the same time it increased brain and platelet monoamine oxidase activity due to lower Km with no change in Vmax. The elevation in both brain and platelet MAO activity was associated with ethanol-induced hypomotility in the rats. Co-administration of phenylethylamine and ethanol to the animals, caused antagonism of the ethanol-induced effectsmore » described above. The effects of phenylethylamine alone, on the above mentioned biochemical and behavioral indices, are more complex. Phenylethylamine on its own, like ethanol, caused reduction of the cytosolic redox, ratio and elevation of monoamine oxidase activity in the brain and platelets. However, in contrast to ethanol, this monoamine produced hypermotility and activation of the hepatic cytosolic alcohol dehydrogenase activity in the animals.« less

Brain Activation during Addition and Subtraction Tasks In-Noise and In-Quiet

PubMed Central

Abd Hamid, Aini Ismafairus; Yusoff, Ahmad Nazlim; Mukari, Siti Zamratol-Mai Sarah; Mohamad, Mazlyfarina

2011-01-01

Background: In spite of extensive research conducted to study how human brain works, little is known about a special function of the brain that stores and manipulates information—the working memory—and how noise influences this special ability. In this study, Functional magnetic resonance imaging (fMRI) was used to investigate brain responses to arithmetic problems solved in noisy and quiet backgrounds. Methods: Eighteen healthy young males performed simple arithmetic operations of addition and subtraction with in-quiet and in-noise backgrounds. The MATLAB-based Statistical Parametric Mapping (SPM8) was implemented on the fMRI datasets to generate and analyse the activated brain regions. Results: Group results showed that addition and subtraction operations evoked extended activation in the left inferior parietal lobe, left precentral gyrus, left superior parietal lobe, left supramarginal gyrus, and left middle temporal gyrus. This supported the hypothesis that the human brain relatively activates its left hemisphere more compared with the right hemisphere when solving arithmetic problems. The insula, middle cingulate cortex, and middle frontal gyrus, however, showed more extended right hemispheric activation, potentially due to the involvement of attention, executive processes, and working memory. For addition operations, there was extensive left hemispheric activation in the superior temporal gyrus, inferior frontal gyrus, and thalamus. In contrast, subtraction tasks evoked a greater activation of similar brain structures in the right hemisphere. For both addition and subtraction operations, the total number of activated voxels was higher for in-noise than in-quiet conditions. Conclusion: These findings suggest that when arithmetic operations were delivered auditorily, the auditory, attention, and working memory functions were required to accomplish the executive processing of the mathematical calculation. The respective brain activation patterns appear to be modulated by the noisy background condition. PMID:22135581

Co-occurring anxiety influences patterns of brain activity in depression.

PubMed

Engels, Anna S; Heller, Wendy; Spielberg, Jeffrey M; Warren, Stacie L; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

2010-03-01

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in the dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in the right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in the anterior cingulate cortex (dorsal ACC and rostral ACC) and the bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala).

Co-occurring Anxiety Influences Patterns of Brain Activity in Depression

PubMed Central

Engels, Anna S.; Heller, Wendy; Spielberg, Jeffrey M.; Warren, Stacie L.; Sutton, Bradley P.; Banich, Marie T.; Miller, Gregory A.

2011-01-01

Brain activation associated with anhedonic depression and co-occurring anxious arousal and anxious apprehension was measured by fMRI during performance of an emotion-word Stroop task. Consistent with EEG findings, depression was associated with rightward frontal lateralization in dorsolateral prefrontal cortex (DLPFC), but only when anxious arousal was elevated and anxious apprehension was low. Activity in right inferior frontal gyrus (IFG) was also reduced for depression under the same conditions. In contrast, depression was associated with more activity in anterior cingulate cortex (dACC and rACC) and bilateral amygdala. Results imply that depression, particularly when accompanied by anxious arousal, may result in a failure to implement top-down processing by appropriate brain regions (left DLPFC, right IFG) due to increased activation in regions associated with responding to emotionally salient information (right DLPFC, amygdala). PMID:20233962

In situ rat brain and liver spontaneous chemiluminescence after acute ethanol intake.

PubMed

Boveris, A; Llesuy, S; Azzalis, L A; Giavarotti, L; Simon, K A; Junqueira, V B; Porta, E A; Videla, L A; Lissi, E A

1997-09-19

The influence of acute ethanol administration on the oxidative stress status of rat brain and liver was assessed by in situ spontaneous organ chemiluminescence (CL). Brain and liver CL was significantly increased after acute ethanol administration to fed rats, a response that is time-dependent and evidenced at doses higher than 1 g/kg. Ethanol-induced CL development is faster in liver compared with brain probably due to the greater ethanol metabolic capacity of the liver, whereas the net enhancement in brain light emission at 3 h after ethanol treatment is higher than that of the liver, which could reflect the greater susceptibility of brain to oxidative stress. The effect of ethanol on brain and liver CL seems to be mediated by acetaldehyde, due to its abolishment by the alcohol dehydrogenase inhibitor 4-methylpyrazole and exacerbation by the aldehyde dehydrogenase inhibitor disulfiram. In brain, these findings were observed in the absence of changes in the activity of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glucose-6-phosphate dehydrogenase. However, the content of brain glutathione was significantly decreased by 31%, by ethanol, thus establishing an enhanced oxidative stress in this tissue.

Linking brains and brawn: exercise and the evolution of human neurobiology.

PubMed

Raichlen, David A; Polk, John D

2013-01-07

The hunting and gathering lifestyle adopted by human ancestors around 2 Ma required a large increase in aerobic activity. High levels of physical activity altered the shape of the human body, enabling access to new food resources (e.g. animal protein) in a changing environment. Recent experimental work provides strong evidence that both acute bouts of exercise and long-term exercise training increase the size of brain components and improve cognitive performance in humans and other taxa. However, to date, researchers have not explored the possibility that the increases in aerobic capacity and physical activity that occurred during human evolution directly influenced the human brain. Here, we hypothesize that proximate mechanisms linking physical activity and neurobiology in living species may help to explain changes in brain size and cognitive function during human evolution. We review evidence that selection acting on endurance increased baseline neurotrophin and growth factor signalling (compounds responsible for both brain growth and for metabolic regulation during exercise) in some mammals, which in turn led to increased overall brain growth and development. This hypothesis suggests that a significant portion of human neurobiology evolved due to selection acting on features unrelated to cognitive performance.

Chronic alcoholism in rats induces a compensatory response, preserving brain thiamine diphosphate, but the brain 2-oxo acid dehydrogenases are inactivated despite unchanged coenzyme levels.

PubMed

Parkhomenko, Yulia M; Kudryavtsev, Pavel A; Pylypchuk, Svetlana Yu; Chekhivska, Lilia I; Stepanenko, Svetlana P; Sergiichuk, Andrej A; Bunik, Victoria I

2011-06-01

Thiamine-dependent changes in alcoholic brain were studied using a rat model. Brain thiamine and its mono- and diphosphates were not reduced after 20 weeks of alcohol exposure. However, alcoholism increased both synaptosomal thiamine uptake and thiamine diphosphate synthesis in brain, pointing to mechanisms preserving thiamine diphosphate in the alcoholic brain. In spite of the unchanged level of the coenzyme thiamine diphosphate, activities of the mitochondrial 2-oxoglutarate and pyruvate dehydrogenase complexes decreased in alcoholic brain. The inactivation of pyruvate dehydrogenase complex was caused by its increased phosphorylation. The inactivation of 2-oxoglutarate dehydrogenase complex (OGDHC) correlated with a decrease in free thiols resulting from an elevation of reactive oxygen species. Abstinence from alcohol following exposure to alcohol reactivated OGDHC along with restoration of the free thiol content. However, restoration of enzyme activity occurred before normalization of reactive oxygen species levels. Hence, the redox status of cellular thiols mediates the action of oxidative stress on OGDHC in alcoholic brain. As a result, upon chronic alcohol consumption, physiological mechanisms to counteract the thiamine deficiency and silence pyruvate dehydrogenase are activated in rat brain, whereas OGDHC is inactivated due to impaired antioxidant ability. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

Complex network analysis of resting-state fMRI of the brain.

PubMed

Anwar, Abdul Rauf; Hashmy, Muhammad Yousaf; Imran, Bilal; Riaz, Muhammad Hussnain; Mehdi, Sabtain Muhammad Muntazir; Muthalib, Makii; Perrey, Stephane; Deuschl, Gunther; Groppa, Sergiu; Muthuraman, Muthuraman

2016-08-01

Due to the fact that the brain activity hardly ever diminishes in healthy individuals, analysis of resting state functionality of the brain seems pertinent. Various resting state networks are active inside the idle brain at any time. Based on various neuro-imaging studies, it is understood that various structurally distant regions of the brain could be functionally connected. Regions of the brain, that are functionally connected, during rest constitutes to the resting state network. In the present study, we employed the complex network measures to estimate the presence of community structures within a network. Such estimate is named as modularity. Instead of using a traditional correlation matrix, we used a coherence matrix taken from the causality measure between different nodes. Our results show that in prolonged resting state the modularity starts to decrease. This decrease was observed in all the resting state networks and on both sides of the brain. Our study highlights the usage of coherence matrix instead of correlation matrix for complex network analysis.

Visualization of cortical, subcortical, and deep brain neural circuit dynamics during naturalistic mammalian behavior with head-mounted microscopes and chronically implanted lenses

PubMed Central

Resendez, Shanna L.; Jennings, Josh H.; Ung, Randall L.; Namboodiri, Vijay Mohan K.; Zhou, Zhe Charles; Otis, James M.; Nomura, Hiroshi; McHenry, Jenna A.; Kosyk, Oksana; Stuber, Garret D.

2016-01-01

Genetically encoded calcium indicators for visualizing dynamic cellular activity have greatly expanded our understanding of the brain. However, due to light scattering properties of the brain as well as the size and rigidity of traditional imaging technology, in vivo calcium imaging has been limited to superficial brain structures during head fixed behavioral tasks. This limitation can now be circumvented by utilizing miniature, integrated microscopes in conjunction with an implantable microendoscopic lens to guide light into and out of the brain, thus permitting optical access to deep brain (or superficial) neural ensembles during naturalistic behaviors. Here, we describe procedural steps to conduct such imaging studies using mice. However, we anticipate the protocol can be easily adapted for use in other small vertebrates. Successful completion of this protocol will permit cellular imaging of neuronal activity and the generation of data sets with sufficient statistical power to correlate neural activity with stimulus presentation, physiological state, and other aspects of complex behavioral tasks. This protocol takes 6–11 weeks to complete. PMID:26914316

Thymoquinone-rich fraction nanoemulsion (TQRFNE) decreases Aβ40 and Aβ42 levels by modulating APP processing, up-regulating IDE and LRP1, and down-regulating BACE1 and RAGE in response to high fat/cholesterol diet-induced rats.

PubMed

Ismail, Norsharina; Ismail, Maznah; Azmi, Nur Hanisah; Bakar, Muhammad Firdaus Abu; Yida, Zhang; Abdullah, Maizaton Atmadini; Basri, Hamidon

2017-11-01

Though the causes of Alzheimer's disease (AD) are yet to be understood, much evidence has suggested that excessive amyloid-β (Aβ) accumulation due to abnormal amyloid-β precursor protein (APP) processing and Aβ metabolism are crucial processes towards AD pathogenesis. Hence, approaches aiming at APP processing and Aβ metabolism are currently being actively pursued for the management of AD. Studies suggest that high cholesterol and a high fat diet have harmful effects on cognitive function and may instigate the commencement of AD pathogenesis. Despite the neuropharmacological attributes of black cumin seed (Nigella sativa) extracts and its main active compound, thymoquinone (TQ), limited records are available in relation to AD research. Nanoemulsion (NE) is exploited as drug delivery systems due to their capacity of solubilising non-polar active compounds and is widely examined for brain targeting. Herewith, the effects of thymoquinone-rich fraction nanoemulsion (TQRFNE), thymoquinone nanoemulsion (TQNE) and their counterparts' conventional emulsion in response to high fat/cholesterol diet (HFCD)-induced rats were investigated. Particularly, the Aβ generation; APP processing, β-secretase 1 (BACE1), γ-secretases of presenilin 1 (PSEN1) and presenilin 2 (PSEN2), Aβ degradation; insulin degrading enzyme (IDE), Aβ transportation; low density lipoprotein receptor-related protein 1 (LRP1) and receptor for advanced glycation end products (RAGE) were measured in brain tissues. TQRFNE reduced the brain Aβ fragment length 1-40 and 1-42 (Aβ40 and Aβ42) levels, which would attenuate the AD pathogenesis. This reduction could be due to the modulation of β- and γ-secretase enzyme activity, and the Aβ degradation and transportation in/out of the brain. The findings show the mechanistic actions of TQRFNE in response to high fat and high cholesterol diet associated to Aβ generation, degradation and transportation in the rat's brain tissue. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of emotional valence and three-dimensionality of visual stimuli on brain activation: an fMRI study.

PubMed

Dores, A R; Almeida, I; Barbosa, F; Castelo-Branco, M; Monteiro, L; Reis, M; de Sousa, L; Caldas, A Castro

2013-01-01

Examining changes in brain activation linked with emotion-inducing stimuli is essential to the study of emotions. Due to the ecological potential of techniques such as virtual reality (VR), inspection of whether brain activation in response to emotional stimuli can be modulated by the three-dimensional (3D) properties of the images is important. The current study sought to test whether the activation of brain areas involved in the emotional processing of scenarios of different valences can be modulated by 3D. Therefore, the focus was made on the interaction effect between emotion-inducing stimuli of different emotional valences (pleasant, unpleasant and neutral valences) and visualization types (2D, 3D). However, main effects were also analyzed. The effect of emotional valence and visualization types and their interaction were analyzed through a 3 × 2 repeated measures ANOVA. Post-hoc t-tests were performed under a ROI-analysis approach. The results show increased brain activation for the 3D affective-inducing stimuli in comparison with the same stimuli in 2D scenarios, mostly in cortical and subcortical regions that are related to emotional processing, in addition to visual processing regions. This study has the potential of clarify brain mechanisms involved in the processing of emotional stimuli (scenarios' valence) and their interaction with three-dimensionality.

When thoughts become action: an fMRI paradigm to study volitional brain activity in non-communicative brain injured patients.

PubMed

Boly, M; Coleman, M R; Davis, M H; Hampshire, A; Bor, D; Moonen, G; Maquet, P A; Pickard, J D; Laureys, S; Owen, A M

2007-07-01

The assessment of voluntary behavior in non-communicative brain injured patients is often challenging due to the existence of profound motor impairment. In the absence of a full understanding of the neural correlates of consciousness, even a normal activation in response to passive sensory stimulation cannot be considered as proof of the presence of awareness in these patients. In contrast, predicted activation in response to the instruction to perform a mental imagery task would provide evidence of voluntary task-dependent brain activity, and hence of consciousness, in non-communicative patients. However, no data yet exist to indicate which imagery instructions would yield reliable single subject activation. The aim of the present study was to establish such a paradigm in healthy volunteers. Two exploratory experiments evaluated the reproducibility of individual brain activation elicited by four distinct mental imagery tasks. The two most robust mental imagery tasks were found to be spatial navigation and motor imagery. In a third experiment, where these two tasks were directly compared, differentiation of each task from one another and from rest periods was assessed blindly using a priori criteria and was correct for every volunteer. The spatial navigation and motor imagery tasks described here permit the identification of volitional brain activation at the single subject level, without a motor response. Volunteer as well as patient data [Owen, A.M., Coleman, M.R., Boly, M., Davis, M.H., Laureys, S., Pickard J.D., 2006. Detecting awareness in the vegetative state. Science 313, 1402] strongly suggest that this paradigm may provide a method for assessing the presence of volitional brain activity, and thus of consciousness, in non-communicative brain-injured patients.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2007-10-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2008-10-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2009-01-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Compensatory Motor Network Connectivity is Associated with Motor Sequence Learning after Subcortical Stroke

PubMed Central

Wadden, Katie P.; Woodward, Todd S.; Metzak, Paul D.; Lavigne, Katie M.; Lakhani, Bimal; Auriat, Angela M.; Boyd, Lara A.

2015-01-01

Following stroke, functional networks reorganize and the brain demonstrates widespread alterations in cortical activity. Implicit motor learning is preserved after stroke. However the manner in which brain reorganization occurs, and how it supports behaviour within the damaged brain remains unclear. In this functional magnetic resonance imaging (fMRI) study, we evaluated whole brain patterns of functional connectivity during the performance of an implicit tracking task at baseline and retention, following 5 days of practice. Following motor practice, a significant difference in connectivity within a motor network, consisting of bihemispheric activation of the sensory and motor cortices, parietal lobules, cerebellar and occipital lobules, was observed at retention. Healthy subjects demonstrated greater activity within this motor network during sequence learning compared to random practice. The stroke group did not show the same level of functional network integration, presumably due to the heterogeneity of functional reorganization following stroke. In a secondary analysis, a binary mask of the functional network activated from the aforementioned whole brain analyses was created to assess within-network connectivity, decreasing the spatial distribution and large variability of activation that exists within the lesioned brain. The stroke group demonstrated reduced clusters of connectivity within the masked brain regions as compared to the whole brain approach. Connectivity within this smaller motor network correlated with repeated sequence performance on the retention test. Increased functional integration within the motor network may be an important neurophysiological predictor of motor learning-related change in individuals with stroke. PMID:25757996

Complexity of EEG-signal in Time Domain - Possible Biomedical Application

NASA Astrophysics Data System (ADS)

Klonowski, Wlodzimierz; Olejarczyk, Elzbieta; Stepien, Robert

2002-07-01

Human brain is a highly complex nonlinear system. So it is not surprising that in analysis of EEG-signal, which represents overall activity of the brain, the methods of Nonlinear Dynamics (or Chaos Theory as it is commonly called) can be used. Even if the signal is not chaotic these methods are a motivating tool to explore changes in brain activity due to different functional activation states, e.g. different sleep stages, or to applied therapy, e.g. exposure to chemical agents (drugs) and physical factors (light, magnetic field). The methods supplied by Nonlinear Dynamics reveal signal characteristics that are not revealed by linear methods like FFT. Better understanding of principles that govern dynamics and complexity of EEG-signal can help to find `the signatures' of different physiological and pathological states of human brain, quantitative characteristics that may find applications in medical diagnostics.

Creating an effective physical activity-based health promotion programme for adults with a brain injury.

PubMed

Driver, Simon; Irwin, Kelley; Woolsey, Anne; Pawlowski, Jill

2012-01-01

To describe the processes involved with developing and implementing a physical activity-based health promotion programme for people with a brain injury, summarize previous health promotion research efforts and provide an actual example of a programme entitled P.A.C.E, a 'Physical Activity Centred Education' programme. REASONING BEHIND LITERATURE SELECTION: Brain injury is a serious public health issue due to the incidence, complexity and high healthcare costs. Health promotion programmes that incorporate physical activity have been shown to improve the health of people with a disability. However, if programmes are to be successful they have to be appropriately designed, otherwise individuals will not adopt and maintain the desired health behaviours. Readers will have an understanding of (1) how a theoretical framework drives programme development, (2) the strategies required to facilitate behaviour change, (3) how previous research supports the use of a physical activity-based health promotion programme and (4) how to implement a programme. Future research ideas are provided so as to stimulate research in the area of physical activity-based health promotion programmes for people with a brain injury.

Comparing consistency of R2* and T2*-weighted BOLD analysis of resting state fetal fMRI

NASA Astrophysics Data System (ADS)

Seshamani, Sharmishtaa; Blazejewska, Anna I.; Gatenby, Christopher; Mckown, Susan; Caucutt, Jason; Dighe, Manjiri; Studholme, Colin

2015-03-01

Understanding when and how resting state brain functional activity begins in the human brain is an increasing area of interest in both basic neuroscience and in the clinical evaluation of the brain during pregnancy and after premature birth. Although fMRI studies have been carried out on pregnant women since the 1990's, reliable mapping of brain function in utero is an extremely challenging problem due to the unconstrained fetal head motion. Recent studies have employed scrubbing to exclude parts of the time series and whole subjects from studies in order to control the confounds of motion. Fundamentally, even after correction of the location of signals due to motion, signal intensity variations are a fundamental limitation, due to coil sensitivity and spin history effects. An alternative technique is to use a more parametric MRI signal derived from multiple echoes that provides a level of independence from basic MRI signal variation. Here we examine the use of R2* mapping combined with slice based multi echo geometric distortion correction for in-utero studies. The challenges for R2* mapping arise from the relatively low signal strength of in-utero data. In this paper we focus on comparing activation detection in-utero using T2W and R2* approaches. We make use a subset of studies with relatively limited motion to compare the activation patterns without the additional confound of significant motion. Results at different gestational ages indicate comparable agreement in many activation patterns when limited motion is present, and the detection of some additional networks in the R2* data, not seen in the T2W results.

Left temporal and temporoparietal brain activity depends on depth of word encoding: a magnetoencephalographic study in healthy young subjects.

PubMed

Walla, P; Hufnagl, B; Lindinger, G; Imhof, H; Deecke, L; Lang, W

2001-03-01

Using a 143-channel whole-head magnetoencephalograph (MEG) we recorded the temporal changes of brain activity from 26 healthy young subjects (14 females) related to shallow perceptual and deep semantic word encoding. During subsequent recognition tests, the subjects had to recognize the previously encoded words which were interspersed with new words. The resulting mean memory performances across all subjects clearly mirrored the different levels of encoding. The grand averaged event-related fields (ERFs) associated with perceptual and semantic word encoding differed significantly between 200 and 550 ms after stimulus onset mainly over left superior temporal and left superior parietal sensors. Semantic encoding elicited higher brain activity than perceptual encoding. Source localization procedures revealed that neural populations of the left temporal and temporoparietal brain areas showed different activity strengths across the whole group of subjects depending on depth of word encoding. We suggest that the higher brain activity associated with deep encoding as compared to shallow encoding was due to the involvement of more neural systems during the processing of visually presented words. Deep encoding required more energy than shallow encoding but for all that led to a better memory performance. Copyright 2001 Academic Press.

Neurotoxic effects of methylcyclopentadienyl manganese tricarbonyl (MMT) in the mouse: basis of MMT-induced seizure activity.

PubMed

Fishman, B E; McGinley, P A; Gianutsos, G

1987-08-01

Methylcyclopentadienyl manganese tricarbonyl (MMT) is an organic manganese-containing compound which is used as an additive in unleaded gasoline. One neurotoxic effect of MMT in mice is seizure activity. In this study, seizures were observed in mice treated with MMT in propylene glycol or corn oil. The LD50 associated with seizure activity was lower in mice receiving MMT in propylene glycol (152 mg/kg) than in those receiving MMT in corn oil (999 mg/kg). Manganese concentrations in the brains of mice which showed seizure activity due to MMT were higher than in those that did not (2.45 micrograms/g vs. 1.14 micrograms/g for MMT treated in propylene glycol and 3.25 micrograms/g vs. 1.63 micrograms/g for MMT in corn oil). Mice treated with manganese chloride (MnCl2) showed increases in brain manganese comparable to those of the mice showing seizure activity due to MMT, but exhibited no sign of seizure activity. MMT in non-lethal seizure-inducing doses had no effect on the accumulation of 4-aminobutyric acid (GABA) in mouse brain. However, MMT inhibited the binding of t-[3H]t-butylbicycloorthobenzoate [3H]-TBOB (a ligand for the GABA-A-receptor linked chloride channel) in mouse brain membranes with an IC50 value of 22.8 microM. The data suggest that MMT (organic manganese) or a closely related metabolite and not elemental manganese itself is responsible for the seizure activity observed. The seizure activity may be the result of an inhibitory effect of MMT at the GABA-A receptor linked chloride channel.

Aggravation of brain infarction through an increase in acrolein production and a decrease in glutathione with aging.

PubMed

Uemura, Takeshi; Watanabe, Kenta; Ishibashi, Misaki; Saiki, Ryotaro; Kuni, Kyoshiro; Nishimura, Kazuhiro; Toida, Toshihiko; Kashiwagi, Keiko; Igarashi, Kazuei

2016-04-29

We previously reported that tissue damage during brain infarction was mainly caused by inactivation of proteins by acrolein. This time, it was tested why brain infarction increases in parallel with aging. A mouse model of photochemically induced thrombosis (PIT) was studied using 2, 6, and 12 month-old female C57BL/6 mice. The size of brain infarction in the mouse PIT model increased with aging. The volume of brain infarction in 12 month-old mice was approximately 2-fold larger than that in 2 month-old mice. The larger brain infarction in 12 month-old mice was due to an increase in acrolein based on an increase in the activity of spermine oxidase, together with a decrease in glutathione (GSH), a major acrolein-detoxifying compound in cells, based on the decrease in one of the subunits of glutathione biosynthesizing enzymes, γ-glutamylcysteine ligase modifier subunit, with aging. The results indicate that aggravation of brain infarction with aging was mainly due to the increase in acrolein production and the decrease in GSH in brain. Copyright © 2016 Elsevier Inc. All rights reserved.

The in vitro isolated whole guinea pig brain as a model to study epileptiform activity patterns.

PubMed

de Curtis, Marco; Librizzi, Laura; Uva, Laura

2016-02-15

Research on ictogenesis is based on the study of activity between seizures and during seizures in animal models of epilepsy (chronic condition) or in in vitro slices obtained from naïve non-epileptic brains after treatment with pro-convulsive drugs, manipulations of the extracellular medium and specific stimulation protocols. The in vitro isolated guinea pig brain retains the functional connectivity between brain structures and maintains interactions between neuronal, glial and vascular compartments. It is a close-to-in vivo preparation that offers experimental advantages not achieved with the use of other experimental models. Neurophysiological and imaging techniques can be utilized in this preparation to study brain activity during and between seizures induced by pharmacological or functional manipulations. Cellular and network determinants of interictal and ictal discharges that reproduce abnormal patterns observed in human focal epilepsies and the associated changes in extracellular ion and blood-brain permeability can be identified and analyzed in the isolated guinea pig brain. Ictal and interictal patterns recorded in in vitro slices may show substantial differences from seizure activity recorded in vivo due to slicing procedure itself. The isolated guinea pig brain maintained in vitro by arterial perfusion combines the typical facilitated access of in vitro preparations, that are difficult to approach during in vivo experiments, with the preservation of larger neuronal networks. The in vitro whole isolated guinea pig brain preparation offers an unique experimental model to study systemic and neurovascular changes during ictogenesis. Published by Elsevier B.V.

At least eighty percent of brain grey matter is modifiable by physical activity: A review study.

PubMed

Batouli, Seyed Amir Hossein; Saba, Valiallah

2017-08-14

The human brain is plastic, i.e. it can show structural changes in response to the altered environment. Physical activity (PA) is a lifestyle factor which has significant associations with the structural and functional aspects of the human brain, as well as with the mind and body health. Many studies have reported regional/global brain volume increments due to exercising; however, a map which shows the overall extent of the influences of PAs on brain structure is not available. In this study, we collected all the reports on brain structural alterations in association with PA in healthy humans, and next, a brain map of the extent of these effects is provided. The results of this study showed that a large network of brain areas, equal to 82% of the total grey matter volume, were associated with PA. This finding has important implications in utilizing PA as a mediator factor for educational purposes in children, rehabilitation applications in patients, improving the cognitive abilities of the human brain such as in learning or memory, and preventing age-related brain deteriorations. Copyright © 2017 Elsevier B.V. All rights reserved.

Anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose isolated from leaves of Mangifera indica.

PubMed

Viswanatha, G L; Mohan, C G; Shylaja, H; Yuvaraj, H C; Sunil, V

2013-07-01

The present study was aimed to evaluate the anticonvulsant activity of 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) isolated from methanolic leaf extracts of Mangifera indica in mice. Anticonvulsant activity of PGG was evaluated against pentylenetetrazole (PTZ)-induced and maximal electroshock (MES)-induced convulsions in mice. Additionally, locomotor activity and GABA levels in the brain were estimated to explore the possible CNS-depressant activity and mechanism behind the anticonvulsant activity, respectively. In these studies, PGG (2.5, 5, and 10 mg/kg, intraperitoneal (i.p.)) showed significant and dose-dependent inhibition of PTZ and MES-induced convulsions. Furthermore, PGG administration showed significant decrease in the locomotor activity as an indication of its CNS-depressant property; also, PGG has significantly increased the GABA levels in the cerebellum and whole brain other than the cerebellum. In conclusion, PGG isolated from M. indica showed potent anticonvulsant activity, and possible mechanism may be due to enhanced GABA levels in the brain.

A Culture-Behavior-Brain Loop Model of Human Development.

PubMed

Han, Shihui; Ma, Yina

2015-11-01

Increasing evidence suggests that cultural influences on brain activity are associated with multiple cognitive and affective processes. These findings prompt an integrative framework to account for dynamic interactions between culture, behavior, and the brain. We put forward a culture-behavior-brain (CBB) loop model of human development that proposes that culture shapes the brain by contextualizing behavior, and the brain fits and modifies culture via behavioral influences. Genes provide a fundamental basis for, and interact with, the CBB loop at both individual and population levels. The CBB loop model advances our understanding of the dynamic relationships between culture, behavior, and the brain, which are crucial for human phylogeny and ontogeny. Future brain changes due to cultural influences are discussed based on the CBB loop model. Copyright © 2015 Elsevier Ltd. All rights reserved.

Brain State Is a Major Factor in Preseizure Hippocampal Network Activity and Influences Success of Seizure Intervention

PubMed Central

Ewell, Laura A.; Liang, Liang; Armstrong, Caren; Soltész, Ivan; Leutgeb, Stefan

2015-01-01

Neural dynamics preceding seizures are of interest because they may shed light on mechanisms of seizure generation and could be predictive. In healthy animals, hippocampal network activity is shaped by behavioral brain state and, in epilepsy, seizures selectively emerge during specific brain states. To determine the degree to which changes in network dynamics before seizure are pathological or reflect ongoing fluctuations in brain state, dorsal hippocampal neurons were recorded during spontaneous seizures in a rat model of temporal lobe epilepsy. Seizures emerged from all brain states, but with a greater likelihood after REM sleep, potentially due to an observed increase in baseline excitability during periods of REM compared with other brains states also characterized by sustained theta oscillations. When comparing the firing patterns of the same neurons across brain states associated with and without seizures, activity dynamics before seizures followed patterns typical of the ongoing brain state, or brain state transitions, and did not differ until the onset of the electrographic seizure. Next, we tested whether disparate activity patterns during distinct brain states would influence the effectiveness of optogenetic curtailment of hippocampal seizures in a mouse model of temporal lobe epilepsy. Optogenetic curtailment was significantly more effective for seizures preceded by non-theta states compared with seizures that emerged from theta states. Our results indicate that consideration of behavioral brain state preceding a seizure is important for the appropriate interpretation of network dynamics leading up to a seizure and for designing effective seizure intervention. SIGNIFICANCE STATEMENT Hippocampal single-unit activity is strongly shaped by behavioral brain state, yet this relationship has been largely ignored when studying activity dynamics before spontaneous seizures in medial temporal lobe epilepsy. In light of the increased attention on using single-unit activity for the prediction of seizure onset and closed-loop seizure intervention, we show a need for monitoring brain state to interpret correctly whether changes in neural activity before seizure onset is pathological or normal. Moreover, we also find that the brain state preceding a seizure determines the success of therapeutic interventions to curtail seizure duration. Together, these findings suggest that seizure prediction and intervention will be more successful if tailored for the specific brain states from which seizures emerge. PMID:26609157

Intranasal insulin modulates intrinsic reward and prefrontal circuitry of the human brain in lean women.

PubMed

Kullmann, Stephanie; Frank, Sabine; Heni, Martin; Ketterer, Caroline; Veit, Ralf; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert

2013-01-01

There is accumulating evidence that food consumption is controlled by a wide range of brain circuits outside of the homeostatic system. Activation in these brain circuits may override the homeostatic system and also contribute to the enormous increase of obesity. However, little is known about the influence of hormonal signals on the brain's non-homeostatic system. Thus, selective insulin action in the brain was investigated by using intranasal application. We performed 'resting-state' functional magnetic resonance imaging in 17 healthy lean female subjects to assess intrinsic brain activity by fractional amplitude of low-frequency fluctuations (fALFF) before, 30 and 90 min after application of intranasal insulin. Here, we showed that insulin modulates intrinsic brain activity in the hypothalamus and orbitofrontal cortex. Furthermore, we could show that the prefrontal and anterior cingulate cortex response to insulin is associated with body mass index. This demonstrates that hormonal signals as insulin may reduce food intake by modifying the reward and prefrontal circuitry of the human brain, thereby potentially decreasing the rewarding properties of food. Due to the alarming increase in obesity worldwide, it is of great importance to identify neural mechanisms of interaction between the homeostatic and non-homeostatic system to generate new targets for obesity therapy. Copyright © 2012 S. Karger AG, Basel.

The protective effect of N-acetylcysteine on oxidative stress in the brain caused by the long-term intake of aspartame by rats.

PubMed

Finamor, Isabela A; Ourique, Giovana M; Pês, Tanise S; Saccol, Etiane M H; Bressan, Caroline A; Scheid, Taína; Baldisserotto, Bernardo; Llesuy, Susana F; Partata, Wânia A; Pavanato, Maria A

2014-09-01

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg(-1), i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg(-1)). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.

Reappraisal inventiveness: impact of appropriate brain activation during efforts to generate alternative appraisals on the perception of chronic stress in women.

PubMed

Perchtold, Corinna M; Fink, Andreas; Rominger, Christian; Weber, Hannelore; de Assunção, Vera Loureiro; Schulter, Günter; Weiss, Elisabeth M; Papousek, Ilona

2018-03-01

Previous research indicated that more left-lateralized prefrontal activation during cognitive reappraisal efforts was linked to a greater capacity for generating reappraisals, which is a prerequisite for the effective implementation of cognitive reappraisal in everyday life. The present study examined whether the supposedly appropriate brain activation is relevant in terms of more distal outcomes, i.e., chronic stress perception. Prefrontal EEG alpha asymmetry was recorded while female participants were generating reappraisals for stressful events and was correlated with their self-reported chronic stress levels in everyday life (n = 80). Women showing less left-lateralized brain activity in the ventrolateral prefrontal cortex during cognitive reappraisal efforts reported experiencing more stress in their daily lives. This effect was independent of self-efficacy beliefs in managing negative emotions. These findings underline the practical relevance of individual differences in appropriate brain activation during emotion regulation efforts and the assumedly related basic capacity for the generation of cognitive reappraisals to the feeling of being stressed. Implications include the selection of interventions for the improvement of coping with stress in women in whom the capability for appropriate brain activation during reappraisal efforts may be impaired, e.g., due to depression or old age.

Novel neuroprotective and hepatoprotective effects of citric acid in acute malathion intoxication.

PubMed

Abdel-Salam, Omar M E; Youness, Eman R; Mohammed, Nadia A; Yassen, Noha N; Khadrawy, Yasser A; El-Toukhy, Safinaz Ebrahim; Sleem, Amany A

2016-12-01

To study the effect of citric acid given alone or combined with atropine on brain oxidative stress, neuronal injury, liver damage, and DNA damage of peripheral blood lymphocytes induced in the rat by acute malathion exposure. Rats were received intraperitoneal (i.p.) injection of malathion 150 mg/kg along with citric acid (200 or 400 mg/kg, orally), atropine (1 mg/kg, i.p.) or citric acid 200 mg/kg + atropine 1 mg/kg and euthanized 4 h later. Malathion resulted in increased lipid peroxidation (malondialdehyde) and nitric oxide concentrations accompanied with a decrease in brain reduced glutathione, glutathione peroxidase (GPx) activity, total antioxidant capacity (TAC) and glucose concentrations. Paraoxonase-1, acetylcholinesterase (AChE) and butyrylcholinesterase activities decreased in brain as well. Liver aspartate aminotransferase and alanine aminotransferase activities were raised. The comet assay showed increased DNA damage of peripheral blood lymphocytes. Histological damage and increased expression of inducible nitric oxide synthase (iNOS) were observed in brain and liver. Citric acid resulted in decreased brain lipid peroxidation and nitric oxide. Meanwhile, glutathione, GPx activity, TAC capacity and brain glucose level increased. Brain AChE increased but PON1 and butyrylcholinesterase activities decreased by citric acid. Liver enzymes, the percentage of damaged blood lymphocytes, histopathological alterations and iNOS expression in brain and liver was decreased by citric acid. Meanwhile, rats treated with atropine showed decreased brain MDA, nitrite but increased GPx activity, TAC, AChE and glucose. The drug also decreased DNA damage of peripheral blood lymphocytes, histopathological alterations and iNOS expression in brain and liver. The study demonstrates a beneficial effect for citric acid upon brain oxidative stress, neuronal injury, liver and DNA damage due to acute malathion exposure. Copyright © 2016 Hainan Medical University. Production and hosting by Elsevier B.V. All rights reserved.

Development of the Korean Academy of Medical Sciences Guideline for Rating the Impairment in the Brain Injured and Brain Diseased Persons with Motor Dysfunction

PubMed Central

Baik, Jong Sam; Jang, Seong Ho; Park, Dong Sik

2009-01-01

To develop an objective and scientific method to evaluate the brain injured and brain diseased persons with motor dysfunction, American Medical Association's Guides to the Evaluation of Permanent Impairment was used as an exemplar. After the motor dysfunction due to brain injury or brain disease was confirmed, active range of motion and muscle strength of affected extremities were measured. Also, the total function of extremities was evaluated through the assessment of activities of daily living, fine coordination of hand, balance and gait. Then, the total score of manual muscle test and functional assessment of impaired upper and lower extremity were added, respectively. Spasticity of upper and lower extremity was used as minus factors. Patients with movement disorder such as Parkinson's disease were assessed based on the degree of dysfunction in response to medication. We develop a new rating system based on the concept of total score. PMID:19503680

International veterinary epilepsy task force recommendations for systematic sampling and processing of brains from epileptic dogs and cats.

PubMed

Matiasek, Kaspar; Pumarola I Batlle, Martí; Rosati, Marco; Fernández-Flores, Francisco; Fischer, Andrea; Wagner, Eva; Berendt, Mette; Bhatti, Sofie F M; De Risio, Luisa; Farquhar, Robyn G; Long, Sam; Muñana, Karen; Patterson, Edward E; Pakozdy, Akos; Penderis, Jacques; Platt, Simon; Podell, Michael; Potschka, Heidrun; Rusbridge, Clare; Stein, Veronika M; Tipold, Andrea; Volk, Holger A

2015-08-28

Traditionally, histological investigations of the epileptic brain are required to identify epileptogenic brain lesions, to evaluate the impact of seizure activity, to search for mechanisms of drug-resistance and to look for comorbidities. For many instances, however, neuropathological studies fail to add substantial data on patients with complete clinical work-up. This may be due to sparse training in epilepsy pathology and or due to lack of neuropathological guidelines for companion animals.The protocols introduced herein shall facilitate systematic sampling and processing of epileptic brains and therefore increase the efficacy, reliability and reproducibility of morphological studies in animals suffering from seizures.Brain dissection protocols of two neuropathological centres with research focus in epilepsy have been optimised with regards to their diagnostic yield and accuracy, their practicability and their feasibility concerning clinical research requirements.The recommended guidelines allow for easy, standardised and ubiquitous collection of brain regions, relevant for seizure generation. Tissues harvested the prescribed way will increase the diagnostic efficacy and provide reliable material for scientific investigations.

MDMA, Methylone, and MDPV: Drug-Induced Brain Hyperthermia and Its Modulation by Activity State and Environment.

PubMed

Kiyatkin, Eugene A; Ren, Suelynn E

2017-01-01

Psychomotor stimulants are frequently used by humans to intensify the subjective experience of different types of social interactions. Since psychomotor stimulants enhance metabolism and increase body temperatures, their use under conditions of physiological activation and in warm humid environments could result in pathological hyperthermia, a life-threatening symptom of acute drug intoxication. Here, we will describe the brain hyperthermic effects of MDMA, MDPV, and methylone, three structurally related recreational drugs commonly used by young adults during raves and other forms of social gatherings. After a short introduction on brain temperature and basic mechanisms underlying its physiological fluctuations, we will consider how MDMA, MDPV, and methylone affect brain and body temperatures in awake freely moving rats. Here, we will discuss the role of drug-induced heat production in the brain due to metabolic brain activation and diminished heat dissipation due to peripheral vasoconstriction as two primary contributors to the hyperthermic effects of these drugs. Then, we will consider how the hyperthermic effects of these drugs are modulated under conditions that model human drug use (social interaction and warm ambient temperature). Since social interaction results in brain and body heat production, coupled with skin vasoconstriction that impairs heat loss to the external environment, these physiological changes interact with drug-induced changes in heat production and loss, resulting in distinct changes in the hyperthermic effects of each tested drug. Finally, we present our recent data, in which we compared the efficacy of different pharmacological strategies for reversing MDMA-induced hyperthermia in both the brain and body. Specifically, we demonstrate increased efficacy of the centrally acting atypical neuroleptic compound clozapine over the peripherally acting vasodilator drug, carvedilol. These data could be important for understanding the potential dangers of MDMA in humans and the development of pharmacological tools to alleviate drug-induced hyperthermia - potentially saving the lives of highly intoxicated individuals.

Mechanism on brain information processing: Energy coding

NASA Astrophysics Data System (ADS)

Wang, Rubin; Zhang, Zhikang; Jiao, Xianfa

2006-09-01

According to the experimental result of signal transmission and neuronal energetic demands being tightly coupled to information coding in the cerebral cortex, the authors present a brand new scientific theory that offers a unique mechanism for brain information processing. They demonstrate that the neural coding produced by the activity of the brain is well described by the theory of energy coding. Due to the energy coding model's ability to reveal mechanisms of brain information processing based upon known biophysical properties, they cannot only reproduce various experimental results of neuroelectrophysiology but also quantitatively explain the recent experimental results from neuroscientists at Yale University by means of the principle of energy coding. Due to the theory of energy coding to bridge the gap between functional connections within a biological neural network and energetic consumption, they estimate that the theory has very important consequences for quantitative research of cognitive function.

When pain and hunger collide; psychological influences on differences in brain activity during physiological and non-physiological gastric distension.

PubMed

Coen, S J

2011-06-01

Functional neuroimaging has been used extensively in conjunction with gastric balloon distension in an attempt to unravel the relationship between the brain, regulation of hunger, satiety, and food intake tolerance. A number of researchers have also adopted a more physiological approach using intra-gastric administration of a liquid meal which has revealed different brain responses to gastric balloon distension. These differences are important as they question the utility and relevance of non-physiological models such as gastric balloon distension, especially when investigating mechanisms of feeding behavior such as satiety. However, an assessment of the relevance of physiological versus non-physiological gastric distension has been problematic due to differences in distension volumes between studies. In this issue of Neurogastroenterology and Motility, Geeraerts et al. compare brain activity during volume matched nutrient gastric distension and balloon distension in healthy volunteers. Gastric balloon distension activated the 'visceral pain neuromatrix'. This network of brain regions was deactivated during nutrient infusion, supporting the notion that brain activity during physiological versus non-physiological distension is indeed different. The authors suggest deactivation of the pain neuromatrix during nutrient infusion serves as a prerequisite for tolerance of normal meal volumes in health. © 2011 Blackwell Publishing Ltd.

Mice with reduced brain-derived neurotrophic factor expression show decreased choline acetyltransferase activity, but regular brain monoamine levels and unaltered emotional behavior.

PubMed

Chourbaji, Sabine; Hellweg, Rainer; Brandis, Dorothee; Zörner, Björn; Zacher, Christiane; Lang, Undine E; Henn, Fritz A; Hörtnagl, Heide; Gass, Peter

2004-02-05

The "neurotrophin hypothesis" of depression predicts that depressive disorders in humans coincide with a decreased activity and/or expression of brain-derived neurotrophic factor (BDNF) in the brain. Therefore, we investigated whether mice with a reduced BDNF expression due to heterozygous gene disruption demonstrate depression-like neurochemical changes or behavioral symptoms. BNDF protein levels of adult BDNF(+/-) mice were reduced to about 60% in several brain areas investigated, including the hippocampus, frontal cortex, striatum, and hypothalamus. The content of monoamines (serotonin, norepinephrine, and dopamine) as well as of serotonin and dopamine degradation products was unchanged in these brain regions. By contrast, choline acetyltransferase activity was significantly reduced by 19% in the hippocampus of BDNF(+/-) mice, indicating that the cholinergic system of the basal forebrain is critically dependent on sufficient endogenous BDNF levels in adulthood. Moreover, BDNF(+/-) mice exhibited normal corticosterone and adrenocorticotropic hormone (ACTH) serum levels under baseline conditions and following immobilization stress. In a panel of behavioral tests investigating locomotor activity, exploration, anxiety, fear-associated learning, and behavioral despair, BDNF(+/-) mice were indistinguishable from wild-type littermates. Thus, a chronic reduction of BDNF protein content in adult mice is not sufficient to induce neurochemical or behavioral alterations that are reminiscent of depressive symptoms in humans.

Attenuation of brain edema and spatial learning deficits by the inhibition of NADPH oxidase activity using apocynin following diffuse traumatic brain injury in rats.

PubMed

Song, Si-Xin; Gao, Jun-Ling; Wang, Kai-Jie; Li, Ran; Tian, Yan-Xia; Wei, Jian-Qiang; Cui, Jian-Zhong

2013-01-01

Diffuse brain injury (DBI) is a leading cause of mortality and disability among young individuals and adults worldwide. In specific cases, DBI is associated with permanent spatial learning dysfunction and motor deficits due to primary and secondary brain damage. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) is a major complex that produces reactive oxygen species (ROS) during the ischemic period. The complex aggravates brain damage and cell death following ischemia/reperfusion injury; however, its role in DBI remains unclear. The present study aimed to investigate the hypothesis that levels of NOX2 (a catalytic subunit of NOX) protein expression and the activation of NOX are enhanced following DBI induction in rats and are involved in aggravating secondary brain damage. A rat model of DBI was created using a modified weight-drop device. Our results demonstrated that NOX2 protein expression and NOX activity were enhanced in the CA1 subfield of the hippocampus at 48 and 72 h following DBI induction. Treatment with apocynin (50 mg/kg body weight), a specific inhibitor of NOX, injected intraperitoneally 30 min prior to DBI significantly attenuated NOX2 protein expression and NOX activation. Moreover, treatment with apocynin reduced brain edema and improved spatial learning function assessed using the Morris water maze. These results reveal that treatment with apocynin may provide a new neuroprotective therapeutic strategy against DBI by diminishing the upregulation of NOX2 protein and NOX activity.

How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

PubMed Central

Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

2015-01-01

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. SLEEP 2015;38(2):233–240. PMID:25409102

Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies.

PubMed

Sarkar, Chaitali; Pal, Sudipta; Das, Niranjan; Dinda, Biswanath

2014-04-01

Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

Efficacy of brain-computer interface-driven neuromuscular electrical stimulation for chronic paresis after stroke.

PubMed

Mukaino, Masahiko; Ono, Takashi; Shindo, Keiichiro; Fujiwara, Toshiyuki; Ota, Tetsuo; Kimura, Akio; Liu, Meigen; Ushiba, Junichi

2014-04-01

Brain computer interface technology is of great interest to researchers as a potential therapeutic measure for people with severe neurological disorders. The aim of this study was to examine the efficacy of brain computer interface, by comparing conventional neuromuscular electrical stimulation and brain computer interface-driven neuromuscular electrical stimulation, using an A-B-A-B withdrawal single-subject design. A 38-year-old male with severe hemiplegia due to a putaminal haemorrhage participated in this study. The design involved 2 epochs. In epoch A, the patient attempted to open his fingers during the application of neuromuscular electrical stimulation, irrespective of his actual brain activity. In epoch B, neuromuscular electrical stimulation was applied only when a significant motor-related cortical potential was observed in the electroencephalogram. The subject initially showed diffuse functional magnetic resonance imaging activation and small electro-encephalogram responses while attempting finger movement. Epoch A was associated with few neurological or clinical signs of improvement. Epoch B, with a brain computer interface, was associated with marked lateralization of electroencephalogram (EEG) and blood oxygenation level dependent responses. Voluntary electromyogram (EMG) activity, with significant EEG-EMG coherence, was also prompted. Clinical improvement in upper-extremity function and muscle tone was observed. These results indicate that self-directed training with a brain computer interface may induce activity- dependent cortical plasticity and promote functional recovery. This preliminary clinical investigation encourages further research using a controlled design.

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

PubMed Central

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; Bourassa, Megan W.; Sleiman, Sama F.; John, Roseleen; Thinnes, Cyrille C.; Yeh, Tzu-Lan; Demetriades, Marina; Neitemeier, Sandra; Cruz, Dana; Gazaryan, Irina; Killilea, David W.; Morgenstern, Lewis; Xi, Guohua; Keep, Richard F.; Schallert, Timothy; Tappero, Ryan V.; Zhong, Jian; Cho, Sunghee; Maxfield, Frederick R.; Holman, Theodore R.; Culmsee, Carsten; Fong, Guo-Hua; Su, Yijing; Ming, Guo-li; Song, Hongjun; Cave, John W.; Schofield, Christopher J.; Colbourne, Frederick; Coppola, Giovanni; Ratan, Rajiv R.

2017-01-01

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron, and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. We show that the hypoxia-inducible factor prolyl hydroxylase domain (HIF-PHD) family of iron-dependent, oxygen-sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in the mouse striatum improved functional recovery after ICH. A low-molecular-weight hydroxyquinoline inhibitor of the HIF-PHD enzymes, adaptaquin, reduced neuronal death and behavioral deficits after ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of activity of the prodeath factor ATF4 rather than activation of an HIF-dependent prosurvival pathway. Together, these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier-permeable inhibitor adaptaquin can improve functional outcomes after ICH in several rodent models. PMID:26936506

Estimating repetitive spatiotemporal patterns from resting-state brain activity data.

PubMed

Takeda, Yusuke; Hiroe, Nobuo; Yamashita, Okito; Sato, Masa-Aki

2016-06-01

Repetitive spatiotemporal patterns in spontaneous brain activities have been widely examined in non-human studies. These studies have reported that such patterns reflect past experiences embedded in neural circuits. In human magnetoencephalography (MEG) and electroencephalography (EEG) studies, however, spatiotemporal patterns in resting-state brain activities have not been extensively examined. This is because estimating spatiotemporal patterns from resting-state MEG/EEG data is difficult due to their unknown onsets. Here, we propose a method to estimate repetitive spatiotemporal patterns from resting-state brain activity data, including MEG/EEG. Without the information of onsets, the proposed method can estimate several spatiotemporal patterns, even if they are overlapping. We verified the performance of the method by detailed simulation tests. Furthermore, we examined whether the proposed method could estimate the visual evoked magnetic fields (VEFs) without using stimulus onset information. The proposed method successfully detected the stimulus onsets and estimated the VEFs, implying the applicability of this method to real MEG data. The proposed method was applied to resting-state functional magnetic resonance imaging (fMRI) data and MEG data. The results revealed informative spatiotemporal patterns representing consecutive brain activities that dynamically change with time. Using this method, it is possible to reveal discrete events spontaneously occurring in our brains, such as memory retrieval. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields.

PubMed

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E; Cohen, Leonardo G; Birbaumer, Niels; Soekadar, Surjo R

2016-10-15

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0-4Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Simultaneous transcranial direct current stimulation (tDCS) and whole-head magnetoencephalography (MEG): assessing the impact of tDCS on slow cortical magnetic fields

PubMed Central

Garcia-Cossio, Eliana; Witkowski, Matthias; Robinson, Stephen E.; Cohen, Leonardo G.; Birbaumer, Niels; Soekadar, Surjo R.

2016-01-01

Transcranial direct current stimulation (tDCS) can influence cognitive, affective or motor brain functions. Whereas previous imaging studies demonstrated widespread tDCS effects on brain metabolism, direct impact of tDCS on electric or magnetic source activity in task-related brain areas could not be confirmed due to the difficulty to record such activity simultaneously during tDCS. The aim of this proof-of-principal study was to demonstrate the feasibility of whole-head source localization and reconstruction of neuromagnetic brain activity during tDCS and to confirm the direct effect of tDCS on ongoing neuromagnetic activity in task-related brain areas. Here we show for the first time that tDCS has an immediate impact on slow cortical magnetic fields (SCF, 0–4 Hz) of task-related areas that are identical with brain regions previously described in metabolic neuroimaging studies. 14 healthy volunteers performed a choice reaction time (RT) task while whole-head magnetoencephalography (MEG) was recorded. Task-related source-activity of SCFs was calculated using synthetic aperture magnetometry (SAM) in absence of stimulation and while anodal, cathodal or sham tDCS was delivered over the right primary motor cortex (M1). Source reconstruction revealed task-related SCF modulations in brain regions that precisely matched prior metabolic neuroimaging studies. Anodal and cathodal tDCS had a polarity-dependent impact on RT and SCF in primary sensorimotor and medial centro-parietal cortices. Combining tDCS and whole-head MEG is a powerful approach to investigate the direct effects of transcranial electric currents on ongoing neuromagnetic source activity, brain function and behavior. PMID:26455796

Brain “fog,” inflammation and obesity: key aspects of neuropsychiatric disorders improved by luteolin

PubMed Central

Theoharides, Theoharis C.; Stewart, Julia M.; Hatziagelaki, Erifili; Kolaitis, Gerasimos

2015-01-01

Brain “fog” is a constellation of symptoms that include reduced cognition, inability to concentrate and multitask, as well as loss of short and long term memory. Brain “fog” characterizes patients with autism spectrum disorders (ASDs), celiac disease, chronic fatigue syndrome, fibromyalgia, mastocytosis, and postural tachycardia syndrome (POTS), as well as “minimal cognitive impairment,” an early clinical presentation of Alzheimer's disease (AD), and other neuropsychiatric disorders. Brain “fog” may be due to inflammatory molecules, including adipocytokines and histamine released from mast cells (MCs) further stimulating microglia activation, and causing focal brain inflammation. Recent reviews have described the potential use of natural flavonoids for the treatment of neuropsychiatric and neurodegenerative diseases. The flavone luteolin has numerous useful actions that include: anti-oxidant, anti-inflammatory, microglia inhibition, neuroprotection, and memory increase. A liposomal luteolin formulation in olive fruit extract improved attention in children with ASDs and brain “fog” in mastocytosis patients. Methylated luteolin analogs with increased activity and better bioavailability could be developed into effective treatments for neuropsychiatric disorders and brain “fog.” PMID:26190965

Common brain regions underlying different arithmetic operations as revealed by conjunct fMRI-BOLD activation.

PubMed

Fehr, Thorsten; Code, Chris; Herrmann, Manfred

2007-10-03

The issue of how and where arithmetic operations are represented in the brain has been addressed in numerous studies. Lesion studies suggest that a network of different brain areas are involved in mental calculation. Neuroimaging studies have reported inferior parietal and lateral frontal activations during mental arithmetic using tasks of different complexities and using different operators (addition, subtraction, etc.). Indeed, it has been difficult to compare brain activation across studies because of the variety of different operators and different presentation modalities used. The present experiment examined fMRI-BOLD activity in participants during calculation tasks entailing different arithmetic operations -- addition, subtraction, multiplication and division -- of different complexities. Functional imaging data revealed a common activation pattern comprising right precuneus, left and right middle and superior frontal regions during all arithmetic operations. All other regional activations were operation specific and distributed in prominently frontal, parietal and central regions when contrasting complex and simple calculation tasks. The present results largely confirm former studies suggesting that activation patterns due to mental arithmetic appear to reflect a basic anatomical substrate of working memory, numerical knowledge and processing based on finger counting, and derived from a network originally related to finger movement. We emphasize that in mental arithmetic research different arithmetic operations should always be examined and discussed independently of each other in order to avoid invalid generalizations on arithmetics and involved brain areas.

Test-Retest Reliability of Brain Activation Using the Face-Name Paired-Associates fMRI Task in Patients with Schizophrenia and Healthy Controls

NASA Astrophysics Data System (ADS)

Louis, Chelsey N.

Schizophrenia is a neurological disorder associated with cognitive impairments, and clinical symptoms of hallucinations and delusions. Recent imaging and behavioral studies have repeatedly shown aberrant brain activity in the hippocampal regions in relation to episodic memory impairments associated with schizophrenia. These findings have warranted further research to elucidate the neural processes associated with episodic memory. Therefore, the current study examined activity in a priori brain regions associated with episodic memory using the face-name paired-associates fMRI task to determine whether there was reliable activation patterns observed in healthy subjects and patients with self-reported schizophrenia. This was evaluated by using ROI analysis and whole brain analysis to examine activity between subjects during a session, and by using Pearson's R correlation coefficients to examine test-retest reliability over time. 30 schizophrenic (SZ) patients and 31 healthy control (HC) volunteers underwent a series of assessments including the fMRI behavioral task, face-name paired-associates task. The tests were conducted twice with a 14-day interval for the subjects. The results indicated no reliable brain activation in the hippocampus between scanning sessions for either the SZ or HC groups. However, distinct activation patterns were observed within sessions for both groups. These patterns were observed in the hippocampus, and regions of the frontal lobe and occipital lobe. Future studies should further explore these brain activity patterns across sessions in SZ patients compared to HC subjects to determine whether these patterns are due to pathological mechanisms associated with schizophrenia.

How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies.

PubMed

Ma, Ning; Dinges, David F; Basner, Mathias; Rao, Hengyi

2015-02-01

Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. © 2015 Associated Professional Sleep Societies, LLC.

Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy.

PubMed

Bauer, Julia; Chen, Wenjing; Nischwitz, Sebastian; Liebl, Jakob; Rieken, Stefan; Welzel, Thomas; Debus, Juergen; Parodi, Katia

2018-04-24

A reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. Two approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. The refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. Current methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification. Copyright © 2018 Elsevier B.V. All rights reserved.

Why Do Some Find it Hard to Disagree? An fMRI Study

PubMed Central

Domínguez D, Juan F.; Taing, Sreyneth A.; Molenberghs, Pascal

2016-01-01

People often find it hard to disagree with others, but how this disposition varies across individuals or how it is influenced by social factors like other people's level of expertise remains little understood. Using functional magnetic resonance imaging (fMRI), we found that activity across a network of brain areas [comprising posterior medial frontal cortex (pMFC), anterior insula (AI), inferior frontal gyrus (IFG), lateral orbitofrontal cortex, and angular gyrus] was modulated by individual differences in the frequency with which participants actively disagreed with statements made by others. Specifically, participants who disagreed less frequently exhibited greater brain activation in these areas when they actually disagreed. Given the role of this network in cognitive dissonance, our results suggest that some participants had more trouble disagreeing due to a heightened cognitive dissonance response. Contrary to expectation, the level of expertise (high or low) had no effect on behavior or brain activity. PMID:26858629

Mapping brain activity with flexible graphene micro-transistors

NASA Astrophysics Data System (ADS)

Blaschke, Benno M.; Tort-Colet, Núria; Guimerà-Brunet, Anton; Weinert, Julia; Rousseau, Lionel; Heimann, Axel; Drieschner, Simon; Kempski, Oliver; Villa, Rosa; Sanchez-Vives, Maria V.; Garrido, Jose A.

2017-06-01

Establishing a reliable communication interface between the brain and electronic devices is of paramount importance for exploiting the full potential of neural prostheses. Current microelectrode technologies for recording electrical activity, however, evidence important shortcomings, e.g. challenging high density integration. Solution-gated field-effect transistors (SGFETs), on the other hand, could overcome these shortcomings if a suitable transistor material were available. Graphene is particularly attractive due to its biocompatibility, chemical stability, flexibility, low intrinsic electronic noise and high charge carrier mobilities. Here, we report on the use of an array of flexible graphene SGFETs for recording spontaneous slow waves, as well as visually evoked and also pre-epileptic activity in vivo in rats. The flexible array of graphene SGFETs allows mapping brain electrical activity with excellent signal-to-noise ratio (SNR), suggesting that this technology could lay the foundation for a future generation of in vivo recording implants.

Effect of Pilates Training on Alpha Rhythm

PubMed Central

Bian, Zhijie; Sun, Hongmin; Lu, Chengbiao; Yao, Li; Chen, Shengyong; Li, Xiaoli

2013-01-01

In this study, the effect of Pilates training on the brain function was investigated through five case studies. Alpha rhythm changes during the Pilates training over the different regions and the whole brain were mainly analyzed, including power spectral density and global synchronization index (GSI). It was found that the neural network of the brain was more active, and the synchronization strength reduced in the frontal and temporal regions due to the Pilates training. These results supported that the Pilates training is very beneficial for improving brain function or intelligence. These findings maybe give us some line evidence to suggest that the Pilates training is very helpful for the intervention of brain degenerative diseases and cogitative dysfunction rehabilitation. PMID:23861723

Identifying differences in brain activities and an accurate detection of autism spectrum disorder using resting state functional-magnetic resonance imaging : A spatial filtering approach.

PubMed

Subbaraju, Vigneshwaran; Suresh, Mahanand Belathur; Sundaram, Suresh; Narasimhan, Sundararajan

2017-01-01

This paper presents a new approach for detecting major differences in brain activities between Autism Spectrum Disorder (ASD) patients and neurotypical subjects using the resting state fMRI. Further the method also extracts discriminative features for an accurate diagnosis of ASD. The proposed approach determines a spatial filter that projects the covariance matrices of the Blood Oxygen Level Dependent (BOLD) time-series signals from both the ASD patients and neurotypical subjects in orthogonal directions such that they are highly separable. The inverse of this filter also provides a spatial pattern map within the brain that highlights those regions responsible for the distinguishable activities between the ASD patients and neurotypical subjects. For a better classification, highly discriminative log-variance features providing the maximum separation between the two classes are extracted from the projected BOLD time-series data. A detailed study has been carried out using the publicly available data from the Autism Brain Imaging Data Exchange (ABIDE) consortium for the different gender and age-groups. The study results indicate that for all the above categories, the regional differences in resting state activities are more commonly found in the right hemisphere compared to the left hemisphere of the brain. Among males, a clear shift in activities to the prefrontal cortex is observed for ASD patients while other parts of the brain show diminished activities compared to neurotypical subjects. Among females, such a clear shift is not evident; however, several regions, especially in the posterior and medial portions of the brain show diminished activities due to ASD. Finally, the classification performance obtained using the log-variance features is found to be better when compared to earlier studies in the literature. Copyright © 2016 Elsevier B.V. All rights reserved.

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis.

PubMed

Kempuraj, Duraisamy; Selvakumar, Govindhasamy P; Thangavel, Ramasamy; Ahmed, Mohammad E; Zaheer, Smita; Raikwar, Sudhanshu P; Iyer, Shankar S; Bhagavan, Sachin M; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

2017-01-01

Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD.

Mast Cell Activation in Brain Injury, Stress, and Post-traumatic Stress Disorder and Alzheimer's Disease Pathogenesis

PubMed Central

Kempuraj, Duraisamy; Selvakumar, Govindhasamy P.; Thangavel, Ramasamy; Ahmed, Mohammad E.; Zaheer, Smita; Raikwar, Sudhanshu P.; Iyer, Shankar S.; Bhagavan, Sachin M.; Beladakere-Ramaswamy, Swathi; Zaheer, Asgar

2017-01-01

Mast cells are localized throughout the body and mediate allergic, immune, and inflammatory reactions. They are heterogeneous, tissue-resident, long-lived, and granulated cells. Mast cells increase their numbers in specific site in the body by proliferation, increased recruitment, increased survival, and increased rate of maturation from its progenitors. Mast cells are implicated in brain injuries, neuropsychiatric disorders, stress, neuroinflammation, and neurodegeneration. Brain mast cells are the first responders before microglia in the brain injuries since mast cells can release prestored mediators. Mast cells also can detect amyloid plaque formation during Alzheimer's disease (AD) pathogenesis. Stress conditions activate mast cells to release prestored and newly synthesized inflammatory mediators and induce increased blood-brain barrier permeability, recruitment of immune and inflammatory cells into the brain and neuroinflammation. Stress induces the release of corticotropin-releasing hormone (CRH) from paraventricular nucleus of hypothalamus and mast cells. CRH activates glial cells and mast cells through CRH receptors and releases neuroinflammatory mediators. Stress also increases proinflammatory mediator release in the peripheral systems that can induce and augment neuroinflammation. Post-traumatic stress disorder (PTSD) is a traumatic-chronic stress related mental dysfunction. Currently there is no specific therapy to treat PTSD since its disease mechanisms are not yet clearly understood. Moreover, recent reports indicate that PTSD could induce and augment neuroinflammation and neurodegeneration in the pathogenesis of neurodegenerative diseases. Mast cells play a crucial role in the peripheral inflammation as well as in neuroinflammation due to brain injuries, stress, depression, and PTSD. Therefore, mast cells activation in brain injury, stress, and PTSD may accelerate the pathogenesis of neuroinflammatory and neurodegenerative diseases including AD. This review focusses on how mast cells in brain injuries, stress, and PTSD may promote the pathogenesis of AD. We suggest that inhibition of mast cells activation and brain cells associated inflammatory pathways in the brain injuries, stress, and PTSD can be explored as a new therapeutic target to delay or prevent the pathogenesis and severity of AD. PMID:29302258

A critical review of 5-HT brain microdialysis and behavior.

PubMed

Rueter, L E; Fornal, C A; Jacobs, B L

1997-01-01

Serotonin (5-HT) has been implicated in many central nervous system-mediated functions including sleep, arousal, feeding, motor activity and the stress response. In order to help establish the precise role of 5-HT in physiology and behavior, in vivo microdialysis studies have sought to identify the conditions under which the release of 5-HT is altered. Extracellular 5-HT levels have been monitored in more than fifteen regions of the brain during a variety of spontaneous behaviors, and in response to several physiological, environmental, and behavioral manipulations. The vast majority of these studies found increases (30-100%) in 5-HT release in almost all brain regions studied. Since electrophysiological studies have shown that behavioral arousal is the primary determinant of brain serotonergic neuronal activity, we suggest that the increase in 5-HT release seen during a wide variety of experimental conditions is largely due to one factor, namely an increase in behavioral arousal/motor activity associated with the manipulation.

Analysis of creatine kinase activity with evaluation of protein expression under the effect of heat and hydrogen peroxide.

PubMed

Rakhmetov, A D; Pil, Lee Sang; Ostapchenko, L I; Zoon, Chae Ho

2015-01-01

Protein oxidation has detrimental effects on the brain functioning, which involves inhibition of the crucial enzyme, brain type creatine kinase (CKBB), responsible for the CK/phosphocreatine shuttle system. Here we demonstrate a susceptibility of CKBB to several ordinary stressors. In our study enzymatic activity of purified recombinant brain-type creatine kinase was evaluated. We assayed 30 nMconcentration of CKBB under normal and stress conditions. In the direction of phosphocreatine formation hydrogen peroxide and heat treatments altered CKBB activity down to 26 and 14%, respectively. Also, examination of immunoblotted membrane patterns by SDS-PAGE electrophoresis and western blot analysis showed a decrease in expression levels of intrinsic CKBB enzyme in HeLa andA549 cells. Hence, our results clearly show that cytosolic CKBB is extremely sensitive to oxidative stress and heat induced inactivation. Therefore, due to its susceptibility, this enzyme may be defined as a potential target in brain damage.

Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

PubMed Central

Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

2017-01-01

Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders. PMID:28744205

Common brain areas engaged in false belief reasoning and visual perspective taking: a meta-analysis of functional brain imaging studies.

PubMed

Schurz, Matthias; Aichhorn, Markus; Martin, Anna; Perner, Josef

2013-01-01

We performed a quantitative meta-analysis of functional neuroimaging studies to identify brain areas which are commonly engaged in social and visuo-spatial perspective taking. Specifically, we compared brain activation for visual-perspective taking to activation for false belief reasoning, which requires awareness of perspective to understand someone's mistaken belief about the world which contrasts with reality. In support of a previous account by Perner and Leekam (2008), our meta-analytic conjunction analysis found common activation for false belief reasoning and visual perspective taking in the left but not the right dorsal temporo-parietal junction (TPJ). This fits with the idea that the left dorsal TPJ is responsible for representing different perspectives in a domain-general fashion. Moreover, our conjunction analysis found activation in the precuneus and the left middle occipital gyrus close to the putative Extrastriate Body Area (EBA). The precuneus is linked to mental-imagery which may aid in the construction of a different perspective. The EBA may be engaged due to imagined body-transformations when another's viewpoint is adopted.

Common brain areas engaged in false belief reasoning and visual perspective taking: a meta-analysis of functional brain imaging studies

PubMed Central

Schurz, Matthias; Aichhorn, Markus; Martin, Anna; Perner, Josef

2013-01-01

We performed a quantitative meta-analysis of functional neuroimaging studies to identify brain areas which are commonly engaged in social and visuo-spatial perspective taking. Specifically, we compared brain activation for visual-perspective taking to activation for false belief reasoning, which requires awareness of perspective to understand someone's mistaken belief about the world which contrasts with reality. In support of a previous account by Perner and Leekam (2008), our meta-analytic conjunction analysis found common activation for false belief reasoning and visual perspective taking in the left but not the right dorsal temporo-parietal junction (TPJ). This fits with the idea that the left dorsal TPJ is responsible for representing different perspectives in a domain-general fashion. Moreover, our conjunction analysis found activation in the precuneus and the left middle occipital gyrus close to the putative Extrastriate Body Area (EBA). The precuneus is linked to mental-imagery which may aid in the construction of a different perspective. The EBA may be engaged due to imagined body-transformations when another's viewpoint is adopted. PMID:24198773

Effects of green and black tea consumption on brain wave activities in healthy volunteers as measured by a simplified Electroencephalogram (EEG): A feasibility study.

PubMed

Okello, Edward J; Abadi, Awatf M; Abadi, Saad A

2016-06-01

Tea has been associated with many mental benefits, such as attention enhancement, clarity of mind, and relaxation. These psychosomatic states can be measured in terms of brain activity using an electroencephalogram (EEG). Brain activity can be assessed either during a state of passive activity or when performing attention tasks and it can provide useful information about the brain's state. This study investigated the effects of green and black consumption on brain activity as measured by a simplified EEG, during passive activity. Eight healthy volunteers participated in the study. The EEG measurements were performed using a two channel EEG brain mapping instrument - HeadCoach™. Fast Fourier transform algorithm and EEGLAB toolbox using the Matlab software were used for data processing and analysis. Alpha, theta, and beta wave activities were all found to increase after 1 hour of green and black tea consumption, albeit, with very considerable inter-individual variations. Our findings provide further evidence for the putative beneficial effects of tea. The highly significant increase in theta waves (P < 0.004) between 30 minutes and 1 hour post-consumption of green tea may be an indication of its putative role in cognitive function, specifically alertness and attention. There were considerable inter-individual variations in response to the two teas which may be due genetic polymorphisms in metabolism and/or influence of variety/blend, dose and content of the selected products whose chemistry and therefore efficacy will have been influenced by 'from field to shelf practices'.

Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity.

PubMed

Ballard, Peter; Yates, James W T; Yang, Zhenfan; Kim, Dong-Wan; Yang, James Chih-Hsin; Cantarini, Mireille; Pickup, Kathryn; Jordan, Angela; Hickey, Mike; Grist, Matthew; Box, Matthew; Johnström, Peter; Varnäs, Katarina; Malmquist, Jonas; Thress, Kenneth S; Jänne, Pasi A; Cross, Darren

2016-10-15

Approximately one-third of patients with non-small cell lung cancer (NSCLC) harboring tumors with EGFR-tyrosine kinase inhibitor (TKI)-sensitizing mutations (EGFRm) experience disease progression during treatment due to brain metastases. Despite anecdotal reports of EGFR-TKIs providing benefit in some patients with EGFRm NSCLC brain metastases, there is a clinical need for novel EGFR-TKIs with improved efficacy against brain lesions. We performed preclinical assessments of brain penetration and activity of osimertinib (AZD9291), an oral, potent, irreversible EGFR-TKI selective for EGFRm and T790M resistance mutations, and other EGFR-TKIs in various animal models of EGFR-mutant NSCLC brain metastases. We also present case reports of previously treated patients with EGFRm-advanced NSCLC and brain metastases who received osimertinib in the phase I/II AURA study (NCT01802632). Osimertinib demonstrated greater penetration of the mouse blood-brain barrier than gefitinib, rociletinib (CO-1686), or afatinib, and at clinically relevant doses induced sustained tumor regression in an EGFRm PC9 mouse brain metastases model; rociletinib did not achieve tumor regression. Under positron emission tomography micro-dosing conditions, [ 11 C]osimertinib showed markedly greater exposure in the cynomolgus monkey brain than [ 11 C]rociletinib and [ 11 C]gefitinib. Early clinical evidence of osimertinib activity in previously treated patients with EGFRm-advanced NSCLC and brain metastases is also reported. Osimertinib may represent a clinically significant treatment option for patients with EGFRm NSCLC and brain metastases. Further investigation of osimertinib in this patient population is ongoing. Clin Cancer Res; 22(20); 5130-40. ©2016 AACR. ©2016 American Association for Cancer Research.

Intrinsic Brain Activity of Cognitively Normal Older Persons Resembles More That of Patients Both with and at Risk for Alzheimer's Disease Than That of Healthy Younger Persons

PubMed Central

Pasquini, Lorenzo; Tonch, Annika; Plant, Claudia; Zherdin, Andrew; Ortner, Marion; Kurz, Alexander; Förstl, Hans; Zimmer, Claus; Grimmer, Timo; Wohlschäger, Afra; Riedl, Valentin

2014-01-01

Abstract In Alzheimer's disease (AD), recent findings suggest that amyloid-β (Aβ)-pathology might start 20–30 years before first cognitive symptoms arise. To account for age as most relevant risk factor for sporadic AD, it has been hypothesized that lifespan intrinsic (i.e., ongoing) activity of hetero-modal brain areas with highest levels of functional connectivity triggers Aβ-pathology. This model induces the simple question whether in older persons without any cognitive symptoms intrinsic activity of hetero-modal areas is more similar to that of symptomatic patients with AD or to that of younger healthy persons. We hypothesize that due to advanced age and therefore potential impact of pre-clinical AD, intrinsic activity of older persons resembles more that of patients than that of younger controls. We tested this hypothesis in younger (ca. 25 years) and older healthy persons (ca. 70 years) and patients with mild cognitive impairment and AD-dementia (ca. 70 years) by the use of resting-state functional magnetic resonance imaging, distinct measures of intrinsic brain activity, and different hierarchical clustering approaches. Independently of applied methods and involved areas, healthy older persons' intrinsic brain activity was consistently more alike that of patients than that of younger controls. Our result provides evidence for larger similarity in intrinsic brain activity between healthy older persons and patients with or at-risk for AD than between older and younger ones, suggesting a significant proportion of pre-clinical AD cases in the group of cognitively normal older people. The observed link of aging and AD with intrinsic brain activity supports the view that lifespan intrinsic activity may contribute critically to the pathogenesis of AD. PMID:24689864

BLOOD AND BRAIN CONCENTRATIONS OF BIFENTHRIN CORRELATE WITH DECREASED MOTOR ACTIVITY INDEPENDENT OF TIME OF EXPOSURE

EPA Science Inventory

Pyrethroids are neurotoxic insecticides used in a variety of agricultural and household activities. Due to the phase-out of organophosphate pesticides, the use of pyrethroids has increased. The potential for human exposure to pyrethroids has prompted pharmacodynamic and pharmac...

Gender-related differences in lateralization of hippocampal activation and cognitive strategy.

PubMed

Frings, Lars; Wagner, Kathrin; Unterrainer, Josef; Spreer, Joachim; Halsband, Ulrike; Schulze-Bonhage, Andreas

2006-03-20

Gender-related differences in brain activation patterns and their lateralization associated with cognitive functions have been reported in the field of language, emotion, and working memory. Differences have been hypothesized to be due to different cognitive strategies. The aim of the present study was to test whether lateralization of brain activation in the hippocampi during memory processing differs between the sexes. We acquired functional magnetic resonance imaging data from healthy female and male study participants performing a spatial memory task and quantitatively assessed the lateralization of hippocampal activation in each participant. Hippocampal activation was significantly more left lateralized in women, and more right lateralized in men. Correspondingly, women rated their strategy as being more verbal than men did.

N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain

PubMed Central

Chen, Sujuan; Ren, Qian; Zhang, Jinfei; Ye, Yangjing; Zhang, Zhen; Xu, Yijiao; Guo, Min; Ji, Haiyan; Xu, Chong; Gu, Chenjian; Gao, Wei; Huang, Shile; Chen, Long

2014-01-01

Aims This study explores the neuroprotective effects and mechanisms of N-acetyl-L-cysteine (NAC) in mice exposed to cadmium (Cd). Methods NAC (150 mg/kg) was intraperitoneally administered to mice exposed to Cd (10-50 mg/L) in drinking water for 6 weeks. The changes of cell damage and death, reactive oxygen species (ROS), antioxidant enzymes, as well as Akt/mammalian target of rapamycin (mTOR) signaling pathway in brain neurons were assessed. To verify the role of mTOR activation in Cd-induced neurotoxicity, mice also received a subacute regimen of intraperitoneally administered Cd (1 mg/kg) with/without rapamycin (7.5 mg/kg) for 11 days. Results Chronic exposure of mice to Cd induced brain damage or neuronal cell death, due to ROS induction. Co-administration of NAC significantly reduced Cd levels in the plasma and brain of the animals. NAC prevented Cd-induced ROS and significantly attenuated Cd-induced brain damage or neuronal cell death. The protective effect of NAC was mediated, at least partially, by elevating the activities of Cu/Zn-superoxide dismutase, catalase and glutathione peroxidase, as well as the level of glutathione in the brain. Furthermore, Cd-induced activation of Akt/mTOR pathway in the brain was also inhibited by NAC. Rapamycin in vitro and in vivo protected against Cd-induced neurotoxicity. Conclusions NAC protects against Cd-induced neuronal apoptosis in mouse brain partially by inhibiting ROS-dependent activation of Akt/mTOR pathway. The findings highlight that NAC may be exploited for prevention and treatment of Cd-induced neurodegenerative diseases. PMID:24299490

Retrieval Search and Strength Evoke Dissociable Brain Activity during Episodic Memory Recall

PubMed Central

Reas, Emilie T.; Brewer, James B.

2014-01-01

Neuroimaging studies of episodic memory retrieval have revealed activations in the human frontal, parietal, and medial-temporal lobes that are associated with memory strength. However, it remains unclear whether these brain responses are veritable signals of memory strength or are instead regulated by concomitant subcomponents of retrieval such as retrieval effort or mental search. This study used event-related fMRI during cued recall of previously memorized word-pair associates to dissociate brain responses modulated by memory search from those modulated by the strength of a recalled memory. Search-related deactivations, dissociated from activity due to memory strength, were observed in regions of the default network, whereas distinctly strength-dependent activations were present in superior and inferior parietal and dorsolateral PFC. Both search and strength regulated activity in dorsal anterior cingulate and anterior insula. These findings suggest that, although highly correlated and partially subserved by overlapping cognitive control mechanisms, search and memory strength engage dissociable regions of frontoparietal attention and default networks. PMID:23190328

Blood-brain barrier-supported neurogenesis in healthy and diseased brain.

PubMed

Pozhilenkova, Elena A; Lopatina, Olga L; Komleva, Yulia K; Salmin, Vladimir V; Salmina, Alla B

2017-05-24

Adult neurogenesis is one of the most important mechanisms contributing to brain development, learning, and memory. Alterations in neurogenesis underlie a wide spectrum of brain diseases. Neurogenesis takes place in highly specialized neurogenic niches. The concept of neurogenic niches is becoming widely accepted due to growing evidence of the important role of the microenvironment established in the close vicinity to stem cells in order to provide adequate control of cell proliferation, differentiation, and apoptosis. Neurogenic niches represent the platform for tight integration of neurogenesis and angiogenesis supported by specific properties of cerebral microvessel endothelial cells contributing to establishment of partially compromised blood-brain barrier (BBB) for the adjustment of local conditions to the current metabolic needs of stem and progenitor cells. Here, we review up-to-date data on microvascular dynamics in activity-dependent neurogenesis, specific properties of BBB in neurogenic niches, endothelial-driven mechanisms of clonogenic activity, and future perspectives for reconstructing the neurogenic niches in vitro.

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

PubMed

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

2011-01-01

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

Dynamic time warping-based averaging framework for functional near-infrared spectroscopy brain imaging studies

NASA Astrophysics Data System (ADS)

Zhu, Li; Najafizadeh, Laleh

2017-06-01

We investigate the problem related to the averaging procedure in functional near-infrared spectroscopy (fNIRS) brain imaging studies. Typically, to reduce noise and to empower the signal strength associated with task-induced activities, recorded signals (e.g., in response to repeated stimuli or from a group of individuals) are averaged through a point-by-point conventional averaging technique. However, due to the existence of variable latencies in recorded activities, the use of the conventional averaging technique can lead to inaccuracies and loss of information in the averaged signal, which may result in inaccurate conclusions about the functionality of the brain. To improve the averaging accuracy in the presence of variable latencies, we present an averaging framework that employs dynamic time warping (DTW) to account for the temporal variation in the alignment of fNIRS signals to be averaged. As a proof of concept, we focus on the problem of localizing task-induced active brain regions. The framework is extensively tested on experimental data (obtained from both block design and event-related design experiments) as well as on simulated data. In all cases, it is shown that the DTW-based averaging technique outperforms the conventional-based averaging technique in estimating the location of task-induced active regions in the brain, suggesting that such advanced averaging methods should be employed in fNIRS brain imaging studies.

A non invasive wearable sensor for the measurement of brain temperature.

PubMed

Dittmar, A; Gehin, C; Delhomme, G; Boivin, D; Dumont, G; Mott, C

2006-01-01

As the thermoregulation centres are deep in the brain, the cerebral temperature is one of the most important markers of fever, circadian rhythms physical and mental activities. However due to a lack of accessibility, the brain temperature is not easily measured. The axillary, buccal, tympanic and rectal temperatures do not reflect exactly the cerebral temperature. Nevertheless the rectal temperature is used as probably the most reliable indicator of the core body temperature. The brain temperature can be measured using NMR spectroscopy, microwave radiometry, near infrared spectroscopy, ultra-sound thermometry. However none of those methods are amenable to long term ambulatory use outside of the laboratory or of the hospital during normal daily activities, sport, etc. The brain core temperature "BCT" sensor, developed by the Biomedical Microsensors dpt of LPM at INSA-Lyon is a flexible active sensor using "zero-heat-flow" principle. The sensor has been used for experimental measurement: brain temperature during mental activity, and in hospital for the study of circadian rhythms. The results are in agreement with the measurement by the rectal probe. There are 2 versions of this sensor: a non ambulatory for the use in hospitals, and an ambulatory version using teletransmission. We are working for improving the autonomy of the ambulatory version up to several days. This wearable biomedical sensor (WBS) can be used for circadian assessment for chronobiology studies and in medical therapies.

Lysophosphatidic acid receptor, LPA6, regulates endothelial blood-brain barrier function: Implication for hepatic encephalopathy.

PubMed

Masago, Kayo; Kihara, Yasuyuki; Yanagida, Keisuke; Hamano, Fumie; Nakagawa, Shinsuke; Niwa, Masami; Shimizu, Takao

2018-07-02

Cerebral edema is a life-threatening neurological condition characterized by brain swelling due to the accumulation of excess fluid both intracellularly and extracellularly. Fulminant hepatic failure (FHF) develops cerebral edema by disrupting blood-brain barrier (BBB). However, the mechanisms by which mediator induces brain edema in FHF remain to be elucidated. Here, we assessed a linkage between brain edema and lysophosphatidic acid (LPA) signaling by utilizing an animal model of FHF and in vitro BBB model. Azoxymethane-treated mice developed FHF and hepatic encephalopathy, associated with higher autotaxin (ATX) activities in serum than controls. Using in vitro BBB model, LPA disrupted the structural integrity of tight junction proteins including claudin-5, occludin, and ZO-1. Furthermore, LPA decreased transendothelial electrical resistances in in vitro BBB model, and induced cell contraction in brain endothelial monolayer cultures, both being inhibited by a Rho-associated protein kinase inhibitor, Y-27632. The brain capillary endothelial cells predominantly expressed LPA 6 mRNA, whose knockdown blocked the LPA-induced endothelial cell contraction. Taken together, the up-regulation of serum ATX in hepatic encephalopathy may activate the LPA-LPA 6 -G 12/13 -Rho pathway in brain capillary endothelial cells, leading to enhancement of BBB permeability and brain edema. Copyright © 2018 Elsevier Inc. All rights reserved.

Joint penalized-likelihood reconstruction of time-activity curves and regions-of-interest from projection data in brain PET

NASA Astrophysics Data System (ADS)

Krestyannikov, E.; Tohka, J.; Ruotsalainen, U.

2008-06-01

This paper presents a novel statistical approach for joint estimation of regions-of-interest (ROIs) and the corresponding time-activity curves (TACs) from dynamic positron emission tomography (PET) brain projection data. It is based on optimizing the joint objective function that consists of a data log-likelihood term and two penalty terms reflecting the available a priori information about the human brain anatomy. The developed local optimization strategy iteratively updates both the ROI and TAC parameters and is guaranteed to monotonically increase the objective function. The quantitative evaluation of the algorithm is performed with numerically and Monte Carlo-simulated dynamic PET brain data of the 11C-Raclopride and 18F-FDG tracers. The results demonstrate that the method outperforms the existing sequential ROI quantification approaches in terms of accuracy, and can noticeably reduce the errors in TACs arising due to the finite spatial resolution and ROI delineation.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities.

PubMed

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-09-30

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal-occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention.

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders

PubMed Central

Ratajczak, Mariusz Z.; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as “sterile inflammation” when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms. PMID:29541038

Sterile Inflammation of Brain, due to Activation of Innate Immunity, as a Culprit in Psychiatric Disorders.

PubMed

Ratajczak, Mariusz Z; Pedziwiatr, Daniel; Cymer, Monika; Kucia, Magda; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy

2018-01-01

Evidence has accumulated that the occurrence of psychiatric disorders is related to chronic inflammation. In support of this linkage, changes in the levels of circulating pro-inflammatory cytokines and chemokines in the peripheral blood (PB) of psychiatric patients as well as correlations between chronic inflammatory processes and psychiatric disorders have been described. Furthermore, an inflammatory process known as "sterile inflammation" when initiated directly in brain tissue may trigger the onset of psychoses. In this review, we will present the hypothesis that prolonged or chronic activation of the complement cascade (ComC) directly triggers inflammation in the brain and affects the proper function of this organ. Based on the current literature and our own work on mechanisms activating the ComC we hypothesize that inflammation in the brain is initiated by the mannan-binding lectin pathway of ComC activation. This activation is triggered by an increase in brain tissue of danger-associated molecular pattern (DAMP) mediators, including extracellular ATP and high-mobility group box 1 (HMGB1) protein, which are recognized by circulating pattern-recognition receptors, including mannan-binding lectin (MBL), that activate the ComC. On the other hand, this process is controlled by the anti-inflammatory action of heme oxygenase 1 (HO-1). In this review, we will try to connect changes in the release of DAMPs in the brain with inflammatory processes triggered by the innate immunity involving activation of the ComC as well as the inflammation-limiting effects of the anti-inflammatory HO-1 pathway. We will also discuss parallel observations that during ComC activation subsets of stem cells are mobilized into PB from bone marrow that are potentially involved in repair mechanisms.

Memory repression: brain mechanisms underlying dissociative amnesia.

PubMed

Kikuchi, Hirokazu; Fujii, Toshikatsu; Abe, Nobuhito; Suzuki, Maki; Takagi, Masahito; Mugikura, Shunji; Takahashi, Shoki; Mori, Etsuro

2010-03-01

Dissociative amnesia usually follows a stressful event and cannot be attributable to explicit brain damage. It is thought to reflect a reversible deficit in memory retrieval probably due to memory repression. However, the neural mechanisms underlying this condition are not clear. We used fMRI to investigate neural activity associated with memory retrieval in two patients with dissociative amnesia. For each patient, three categories of face photographs and three categories of people's names corresponding to the photographs were prepared: those of "recognizable" high school friends who were acquainted with and recognizable to the patients, those of "unrecognizable" colleagues who were actually acquainted with but unrecognizable to the patients due to their memory impairments, and "control" distracters who were unacquainted with the patients. During fMRI, the patients were visually presented with these stimuli and asked to indicate whether they were personally acquainted with them. In the comparison of the unrecognizable condition with the recognizable condition, we found increased activity in the pFC and decreased activity in the hippocampus in both patients. After treatment for retrograde amnesia, the altered pattern of brain activation disappeared in one patient whose retrograde memories were recovered, whereas it remained unchanged in the other patient whose retrograde memories were not recovered. Our findings provide direct evidence that memory repression in dissociative amnesia is associated with an altered pattern of neural activity, and they suggest the possibility that the pFC has an important role in inhibiting the activity of the hippocampus in memory repression.

The effects of analgesics on central processing of tonic pain: A cross-over placebo controlled study.

PubMed

Lelic, Dina; Hansen, Tine M; Mark, Esben B; Olesen, Anne E; Drewes, Asbjørn M

2017-09-01

Opioids and antidepressants that inhibit serotonin and norepinephrine reuptake (SNRI) are recognized as analgesics to treat moderate to severe pain, but the central mechanisms underlying their analgesia remain unclear. This study investigated how brain activity at rest and exposed to tonic pain is modified by oxycodone (opioid) and venlafaxine (SNRI). Twenty healthy males were included in this randomized, cross-over, double-blinded study. 61-channel electroencephalogram (EEG) was recorded before and after five days of treatment with placebo, oxycodone (10 mg extended release b.i.d) or venlafaxine (37.5 mg extended release b.i.d) at rest and during tonic pain (hand immersed in 2 °C water for 80 s). Subjective pain and unpleasantness scores of tonic pain were recorded. Spectral analysis and sLORETA source localization were done in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta1 (12-18 Hz) and beta2 (18-32 Hz) frequency bands. Oxycodone decreased pain and unpleasantness scores (P < 0.05), whereas venlafaxine decreased the pain scores (P < 0.05). None of the treatments changed the spectral indices or brain sources underlying resting EEG. Venlafaxine decreased spectral indices in alpha band of the EEG to tonic pain, whereas oxycodone decreased the spectral indices and brain source activity in delta and theta frequency bands (all P < 0.05). The brain source activity predominantly decreased in the insula and inferior frontal gyrus. The decrease of activity within insula and inferior frontal gyrus is likely involved in pain inhibition due to oxycodone treatment, whereas the decrease in alpha activity is likely involved in pain inhibition due to venlafaxine treatment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neural basis of exertional fatigue in the heat: A review of magnetic resonance imaging methods.

PubMed

Tan, X R; Low, I C C; Stephenson, M C; Soong, T W; Lee, J K W

2018-03-01

The central nervous system, specifically the brain, is implicated in the development of exertional fatigue under a hot environment. Diverse neuroimaging techniques have been used to visualize the brain activity during or after exercise. Notably, the use of magnetic resonance imaging (MRI) has become prevalent due to its excellent spatial resolution and versatility. This review evaluates the significance and limitations of various brain MRI techniques in exercise studies-brain volumetric analysis, functional MRI, functional connectivity MRI, and arterial spin labeling. The review aims to provide a summary on the neural basis of exertional fatigue and proposes future directions for brain MRI studies. A systematic literature search was performed where a total of thirty-seven brain MRI studies associated with exercise, fatigue, or related physiological factors were reviewed. The findings suggest that with moderate dehydration, there is a decrease in total brain volume accompanied with expansion of ventricular volume. With exercise fatigue, there is increased activation of sensorimotor and cognitive brain areas, increased thalamo-insular activation and decreased interhemispheric connectivity in motor cortex. Under passive hyperthermia, there are regional changes in cerebral perfusion, a reduction in local connectivity in functional brain networks and an impairment to executive function. Current literature suggests that the brain structure and function are influenced by exercise, fatigue, and related physiological perturbations. However, there is still a dearth of knowledge and it is hoped that through understanding of MRI advantages and limitations, future studies will shed light on the central origin of exertional fatigue in the heat. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[Changes in brain serotonin biosynthesis in rats with diabetes mellitus induced by streptozocin: effect of insulin treatment].

PubMed

Manjarrez-Gutiérrez, G; Rocío Herrera-Márquez, J R; Bueno-Santoyo, S; González-Ramírez, M; Hernández, J

2000-01-01

To investigate if the changes in the activity of the tryptophan-5-hydroxylase and in brain serotonin synthesis provoked by diabetes mellitus persist or return to normal in the diabetic rats submitted to treatment with insulin. Diabetes induced by the administration of streptozotocin in rats and their treatment with insulin was the paradigm used. At days 7, 14 and 21 of evolution, the brain serotonergic biosynthetic activity was evaluated. The diabetic rats showed a significant decrease of body weight. Also, they showed a low concentration of I-tryptophan, as well as a diminution in the activity of the key enzyme tryptophan-5-hydroxylase and its product serotonin in the cerebral cortex and brainstem. Interestingly, the activity of the enzyme was higher in the brainstem from day 14, accompanied with an elevation of the neurotransmitter. The diabetic rats submitted to treatment with insulin showed a complete physical recovery and a return to normal of plasma and brain I-tryptophan. The activity of the enzyme not only normalized but was elevated and with an increase of serotonin in the brainstem and cerebral cortex. The present findings confirm that diabetes mellitus produced a chronic anabolic deficit and a decrease in some brain regions of serotonin synthesis. Also, demonstrate that the diabetic rats under specific treatment with insulin had a complete physical recovery and a return to normal of the serotonin precursor in the blood and brain. However, the activity of the limiting enzyme TrpOH case was elevated with an increase of the neurotransmitter in all regions studied. Since the diabetic animal, insulin treated, does recover metabolically, the mechanism of activation of the serotonin biosynthetic path in the brain may not be dependent on the decreased availability of its precursor the free plasma I-tryptophan. Instead, it might be due to a change in the kinetics of tryptophan-5-hydroxylase, since its activity remains significantly increased in spite of plasma and brain normalization of its substrate. Altogether these changes in the biosynthesis of an important brain neurotransmitter may be of relevance in the pathophysiology of the psychoneurological complications in diabetic patients.

Management of severe head injury with brain exposure in three loggerhead sea turtles Caretta caretta.

PubMed

Franchini, D; Cavaliere, L; Valastro, C; Carnevali, F; van der Esch, A; Lai, O; Di Bello, A

2016-05-03

The loggerhead Caretta caretta is the most common sea turtle in the Mediterranean. Currently, sea turtles are considered endangered, mainly due to the impact of human activities. Among traumatic lesions, those involving the skull, if complicated by brain exposure, are often life-threatening. In these cases, death could be the outcome of direct trauma of the cerebral tissue or of secondary meningoencephalitis. This uncontrolled study aims to evaluate the use of a plant-derived dressing (1 Primary Wound Dressing®) in 3 sea turtles with severe lesions of the skull exposing the brain. Following surgical curettage, the treatment protocol involved exclusive use of the plant-derived dressing applied on the wound surface as the primary dressing, daily for the first month and then every other day until the end of treatment. The wound and peri-wound skin were covered with a simple secondary dressing without any active compound (non-woven gauze with petroleum jelly). Data presented herein show an excellent healing process in all 3 cases and no side effects due to contact of the medication with the cerebral tissue.

[Stem Cells in the Brain of Mammals and Human: Fundamental and Applied Aspects].

PubMed

Aleksandrova, M A; Marey, M V

2015-01-01

Brain stem cells represent an extremely intriguing phenomenon. The aim of our review is to present an integrity vision of their role in the brain of mammals and humans, and their clinical perspectives. Over last two decades, investigations of biology of the neural stem cells produced significant changes in general knowledge about the processes of development and functioning of the brain. Researches on the cellular and molecular mechanisms of NSC differentiation and behavior led to new understanding of their involvement in learning and memory. In the regenerative medicine, original therapeutic approaches to neurodegenerative brain diseases have been elaborated due to fundamental achievements in this field. They are based on specific regenerative potential of neural stem cells and progenitor cells, which possess the ability to replace dead cells and express crucially significant biologically active factors that are missing in the pathological brain. For the needs of cell substitution therapy in the neural diseases, adequate methods of maintaining stem cells in culture and their differentiation into different types of neurons and glial cells, have been developed currently. The success of modern cellular technologies has significantly expanded the range of cells used for cell therapy. The near future may bring new perspective and distinct progress in brain cell therapy due to optimizing the cells types most promising for medical needs.

Poly-Ub-Substrate-Degradative Activity of 26S Proteasome Is Not Impaired in the Aging Rat Brain

PubMed Central

Giannini, Carolin; Kloß, Alexander; Gohlke, Sabrina; Mishto, Michele; Nicholson, Thomas P.; Sheppard, Paul W.; Kloetzel, Peter-Michael; Dahlmann, Burkhardt

2013-01-01

Proteostasis is critical for the maintenance of life. In neuronal cells an imbalance between protein synthesis and degradation is thought to be involved in the pathogenesis of neurodegenerative diseases during aging. Partly, this seems to be due to a decrease in the activity of the ubiquitin-proteasome system, wherein the 20S/26S proteasome complexes catalyse the proteolytic step. We have characterised 20S and 26S proteasomes from cerebrum, cerebellum and hippocampus of 3 weeks old (young) and 24 month old (aged) rats. Our data reveal that the absolute amount of the proteasome is not dfferent between both age groups. Within the majority of standard proteasomes in brain the minute amounts of immuno-subunits are slightly increased in aged rat brain. While this goes along with a decrease in the activities of 20S and 26S proteasomes to hydrolyse synthetic fluorogenic tripeptide substrates from young to aged rats, the capacity of 26S proteasomes for degradation of poly-Ub-model substrates and its activation by poly-Ub-substrates is not impaired or even slightly increased in brain of aged rats. We conclude that these alterations in proteasome properties are important for maintaining proteostasis in the brain during an uncomplicated aging process. PMID:23667697

Toll-like receptor 4 knockout ameliorates neuroinflammation due to lung-brain interaction in mechanically ventilated mice.

PubMed

Chen, Ting; Chen, Chang; Zhang, Zongze; Zou, Yufeng; Peng, Mian; Wang, Yanlin

2016-08-01

Toll-like receptor 4 (TLR4) is a crucial receptor in the innate immune system, and increasing evidence supports its role in inflammation, stress, and tissue injury, including injury to the lung and brain. We aimed to investigate the effects of TLR4 on neuroinflammation due to the lung-brain interaction in mechanically ventilated mice. Male wild-type (WT) C57BL/6 and TLR4 knockout (TLR4 KO) mice were divided into three groups: (1) control group (C): spontaneous breathing; (2) anesthesia group (A): spontaneous breathing under anesthesia; and (3) mechanical ventilation group (MV): 6h of MV under anesthesia. The behavioral responses of mice were tested with fear conditioning tests. The histological changes in the lung and brain were assessed using hematoxylin-eosin (HE) staining. The level of TLR4 mRNA in tissue was measured using reverse transcription-polymerase chain reaction (RT-PCR). The levels of inflammatory cytokines were measured with an enzyme-linked immunosorbent assay (ELISA). Microgliosis, astrocytosis, and the TLR4 immunoreactivity in the hippocampus were measured by double immunofluorescence. MV mice exhibited impaired cognition, and this impairment was less severe in TLR4 KO mice than in WT mice. In WT mice, MV increased TLR4 mRNA expression in the lung and brain. MV induced mild lung injury, which was prevented in TLR4 KO mice. MV mice exhibited increased levels of inflammatory cytokines, increased microglia and astrocyte activation. Microgliosis was alleviated in TLR4 KO mice. MV mice exhibited increased TLR4 immunoreactivity, which was expressed in microglia and astrocytes. These results demonstrate that TLR4 is involved in neuroinflammation due to the lung-brain interaction and that TLR4 KO ameliorates neuroinflammation due to lung-brain interaction after prolonged MV. In addition, Administration of a TLR4 antagonist (100μg/mice) to WT mice also significantly attenuated neuroinflammation of lung-brain interaction due to prolonged MV. TLR4 antagonism may be a new and novel approach for the treatment and management of neuroinflammation in long-term mechanically ventilated patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain susceptibility to oxidative stress in the perinatal period.

PubMed

Perrone, Serafina; Tataranno, Luisa M; Stazzoni, Gemma; Ramenghi, Luca; Buonocore, Giuseppe

2015-11-01

Oxidative stress (OS) occurs at birth in all newborns as a consequence of the hyperoxic challenge due to the transition from the hypoxic intrauterine environment to extrauterine life. Free radical (FRs) sources such as inflammation, hyperoxia, hypoxia, ischaemia-reperfusion, neutrophil and macrophage activation, glutamate and free iron release, all increases the OS during the perinatal period. Newborns, and particularly preterm infants, have reduced antioxidant defences and are not able to counteract the harmful effects of FRs. Energy metabolism is central to life because cells cannot exist without an adequate supply of ATP. Due to its growth, the mammalian brain can be considered as a steady-state system in which ATP production matches ATP utilisation. The developing brain is particularly sensitive to any disturbances in energy generation, and even a short-term interruption can lead to long-lasting and irreversible damage. Whenever energy failure develops, brain damage can occur. Accumulating evidence indicates that OS is implicated in the pathogenesis of many neurological diseases, such as intraventricular haemorrhage, hypoxic-ischaemic encephalopathy and epilepsy.

Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice.

PubMed

Gu, Yeunhwa; Huang, Chien-Sheng; Inoue, Tota; Yamashita, Takenori; Ishida, Torao; Kang, Ki-Mun; Nakao, Atsunori

2010-05-01

Hydrogen has been reported to have neuron protective effects due to its antioxidant properties, but the effects of hydrogen on cognitive impairment due to senescence-related brain alterations and the underlying mechanisms have not been characterized. In this study, we investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability seen in SAMP8 as assessed by a water maze test and was associated with increased brain serotonin levels and elevated serum antioxidant activity. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of our results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.

Converging early responses to brain injury pave the road to epileptogenesis.

PubMed

Neuberger, Eric J; Gupta, Akshay; Subramanian, Deepak; Korgaonkar, Akshata A; Santhakumar, Vijayalakshmi

2017-11-29

Epilepsy, characterized by recurrent seizures and abnormal electrical activity in the brain, is one of the most prevalent brain disorders. Over two million people in the United States have been diagnosed with epilepsy and 3% of the general population will be diagnosed with it at some point in their lives. While most developmental epilepsies occur due to genetic predisposition, a class of "acquired" epilepsies results from a variety of brain insults. A leading etiological factor for epilepsy that is currently on the rise is traumatic brain injury (TBI), which accounts for up to 20% of all symptomatic epilepsies. Remarkably, the presence of an identified early insult that constitutes a risk for development of epilepsy provides a therapeutic window in which the pathological processes associated with brain injury can be manipulated to limit the subsequent development of recurrent seizure activity and epilepsy. Recent studies have revealed diverse pathologies, including enhanced excitability, activated immune signaling, cell death, and enhanced neurogenesis within a week after injury, suggesting a period of heightened adaptive and maladaptive plasticity. An integrated understanding of these processes and their cellular and molecular underpinnings could lead to novel targets to arrest epileptogenesis after trauma. This review attempts to highlight and relate the diverse early changes after trauma and their role in development of epilepsy and suggests potential strategies to limit neurological complications in the injured brain. © 2017 Wiley Periodicals, Inc.

Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age

PubMed Central

Doesburg, Sam M.; Chau, Cecil M.; Cheung, Teresa P.L.; Moiseev, Alexander; Ribary, Urs; Herdman, Anthony T.; Miller, Steven P.; Cepeda, Ivan L.; Synnes, Anne; Grunau, Ruth E.

2013-01-01

Children born very prematurely (≤32 weeks) often exhibit visual-perceptual difficulties at school-age, even in the absence of major neurological impairment. The alterations in functional brain activity that give rise to such problems, as well as the relationship between adverse neonatal experience and neurodevelopment, remain poorly understood. Repeated procedural pain-related stress during neonatal intensive care has been proposed to contribute to altered neurocognitive development in these children. Due to critical periods in the development of thalamocortical systems, the immature brain of infants born at extremely low gestational age (ELGA; ≤28 weeks) may have heightened vulnerability to neonatal pain. In a cohort of school-age children followed since birth we assessed relations between functional brain activity measured using magnetoencephalogragy (MEG), visual-perceptual abilities and cumulative neonatal pain. We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school-age. Cumulative neonatal pain-related stress was associated with changes in background cortical rhythmicity in these children, and these alterations in spontaneous brain oscillations were negatively correlated with visual-perceptual abilities at school-age, and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal painrelated stress, the development of functional brain activity, and school-age cognitive outcome in these vulnerable children. PMID:23711638

Localization of spontaneous magnetoencephalographic activity of neonates and fetuses using independent component and Hilbert phase analysis.

PubMed

Vairavan, Srinivasan; Eswaran, Hari; Preissl, Hubert; Wilson, James D; Haddad, Naim; Lowery, Curtis L; Govindan, Rathinaswamy B

2010-01-01

The fetal magnetoencephalogram (fMEG) is measured in the presence of large interference from maternal and fetal magnetocardiograms (mMCG and fMCG). These cardiac interferences can be attenuated by orthogonal projection (OP) technique of the corresponding spatial vectors. However, the OP technique redistributes the fMEG signal among the channels and also leaves some cardiac residuals (partially attenuated mMCG and fMCG) due to loss of stationarity in the signal. In this paper, we propose a novel way to extract and localize the neonatal and fetal spontaneous brain activity by using independent component analysis (ICA) technique. In this approach, we perform ICA on a small subset of sensors for 1-min duration. The independent components obtained are further investigated for the presence of discontinuous patterns as identified by the Hilbert phase analysis and are used as decision criteria for localizing the spontaneous brain activity. In order to locate the region of highest spontaneous brain activity content, this analysis is performed on the sensor subsets, which are traversed across the entire sensor space. The region of the spontaneous brain activity as identified by the proposed approach correlated well with the neonatal and fetal head location. In addition, the burst duration and the inter-burst interval computed for the identified discontinuous brain patterns are in agreement with the reported values.

Characterization of EEG patterns in brain-injured subjects and controls after a Snoezelen(®) intervention.

PubMed

Gómez, Carlos; Poza, Jesús; Gutiérrez, María T; Prada, Esther; Mendoza, Nuria; Hornero, Roberto

2016-11-01

The aim of this study was to assess the changes induced in electroencephalographic (EEG) activity by a Snoezelen(®) intervention on individuals with brain-injury and control subjects. EEG activity was recorded preceding and following a Snoezelen(®) session in 18 people with cerebral palsy (CP), 18 subjects who have sustained traumatic brain-injury (TBI) and 18 controls. EEG data were analyzed by means of spectral and nonlinear measures: median frequency (MF), individual alpha frequency (IAF), sample entropy (SampEn) and Lempel-Ziv complexity (LZC). Our results showed decreased values for MF, IAF, SampEn and LZC as a consequence of the therapy. The main changes between pre-stimulation and post-stimulation conditions were found in occipital and parietal brain areas. Additionally, these changes are more widespread in controls than in brain-injured subjects, which can be due to cognitive deficits in TBI and CP groups. Our findings support the notion that Snoezelen(®) therapy affects central nervous system, inducing a slowing of oscillatory activity, as well as a decrease of EEG complexity and irregularity. These alterations seem to be related with higher levels of relaxation of the participants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Detecting switching and intermittent causalities in time series

NASA Astrophysics Data System (ADS)

Zanin, Massimiliano; Papo, David

2017-04-01

During the last decade, complex network representations have emerged as a powerful instrument for describing the cross-talk between different brain regions both at rest and as subjects are carrying out cognitive tasks, in healthy brains and neurological pathologies. The transient nature of such cross-talk has nevertheless by and large been neglected, mainly due to the inherent limitations of some metrics, e.g., causality ones, which require a long time series in order to yield statistically significant results. Here, we present a methodology to account for intermittent causal coupling in neural activity, based on the identification of non-overlapping windows within the original time series in which the causality is strongest. The result is a less coarse-grained assessment of the time-varying properties of brain interactions, which can be used to create a high temporal resolution time-varying network. We apply the proposed methodology to the analysis of the brain activity of control subjects and alcoholic patients performing an image recognition task. Our results show that short-lived, intermittent, local-scale causality is better at discriminating both groups than global network metrics. These results highlight the importance of the transient nature of brain activity, at least under some pathological conditions.

Evidence for hubs in human functional brain networks

PubMed Central

Power, Jonathan D; Schlaggar, Bradley L; Lessov-Schlaggar, Christina N; Petersen, Steven E

2013-01-01

Summary Hubs integrate and distribute information in powerful ways due to the number and positioning of their contacts in a network. Several resting state functional connectivity MRI reports have implicated regions of the default mode system as brain hubs; we demonstrate that previous degree-based approaches to hub identification may have identified portions of large brain systems rather than critical nodes of brain networks. We utilize two methods to identify hub-like brain regions: 1) finding network nodes that participate in multiple sub-networks of the brain, and 2) finding spatial locations where several systems are represented within a small volume. These methods converge on a distributed set of regions that differ from previous reports on hubs. This work identifies regions that support multiple systems, leading to spatially constrained predictions about brain function that may be tested in terms of lesions, evoked responses, and dynamic patterns of activity. PMID:23972601

Atlas-guided volumetric diffuse optical tomography enhanced by generalized linear model analysis to image risk decision-making responses in young adults.

PubMed

Lin, Zi-Jing; Li, Lin; Cazzell, Mary; Liu, Hanli

2014-08-01

Diffuse optical tomography (DOT) is a variant of functional near infrared spectroscopy and has the capability of mapping or reconstructing three dimensional (3D) hemodynamic changes due to brain activity. Common methods used in DOT image analysis to define brain activation have limitations because the selection of activation period is relatively subjective. General linear model (GLM)-based analysis can overcome this limitation. In this study, we combine the atlas-guided 3D DOT image reconstruction with GLM-based analysis (i.e., voxel-wise GLM analysis) to investigate the brain activity that is associated with risk decision-making processes. Risk decision-making is an important cognitive process and thus is an essential topic in the field of neuroscience. The Balloon Analog Risk Task (BART) is a valid experimental model and has been commonly used to assess human risk-taking actions and tendencies while facing risks. We have used the BART paradigm with a blocked design to investigate brain activations in the prefrontal and frontal cortical areas during decision-making from 37 human participants (22 males and 15 females). Voxel-wise GLM analysis was performed after a human brain atlas template and a depth compensation algorithm were combined to form atlas-guided DOT images. In this work, we wish to demonstrate the excellence of using voxel-wise GLM analysis with DOT to image and study cognitive functions in response to risk decision-making. Results have shown significant hemodynamic changes in the dorsal lateral prefrontal cortex (DLPFC) during the active-choice mode and a different activation pattern between genders; these findings correlate well with published literature in functional magnetic resonance imaging (fMRI) and fNIRS studies. Copyright © 2014 The Authors. Human Brain Mapping Published by Wiley Periodicals, Inc.

Brain activation associated with pride and shame.

PubMed

Roth, Lilian; Kaffenberger, Tina; Herwig, Uwe; Brühl, Annette B

2014-01-01

Self-referential emotions such as shame/guilt and pride provide evaluative information about persons themselves. In addition to emotional aspects, social and self-referential processes play a role in self-referential emotions. Prior studies have rather focused on comparing self-referential and other-referential processes of one valence, triggered mostly by external stimuli. In the current study, we aimed at investigating the valence-specific neural correlates of shame/guilt and pride, evoked by the remembrance of a corresponding autobiographical event during functional magnetic resonance imaging. A total of 25 healthy volunteers were studied. The task comprised a negative (shame/guilt), a positive (pride) and a neutral condition (expecting the distractor). Each condition was initiated by a simple cue, followed by the remembrance and finished by a distracting picture. Pride and shame/guilt conditions both activated typical emotion-processing circuits including the amygdala, insula and ventral striatum, as well as self-referential brain regions such as the bilateral dorsomedial prefrontal cortex. Comparing the two emotional conditions, emotion-processing circuits were more activated by pride than by shame, possibly due to either hedonic experiences or stronger involvement of the participants in positive self-referential emotions due to a self-positivity bias. However, the ventral striatum was similarly activated by pride and shame/guilt. In the whole-brain analysis, both self-referential emotion conditions activated medial prefrontal and posterior cingulate regions, corresponding to the self-referential aspect and the autobiographical evocation of the respective emotions. Autobiographically evoked self-referential emotions activated basic emotional as well as self-referential circuits. Except for the ventral striatum, emotional circuits were more active with pride than with shame.

Dorsal and ventral stream contributions to form-from-motion perception in a patient with form-from motion deficit: a case report.

PubMed

Mercier, Manuel R; Schwartz, Sophie; Spinelli, Laurent; Michel, Christoph M; Blanke, Olaf

2017-03-01

The main model of visual processing in primates proposes an anatomo-functional distinction between the dorsal stream, specialized in spatio-temporal information, and the ventral stream, processing essentially form information. However, these two pathways also communicate to share much visual information. These dorso-ventral interactions have been studied using form-from-motion (FfM) stimuli, revealing that FfM perception first activates dorsal regions (e.g., MT+/V5), followed by successive activations of ventral regions (e.g., LOC). However, relatively little is known about the implications of focal brain damage of visual areas on these dorso-ventral interactions. In the present case report, we investigated the dynamics of dorsal and ventral activations related to FfM perception (using topographical ERP analysis and electrical source imaging) in a patient suffering from a deficit in FfM perception due to right extrastriate brain damage in the ventral stream. Despite the patient's FfM impairment, both successful (observed for the highest level of FfM signal) and absent/failed FfM perception evoked the same temporal sequence of three processing states observed previously in healthy subjects. During the first period, brain source localization revealed cortical activations along the dorsal stream, currently associated with preserved elementary motion processing. During the latter two periods, the patterns of activity differed from normal subjects: activations were observed in the ventral stream (as reported for normal subjects), but also in the dorsal pathway, with the strongest and most sustained activity localized in the parieto-occipital regions. On the other hand, absent/failed FfM perception was characterized by weaker brain activity, restricted to the more lateral regions. This study shows that in the present case report, successful FfM perception, while following the same temporal sequence of processing steps as in normal subjects, evoked different patterns of brain activity. By revealing a brain circuit involving the most rostral part of the dorsal pathway, this study provides further support for neuro-imaging studies and brain lesion investigations that have suggested the existence of different brain circuits associated with different profiles of interaction between the dorsal and the ventral streams.

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

PubMed Central

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

2011-01-01

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

The neural representation of emotionally neutral faces and places in patients with panic disorder with agoraphobia.

PubMed

Petrowski, Katja; Wintermann, Gloria; Smolka, Michael N; Huebner, Thomas; Donix, Markus

2014-01-01

Panic disorder with agoraphobia (PD-A) has been associated with abnormal neural activity for threat-related stimuli (faces, places). Recent findings suggest a disturbed neural processing of emotionally neutral stimuli at a more general level. Using functional magnetic resonance imaging (fMRI) we investigated the neural processing of emotionally neutral faces and places in PD-A. Fifteen patients with PD-A and fifteen healthy subjects participated in the study. When they perceived neutral faces and places, the patients with PD-A showed significantly less brain activity in the fusiform gyrus, the inferior occipital gyrus, the calcarine gyrus, the cerebellum, and the cuneus compared with the healthy controls. However, the patients with PD-A showed significantly more brain activity in the precuneus compared with controls subjects. It was not possible to distinguish the agoraphobia-associated effects from possible contributions due to general anxiety induced by fMRI. For future investigations, an additional clinical control group with patients suffering from panic disorder without agoraphobia would be of interest. In addition, the psychopathology concerning the agoraphobic symptoms needs to be investigated in more detail. The findings suggest altered neural processing of emotionally neutral faces and places in patients with PD-A. Reduced neural activity in different brain regions may indicate difficulties in recognizing the emotional content in face and place stimuli due to anxiety-related hyper-arousal. © 2013 Published by Elsevier B.V.

Imaging Odor-Evoked Activities in the Mouse Olfactory Bulb using Optical Reflectance and Autofluorescence Signals

PubMed Central

Chery, Romain; L'Heureux, Barbara; Bendahmane, Mounir; Renaud, Rémi; Martin, Claire; Pain, Frédéric; Gurden, Hirac

2011-01-01

In the brain, sensory stimulation activates distributed populations of neurons among functional modules which participate to the coding of the stimulus. Functional optical imaging techniques are advantageous to visualize the activation of these modules in sensory cortices with high spatial resolution. In this context, endogenous optical signals that arise from molecular mechanisms linked to neuroenergetics are valuable sources of contrast to record spatial maps of sensory stimuli over wide fields in the rodent brain. Here, we present two techniques based on changes of endogenous optical properties of the brain tissue during activation. First the intrinsic optical signals (IOS) are produced by a local alteration in red light reflectance due to: (i) absorption by changes in blood oxygenation level and blood volume (ii) photon scattering. The use of in vivo IOS to record spatial maps started in the mid 1980's with the observation of optical maps of whisker barrels in the rat and the orientation columns in the cat visual cortex1. IOS imaging of the surface of the rodent main olfactory bulb (OB) in response to odorants was later demonstrated by Larry Katz's group2. The second approach relies on flavoprotein autofluorescence signals (FAS) due to changes in the redox state of these mitochondrial metabolic intermediates. More precisely, the technique is based on the green fluorescence due to oxidized state of flavoproteins when the tissue is excited with blue light. Although such signals were probably among the first fluorescent molecules recorded for the study of brain activity by the pioneer studies of Britton Chances and colleagues3, it was not until recently that they have been used for mapping of brain activation in vivo. FAS imaging was first applied to the somatosensory cortex in rodents in response to hindpaw stimulation by Katsuei Shibuki's group4. The olfactory system is of central importance for the survival of the vast majority of living species because it allows efficient detection and identification of chemical substances in the environment (food, predators). The OB is the first relay of olfactory information processing in the brain. It receives afferent projections from the olfactory primary sensory neurons that detect volatile odorant molecules. Each sensory neuron expresses only one type of odorant receptor and neurons carrying the same type of receptor send their nerve processes to the same well-defined microregions of ˜100μm3 constituted of discrete neuropil, the olfactory glomerulus (Fig. 1). In the last decade, IOS imaging has fostered the functional exploration of the OB5, 6, 7 which has become one of the most studied sensory structures. The mapping of OB activity with FAS imaging has not been performed yet. Here, we show the successive steps of an efficient protocol for IOS and FAS imaging to map odor-evoked activities in the mouse OB. PMID:22064685

Action video gaming and the brain: fMRI effects without behavioral effects in visual and verbal cognitive tasks.

PubMed

Richlan, Fabio; Schubert, Juliane; Mayer, Rebecca; Hutzler, Florian; Kronbichler, Martin

2018-01-01

In this functional magnetic resonance imaging (fMRI) study, we compared task performance together with brain activation in a visuospatial task (VST) and a letter detection task (LDT) between longtime action video gamers ( N  =   14) and nongamers ( N  =   14) in order to investigate possible effects of gaming on cognitive and brain abilities. Based on previous research, we expected advantages in performance for experienced action video gamers accompanied by less activation (due to higher efficiency) as measured by fMRI in the frontoparietal attention network. Contrary to these expectations, we did not find differences in overall task performance, nor in brain activation during the VST. We identified, however, a significantly different increase in the BOLD signal from a baseline task to the LDT in action video gamers compared with nongamers. This increased activation was evident in a number of frontoparietal regions including the left middle paracingulate cortex, the left superior frontal sulcus, the opercular part of the left inferior frontal gyrus, and the left and right posterior parietal cortex. Furthermore, we found increased activation in the triangular part of the left inferior frontal gyrus in gamers relative to nongamers when activation during the LDT was compared with activation during the VST. In sum, the expected positive relation between action video game experience and cognitive performance could not be confirmed. Despite their comparable task performance, however, gamers and nongamers exhibited clear-cut differences in brain activation patterns presumably reflecting differences in neural engagement, especially during verbal cognitive tasks.

Lifting the veil on the dynamics of neuronal activities evoked by transcranial magnetic stimulation

PubMed Central

Li, Bingshuo; Virtanen, Juha P; Oeltermann, Axel; Schwarz, Cornelius; Giese, Martin A; Ziemann, Ulf

2017-01-01

Transcranial magnetic stimulation (TMS) is a widely used non-invasive tool to study and modulate human brain functions. However, TMS-evoked activity of individual neurons has remained largely inaccessible due to the large TMS-induced electromagnetic fields. Here, we present a general method providing direct in vivo electrophysiological access to TMS-evoked neuronal activity 0.8–1 ms after TMS onset. We translated human single-pulse TMS to rodents and unveiled time-grained evoked activities of motor cortex layer V neurons that show high-frequency spiking within the first 6 ms depending on TMS-induced current orientation and a multiphasic spike-rhythm alternating between excitation and inhibition in the 6–300 ms epoch, all of which can be linked to various human TMS responses recorded at the level of spinal cord and muscles. The advance here facilitates a new level of insight into the TMS-brain interaction that is vital for developing this non-invasive tool to purposefully explore and effectively treat the human brain. PMID:29165241

Brain stimulation used as biofeedback in neuronal activation of the temporal lobe area in autistic children.

PubMed

Silva, Vernon Furtado da; Calomeni, Mauricio Rocha; Nunes, Rodolfo Alkmim Moreira; Pimentel, Carlos Elias; Martins, Gabriela Paes; Oliveira, Patrícia da Cruz Araruna; Silva, Patrícia Bagno; Silva, Alair Pedro Ribeiro de Souza E

2016-08-01

This study focused upon the functional capacity of mirror neurons in autistic children. 30 individuals, 10 carriers of the autistic syndrome (GCA), 10 with intellectual impairments (GDI), and 10 non-autistics (GCN) had registered eletroencephalogram from the brain area theoretically related to mirror neurons. Data collection procedure occurred prior to brain stimulation and after the stimulation session. During the second session, participants had to alternately process figures evoking neutral, happy, and/or sorrowful feelings. Results proved that, for all groups, the stimulation process in fact produced additional activation in the neural area under study. The level of activation was related to the format of emotional stimuli and the likelihood of boosting such stimuli. Since the increase of activation occurred in a model similar to the one observed for the control group, we may suggest that the difficulty people with autism have at expressing emotions is not due to nonexistence of mirror neurons.

Analysis of Time-Dependent Brain Network on Active and MI Tasks for Chronic Stroke Patients

PubMed Central

Chang, Won Hyuk; Kim, Yun-Hee; Lee, Seong-Whan; Kwon, Gyu Hyun

2015-01-01

Several researchers have analyzed brain activities by investigating brain networks. However, there is a lack of the research on the temporal characteristics of the brain network during a stroke by EEG and the comparative studies between motor execution and imagery, which became known to have similar motor functions and pathways. In this study, we proposed the possibility of temporal characteristics on the brain networks of a stroke. We analyzed the temporal properties of the brain networks for nine chronic stroke patients by the active and motor imagery tasks by EEG. High beta band has a specific role in the brain network during motor tasks. In the high beta band, for the active task, there were significant characteristics of centrality and small-worldness on bilateral primary motor cortices at the initial motor execution. The degree centrality significantly increased on the contralateral primary motor cortex, and local efficiency increased on the ipsilateral primary motor cortex. These results indicate that the ipsilateral primary motor cortex constructed a powerful subnetwork by influencing the linked channels as compensatory effect, although the contralateral primary motor cortex organized an inefficient network by using the connected channels due to lesions. For the MI task, degree centrality and local efficiency significantly decreased on the somatosensory area at the initial motor imagery. Then, there were significant correlations between the properties of brain networks and motor function on the contralateral primary motor cortex and somatosensory area for each motor execution/imagery task. Our results represented that the active and MI tasks have different mechanisms of motor acts. Based on these results, we indicated the possibility of customized rehabilitation according to different motor tasks. We expect these results to help in the construction of the customized rehabilitation system depending on motor tasks by understanding temporal functional characteristics on brain network for a stroke. PMID:26656269

Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults

PubMed Central

Flodin, Pär; Jonasson, Lars S.; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C. J.

2017-01-01

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64–78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO2-peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO2-peak was negativly related to BOLD-signal fluctuations (BOLDSTD) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO2-related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO2-peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas. PMID:28848424

Does Aerobic Exercise Influence Intrinsic Brain Activity? An Aerobic Exercise Intervention among Healthy Old Adults.

PubMed

Flodin, Pär; Jonasson, Lars S; Riklund, Katrin; Nyberg, Lars; Boraxbekk, C J

2017-01-01

Previous studies have indicated that aerobic exercise could reduce age related decline in cognition and brain functioning. Here we investigated the effects of aerobic exercise on intrinsic brain activity. Sixty sedentary healthy males and females (64-78 years) were randomized into either an aerobic exercise group or an active control group. Both groups recieved supervised training, 3 days a week for 6 months. Multimodal brain imaging data was acquired before and after the intervention, including 10 min of resting state brain functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL). Additionally, a comprehensive battery of cognitive tasks assessing, e.g., executive function and episodic memory was administered. Both the aerobic and the control group improved in aerobic capacity (VO 2 -peak) over 6 months, but a significant group by time interaction confirmed that the aerobic group improved more. Contrary to our hypothesis, we did not observe any significant group by time interactions with regard to any measure of intrinsic activity. To further probe putative relationships between fitness and brain activity, we performed post hoc analyses disregarding group belongings. At baseline, VO 2 -peak was negativly related to BOLD-signal fluctuations (BOLD STD ) in mid temporal areas. Over 6 months, improvements in aerobic capacity were associated with decreased connectivity between left hippocampus and contralateral precentral gyrus, and positively to connectivity between right mid-temporal areas and frontal and parietal regions. Independent component analysis identified a VO 2 -related increase in coupling between the default mode network and left orbitofrontal cortex, as well as a decreased connectivity between the sensorimotor network and thalamus. Extensive exploratory data analyses of global efficiency, connectome wide multivariate pattern analysis (connectome-MVPA), as well as ASL, did not reveal any relationships between aerobic fitness and intrinsic brain activity. Moreover, fitness-predicted changes in functional connectivity did not relate to changes in cognition, which is likely due to absent cross-sectional or longitudinal relationships between VO 2 -peak and cognition. We conclude that the aerobic exercise intervention had limited influence on patterns of intrinsic brain activity, although post hoc analyses indicated that individual changes in aerobic capacity preferentially influenced mid-temporal brain areas.

Single unit approaches to human vision and memory.

PubMed

Kreiman, Gabriel

2007-08-01

Research on the visual system focuses on using electrophysiology, pharmacology and other invasive tools in animal models. Non-invasive tools such as scalp electroencephalography and imaging allow examining humans but show a much lower spatial and/or temporal resolution. Under special clinical conditions, it is possible to monitor single-unit activity in humans when invasive procedures are required due to particular pathological conditions including epilepsy and Parkinson's disease. We review our knowledge about the visual system and visual memories in the human brain at the single neuron level. The properties of the human brain seem to be broadly compatible with the knowledge derived from animal models. The possibility of examining high-resolution brain activity in conscious human subjects allows investigators to ask novel questions that are challenging to address in animal models.

Influence of radioactivity out of the field of view on 3D PET dynamic measurement with [/sup 11/C]MP4A

NASA Astrophysics Data System (ADS)

Hasegawa, T.; Suzuki, M.; Murayama, H.; Irie, T.; Fukushi, K.; Wada, Y.

1999-08-01

This study assessed the influence of radioactivity out of the field of view (out-of-FOV) on the measurement of brain acetylcholinesterase (AChE) activity with the tracer [/sup 11/C]N-methyl-4-piperidyl-acetate by positron emission tomography in three-dimensional mode. Dynamic scans on a volunteer showed that the out-of-FOV radioactivity in the chest was much higher than that of the brain immediately after tracer injection. A representative phantom measurement was performed to quantitate the systematic errors due to the out-of-FOV radioactivity. Resultant errors in the AChE activity (k3 parameter) as calculated by compartment model analysis were found to be less than one percent in all of the brain regions studied.

Non-symbolic numerical distance effect in children with and without developmental dyscalculia: a parametric fMRI study.

PubMed

Kucian, Karin; Loenneker, Thomas; Martin, Ernst; von Aster, Michael

2011-01-01

This study investigated areas of brain activation related to non-symbolic distance effects in children with and without developmental dyscalculia (DD). We examined 15 children with DD (11.3 years) and 15 controls (10.6 years) by means of functional magnetic resonance imaging (fMRI). Both groups displayed similar behavioral performance, but differences in brain activation were observed, particularly in the supplementary motor area and the right fusiform gyrus, where children with DD demonstrated stronger activation. These results suggest that dyscalculic children engage areas attributed to higher difficulty in response selection more than control children, possibly due to a deficient development of a spatial number representation in DD.

Using the Wiener estimator to determine optimal imaging parameters in a synthetic-collimator SPECT system used for small animal imaging

NASA Astrophysics Data System (ADS)

Lin, Alexander; Johnson, Lindsay C.; Shokouhi, Sepideh; Peterson, Todd E.; Kupinski, Matthew A.

2015-03-01

In synthetic-collimator SPECT imaging, two detectors are placed at different distances behind a multi-pinhole aperture. This configuration allows for image detection at different magnifications and photon energies, resulting in higher overall sensitivity while maintaining high resolution. Image multiplexing the undesired overlapping between images due to photon origin uncertainty may occur in both detector planes and is often present in the second detector plane due to greater magnification. However, artifact-free image reconstruction is possible by combining data from both the front detector (little to no multiplexing) and the back detector (noticeable multiplexing). When the two detectors are used in tandem, spatial resolution is increased, allowing for a higher sensitivity-to-detector-area ratio. Due to variability in detector distances and pinhole spacings found in synthetic-collimator SPECT systems, a large parameter space must be examined to determine optimal imaging configurations. We chose to assess image quality based on the task of estimating activity in various regions of a mouse brain. Phantom objects were simulated using mouse brain data from the Magnetic Resonance Microimaging Neurological Atlas (MRM NeAt) and projected at different angles through models of a synthetic-collimator SPECT system, which was developed by collaborators at Vanderbilt University. Uptake in the different brain regions was modeled as being normally distributed about predetermined means and variances. We computed the performance of the Wiener estimator for the task of estimating activity in different regions of the mouse brain. Our results demonstrate the utility of the method for optimizing synthetic-collimator system design.

Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers.

PubMed

Raine, A; Meloy, J R; Bihrle, S; Stoddard, J; LaCasse, L; Buchsbaum, M S

1998-01-01

There appear to be no brain imaging studies investigating which brain mechanisms subserve affective, impulsive violence versus planned, predatory violence. It was hypothesized that affectively violent offenders would have lower prefrontal activity, higher subcortical activity, and reduced prefrontal/subcortical ratios relative to controls, while predatory violent offenders would show relatively normal brain functioning. Glucose metabolism was assessed using positron emission tomography in 41 comparisons, 15 predatory murderers, and nine affective murderers in left and right hemisphere prefrontal (medial and lateral) and subcortical (amygdala, midbrain, hippocampus, and thalamus) regions. Affective murderers relative to comparisons had lower left and right prefrontal functioning, higher right hemisphere subcortical functioning, and lower right hemisphere prefrontal/subcortical ratios. In contrast, predatory murderers had prefrontal functioning that was more equivalent to comparisons, while also having excessively high right subcortical activity. Results support the hypothesis that emotional, unplanned impulsive murderers are less able to regulate and control aggressive impulses generated from subcortical structures due to deficient prefrontal regulation. It is hypothesized that excessive subcortical activity predisposes to aggressive behaviour, but that while predatory murderers have sufficiently good prefrontal functioning to regulate these aggressive impulses, the affective murderers lack such prefrontal control over emotion regulation.

Blood-brain barrier permeation and efflux exclusion of anticholinergics used in the treatment of overactive bladder.

PubMed

Chancellor, Michael B; Staskin, David R; Kay, Gary G; Sandage, Bobby W; Oefelein, Michael G; Tsao, Jack W

2012-04-01

Overactive bladder (OAB) is a common condition, particularly in the elderly. Anticholinergic agents are the mainstay of pharmacological treatment of OAB; however, many anticholinergics can cross the blood-brain barrier (BBB) and may cause central nervous system (CNS) effects, including cognitive deficits, which can be especially detrimental in older patients. Many anticholinergics have the potential to cause adverse CNS effects due to muscarinic (M(1)) receptor binding in the brain. Of note, permeability of the BBB increases with age and can also be affected by trauma, stress, and some diseases and medications. Passive crossing of a molecule across the BBB into the brain is dependent upon its physicochemical properties. Molecular characteristics that hinder passive BBB penetration include a large molecular size, positive or negative ionic charge at physiological pH, and a hydrophilic structure. Active transport across the BBB is dependent upon protein-mediated transporter systems, such as that of permeability-glycoprotein (P-gp), which occurs only for P-gp substrates, such as trospium chloride, darifenacin and fesoterodine. Reliance on active transport can be problematic since genetic polymorphisms of P-gp exist, and many commonly used drugs and even some foods are P-gp inhibitors or are substrates themselves and, due to competition, can reduce the amount of the drug that is actively transported out of the CNS. Therefore, for drugs that are preferred not to cross into the CNS, such as potent anticholinergics intended for the bladder, it is optimal to have minimal passive crossing of the BBB, although it may also be beneficial for the drug to be a substrate for an active efflux transport system. Anticholinergics demonstrate different propensities to cross the BBB. Darifenacin, fesoterodine and trospium chloride are substrates for P-gp and, therefore, are actively transported away from the brain. In addition, trospium chloride has not been detected in cerebrospinal fluid assays and does not appear to have significant CNS penetration. This article reviews the properties of anticholinergics that affect BBB penetration and active transport out of the CNS, discusses issues of increased BBB permeability in patients with OAB, and examines the clinical implications of BBB penetration on adverse events associated with anticholinergics.

Hyperactivation of working memory related brain circuits in newly-diagnosed middle-aged type 2 diabetics

PubMed Central

He, Xiao-Song; Wang, Zhao-Xin; Zhu, You-Zhi; Wang, Nan; Hu, Xiaoping; Zhang, Da-Ren; Zhu, De-Fa; Zhou, Jiang-Ning

2014-01-01

Type 2 diabetes mellitus (T2DM) is well known for its adverse impacts on brain and cognition, which lead to multidimensional cognitive deficits and wildly-spread cerebral structure abnormalities. However, existing literatures are mainly focused on patients with advanced age or extended T2DM duration. Therefore, it remains unclear whether and how brain function would be affected at the initial onset stage of T2DM in relatively younger population. In current study, twelve newly-diagnosed middle-aged T2DM patients with no previous diabetic treatment history and twelve matched controls were recruited. Brain activations during a working memory task, the digit n-back paradigm (0-, 1- and 2-back), were obtained with functional magnetic resonance imaging (fMRI) and tested by repeated measures ANOVA. Whereas patients performed the n-back task comparably well as controls, significant load-by-group interactions of brain activation were found in the right dorsolateral prefrontal cortex (DLPFC), left middle/inferior frontal gyrus, and left parietal cortex, where patients exhibited hyperactivation in the 2-back but not the 0-back or 1-back condition compared to controls. Furthermore, the severity of chronic hyperglycemia, estimated by glycosylated hemoglobin (HbA1c) level, was entered into partial correlational analyses with task-related brain activations, while controlling for the real-time influence of glucose, estimated by instant plasma glucose level measured before scanning. Significant positive correlations were found between HbA1c and brain activations in the anterior cingulate cortex and bilateral DLPFC only in patients. Taken together, these findings suggest there might be a compensatory mechanism due to brain inefficiency related to chronic hyperglycemia at the initial onset stage of T2DM. PMID:24993663

Functional brain mapping of actual car-driving using [18F]FDG-PET.

PubMed

Jeong, Myeonggi; Tashiro, Manabu; Singh, Laxsmi N; Yamaguchi, Keiichiro; Horikawa, Etsuo; Miyake, Masayasu; Watanuki, Shouichi; Iwata, Ren; Fukuda, Hiroshi; Takahashi, Yasuo; Itoh, Masatoshi

2006-11-01

This study aims at identifying the brain activation during actual car-driving on the road, and at comparing the results to those of previous studies on simulated car-driving. Thirty normal volunteers, aged 20 to 56 years, were divided into three subgroups, active driving, passive driving and control groups, for examination by positron emission tomography (PET) and [18F]2-deoxy-2-fluoro-D-glucose (FDG). The active driving subjects (n = 10) drove for 30 minutes on quiet normal roads with a few traffic signals. The passive driving subjects (n = 10) participated as passengers on the front seat. The control subjects (n = 10) remained seated in a lit room with their eyes open. Voxel-based t-statistics were applied using SPM2 to search brain activation among the subgroups mentioned above. Significant brain activation was detected during active driving in the primary and secondary visual cortices, primary sensorimotor areas, premotor area, parietal association area, cingulate gyrus, the parahippocampal gyrus as well as in thalamus and cerebellum. The passive driving manifested a similar-looking activation pattern, lacking activations in the premotor area, cingulate and parahippocampal gyri and thalamus. Direct comparison of the active and passive driving conditions revealed activation in the cerebellum. The result of actual driving looked similar to that of simulated driving, suggesting that visual perception and visuomotor coordination were the main brain functions while driving. In terms of attention and autonomic arousal, however, it seems there was a significant difference between simulated and actual driving possibly due to risk of accidents. Autonomic and emotional aspects of driving should be studied using an actual driving study-design.

Brain CYP2B induction can decrease nicotine levels in the brain.

PubMed

Garcia, Kristine L P; Lê, Anh Dzung; Tyndale, Rachel F

2017-09-01

Nicotine can be metabolized by the enzyme CYP2B; brain CYP2B is higher in rats and monkeys treated with nicotine, and in human smokers. A 7-day nicotine treatment increased CYP2B expression in rat brain but not liver, and decreased the behavioral response and brain levels (ex vivo) to the CYP2B substrate propofol. However, the effect of CYP2B induction on the time course and levels of circulating brain nicotine in vivo has not been demonstrated. Using brain microdialysis, nicotine levels following a subcutaneous nicotine injection were measured on day one and after a 7-day nicotine treatment. There was a significant time x treatment interaction (p = 0.01); peak nicotine levels (15-45 minutes post-injection) were lower after treatment (p = 0.04) consistent with CYP2B induction. Following a two-week washout period, brain nicotine levels increased to day one levels (p = 0.02), consistent with brain CYP2B levels returning to baseline. Brain pretreatment of the CYP2B inhibitor, C8-xanthate, increased brain nicotine levels acutely and after 7-day nicotine treatment, indicating the alterations in brain nicotine levels were due to changes in brain CYP2B activity. Plasma nicotine levels were not altered for any time or treatment sampled, confirming no effect on peripheral nicotine metabolism. These results demonstrate that chronic nicotine, by increasing brain CYP2B activity, reduces brain nicotine levels, which could alter nicotine's reinforcing effects. Higher brain CYP2B levels in smokers could lower brain nicotine levels; as this induction would occur following continued nicotine exposure it could increase withdrawal symptoms and contribute to sustaining smoking behavior. © 2016 Society for the Study of Addiction.

Preserved speech abilities and compensation following prefrontal damage.

PubMed

Buckner, R L; Corbetta, M; Schatz, J; Raichle, M E; Petersen, S E

1996-02-06

Lesions to left frontal cortex in humans produce speech production impairments (nonfluent aphasia). These impairments vary from subject to subject and performance on certain speech production tasks can be relatively preserved in some patients. A possible explanation for preservation of function under these circumstances is that areas outside left prefrontal cortex are used to compensate for the injured brain area. We report here a direct demonstration of preserved language function in a stroke patient (LF1) apparently due to the activation of a compensatory brain pathway. We used functional brain imaging with positron emission tomography (PET) as a basis for this study.

[Paralysis, organic brain syndrome, and cardiac dysrhythmias caused by chronic laxative abuse (author's transl)].

PubMed

Dahlmann, W; Volles, E; Lüderitz, B

1977-10-28

A 39-year-old woman developed generalised paralysis, reversible organic brain syndrome, and cardiac dysrhythmias after 15 years of laxative abuse. Under continuous and cautious administration of potassium the cardiac rhythm became normal within four days and two days later the paralysis and organic brain syndrome almost disappeared. The cause of the psychiatric symptoms is thought to be cerebral potassium deficiency and an abnormal sodium/potassium equilibrium. Other clinical signs and symptoms due to extreme potassium depletion are presented. The importance of Na+/K+-activated membrane ATP-ase in myocardium and CNS is discussed.

Treatment with Selective Serotonin Reuptake Inhibitors and Mirtapazine Results in Differential Brain Activation by Visual Erotic Stimuli in Patients with Major Depressive Disorder

PubMed Central

Kim, Won; Jin, Bo-Ra; Yang, Wan-Seok; Lee, Kyuong-Uk; Juh, Ra-Hyung; Ahn, Kook-Jin; Chung, Yong-An

2009-01-01

Objective The objective of this study was to identify patterns of brain activation elicited by erotic visual stimuli in patients treated with either Selective Serotonin Reuptake Inhibitors (SSRIs) or mirtazipine. Methods Nine middle-aged men with major depressive disorder treated with an SSRI and ten middle-aged men with major depressive disorder treated with mirtazapine completed the trial. Ten subjects with no psychiatric illness were included as a control group. We conducted functional brain magnetic resonance imaging (fMRI) while a film alternatively played erotic and non-erotic contents for 14 minutes and 9 seconds. Results The control group showed activation in the occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, and caudate nucleus. For subjects treated with SSRIs, the intensity of activity in these regions was much lower compared to the control group. Intensity of activation in the group treated with mirtazapine was less than the control group but grea-ter than those treated with SSRIs. Using subtraction analysis, the SSRI group showed significantly lower activation than the mirtazapine group in the anterior cingulate gyrus and the caudate nucleus. Conclusion Our study suggests that the different rates of sexual side effects between the patients in the SSRI-treated group and the mirtazapine-treated group may be due to different effects on brain activation. PMID:20046380

Treatment with selective serotonin reuptake inhibitors and mirtapazine results in differential brain activation by visual erotic stimuli in patients with major depressive disorder.

PubMed

Kim, Won; Jin, Bo-Ra; Yang, Wan-Seok; Lee, Kyuong-Uk; Juh, Ra-Hyung; Ahn, Kook-Jin; Chung, Yong-An; Chae, Jeong-Ho

2009-06-01

The objective of this study was to identify patterns of brain activation elicited by erotic visual stimuli in patients treated with either Selective Serotonin Reuptake Inhibitors (SSRIs) or mirtazipine. Nine middle-aged men with major depressive disorder treated with an SSRI and ten middle-aged men with major depressive disorder treated with mirtazapine completed the trial. Ten subjects with no psychiatric illness were included as a control group. We conducted functional brain magnetic resonance imaging (fMRI) while a film alternatively played erotic and non-erotic contents for 14 minutes and 9 seconds. The control group showed activation in the occipitotemporal area, anterior cingulate gyrus, insula, orbitofrontal cortex, and caudate nucleus. For subjects treated with SSRIs, the intensity of activity in these regions was much lower compared to the control group. Intensity of activation in the group treated with mirtazapine was less than the control group but grea-ter than those treated with SSRIs. Using subtraction analysis, the SSRI group showed significantly lower activation than the mirtazapine group in the anterior cingulate gyrus and the caudate nucleus. Our study suggests that the different rates of sexual side effects between the patients in the SSRI-treated group and the mirtazapine-treated group may be due to different effects on brain activation.

Decorticate posture

MedlinePlus

Abnormal posturing - decorticate posture; Traumatic brain injury - decorticate posture ... Brain problem due to drugs, poisoning, or infection Traumatic brain injury Brain problem due to liver failure Increased pressure ...

Brain activity during auditory and visual phonological, spatial and simple discrimination tasks.

PubMed

Salo, Emma; Rinne, Teemu; Salonen, Oili; Alho, Kimmo

2013-02-16

We used functional magnetic resonance imaging to measure human brain activity during tasks demanding selective attention to auditory or visual stimuli delivered in concurrent streams. Auditory stimuli were syllables spoken by different voices and occurring in central or peripheral space. Visual stimuli were centrally or more peripherally presented letters in darker or lighter fonts. The participants performed a phonological, spatial or "simple" (speaker-gender or font-shade) discrimination task in either modality. Within each modality, we expected a clear distinction between brain activations related to nonspatial and spatial processing, as reported in previous studies. However, within each modality, different tasks activated largely overlapping areas in modality-specific (auditory and visual) cortices, as well as in the parietal and frontal brain regions. These overlaps may be due to effects of attention common for all three tasks within each modality or interaction of processing task-relevant features and varying task-irrelevant features in the attended-modality stimuli. Nevertheless, brain activations caused by auditory and visual phonological tasks overlapped in the left mid-lateral prefrontal cortex, while those caused by the auditory and visual spatial tasks overlapped in the inferior parietal cortex. These overlapping activations reveal areas of multimodal phonological and spatial processing. There was also some evidence for intermodal attention-related interaction. Most importantly, activity in the superior temporal sulcus elicited by unattended speech sounds was attenuated during the visual phonological task in comparison with the other visual tasks. This effect might be related to suppression of processing irrelevant speech presumably distracting the phonological task involving the letters. Copyright © 2012 Elsevier B.V. All rights reserved.

User Experience May be Producing Greater Heart Rate Variability than Motor Imagery Related Control Tasks during the User-System Adaptation in Brain-Computer Interfaces

PubMed Central

Alonso-Valerdi, Luz M.; Gutiérrez-Begovich, David A.; Argüello-García, Janet; Sepulveda, Francisco; Ramírez-Mendoza, Ricardo A.

2016-01-01

Brain-computer interface (BCI) is technology that is developing fast, but it remains inaccurate, unreliable and slow due to the difficulty to obtain precise information from the brain. Consequently, the involvement of other biosignals to decode the user control tasks has risen in importance. A traditional way to operate a BCI system is via motor imagery (MI) tasks. As imaginary movements activate similar cortical structures and vegetative mechanisms as a voluntary movement does, heart rate variability (HRV) has been proposed as a parameter to improve the detection of MI related control tasks. However, HR is very susceptible to body needs and environmental demands, and as BCI systems require high levels of attention, perceptual processing and mental workload, it is important to assess the practical effectiveness of HRV. The present study aimed to determine if brain and heart electrical signals (HRV) are modulated by MI activity used to control a BCI system, or if HRV is modulated by the user perceptions and responses that result from the operation of a BCI system (i.e., user experience). For this purpose, a database of 11 participants who were exposed to eight different situations was used. The sensory-cognitive load (intake and rejection tasks) was controlled in those situations. Two electrophysiological signals were utilized: electroencephalography and electrocardiography. From those biosignals, event-related (de-)synchronization maps and event-related HR changes were respectively estimated. The maps and the HR changes were cross-correlated in order to verify if both biosignals were modulated due to MI activity. The results suggest that HR varies according to the experience undergone by the user in a BCI working environment, and not because of the MI activity used to operate the system. PMID:27458384

Estradiol modulates neural response to conspecific and heterospecific song in female house sparrows: An in vivo positron emission tomography study

PubMed Central

Stabile, Frank A.; Carson, Richard E.

2017-01-01

Although there is growing evidence that estradiol modulates female perception of male sexual signals, relatively little research has focused on female auditory processing. We used in vivo 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging to examine the neuronal effects of estradiol and conspecific song in female house sparrows (Passer domesticus). We assessed brain glucose metabolism, a measure of neuronal activity, in females with empty implants, estradiol implants, and empty implants ~1 month after estradiol implant removal. Females were exposed to conspecific or heterospecific songs immediately prior to imaging. The activity of brain regions involved in auditory perception did not differ between females with empty implants exposed to conspecific vs. heterospecific song, but neuronal activity was significantly reduced in females with estradiol implants exposed to heterospecific song. Furthermore, our within-individual design revealed that changes in brain activity due to high estradiol were actually greater several weeks after peak hormone exposure. Overall, this study demonstrates that PET imaging is a powerful tool for assessing large-scale changes in brain activity in living songbirds, and suggests that after breeding is done, specific environmental and physiological cues are necessary for estradiol-stimulated females to lose the selectivity they display in neural response to conspecific song. PMID:28832614

Energy coding in biological neural networks

PubMed Central

Zhang, Zhikang

2007-01-01

According to the experimental result of signal transmission and neuronal energetic demands being tightly coupled to information coding in the cerebral cortex, we present a brand new scientific theory that offers an unique mechanism for brain information processing. We demonstrate that the neural coding produced by the activity of the brain is well described by our theory of energy coding. Due to the energy coding model’s ability to reveal mechanisms of brain information processing based upon known biophysical properties, we can not only reproduce various experimental results of neuro-electrophysiology, but also quantitatively explain the recent experimental results from neuroscientists at Yale University by means of the principle of energy coding. Due to the theory of energy coding to bridge the gap between functional connections within a biological neural network and energetic consumption, we estimate that the theory has very important consequences for quantitative research of cognitive function. PMID:19003513

Identification of active compounds from Aurantii Immatri Pericarpium attenuating brain injury in a rat model of ischemia-reperfusion.

PubMed

Yang, Eun-Ju; Lim, Sun Ha; Song, Kyung-Sik; Han, Hyung Soo; Lee, Jongwon

2013-05-01

Ischemic stroke is caused by brain injury due to prolonged ischemia by occlusion of cerebral arteries. In this study, we isolated active compounds from an ethanol extract of Aurantii Immatri Pericarpium (HY5356). We first showed by DNA fragmentation assay that HY5356 improved human hepatocellular carcinoma cells (HepG2) under hypoxic conditions by inhibiting apoptosis. When HY5356 was fractionated with dichloromethane (MC), ethyl acetate (EA) and n-butanol (BU), the MC fraction improved cell viability at the lowest concentration (100 μg/ml). Intraperitoneal injection of HY5356 (200 mg/kg) or the MC fraction (200 mg/kg) to rats prior to occlusion attenuated brain injury significantly in a rat model of ischemia-reperfusion. Adopting cell viability under hypoxic conditions as an activity screening system, we isolated nobiletin and tangeretin as active compounds. The results suggest that intake of Aurantii Immatri Pericarpium containing nobiletin and tangeretin as active compounds might be beneficial for preventing ischemic stroke. Copyright © 2012 Elsevier Ltd. All rights reserved.

Type 1 Diabetes Modifies Brain Activation in Young Patients While Performing Visuospatial Working Memory Tasks

PubMed Central

González-Garrido, Andrés A.; Gudayol-Ferré, Esteban; Guàrdia-Olmos, Joan

2015-01-01

In recent years, increasing attention has been paid to the effects of Type 1 Diabetes (T1D) on cognitive functions. T1D onset usually occurs during childhood, so it is possible that the brain could be affected during neurodevelopment. We selected young patients of normal intelligence with T1D onset during neurodevelopment, no complications from diabetes, and adequate glycemic control. The purpose of this study was to compare the neural BOLD activation pattern in a group of patients with T1D versus healthy control subjects while performing a visuospatial working memory task. Sixteen patients and 16 matched healthy control subjects participated. There was no significant statistical difference in behavioral performance between the groups, but, in accordance with our hypothesis, results showed distinct brain activation patterns. Control subjects presented the expected activations related to the task, whereas the patients had greater activation in the prefrontal inferior cortex, basal ganglia, posterior cerebellum, and substantia nigra. These different patterns could be due to compensation mechanisms that allow them to maintain a behavioral performance similar to that of control subjects. PMID:26266268

Atypical temporal activation pattern and central-right brain compensation during semantic judgment task in children with early left brain damage.

PubMed

Chang, Yi-Tzu; Lin, Shih-Che; Meng, Ling-Fu; Fan, Yang-Teng

In this study we investigated the event-related potentials (ERPs) during the semantic judgment task (deciding if the two Chinese characters were semantically related or unrelated) to identify the timing of neural activation in children with early left brain damage (ELBD). The results demonstrated that compared with the controls, children with ELBD had (1) competitive accuracy and reaction time in the semantic judgment task, (2) weak operation of the N400, (3) stronger, earlier and later compensational positivities (referred to the enhanced P200, P250, and P600 amplitudes) in the central and right region of the brain to successfully engage in semantic judgment. Our preliminary findings indicate that temporally postlesional reorganization is in accordance with the proposed right-hemispheric organization of speech after early left-sided brain lesion. During semantic processing, the orthography has a greater effect on the children with ELBD, and a later semantic reanalysis (P600) is required due to the less efficient N400 at the former stage for semantic integration. Copyright © 2018 Elsevier Inc. All rights reserved.

Carbohydrate Nanoparticles for Brain Delivery.

PubMed

Lalatsa, A; Barbu, E

2016-01-01

Many brain tumors and neurological diseases can greatly benefit from the use of emerging nanotechnologies based on targeted nanomedicines that are able to noninvasively transport highly potent and specific pharmaceuticals across the blood-brain barrier. Carbohydrates have received considerable interest as materials for drug carriers due to their natural origin and inherent biodegradability and biocompatibility, as well as due to their hydrophilic character and ease of chemical modification combined with low cost and the possibility for large-scale manufacturing. This chapter provides an overview of the latest research involving the use of carbohydrate-based nanoparticles for drug delivery to the central nervous system. After reviewing the challenges posed by delivering drugs into the brain, the current state-of-the-art approaches for delivery of actives across the blood-brain barrier, including invasive and noninvasive strategies, are presented. A particular focus has been placed on chitosan polymers as they are among the most promising carbohydrate nanocarriers for the preparation and testing of chitosan-based nanomedicines that led, in preclinical proof-of-concept studies, to enhanced brain drug levels and increased pharmacodynamics responses after intravenous, nasal, and oral administration. While chitosan nanoparticles are to date among the most studied and most promising carriers, approaches based on other polysaccharides such as dextran, pullulan, and cellulose warrant further research in the attempt to advance the existing technologies for overcoming the blood-brain barrier. © 2016 Elsevier Inc. All rights reserved.

Solute Carriers in the Blood-Brain Barier: Safety in Abundance.

PubMed

Nałęcz, Katarzyna A

2017-03-01

Blood-brain barrier formed by brain capillary endothelial cells, being in contact with astrocytes endfeet and pericytes, separates extracellular fluid from plasma. Supply of necessary nutrients and removal of certain metabolites takes place due to the activity of transporting proteins from ABC (ATP binding cassette) and SLC (solute carrier) superfamilies. This review is focused on the SLC families involved in transport though the blood-brain barrier of energetic substrates (glucose, monocarboxylates, creatine), amino acids, neurotransmitters and their precursors, as well as organic ions. Members of SLC1, SLC2, SLC3/SLC7, SLC5, SLC6, SLC16, SLC22, SLC38, SLC44, SLC47 and SLCO (SLC21), whose presence in the blood-brain barriers has been demonstrated are characterized with a special emphasis put on polarity of transporters localization in a luminal (blood side) versus an abluminal (brain side) membrane.

In situ immunodetection of neuronal caspase-3 activation in Alzheimer disease.

PubMed

Selznick, L A; Holtzman, D M; Han, B H; Gökden, M; Srinivasan, A N; Johnson, E M; Roth, K A

1999-09-01

The mechanism by which cells die in Alzheimer disease (AD) is unknown. Several investigators speculate that much of the cell loss may be due to apoptosis, a highly regulated form of programmed cell death. Caspase-3 is a critical effector of neuronal apoptosis and may be inappropriately activated in AD. To address this possibility, we examined cortical and hippocampal brain sections from AD patients, as well as 2 animal models of AD, for in situ evidence of caspase-3 activation. We report here that senile plaques and neurofibrillary tangles in the AD brain are not associated with caspase-3 activation. Furthermore, amyloid beta (A beta) deposition in the APPsw transgenic mouse model of AD does not result in caspase-3 activation despite the ability of A beta to induce caspase-3 activation and neuronal apoptosis in vitro. AD brain sections do, however, exhibit caspase-3 activation in hippocampal neurons undergoing granulovacuolar degeneration. Our data suggests that caspase-3 does not have a significant role in the widespread neuronal cell death that occurs in AD, but may contribute to the specific loss of hippocampal neurons involved in learning and memory.

Promethazine as a Novel Prophylaxis and Treatment for Nerve Agent Poisoning

DTIC Science & Technology

2008-12-01

mitochondrial dysfunction. Mitochondrial damage after seizure activity has been previously documented (Cock et al., 2002), and mitochondrial...McDonough et al., 1998), the lack of brain pathology in surviving animals is solely due to the secondary anticholinergic activity of promethazine...rats, Experientia, 41(11), 1457-1458. Department of Health, Expert group on the management of chemical casualties by terrorist activity , 2003: Use

Neonatal pain-related stress, functional cortical activity and visual-perceptual abilities in school-age children born at extremely low gestational age.

PubMed

Doesburg, Sam M; Chau, Cecil M; Cheung, Teresa P L; Moiseev, Alexander; Ribary, Urs; Herdman, Anthony T; Miller, Steven P; Cepeda, Ivan L; Synnes, Anne; Grunau, Ruth E

2013-10-01

Children born very prematurely (< or =32 weeks) often exhibit visual-perceptual difficulties at school-age, even in the absence of major neurological impairment. The alterations in functional brain activity that give rise to such problems, as well as the relationship between adverse neonatal experience and neurodevelopment, remain poorly understood. Repeated procedural pain-related stress during neonatal intensive care has been proposed to contribute to altered neurocognitive development in these children. Due to critical periods in the development of thalamocortical systems, the immature brain of infants born at extremely low gestational age (ELGA; < or =28 weeks) may have heightened vulnerability to neonatal pain. In a cohort of school-age children followed since birth we assessed relations between functional brain activity measured using magnetoencephalogragy (MEG), visual-perceptual abilities and cumulative neonatal pain. We demonstrated alterations in the spectral structure of spontaneous cortical oscillatory activity in ELGA children at school-age. Cumulative neonatal pain-related stress was associated with changes in background cortical rhythmicity in these children, and these alterations in spontaneous brain oscillations were negatively correlated with visual-perceptual abilities at school-age, and were not driven by potentially confounding neonatal variables. These findings provide the first evidence linking neonatal pain-related stress, the development of functional brain activity, and school-age cognitive outcome in these vulnerable children. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Brain activation associated with eccentric movement: A narrative review of the literature.

PubMed

Perrey, Stéphane

2018-02-01

The movement occurring when a muscle exerts tension while lengthening is known as eccentric muscle action. Literature contains limited evidence on how our brain controls eccentric movement. However, how the cortical regions in the motor network are activated during eccentric muscle actions may be critical for understanding the underlying control mechanism of eccentric movements encountered in daily tasks. This is a novel topic that has only recently begun to be investigated through advancements in neuroimaging methods (electroencephalography, EEG; functional magnetic resonance imaging, fMRI). This review summarizes a selection of seven studies indicating mainly: longer time and higher cortical signal amplitude (EEG) for eccentric movement preparation and execution, greater magnitude of cortical signals with wider activated brain area (EEG, fMRI), and weaker brain functional connectivity (fMRI) between primary motor cortex (M1) and other cortical areas involved in the motor network during eccentric muscle actions. Only some differences among studies due to the forms of movement with overload were observed in the contralateral (to the active hand) M1 activity during eccentric movement. Altogether, the findings indicate an important challenge to the brain for controlling the eccentric movement. However, our understanding remains limited regarding the acute effects of eccentric exercise on cortical regions and their cooperation as functional networks that support motor functions. Further analysis and standardized protocols will provide deeper insights into how different cortical regions of the underlying motor network interplay with each other in increasingly demanding muscle exertions in eccentric mode.

Intravenous Heroin Induces Rapid Brain Hypoxia and Hyperglycemia that Precede Brain Metabolic Response.

PubMed

Solis, Ernesto; Cameron-Burr, Keaton T; Shaham, Yavin; Kiyatkin, Eugene A

2017-01-01

Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100-200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO 2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity.

Learning Computational Models of Video Memorability from fMRI Brain Imaging.

PubMed

Han, Junwei; Chen, Changyuan; Shao, Ling; Hu, Xintao; Han, Jungong; Liu, Tianming

2015-08-01

Generally, various visual media are unequally memorable by the human brain. This paper looks into a new direction of modeling the memorability of video clips and automatically predicting how memorable they are by learning from brain functional magnetic resonance imaging (fMRI). We propose a novel computational framework by integrating the power of low-level audiovisual features and brain activity decoding via fMRI. Initially, a user study experiment is performed to create a ground truth database for measuring video memorability and a set of effective low-level audiovisual features is examined in this database. Then, human subjects' brain fMRI data are obtained when they are watching the video clips. The fMRI-derived features that convey the brain activity of memorizing videos are extracted using a universal brain reference system. Finally, due to the fact that fMRI scanning is expensive and time-consuming, a computational model is learned on our benchmark dataset with the objective of maximizing the correlation between the low-level audiovisual features and the fMRI-derived features using joint subspace learning. The learned model can then automatically predict the memorability of videos without fMRI scans. Evaluations on publically available image and video databases demonstrate the effectiveness of the proposed framework.

Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

NASA Astrophysics Data System (ADS)

Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

2016-11-01

Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications.

Characterizing Focused-Ultrasound Mediated Drug Delivery to the Heterogeneous Primate Brain In Vivo with Acoustic Monitoring

PubMed Central

Wu, Shih-Ying; Sanchez, Carlos Sierra; Samiotaki, Gesthimani; Buch, Amanda; Ferrera, Vincent P.; Konofagou, Elisa E.

2016-01-01

Focused ultrasound with microbubbles has been used to noninvasively and selectively deliver pharmacological agents across the blood-brain barrier (BBB) for treating brain diseases. Acoustic cavitation monitoring could serve as an on-line tool to assess and control the treatment. While it demonstrated a strong correlation in small animals, its translation to primates remains in question due to the anatomically different and highly heterogeneous brain structures with gray and white matteras well as dense vasculature. In addition, the drug delivery efficiency and the BBB opening volume have never been shown to be predictable through cavitation monitoring in primates. This study aimed at determining how cavitation activity is correlated with the amount and concentration of gadolinium delivered through the BBB and its associated delivery efficiency as well as the BBB opening volume in non-human primates. Another important finding entails the effect of heterogeneous brain anatomy and vasculature of a primate brain, i.e., presence of large cerebral vessels, gray and white matter that will also affect the cavitation activity associated with variation of BBB opening in different tissue types, which is not typically observed in small animals. Both these new findings are critical in the primate brain and provide essential information for clinical applications. PMID:27853267

Role of connexins in metastatic breast cancer and melanoma brain colonization

PubMed Central

Stoletov, Konstantin; Strnadel, Jan; Zardouzian, Erin; Momiyama, Masashi; Park, Frederick D.; Kelber, Jonathan A.; Pizzo, Donald P.; Hoffman, Robert; VandenBerg, Scott R.; Klemke, Richard L.

2013-01-01

Summary Breast cancer and melanoma cells commonly metastasize to the brain using homing mechanisms that are poorly understood. Cancer patients with brain metastases display poor prognosis and survival due to the lack of effective therapeutics and treatment strategies. Recent work using intravital microscopy and preclinical animal models indicates that metastatic cells colonize the brain, specifically in close contact with the existing brain vasculature. However, it is not known how contact with the vascular niche promotes microtumor formation. Here, we investigate the role of connexins in mediating early events in brain colonization using transparent zebrafish and chicken embryo models of brain metastasis. We provide evidence that breast cancer and melanoma cells utilize connexin gap junction proteins (Cx43, Cx26) to initiate brain metastatic lesion formation in association with the vasculature. RNAi depletion of connexins or pharmacological blocking of connexin-mediated cell–cell communication with carbenoxolone inhibited brain colonization by blocking tumor cell extravasation and blood vessel co-option. Activation of the metastatic gene twist in breast cancer cells increased Cx43 protein expression and gap junction communication, leading to increased extravasation, blood vessel co-option and brain colonization. Conversely, inhibiting twist activity reduced Cx43-mediated gap junction coupling and brain colonization. Database analyses of patient histories revealed increased expression of Cx26 and Cx43 in primary melanoma and breast cancer tumors, respectively, which correlated with increased cancer recurrence and metastasis. Together, our data indicate that Cx43 and Cx26 mediate cancer cell metastasis to the brain and suggest that connexins might be exploited therapeutically to benefit cancer patients with metastatic disease. PMID:23321642

Alteration of Electro-Cortical Activity in Microgravity

NASA Astrophysics Data System (ADS)

Schneider, Stefan; Brummer, Vera; Carnahan, Heather; Askew, Christopher D.; Guardiera, Simon; Struder, Heiko K.

2008-06-01

There is growing interest in the effects of weightlessness on central nervous system (CNS) activity. Due to technical and logistical limitations it presently seems impossible to apply imaging techniques as fMRI or PET in weightless environments e.g. on ISS or during parabolic flights. Within this study we evaluated changes in brain cortical activity using low resolution brain electromagnetic tomography (LORETA) during parabolic flights. Results showed a distinct inhibition of right frontal area activity >12Hz during phases of microgravity compared to normal gravity. We conclude that the inhibition of high frequency frontal activity during microgravity may serve as a marker of emotional anxiety and/or indisposition associated with weightlessness. This puts a new light on the debate as to whether cognitive and sensorimotor impairments are attributable to primary physiological effects or secondary psychological effects of a weightless environment.

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia

PubMed Central

Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

2016-01-01

Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities. PMID:27273195

CRF receptor 1 antagonism and brain distribution of active components contribute to the ameliorative effect of rikkunshito on stress-induced anorexia.

PubMed

Mogami, Sachiko; Sadakane, Chiharu; Nahata, Miwa; Mizuhara, Yasuharu; Yamada, Chihiro; Hattori, Tomohisa; Takeda, Hiroshi

2016-06-08

Rikkunshito (RKT), a Kampo medicine, has been reported to show an ameliorative effect on sustained hypophagia after novelty stress exposure in aged mice through serotonin 2C receptor (5-HT2CR) antagonism. We aimed to determine (1) whether the activation of anorexigenic neurons, corticotropin-releasing factor (CRF), and pro-opiomelanocortin (POMC) neurons, is involved in the initiation of hypophagia induced by novelty stress in aged mice; (2) whether the ameliorative effect of RKT is associated with CRF and POMC neurons and downstream signal transduction; and (3) the plasma and brain distribution of the active components of RKT. The administration of RKT or 5-HT2CR, CRF receptor 1 (CRFR1), and melanocortin-4 receptor antagonists significantly restored the decreased food intake observed in aged male C57BL/6 mice in the early stage after novelty stress exposure. Seven components of RKT exhibited antagonistic activity against CRFR1. Hesperetin and isoliquiritigenin, which showed antagonistic effects against both CRFR1 and 5-HT2CR, were distributed in the plasma and brain of male Sprague-Dawley rats after a single oral administration of RKT. In conclusion, the ameliorative effect of RKT in this model is assumed to be at least partly due to brain-distributed active components possessing 5-HT2CR and CRFR1 antagonistic activities.

Brain activation changes during locomotion in middle-aged to older adults with multiple sclerosis.

PubMed

Hernandez, Manuel E; Holtzer, Roee; Chaparro, Gioella; Jean, Kharine; Balto, Julia M; Sandroff, Brian M; Izzetoglu, Meltem; Motl, Robert W

2016-11-15

Mobility and cognitive impairments are common in persons with multiple sclerosis (MS), and are expected to worsen with increasing age. However, no studies, to date, in part due to limitations of conventional neuroimaging methods, have examined changes in brain activation patterns during active locomotion in older patients with MS. This study used functional Near Infrared Spectroscopy (fNIRS) to evaluate real-time neural activation differences in the pre-frontal cortex (PFC) between middle-aged to older adults with MS and healthy controls during single (Normal Walk; NW) and dual-task (Walking While Talking; WWT) locomotion tasks. Eight middle-aged to older adults with MS and eight healthy controls underwent fNIRS recording while performing the NW and WWT tasks with an fNIRS cap consisting of 16 optodes positioned over the forehead. The MS group had greater elevations in PFC oxygenation levels during WWT compared to NW than healthy controls. There was no walking performance difference between groups during locomotion. These findings suggest that middle-aged to older individuals with MS might be able to achieve similar levels of performance through the use of increased brain activation. This study is the first to investigate brain activation changes during the performance of simple and divided-attention locomotion tasks in MS using fNIRS. Copyright © 2016 Elsevier B.V. All rights reserved.

Cognitive tutoring induces widespread neuroplasticity and remediates brain function in children with mathematical learning disabilities

PubMed Central

Iuculano, Teresa; Rosenberg-Lee, Miriam; Richardson, Jennifer; Tenison, Caitlin; Fuchs, Lynn; Supekar, Kaustubh; Menon, Vinod

2015-01-01

Competency with numbers is essential in today's society; yet, up to 20% of children exhibit moderate to severe mathematical learning disabilities (MLD). Behavioural intervention can be effective, but the neurobiological mechanisms underlying successful intervention are unknown. Here we demonstrate that eight weeks of 1:1 cognitive tutoring not only remediates poor performance in children with MLD, but also induces widespread changes in brain activity. Neuroplasticity manifests as normalization of aberrant functional responses in a distributed network of parietal, prefrontal and ventral temporal–occipital areas that support successful numerical problem solving, and is correlated with performance gains. Remarkably, machine learning algorithms show that brain activity patterns in children with MLD are significantly discriminable from neurotypical peers before, but not after, tutoring, suggesting that behavioural gains are not due to compensatory mechanisms. Our study identifies functional brain mechanisms underlying effective intervention in children with MLD and provides novel metrics for assessing response to intervention. PMID:26419418

Using EEG/MEG Data of Cognitive Processes in Brain-Computer Interfaces

NASA Astrophysics Data System (ADS)

Gutiérrez, David

2008-08-01

Brain-computer interfaces (BCIs) aim at providing a non-muscular channel for sending commands to the external world using electroencephalographic (EEG) and, more recently, magnetoencephalographic (MEG) measurements of the brain function. Most of the current implementations of BCIs rely on EEG/MEG data of motor activities as such neural processes are well characterized, while the use of data related to cognitive activities has been neglected due to its intrinsic complexity. However, cognitive data usually has larger amplitude, lasts longer and, in some cases, cognitive brain signals are easier to control at will than motor signals. This paper briefy reviews the use of EEG/MEG data of cognitive processes in the implementation of BCIs. Specifically, this paper reviews some of the neuromechanisms, signal features, and processing methods involved. This paper also refers to some of the author's work in the area of detection and classifcation of cognitive signals for BCIs using variability enhancement, parametric modeling, and spatial fltering, as well as recent developments in BCI performance evaluation.

Using EEG/MEG Data of Cognitive Processes in Brain-Computer Interfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gutierrez, David

2008-08-11

Brain-computer interfaces (BCIs) aim at providing a non-muscular channel for sending commands to the external world using electroencephalographic (EEG) and, more recently, magnetoencephalographic (MEG) measurements of the brain function. Most of the current implementations of BCIs rely on EEG/MEG data of motor activities as such neural processes are well characterized, while the use of data related to cognitive activities has been neglected due to its intrinsic complexity. However, cognitive data usually has larger amplitude, lasts longer and, in some cases, cognitive brain signals are easier to control at will than motor signals. This paper briefy reviews the use of EEG/MEGmore » data of cognitive processes in the implementation of BCIs. Specifically, this paper reviews some of the neuromechanisms, signal features, and processing methods involved. This paper also refers to some of the author's work in the area of detection and classifcation of cognitive signals for BCIs using variability enhancement, parametric modeling, and spatial fltering, as well as recent developments in BCI performance evaluation.« less

Zolpidem efficacy and safety in disorders of consciousness.

PubMed

Machado, Calixto; Estévez, Mario; Rodriguez-Rojas, Rafael

2018-01-01

Sutton and Clauss presented a detailed review about the effectiveness of zolpidem, discussing recoveries from brain damage due to strokes, trauma and hypoxia. A significant finding has been the unexpected and paradoxical increment of brain activity in vegetative state/unresponsive wakefulness syndrome (VS/UWS). On the contrary, zolpidem is considered one of the best sleep inducers in normal subjects. We have studied series of VS/UWS cases after zolpidem intake. We have demonstrated EEG activation, increment of BOLD signal in different brain regions, and an autonomic influence, mainly characterized by a vagolytic chronotropic effect without a significant increment of the vasomotor sympathetic tone. As this autonomic imbalance might induce cardio- circulatory complications, which we didn't find in any of our patients, we suggest developing future trials under control of physiological indices by bedside monitoring. However, considering that the paradoxical arousing zolpidem effect might be certainly related to brain function improvement, we agree with Sutton and Clauss that future multicentre and multinational clinical trials should be developed, but under control of physiological indices.

N-Benzoyl-D-phenylalanine attenuates brain acetylcholinesterase in neonatal streptozotocin-diabetic rats.

PubMed

Ashokkumar, Natarajan; Pari, Leelavinothan; Ramkumar, Kunga Mohan

2006-09-01

The effect of hyperglycaemia due to experimental diabetes in male Wistar rats causes a decrease in the level of acetylcholinesterase (AChE) with significant increase in lipid peroxidative markers: thiobarbituric acid-reactive substances (TBARS) and hydroperoxides in brains of experimental animals. The decreased activity of both salt soluble and detergent soluble acetylcholinesterase observed in diabetes may be attributed to lack of insulin which causes specific alterations in the level of neurotransmitter, thus causing brain dysfunction. Administration of non-sulfonylurea drug N-benzoyl-D-phenylalanine (NBDP) could protect against direct action of lipid peroxidation on brain AChE and in this way it might be useful in the prevention of cholinergic neural dysfunction, which is one of the major complications in diabetes.

A prediction of templates in the auditory cortex system

NASA Astrophysics Data System (ADS)

Ghanbeigi, Kimia

In this study variation of human auditory evoked mismatch field amplitudes in response to complex tones as a function of the removal in single partials in the onset period was investigated. It was determined: 1-A single frequency elimination in a sound stimulus plays a significant role in human brain sound recognition. 2-By comparing the mismatches of the brain response due to a single frequency elimination in the "Starting Transient" and "Sustain Part" of the sound stimulus, it is found that the brain is more sensitive to frequency elimination in the Starting Transient. This study involves 4 healthy subjects with normal hearing. Neural activity was recorded with stimulus whole-head MEG. Verification of spatial location in the auditory cortex was determined by comparing with MRI images. In the first set of stimuli, repetitive ('standard') tones with five selected onset frequencies were randomly embedded in the string of rare ('deviant') tones with randomly varying inter stimulus intervals. In the deviant tones one of the frequency components was omitted relative to the deviant tones during the onset period. The frequency of the test partial of the complex tone was intentionally selected to preclude its reinsertion by generation of harmonics or combination tones due to either the nonlinearity of the ear, the electronic equipment or the brain processing. In the second set of stimuli, time structured as above, repetitive ('standard') tones with five selected sustained frequency components were embedded in the string of rare '(deviant') tones for which one of these selected frequencies was omitted in the sustained tone. In both measurements, the carefully frequency selection precluded their reinsertion by generation of harmonics or combination tones due to the nonlinearity of the ear, the electronic equipment and brain processing. The same considerations for selecting the test frequency partial were applied. Results. By comparing MMN of the two data sets, the relative contribution to sound recognition of the omitted partial frequency components in the onset and sustained regions has been determined. Conclusion. The presence of significant mismatch negativity, due to neural activity of auditory cortex, emphasizes that the brain recognizes the elimination of a single frequency of carefully chosen anharmonic frequencies. It was shown this mismatch is more significant if the single frequency elimination occurs in the onset period.

Characterization of task-free and task-performance brain states via functional connectome patterns.

PubMed

Zhang, Xin; Guo, Lei; Li, Xiang; Zhang, Tuo; Zhu, Dajiang; Li, Kaiming; Chen, Hanbo; Lv, Jinglei; Jin, Changfeng; Zhao, Qun; Li, Lingjiang; Liu, Tianming

2013-12-01

Both resting state fMRI (R-fMRI) and task-based fMRI (T-fMRI) have been widely used to study the functional activities of the human brain during task-free and task-performance periods, respectively. However, due to the difficulty in strictly controlling the participating subject's mental status and their cognitive behaviors during R-fMRI/T-fMRI scans, it has been challenging to ascertain whether or not an R-fMRI/T-fMRI scan truly reflects the participant's functional brain states during task-free/task-performance periods. This paper presents a novel computational approach to characterizing and differentiating the brain's functional status into task-free or task-performance states, by which the functional brain activities can be effectively understood and differentiated. Briefly, the brain's functional state is represented by a whole-brain quasi-stable connectome pattern (WQCP) of R-fMRI or T-fMRI data based on 358 consistent cortical landmarks across individuals, and then an effective sparse representation method was applied to learn the atomic connectome patterns (ACPs) of both task-free and task-performance states. Experimental results demonstrated that the learned ACPs for R-fMRI and T-fMRI datasets are substantially different, as expected. A certain portion of ACPs from R-fMRI and T-fMRI data were overlapped, suggesting some subjects with overlapping ACPs were not in the expected task-free/task-performance brain states. Besides, potential outliers in the T-fMRI dataset were further investigated via functional activation detections in different groups, and our results revealed unexpected task-performances of some subjects. This work offers novel insights into the functional architectures of the brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Characterization of Task-free and Task-performance Brain States via Functional Connectome Patterns

PubMed Central

Zhang, Xin; Guo, Lei; Li, Xiang; Zhang, Tuo; Zhu, Dajiang; Li, Kaiming; Chen, Hanbo; Lv, Jinglei; Jin, Changfeng; Zhao, Qun; Li, Lingjiang; Liu, Tianming

2014-01-01

Both resting state fMRI (R-fMRI) and task-based fMRI (T-fMRI) have been widely used to study the functional activities of the human brain during task-free and task-performance periods, respectively. However, due to the difficulty in strictly controlling the participating subject's mental status and their cognitive behaviors during R-fMRI/T-fMRI scans, it has been challenging to ascertain whether or not an R-fMRI/T-fMRI scan truly reflects the participant's functional brain states during task-free/task-performance periods. This paper presents a novel computational approach to characterizing and differentiating the brain's functional status into task-free or task-performance states, by which the functional brain activities can be effectively understood and differentiated. Briefly, the brain's functional state is represented by a whole-brain quasi-stable connectome pattern (WQCP) of R-fMRI or T-fMRI data based on 358 consistent cortical landmarks across individuals, and then an effective sparse representation method was applied to learn the atomic connectome patterns (ACP) of both task-free and task-performance states. Experimental results demonstrated that the learned ACPs for R-fMRI and T-fMRI datasets are substantially different, as expected. A certain portion of ACPs from R-fMRI and T-fMRI data were overlapped, suggesting some subjects with overlapping ACPs were not in the expected task-free/task-performance brain states. Besides, potential outliers in the T-fMRI dataset were further investigated via functional activation detections in different groups, and our results revealed unexpected task-performances of some subjects. This work offers novel insights into the functional architectures of the brain. PMID:23938590

Monitoring of human brain functions in risk decision-making task by diffuse optical tomography using voxel-wise general linear model

NASA Astrophysics Data System (ADS)

Lin, Zi-Jing; Li, Lin; Cazzell, Marry; Liu, Hanli

2013-03-01

Functional near-infrared spectroscopy (fNIRS) is a non-invasive imaging technique which measures the hemodynamic changes that reflect the brain activity. Diffuse optical tomography (DOT), a variant of fNIRS with multi-channel NIRS measurements, has demonstrated capability of three dimensional (3D) reconstructions of hemodynamic changes due to the brain activity. Conventional method of DOT image analysis to define the brain activation is based upon the paired t-test between two different states, such as resting-state versus task-state. However, it has limitation because the selection of activation and post-activation period is relatively subjective. General linear model (GLM) based analysis can overcome this limitation. In this study, we combine the 3D DOT image reconstruction with GLM-based analysis (i.e., voxel-wise GLM analysis) to investigate the brain activity that is associated with the risk-decision making process. Risk decision-making is an important cognitive process and thus is an essential topic in the field of neuroscience. The balloon analogue risk task (BART) is a valid experimental model and has been commonly used in behavioral measures to assess human risk taking action and tendency while facing risks. We have utilized the BART paradigm with a blocked design to investigate brain activations in the prefrontal and frontal cortical areas during decision-making. Voxel-wise GLM analysis was performed on 18human participants (10 males and 8females).In this work, we wish to demonstrate the feasibility of using voxel-wise GLM analysis to image and study cognitive functions in response to risk decision making by DOT. Results have shown significant changes in the dorsal lateral prefrontal cortex (DLPFC) during the active choice mode and a different hemodynamic pattern between genders, which are in good agreements with published literatures in functional magnetic resonance imaging (fMRI) and fNIRS studies.

Distinct subcellular patterns of neprilysin protein and activity in the brains of Alzheimer’s disease patients, transgenic mice and cultured human neuronal cells

PubMed Central

Zhou, Li; Wei, Chunsheng; Huang, Wei; Bennett, David A; Dickson, Dennis W; Wang, Rui; Wang, Dengshun

2013-01-01

We investigated the subcellular distribution of NEP protein and activity in brains of human individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI) and AD dementia, as well as double transgenic mice and human neuronal cell line treated with Aβ and 4-hydroxy-2-nonenal (HNE). Total cortical neuronal-related NEP was significantly increased in MCI compared to NCI brains. NeuN was decreased in both MCI and AD, consistent with neuronal loss occurring in MCI and AD. Negative relationship between NEP protein and NeuN in MCI brains, and positive correlation between NEP and pan-cadherin in NCI and MCI brains, suggesting the increased NEP expression in NCI and MCI might be due to membrane associated NEP in non-neuronal cells. In subcellular extracts, NEP protein decreased in cytoplasmic fractions in MCI and AD, but increased in membrane fractions, with a significant increase in the membrane/cytoplasmic ratio of NEP protein in AD brains. By contrast, NEP activity was decreased in AD. Similar results were observed in AD-mimic transgenic mice. Studies of SH-SY5Y neuroblastoma showed an up-regulation of NEP protein in the cytoplasmic compartment induced by HNE and Aβ; however, NEP activity decreased in cytoplasmic fractions. Activity of NEP in membrane fractions increased at 48 hours and then significantly decreased after treatment with HNE and Aβ. The cytoplasmic/membrane ratio of NEP protein increased at 24 hours and then decreased in both HNE and Aβ treated cells. Both HNE and Aβ up-regulate NEP expression, but NEP enzyme activity did not show the same increase, possibly indicating immature cytoplasmic NEP is less active than membrane associated NEP. These observations indicate that modulation of NEP protein levels and its subcellular location influence the net proteolytic activity and this complex association might participate in deficiency of Aβ degradation that is associated with amyloid deposition in AD. PMID:24093058

Pathophysiology and the Monitoring Methods for Cardiac Arrest Associated Brain Injury.

PubMed

Reis, Cesar; Akyol, Onat; Araujo, Camila; Huang, Lei; Enkhjargal, Budbazar; Malaguit, Jay; Gospodarev, Vadim; Zhang, John H

2017-01-11

Cardiac arrest (CA) is a well-known cause of global brain ischemia. After CA and subsequent loss of consciousness, oxygen tension starts to decline and leads to a series of cellular changes that will lead to cellular death, if not reversed immediately, with brain edema as a result. The electroencephalographic activity starts to change as well. Although increased intracranial pressure (ICP) is not a direct result of cardiac arrest, it can still occur due to hypoxic-ischemic encephalopathy induced changes in brain tissue, and is a measure of brain edema after CA and ischemic brain injury. In this review, we will discuss the pathophysiology of brain edema after CA, some available techniques, and methods to monitor brain oxygen, electroencephalography (EEG), ICP (intracranial pressure), and microdialysis on its measurement of cerebral metabolism and its usefulness both in clinical practice and possible basic science research in development. With this review, we hope to gain knowledge of the more personalized information about patient status and specifics of their brain injury, and thus facilitating the physicians' decision making in terms of which treatments to pursue.

Circulating Neprilysin Clears Brain Amyloid

PubMed Central

Liu, Yinxing; Studzinski, Christa; Beckett, Tina; Murphy, M. Paul; Klein, Ronald L.; Hersh, Louis B.

2010-01-01

The use of the peptidase neprilysin (NEP) as a therapeutic for lowering brain amyloid burden is receiving increasing attention. We have previously demonstrated that peripheral expression of NEP on the surface of hindlimb muscle lowers brain amyloid burden in a transgenic mouse model of Alzheimer’s disease. In this study we now show that using adeno-associated virus expressing a soluble secreted form of NEP (secNEP-AAV8), NEP secreted into plasma is effective in clearing brain Aβ. Soluble NEP expression in plasma was sustained over the 3-month time period it was measured. Secreted NEP decreased plasma Aβ by 30%, soluble brain Aβ by ~28%, insoluble brain Aβ by ~55%, and Aβ oligomers by 12%. This secNEP did not change plasma levels of substance P or bradykinin, nor did it alter blood pressure. No NEP was detected in CSF, nor did the AAV virus produce brain expression of NEP. Thus the lowering of brain Aβ was due to plasma NEP which altered blood-brain Aβ transport dynamics. Expressing NEP in plasma provides a convenient way to monitor enzyme activity during the course of its therapeutic testing. PMID:20558294

Neural dynamics in Parkinsonian brain: The boundary between synchronized and nonsynchronized dynamics

NASA Astrophysics Data System (ADS)

Park, Choongseok; Worth, Robert M.; Rubchinsky, Leonid L.

2011-04-01

Synchronous oscillatory dynamics is frequently observed in the human brain. We analyze the fine temporal structure of phase-locking in a realistic network model and match it with the experimental data from Parkinsonian patients. We show that the experimentally observed intermittent synchrony can be generated just by moderately increased coupling strength in the basal ganglia circuits due to the lack of dopamine. Comparison of the experimental and modeling data suggest that brain activity in Parkinson's disease resides in the large boundary region between synchronized and nonsynchronized dynamics. Being on the edge of synchrony may allow for easy formation of transient neuronal assemblies.

Role of erythropoietin in the brain

PubMed Central

Noguchi, Constance Tom; Asavaritikrai, Pundit; Teng, Ruifeng; Jia, Yi

2007-01-01

Multi-tissue erythropoietin receptor (EPO-R) expression provides for erythropoietin (EPO) activity beyond its known regulation of red blood cell production. This review highlights the role of EPO and EPO-R in brain development and neuroprotection. EPO-R brain expression includes neural progenitor cells (NPC), neurons, glial cells and endothelial cells. EPO is produced in brain in a hypoxia sensitive manner, stimulates NPC proliferation and differentiation, and neuron survival, and contributes to ischemic preconditioning. Mice lacking EPO or EPO-R exhibit increased neural cell apoptosis during development before embryonic death due to severe anemia. EPO administration provides neural protection in animal models of brain ischemia and trauma, reducing the extent of injury and damage. EPO stimulation of endothelial cells contributes to neuroprotection and is of particular importance since only low levels of EPO appear to cross the blood-brain barrier when administered at high dose intravenously. The therapeutic potential of EPO for brain ischemia/trauma and neurodegenerative diseases has shown promise in early clinical trial and awaits further validation. PMID:17482474

Roadmap on neurophotonics

NASA Astrophysics Data System (ADS)

Cho, Yong Ku; Zheng, Guoan; Augustine, George J.; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S.; Vellekoop, Ivo M.; Booth, Martin J.; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2016-09-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken.

Roadmap on neurophotonics

PubMed Central

Cho, Yong Ku; Zheng, Guoan; Augustine, George J; Hochbaum, Daniel; Cohen, Adam; Knöpfel, Thomas; Pisanello, Ferruccio; Pavone, Francesco S; Vellekoop, Ivo M; Booth, Martin J; Hu, Song; Zhu, Jiang; Chen, Zhongping; Hoshi, Yoko

2017-01-01

Mechanistic understanding of how the brain gives rise to complex behavioral and cognitive functions is one of science’s grand challenges. The technical challenges that we face as we attempt to gain a systems-level understanding of the brain are manifold. The brain’s structural complexity requires us to push the limit of imaging resolution and depth, while being able to cover large areas, resulting in enormous data acquisition and processing needs. Furthermore, it is necessary to detect functional activities and ‘map’ them onto the structural features. The functional activity occurs at multiple levels, using electrical and chemical signals. Certain electrical signals are only decipherable with sub-millisecond timescale resolution, while other modes of signals occur in minutes to hours. For these reasons, there is a wide consensus that new tools are necessary to undertake this daunting task. Optical techniques, due to their versatile and scalable nature, have great potentials to answer these challenges. Optical microscopy can now image beyond the diffraction limit, record multiple types of brain activity, and trace structural features across large areas of tissue. Genetically encoded molecular tools opened doors to controlling and detecting neural activity using light in specific cell types within the intact brain. Novel sample preparation methods that reduce light scattering have been developed, allowing whole brain imaging in rodent models. Adaptive optical methods have the potential to resolve images from deep brain regions. In this roadmap article, we showcase a few major advances in this area, survey the current challenges, and identify potential future needs that may be used as a guideline for the next steps to be taken. PMID:28386392

How are things adding up? Neural differences between arithmetic operations are due to general problem solving strategies.

PubMed

Tschentscher, Nadja; Hauk, Olaf

2014-05-15

A number of previous studies have interpreted differences in brain activation between arithmetic operation types (e.g. addition and multiplication) as evidence in favor of distinct cortical representations, processes or neural systems. It is still not clear how differences in general task complexity contribute to these neural differences. Here, we used a mental arithmetic paradigm to disentangle brain areas related to general problem solving from those involved in operation type specific processes (addition versus multiplication). We orthogonally varied operation type and complexity. Importantly, complexity was defined not only based on surface criteria (for example number size), but also on the basis of individual participants' strategy ratings, which were validated in a detailed behavioral analysis. We replicated previously reported operation type effects in our analyses based on surface criteria. However, these effects vanished when controlling for individual strategies. Instead, procedural strategies contrasted with memory retrieval reliably activated fronto-parietal and motor regions, while retrieval strategies activated parietal cortices. This challenges views that operation types rely on partially different neural systems, and suggests that previously reported differences between operation types may have emerged due to invalid measures of complexity. We conclude that mental arithmetic is a powerful paradigm to study brain networks of abstract problem solving, as long as individual participants' strategies are taken into account. Copyright © 2014 Elsevier Inc. All rights reserved.

I(2)(PP2A) regulates p53 and Akt correlatively and leads the neurons to abort apoptosis.

PubMed

Liu, Gong-Ping; Wei, Wei; Zhou, Xin; Zhang, Yao; Shi, Hai-Hong; Yin, Jun; Yao, Xiu-Qing; Peng, Cai-Xia; Hu, Juan; Wang, Qun; Li, Hong-Lian; Wang, Jian-Zhi

2012-02-01

A chronic neuron loss is the cardinal pathology in Alzheimer disease (AD), but it is still not understood why most neurons in AD brain do not accomplish apoptosis even though they are actually exposed to an environment with enriched proapoptotic factors. Protein phosphatase-2A inhibitor-2 (I(2)(PP2A)), an endogenous PP2A inhibitor, is significantly increased in AD brain, but the role of I(2)(PP2A) in AD-like neuron loss is elusive. Here, we show that I(2)(PP2A) regulates p53 and Akt correlatively. The mechanisms involve activated transcription and p38 MAPK activities. More importantly, we demonstrate that the simultaneous activation of Akt induced by I(2)(PP2A) counteracts the hyperactivated p53-induced cell apoptosis. Furthermore, I(2)(PP2A), p53 and Akt are all elevated in the brain of mouse model and AD patients. Our results suggest that the increased I(2)(PP2A) may trigger apoptosis by p53 upregulation, but due to simultaneous activation of Akt, the neurons are aborted from the apoptotic pathway. This finding contributes to the understanding of why most neurons in AD brain do not undergo apoptosis. Copyright © 2010. Published by Elsevier Inc.

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

PubMed

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

2016-04-01

Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12 years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain. Copyright © 2016 Elsevier Inc. All rights reserved.

Novel Genetic Models to Study the Role of Inflammation in Brain Injury-Induced Alzheimer’s Pathology

DTIC Science & Technology

2013-10-01

REPORT TYPE Annual 3. DATES COVERED 30 Sep 2012 – 29 Sep 2013 4 . TITLE AND SUBTITLE 5a. CONTRACT NUMBER Novel Genetic Models to Study the Role...infiltration and activation of monocytes due to disruption of the blood-brain barrier [ 4 -6]. Assessing the exact roles of these cells in AD pathogenesis...paradigm of TBI Statement of Work: Task 1. Generate animals required for studies (timeframe, months 2- 4 ) Task 2. Perform FPI (timeframe, months 4 -8

Pain when love is near

NASA Astrophysics Data System (ADS)

Tamam, S.; Ahmad, A. H.; Aziz, M. E.; Kamil, W. A.

2017-05-01

The aim of the study is to investigate brain responses to acute laser pain when a loved one is nearby. Laser pain stimuli at individual pain threshold were delivered using Th:YAG laser to 17 female participants. The participants were categorised into two groups, Love Hurts or Love Heals, according to their responses to pain stimulation during the presence of their loved ones. fMRI brain activation was obtained using 3 T Philips Achieva MRI scanner utilising blocked design paradigm comprising 15 blocks of stimulation phase and 15 blocks of no stimulation. fMRI images were analysed using statistical parametric mapping (SPM) focusing on random effects (RFX) analysis. We found that both groups activated pain-related areas such as the thalamus, secondary somatosensory cortex, insula and cingulate cortex. However, Love Hurts showed more activity in thalamus, parahippocampal gyrus and hippocampus; while Love Heals showed more activity in the entire part of cingulate cortex during the presence of their loved ones. In conclusion, there may be specific brain regions responsible for modulation of pain due to the presence of a loved one thus manifesting as Love Hurts or Love Heals.

Platelet activating factor induces transient blood-brain barrier opening to facilitate edaravone penetration into the brain.

PubMed

Fang, Weirong; Zhang, Rui; Sha, Lan; Lv, Peng; Shang, Erxin; Han, Dan; Wei, Jie; Geng, Xiaohan; Yang, Qichuan; Li, Yunman

2014-03-01

The blood-brain barrier (BBB) greatly limits the efficacy of many neuroprotective drugs' delivery to the brain, so improving drug penetration through the BBB has been an important focus of research. Here we report that platelet activating factor (PAF) transiently opened BBB and facilitated neuroprotectant edaravone penetration into the brain. Intravenous infusion with PAF induced a transient BBB opening in rats, reflected by increased Evans blue leakage and mild edema formation, which ceased within 6 h. Furthermore, rat regional cerebral blood flow (rCBF) declined acutely during PAF infusion, but recovered slowly. More importantly, this transient BBB opening significantly increased the penetration of edaravone into the brain, evidenced by increased edaravone concentrations in tissue interstitial fluid collected by microdialysis and analyzed by Ultra-performance liquid chromatograph combined with a hybrid quadrupole time-of-flight mass spectrometer (UPLC-MS/MS). Similarly, incubation of rat brain microvessel endothelial cells monolayer with 1 μM PAF for 1 h significantly increased monolayer permeability to (125)I-albumin, which recovered 1 h after PAF elimination. However, PAF incubation with rat brain microvessel endothelial cells for 1 h did not cause detectable cytotoxicity, and did not regulate intercellular adhesion molecule-1, matrix-metalloproteinase-9 and P-glycoprotein expression. In conclusion, PAF could induce transient and reversible BBB opening through abrupt rCBF decline, which significantly improved edaravone penetration into the brain. Platelet activating factor (PAF) transiently induces BBB dysfunction and increases BBB permeability, which may be due to vessel contraction and a temporary decline of regional cerebral blood flow (rCBF) triggered by PAF. More importantly, the PAF induced transient BBB opening facilitates neuroprotectant edaravone penetration into brain. The results of this study may provide a new approach to improve drug delivery into the brain. © 2013 International Society for Neurochemistry.

The behavioral and neural binding phenomena during visuomotor integration of angry facial expressions.

PubMed

Coll, Sélim Yahia; Ceravolo, Leonardo; Frühholz, Sascha; Grandjean, Didier

2018-05-02

Different parts of our brain code the perceptual features and actions related to an object, causing a binding problem, in which the brain has to integrate information related to an event without any interference regarding the features and actions involved in other concurrently processed events. Using a paradigm similar to Hommel, who revealed perception-action bindings, we showed that emotion could bind with motor actions when relevant, and in specific conditions, irrelevant for the task. By adapting our protocol to a functional Magnetic Resonance Imaging paradigm we investigated, in the present study, the neural bases of the emotion-action binding with task-relevant angry faces. Our results showed that emotion bound with motor responses. This integration revealed increased activity in distributed brain areas involved in: (i) memory, including the hippocampi; (ii) motor actions with the precentral gyri; (iii) and emotion processing with the insula. Interestingly, increased activations in the cingulate gyri and putamen, highlighted their potential key role in the emotion-action binding, due to their involvement in emotion processing, motor actions, and memory. The present study confirmed our previous results and point out for the first time the functional brain activity related to the emotion-action association.

Fetal brain extracellular matrix boosts neuronal network formation in 3D bioengineered model of cortical brain tissue.

PubMed

Sood, Disha; Chwalek, Karolina; Stuntz, Emily; Pouli, Dimitra; Du, Chuang; Tang-Schomer, Min; Georgakoudi, Irene; Black, Lauren D; Kaplan, David L

2016-01-01

The extracellular matrix (ECM) constituting up to 20% of the organ volume is a significant component of the brain due to its instructive role in the compartmentalization of functional microdomains in every brain structure. The composition, quantity and structure of ECM changes dramatically during the development of an organism greatly contributing to the remarkably sophisticated architecture and function of the brain. Since fetal brain is highly plastic, we hypothesize that the fetal brain ECM may contain cues promoting neural growth and differentiation, highly desired in regenerative medicine. Thus, we studied the effect of brain-derived fetal and adult ECM complemented with matricellular proteins on cortical neurons using in vitro 3D bioengineered model of cortical brain tissue. The tested parameters included neuronal network density, cell viability, calcium signaling and electrophysiology. Both, adult and fetal brain ECM as well as matricellular proteins significantly improved neural network formation as compared to single component, collagen I matrix. Additionally, the brain ECM improved cell viability and lowered glutamate release. The fetal brain ECM induced superior neural network formation, calcium signaling and spontaneous spiking activity over adult brain ECM. This study highlights the difference in the neuroinductive properties of fetal and adult brain ECM and suggests that delineating the basis for this divergence may have implications for regenerative medicine.

State-Dependent Decoding Algorithms Improve the Performance of a Bidirectional BMI in Anesthetized Rats.

PubMed

De Feo, Vito; Boi, Fabio; Safaai, Houman; Onken, Arno; Panzeri, Stefano; Vato, Alessandro

2017-01-01

Brain-machine interfaces (BMIs) promise to improve the quality of life of patients suffering from sensory and motor disabilities by creating a direct communication channel between the brain and the external world. Yet, their performance is currently limited by the relatively small amount of information that can be decoded from neural activity recorded form the brain. We have recently proposed that such decoding performance may be improved when using state-dependent decoding algorithms that predict and discount the large component of the trial-to-trial variability of neural activity which is due to the dependence of neural responses on the network's current internal state. Here we tested this idea by using a bidirectional BMI to investigate the gain in performance arising from using a state-dependent decoding algorithm. This BMI, implemented in anesthetized rats, controlled the movement of a dynamical system using neural activity decoded from motor cortex and fed back to the brain the dynamical system's position by electrically microstimulating somatosensory cortex. We found that using state-dependent algorithms that tracked the dynamics of ongoing activity led to an increase in the amount of information extracted form neural activity by 22%, with a consequently increase in all of the indices measuring the BMI's performance in controlling the dynamical system. This suggests that state-dependent decoding algorithms may be used to enhance BMIs at moderate computational cost.

Assessing the feasibility of time-resolved fNIRS to detect brain activity during motor imagery

NASA Astrophysics Data System (ADS)

Abdalmalak, Androu; Milej, Daniel; Diop, Mamadou; Naci, Lorina; Owen, Adrian M.; St. Lawrence, Keith

2016-03-01

Functional near-infrared spectroscopy (fNIRS) is a non-invasive optical technique for detecting brain activity, which has been previously used during motor and motor executive tasks. There is an increasing interest in using fNIRS as a brain computer interface (BCI) for patients who lack the physical, but not the mental, ability to respond to commands. The goal of this study is to assess the feasibility of time-resolved fNIRS to detect brain activity during motor imagery. Stability tests were conducted to ensure the temporal stability of the signal, and motor imagery data were acquired on healthy subjects. The NIRS probes were placed on the scalp over the premotor cortex (PMC) and supplementary motor area (SMA), as these areas are responsible for motion planning. To confirm the fNIRS results, subjects underwent functional magnetic resonance imaging (fMRI) while performing the same task. Seven subjects have participated to date, and significant activation in the SMA and/or the PMC during motor imagery was detected by both fMRI and fNIRS in 4 of the 7 subjects. No activation was detected by either technique in the remaining three participants, which was not unexpected due to the nature of the task. The agreement between the two imaging modalities highlights the potential of fNIRS as a BCI, which could be adapted for bedside studies of patients with disorders of consciousness.

Brain reflections: A circuit-based framework for understanding information processing and cognitive control.

PubMed

Gratton, Gabriele

2018-03-01

Here, I propose a view of the architecture of the human information processing system, and of how it can be adapted to changing task demands (which is the hallmark of cognitive control). This view is informed by an interpretation of brain activity as reflecting the excitability level of neural representations, encoding not only stimuli and temporal contexts, but also action plans and task goals. The proposed cognitive architecture includes three types of circuits: open circuits, involved in feed-forward processing such as that connecting stimuli with responses and characterized by brief, transient brain activity; and two types of closed circuits, positive feedback circuits (characterized by sustained, high-frequency oscillatory activity), which help select and maintain representations, and negative feedback circuits (characterized by brief, low-frequency oscillatory bursts), which are instead associated with changes in representations. Feed-forward activity is primarily responsible for the spread of activation along the information processing system. Oscillatory activity, instead, controls this spread. Sustained oscillatory activity due to both local cortical circuits (gamma) and longer corticothalamic circuits (alpha and beta) allows for the selection of individuated representations. Through the interaction of these circuits, it also allows for the preservation of representations across different temporal spans (sensory and working memory) and their spread across the brain. In contrast, brief bursts of oscillatory activity, generated by novel and/or conflicting information, lead to the interruption of sustained oscillatory activity and promote the generation of new representations. I discuss how this framework can account for a number of psychological and behavioral phenomena. © 2017 Society for Psychophysiological Research.

The Brain Computer Interface Future: Time for a Strategy

DTIC Science & Technology

2013-02-14

electrophysiological activity can be measured by electroencepholography ( EEG ), electrocorticography (ECoG), magnetoencephalography (MEG), or signal activity...magnetic resonance imaging (MRI) or near infrared spectroscopy. Currently EEG is most the most widely used BCI interface due to high temporal...resolution, less user risk, and lower costs.12 EEG technology has been widely available for many decades but has significantly expanded as researchers

The Neural Mechanisms of Meditative Practices: Novel Approaches for Healthy Aging.

PubMed

Acevedo, Bianca P; Pospos, Sarah; Lavretsky, Helen

2016-01-01

Meditation has been shown to have physical, cognitive, and psychological health benefits that can be used to promote healthy aging. However, the common and specific mechanisms of response remain elusive due to the diverse nature of mind-body practices. In this review, we aim to compare the neural circuits implicated in focused-attention meditative practices that focus on present-moment awareness to those involved in active-type meditative practices (e.g., yoga) that combine movement, including chanting, with breath practices and meditation. Recent meta-analyses and individual studies demonstrated common brain effects for attention-based meditative practices and active-based meditations in areas involved in reward processing and learning, attention and memory, awareness and sensory integration, and self-referential processing and emotional control, while deactivation was seen in the amygdala, an area implicated in emotion processing. Unique effects for mindfulness practices were found in brain regions involved in body awareness, attention, and the integration of emotion and sensory processing. Effects specific to active-based meditations appeared in brain areas involved in self-control, social cognition, language, speech, tactile stimulation, sensorimotor integration, and motor function. This review suggests that mind-body practices can target different brain systems that are involved in the regulation of attention, emotional control, mood, and executive cognition that can be used to treat or prevent mood and cognitive disorders of aging, such as depression and caregiver stress, or serve as "brain fitness" exercise. Benefits may include improving brain functional connectivity in brain systems that generally degenerate with Alzheimer's disease, Parkinson's disease, and other aging-related diseases.

Intravenous Heroin Induces Rapid Brain Hypoxia and Hyperglycemia that Precede Brain Metabolic Response

PubMed Central

Cameron-Burr, Keaton T.; Shaham, Yavin

2017-01-01

Heroin use and overdose have increased in recent years as people transition from abusing prescription opiates to using the cheaper street drug. Despite a long history of research, many physiological effects of heroin and their underlying mechanisms remain unknown. Here, we used high-speed amperometry to examine the effects of intravenous heroin on oxygen and glucose levels in the nucleus accumbens (NAc) in freely-moving rats. Heroin within the dose range of human drug use and rat self-administration (100–200 μg/kg) induced a rapid, strong, but transient drop in NAc oxygen that was followed by a slower and more prolonged rise in glucose. Using oxygen recordings in the subcutaneous space, a densely-vascularized site with no metabolic activity, we confirmed that heroin-induced brain hypoxia results from decreased blood oxygen, presumably due to drug-induced respiratory depression. Respiratory depression and the associated rise in CO2 levels appear to drive tonic increases in NAc glucose via local vasodilation. Heroin-induced changes in oxygen and glucose were rapid and preceded the slow and prolonged increase in brain temperature and were independent of enhanced intra-brain heat production, an index of metabolic activation. A very high heroin dose (3.2 mg/kg), corresponding to doses used by experienced drug users in overdose conditions, caused strong and prolonged brain hypoxia and hyperglycemia coupled with robust initial hypothermia that preceded an extended hyperthermic response. Our data suggest heroin-induced respiratory depression as a trigger for brain hypoxia, which leads to hyperglycemia, both of which appear independent of subsequent changes in brain temperature and metabolic neural activity. PMID:28593192

Multicenter phase 2 study of patupilone for recurrent or progressive brain metastases from non-small cell lung cancer.

PubMed

Nayak, Lakshmi; DeAngelis, Lisa M; Robins, H Ian; Govindan, Ramaswamy; Gadgeel, Shirish; Kelly, Karen; Rigas, James R; Peereboom, David M; Rosenfeld, Steven S; Muzikansky, Alona; Zheng, Ming; Urban, Patrick; Abrey, Lauren E; Omuro, Antonio; Wen, Patrick Y

2015-12-01

Treatment options for patients with non-small cell lung cancer (NSCLC) with brain metastases are limited. Patupilone (EPO906), a blood-brain barrier-penetrating, microtubule-targeting, cytotoxic agent, has shown clinical activity in phase 1/2 studies in patients with NSCLC. This study evaluates the efficacy, pharmacokinetics, and safety of patupilone in NSCLC brain metastases. Adult patients with NSCLC and confirmed progressive brain metastases received patupilone intravenously at 10 mg/m(2) every 3 weeks. The primary endpoint of this multinomial 2-stage study combined early progression (EP; death or progression within 3 weeks) and progression-free survival at 9 weeks (PFS9w) to determine drug activity. Fifty patients with a median age of 60 years (range, 33-74 years) were enrolled; the majority were men (58%), and most had received prior therapy for brain metastases (98%). The PFS9w rate was 36%, and the EP rate was 26%. Patupilone blood pharmacokinetic analyses showed mean areas under the concentration-time curve from time zero to 504 hours for cycles 1 and 3 of 1544 and 1978 ng h/mL, respectively, and a mean steady state distribution volume of 755 L/m(2) . Grade 3/4 adverse events (AEs), regardless of their relation with the study drug, included diarrhea (24%), pulmonary embolisms (8%), convulsions (4%), and peripheral neuropathy (4%). All patients discontinued the study drug: 31 (62%) for disease progression and 13 (26%) for AEs. Twenty-five of 32 deaths were due to brain metastases. The median time to progression and the overall survival were 3.2 and 8.8 months, respectively. This is the first prospective study of chemotherapy for recurrent brain metastases from NSCLC. In this population, patupilone demonstrated activity in heavily treated patients. © 2015 American Cancer Society.

Attenuating Ischemic Disruption of K+ Homeostasis in the Cortex of Hypoxic-Ischemic Neonatal Rats: DOR Activation vs. Acupuncture Treatment.

PubMed

Chao, Dongman; Wang, Qinyu; Balboni, Gianfranco; Ding, Guanghong; Xia, Ying

2016-12-01

Perinatal hypoxic-ischemic (HI) brain injury results in death or profound long-term neurologic disability in both children and adults. However, there is no effective pharmacological therapy due to a poor understanding of HI events, especially the initial triggers for hypoxic-ischemic injury such as disrupted ionic homeostasis and the lack of effective intervention strategy. In the present study, we showed that neonatal brains undergo a developmental increase in the disruption of K + homeostasis during simulated ischemia, oxygen-glucose deprivation (OGD) and neonatal HI cortex has a triple phasic response (earlier attenuation, later enhancement, and then recovery) of disrupted K + homeostasis to OGD. This response partially involves the activity of the δ-opioid receptor (DOR) since the earlier attenuation of ischemic disruption of K + homeostasis could be blocked by DOR antagonism, while the later enhancement was reversed by DOR activation. Similar to DOR activation, acupuncture, a strategy to promote DOR activity, could partially reverse the later enhanced ischemic disruption of K + homeostasis in the neonatal cortex. Since maintaining cellular K + homeostasis and inhibiting excessive K + fluxes in the early phase of hypoxic-ischemic insults may be of therapeutic benefit in the treatment of ischemic brain injury and related neurodegenerative conditions, and since many neurons and other cells can be rescued during the "window of opportunity" after HI insults, our first findings regarding the role of acupuncture and DOR in attenuating ischemic disruption of K + homeostasis in the neonatal HI brain suggest a potential intervention therapy in the treatment of neonatal brain injury, especially hypoxic-ischemic encephalopathy.

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

PubMed

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

2013-10-09

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

The Increase of the Functional Entropy of the Human Brain with Age

PubMed Central

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

2013-01-01

We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy. PMID:24103922

Single-task fMRI overlap predicts concurrent multitasking interference.

PubMed

Nijboer, Menno; Borst, Jelmer; van Rijn, Hedderik; Taatgen, Niels

2014-10-15

There is no consensus regarding the origin of behavioral interference that occurs during concurrent multitasking. Some evidence points toward a multitasking locus in the brain, while other results imply that interference is the consequence of task interactions in several brain regions. To investigate this issue, we conducted a functional MRI (fMRI) study consisting of three component tasks, which were performed both separately and in combination. The results indicated that no specific multitasking area exists. Instead, different patterns of activation across conditions could be explained by assuming that the interference is a result of task interactions. Additionally, similarity in single-task activation patterns correlated with a decrease in accuracy during dual-task conditions. Taken together, these results support the view that multitasking interference is not due to a bottleneck in a single "multitasking" brain region, but is a result of interactions between concurrently running processes. Copyright © 2014 Elsevier Inc. All rights reserved.

[NO and H2S brain systems of the Japanese shore crab Hemigrapsus sanguineus under conditions of anoxia].

PubMed

Kotsiuba, E P

2012-01-01

The topography and dynamics of the activity of the enzymes of the synthesis of nitric oxide (NO) and hydrogen sulfide (H2S) in the brain of the Japanese shore crab Hemigrapsus sanguineus after 1, 6, and 12 h ofanoxia was studied histochemically and immunocytochemically. Changes in the activity and number of NO- and CBS-immune-positive cells that take place due to anoxia and the intensity of which depends on the duration of the influence were revealed. The fact that the balance between the nitric oxide and hydrogen sulfide systems in the brain of the crabs H. sanguineus is preserved indicates the joint participation of those systems in the central regulation of adaptive mechanisms under the influence of anoxia and, apparently, plays an important role in the adaptation of these hydrobionts to oxygen deficit.

Hyperbaric oxygen can induce neuroplasticity and improve cognitive functions of patients suffering from anoxic brain damage

PubMed Central

Hadanny, A.; Golan, H.; Fishlev, G.; Bechor, Y.; Volkov, O.; Suzin, G.; Ben-Jacob, E.; Efrati, S.

2015-01-01

Abstract Purpose: Cognitive impairment may occur in 42–50% of cardiac arrest survivors. Hyperbaric oxygen therapy (HBO2) has recently been shown to have neurotherapeutic effects in patients suffering from chronic cognitive impairments (CCI) consequent to stroke and mild traumatic brain injury. The objective of this study was to assess the neurotherapeutic effect of HBO2 in patients suffering from CCI due to cardiac arrest. Methods: Retrospective analysis of patients with CCI caused by cardiac arrest, treated with 60 daily sessions of HBO2. Evaluation included objective computerized cognitive tests (NeuroTrax), Activity of Daily Living (ADL) and Quality of life questionnaires. The results of these tests were compared with changes in brain activity as assessed by single photon emission computed tomography (SPECT) brain imaging. Results: The study included 11 cases of CCI patients. Patients were treated with HBO2, 0.5–7.5 years (mean 2.6 ± 0.6 years) after the cardiac arrest. HBO2 was found to induce modest, but statistically significant improvement in memory, attention and executive function (mean scores) of 12% , 20% and 24% respectively. The clinical improvements were found to be well correlated with increased brain activity in relevant brain areas as assessed by computerized analysis of the SPECT imaging. Conclusions: Although further research is needed, the results demonstrate the beneficial effects of HBO2 on CCI in patients after cardiac arrest, even months to years after the acute event. PMID:26409406

The inhibitory effect of convulsant agents on the enzyme in brain which inactivates nerveside.

PubMed

Toh, C C

1969-07-01

1. An enzyme which can be extracted from brain inactivates nerveside in the optimum pH range 5.8-7.0.2. The polybasic acids trypan blue and its analogue trypan red, bromphenol blue and its analogue bromthymol blue at concentrations of 0.22 mM and ethylenediaminetetra-acetic acid (EDTA) at a concentration of 1 mM are strong inhibitors of the enzyme.3. Penicillin which is a monobasic carboxylic acid also inhibits the enzyme but only if concentrations as high as 3.6 mM are used. The antibiotic streptomycin which is a basic substance does not inhibit the enzyme.4. Caffeine at a concentration of 7.2 mM only weakly inhibits the enzyme.5. Chymotrypsin and wheat germ acid phosphatase also inactivate nerveside at pH 5.9 and are inhibited by the acidic dyes and penicillin. EDTA inhibits wheat germ phosphatase but activates chymotrypsin.6. Inactivation of nerveside by the brain enzyme and by wheat germ phosphatase is different from the action of chymotrypsin. Nerveside solutions incubated with chymotrypsin completely lose all biological activity whereas if incubation is carried out with either the brain enzyme or wheat germ acid phosphatase a residual biological activity remains even when the concentration of these two enzymes is increased. This residual biological activity is due to a peptide as it is destroyed by chymotrypsin.7. The manner in which nerveside is inactivated by the brain enzyme is uncertain as the preparation of the latter contained phosphodiesterase and protease activities which were similarly inhibited by the acid dyes, penicillin and EDTA.8. Pentylenetetrazole, picrotoxin, strychnine and tetanus toxin do not inhibit the brain enzyme.9. The nerveside-inactivating enzyme is not identical with the Substance P-inactivating enzyme in brain as the former is inhibited by EDTA while the latter is not.

Selfish brain and selfish immune system interplay: A theoretical framework for metabolic comorbidities of mood disorders.

PubMed

Yamagata, Ana Sayuri; Mansur, Rodrigo Barbachan; Rizzo, Lucas Bortolotto; Rosenstock, Tatiana; McIntyre, Roger S; Brietzke, Elisa

2017-01-01

According to the "selfish brain" theory, the brain regulates its own energy supply influencing the peripheral metabolism and food intake according to its needs. The immune system has been likewise "selfish" due to independent energy consumption; and it may compete with the brain (another high energy-consumer) for glucose. In mood disorders, stress in mood episodes or physiological stress activate homeostasis mechanisms from the brain and the immune system to solve the imbalance. The interaction between the selfish brain and the selfish immune system may explain various conditions of medical impairment in mood disorders, such as Metabolic Syndrome (MetS), obesity, type 2 diabetes mellitus (T2DM) and immune dysregulation. The objective of this study is to comprehensively review the literature regarding the competition between the brain and the immune system for energy substrate. Targeting the energetic regulation of the brain and the immune system and their cross-talk open alternative treatments and a different approach in the study of general medical comorbidities in mood disorders, although more investigation is needed. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Blood-brain barrier part III: therapeutic approaches to cross the blood-brain barrier and target the brain].

PubMed

Weiss, N; Miller, F; Cazaubon, S; Couraud, P-O

2010-03-01

Over the last few years, the blood-brain barrier has come to be considered as the main limitation for the treatment of neurological diseases caused by inflammatory, tumor or neurodegenerative disorders. In the blood-brain barrier, the close intercellular contact between cerebral endothelial cells due to tight junctions prevents the passive diffusion of hydrophilic components from the bloodstream into the brain. Several specific transport systems (via transporters expressed on cerebral endothelial cells) are implicated in the delivery of nutriments, ions and vitamins to the brain; other transporters expressed on cerebral endothelial cells extrude endogenous substances or xenobiotics, which have crossed the cerebral endothelium, out of the brain and into the bloodstream. Recently, several strategies have been proposed to target the brain, (i) by by-passing the blood-brain barrier by central drug administration, (ii) by increasing permeability of the blood-brain barrier, (iii) by modulating the expression and/or the activity of efflux transporters, (iv) by using the physiological receptor-dependent blood-brain barrier transport, and (v) by creating new viral or chemical vectors to cross the blood-brain barrier. This review focuses on the illustration of these different approaches. Copyright (c) 2009 Elsevier Masson SAS. All rights reserved.

Corticotropin-releasing hormone-mediated metamorphosis in the neotenic axolotl Ambystoma mexicanum: synergistic involvement of thyroxine and corticoids on brain type II deiodinase.

PubMed

Kühn, Eduard R; De Groef, Bert; Van der Geyten, Serge; Darras, Veerle M

2005-08-01

In the present study, morphological changes leading to complete metamorphosis have been induced in the neotenic axolotl Ambystoma mexicanum using a submetamorphic dose of T(4) together with an injection of corticotropin-releasing hormone (CRH). An injection of CRH alone is ineffective in this regard presumably due to a lack of thyrotropic stimulation. Using this low hormone profile for induction of metamorphosis, the deiodinating enzymes D2 and D3 known to be present in amphibians were measured in liver and brain 24h following an intraperitoneal injection. An injection of T(4) alone did not influence liver nor brain D2 and D3, but dexamethasone (DEX) or CRH alone or in combination with T(4) decreased liver D2 and D3. Brain D2 activity was slightly increased with a higher dose of DEX, though CRH did not have this effect. A profound synergistic effect occurred when T(4) and DEX or CRH were injected together, in the dose range leading to metamorphosis, increasing brain D2 activity more than fivefold. This synergistic effect was not found in the liver. It is concluded that brain T(3) availability may play an important role for the onset of metamorphosis in the neotenic axolotl.

Alpha shape theory for 3D visualization and volumetric measurement of brain tumor progression using magnetic resonance images.

PubMed

Hamoud Al-Tamimi, Mohammed Sabbih; Sulong, Ghazali; Shuaib, Ibrahim Lutfi

2015-07-01

Resection of brain tumors is a tricky task in surgery due to its direct influence on the patients' survival rate. Determining the tumor resection extent for its complete information via-à-vis volume and dimensions in pre- and post-operative Magnetic Resonance Images (MRI) requires accurate estimation and comparison. The active contour segmentation technique is used to segment brain tumors on pre-operative MR images using self-developed software. Tumor volume is acquired from its contours via alpha shape theory. The graphical user interface is developed for rendering, visualizing and estimating the volume of a brain tumor. Internet Brain Segmentation Repository dataset (IBSR) is employed to analyze and determine the repeatability and reproducibility of tumor volume. Accuracy of the method is validated by comparing the estimated volume using the proposed method with that of gold-standard. Segmentation by active contour technique is found to be capable of detecting the brain tumor boundaries. Furthermore, the volume description and visualization enable an interactive examination of tumor tissue and its surrounding. Admirable features of our results demonstrate that alpha shape theory in comparison to other existing standard methods is superior for precise volumetric measurement of tumor. Copyright © 2015 Elsevier Inc. All rights reserved.

Gut Microbiota Dysfunction as Reliable Non-invasive Early Diagnostic Biomarkers in the Pathophysiology of Parkinson’s Disease: A Critical Review

PubMed Central

Nair, Arun T; Ramachandran, Vadivelan; Joghee, Nanjan M; Antony, Shanish; Ramalingam, Gopalakrishnan

2018-01-01

Recent investigations suggest that gut microbiota affects the brain activity through the microbiota-gut-brain axis under both physiological and pathological disease conditions like Parkinson’s disease. Further dopamine synthesis in the brain is induced by dopamine producing enzymes that are controlled by gut microbiota via the microbiota-gut-brain axis. Also alpha synuclein deposition and the associated neurodegeneration in the enteric nervous system that increase intestinal permeability, oxidative stress, and local inflammation, accounts for constipation in Parkinson’s disease patients. The trigger that causes blood brain barrier leakage, immune cell activation and inflammation, and ultimately neuroinflammation in the central nervous system is believed to be due to the chronic low-grade inflammation in the gut. The non-motor symptoms that appear years before motor symptoms could be reliable early biomarkers, if they could be correlated with the established and reliable neuroimaging techniques or behavioral indices. The future directions should therefore, focus on the exploration of newer investigational techniques to identify these reliable early biomarkers and define the specific gut microbes that contribute to the development of Parkinson’s disease. This ultimately should pave the way to safer and novel therapeutic approaches that avoid the complications of the drugs delivered today to the brain of Parkinson’s disease patients. PMID:29291606

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation.

PubMed

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S; Weisz, Nathan

2015-09-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. Copyright © 2015. Published by Elsevier Inc.

Friends, not foes: Magnetoencephalography as a tool to uncover brain dynamics during transcranial alternating current stimulation

PubMed Central

Neuling, Toralf; Ruhnau, Philipp; Fuscà, Marco; Demarchi, Gianpaolo; Herrmann, Christoph S.; Weisz, Nathan

2015-01-01

Brain oscillations are supposedly crucial for normal cognitive functioning and alterations are associated with cognitive dysfunctions. To demonstrate their causal role on behavior, entrainment approaches in particular aim at driving endogenous oscillations via rhythmic stimulation. Within this context, transcranial electrical stimulation, especially transcranial alternating current stimulation (tACS), has received renewed attention. This is likely due to the possibility of defining oscillatory stimulation properties precisely. Also, measurements comparing pre-tACS with post-tACS electroencephalography (EEG) have shown impressive modulations. However, the period during tACS has remained a blackbox until now, due to the enormous stimulation artifact. By means of application of beamforming to magnetoencephalography (MEG) data, we successfully recovered modulations of the amplitude of brain oscillations during weak and strong tACS. Additionally, we demonstrate that also evoked responses to visual and auditory stimuli can be recovered during tACS. The main contribution of the present study is to provide critical evidence that during ongoing tACS, subtle modulations of oscillatory brain activity can be reconstructed even at the stimulation frequency. Future tACS experiments will be able to deliver direct physiological insights in order to further the understanding of the contribution of brain oscillations to cognition and behavior. PMID:26080310

Cortical Reorganization after Hand Immobilization: The beta qEEG Spectral Coherence Evidences

PubMed Central

Fortuna, Marina; Teixeira, Silmar; Machado, Sérgio; Velasques, Bruna; Bittencourt, Juliana; Peressutti, Caroline; Budde, Henning; Cagy, Mauricio; Nardi, Antonio E.; Piedade, Roberto; Ribeiro, Pedro; Arias-Carrión, Oscar

2013-01-01

There is increasing evidence that hand immobilization is associated with various changes in the brain. Indeed, beta band coherence is strongly related to motor act and sensitive stimuli. In this study we investigate the electrophysiological and cortical changes that occur when subjects are submitted to hand immobilization. We hypothesized that beta coherence oscillations act as a mechanism underlying inter- and intra-hemispheric changes. As a methodology for our study fifteen healthy individuals between the ages of 20 and 30 years were subjected to a right index finger task before and after hand immobilization while their brain activity pattern was recorded using quantitative electroencephalography. This analysis revealed that hand immobilization caused changes in frontal, central and parietal areas of the brain. The main findings showed a lower beta-2 band in frontal regions and greater cortical activity in central and parietal areas. In summary, the coherence increased in the frontal, central and parietal cortex, due to hand immobilization and it adjusted the brains functioning, which had been disrupted by the procedure. Moreover, the brain adaptation upon hand immobilization of the subjects involved inter- and intra-hemispheric changes. PMID:24278213

Brain Interaction during Cooperation: Evaluating Local Properties of Multiple-Brain Network.

PubMed

Sciaraffa, Nicolina; Borghini, Gianluca; Aricò, Pietro; Di Flumeri, Gianluca; Colosimo, Alfredo; Bezerianos, Anastasios; Thakor, Nitish V; Babiloni, Fabio

2017-07-21

Subjects' interaction is the core of most human activities. This is the reason why a lack of coordination is often the cause of missing goals, more than individual failure. While there are different subjective and objective measures to assess the level of mental effort required by subjects while facing a situation that is getting harder, that is, mental workload, to define an objective measure based on how and if team members are interacting is not so straightforward. In this study, behavioral, subjective and synchronized electroencephalographic data were collected from couples involved in a cooperative task to describe the relationship between task difficulty and team coordination, in the sense of interaction aimed at cooperatively performing the assignment. Multiple-brain connectivity analysis provided information about the whole interacting system. The results showed that averaged local properties of a brain network were affected by task difficulty. In particular, strength changed significantly with task difficulty and clustering coefficients strongly correlated with the workload itself. In particular, a higher workload corresponded to lower clustering values over the central and parietal brain areas. Such results has been interpreted as less efficient organization of the network when the subjects' activities, due to high workload tendencies, were less coordinated.

Modulation of antioxidant and detoxification responses mediated by lipoic acid in the fish Corydoras paleatus (Callychthyidae).

PubMed

Monserrat, José Maria; Lima, Juliane Ventura; Ferreira, Josencler Luis Ribas; Acosta, Daiane; Garcia, Márcia Longaray; Ramos, Patricia Baptista; Moraes, Tarsila Barros; Dos Santos, Luciane Cougo; Amado, Lílian Lund

2008-09-01

Lipoic acid (LA) has been reported as a potential therapeutic agent due its antioxidants proprieties. It was considered its effect in different organs (gills, brain, muscle and liver) of the fish Corydoras paleatus (Callychthyidae). LA (70 mg/kg of body mass) was added to a commercial fish diet, organisms being fed daily (1% body weight). Sixty animals (mean mass: 2.37+/-0.09 g) were placed randomly in aquariums and received (+LA) or not (-LA) lipoic acid enriched diet during four weeks. After, fish were killed and the brain, muscle, gills and liver were dissected. LA treatment reduced significantly (p<0.05) reactive oxygen species concentration in brain and increased (p<0.05) glutamate-cysteine ligase activity in brain and liver of the same experimental group. LA fed organisms showed higher (p<0.05) brain glutathione-S-transferase activity, indicating that LA improves the detoxification and antioxidant capacity face components that waste glutathione in phase II reactions. A conspicuous reduction of protein oxidation was observed in muscle and liver of +LA organisms, indicating that the treatment was also effective in reducing oxidative stress parameters.

Animal imaging studies of potential brain damage

NASA Astrophysics Data System (ADS)

Gatley, S. J.; Vazquez, M. E.; Rice, O.

To date, animal studies have not been able to predict the likelihood of problems in human neurological health due to HZE particle exposure during space missions outside the Earth's magnetosphere. In ongoing studies in mice, we have demonstrated that cocaine stimulated locomotor activity is reduced by a moderate dose (120 cGy) of 1 GeV 56Fe particles. We postulate that imaging experiments in animals may provide more sensitive and earlier indicators of damage due to HZE particles than behavioral tests. Since the small size of the mouse brain is not well suited to the spatial resolution offered by microPET, we are now repeating some of our studies in a rat model. We anticipate that this will enable us to identify imaging correlates of behavioral endpoints. A specific hypothesis of our studies is that changes in the metabolic rate for glucose in striatum of animals will be correlated with alterations in locomotor activity. We will also evaluate whether the neuroprotective drug L-deprenyl reduces the effect of radiation on locomotor activity. In addition, we will conduct microPET studies of brain monoamine oxidase A and monoamine oxidase B in rats before and at various times after irradiation with HZE particles. The hypothesis is that monoamine oxidase A, which is located in nerve terminals, will be unchanged or decreased after irradiation, while monoamine oxidase B, which is located in glial cells, will be increased after irradiation. Neurochemical effects that could be measured using PET could in principle be applied in astronauts, in terms of detecting and monitoring subtle neurological damage that might have occurred during long space missions. More speculative uses of PET are in screening candidates for prolonged space missions (for example, for adequate reserve in critical brain circuits) and in optimizing medications to treat impairments after missions.

Black-bellied whistling duck (Dendrocygna autumnalis) brain cholinesterase characterization and diagnosis of anticholinesterase pesticide exposure in wild populations from Mexico.

PubMed

Osten, Jaime Rendón-von; Soares, Amadeu M V M; Guilhermino, Lucia

2005-02-01

Rice is the main crop in the subbasin of the fluvial lagoon system of Palizada River (FLSPR) in the state of Campeche, Mexico. The pesticides used to control pests of this crop mainly are carbofuran, chlorpyrifos, and glyphosate. Black-bellied whistling duck (Dendrocygna autumnalis) is an ecologically and economically important species in the area. This duck is consumed by local inhabitants throughout the year, despite its potential exposure to pesticides. Due to its feeding habits, abundance, and nutritional value, D. autumnalis is a good indicator of environmental contamination and a potential route of human exposure to organophosphate and carbamate pesticides. In this study, the brain cholinesterase (ChE) in the frontal cerebral cortex of autochthonous ducks was characterized. In addition, the potential of the three locally used pesticides and mixtures to inhibit ChE activity was investigated and the exposure of the wild duck population during intensive pesticide applications in rice fields was evaluated. We found that acetylcholinesterase (AChE) seems to be the predominant ChE form in the biological fraction analyzed. Carbofuran was the most potent ChE inhibitor of D. autumnalis brain ChE activity from the three pesticides analyzed. Cholinesterase inhibition after exposure to pesticide mixtures predominantly was due to carbofuran. A decrease (p < 0.05) in AChE activity (>30%) was apparent in wild ducks compared to reference ducks, with recovery of ChE inhibition in wild ducks occurring months later when no pesticides were applied in the field. Dendrocygna autumnalis brain ChE is a suitable parameter for inclusion in biomonitoring programs for both environmental protection and human safety.

On-farm euthanasia of broiler chickens: effects of different gas mixtures on behavior and brain activity.

PubMed

Gerritzen, M A; Lambooij, B; Reimert, H; Stegeman, A; Spruijt, B

2004-08-01

The purpose of this study was to investigate the suitability of gas mixtures for euthanasia of groups of broilers in their housing by increasing the percentage of CO2. The suitability was assessed by the level of discomfort before loss of consciousness, and the killing rate. The gas mixtures injected into the housing were 1) 100% CO2, 2) 50% N2 + 50% CO2, and 3) 30% O2 + 40% CO2 + 30% N2, followed by 100% CO2. At 2 and 6 wk of age, groups of 20 broiler chickens per trial were exposed to increasing CO2 percentages due to the injection of these gas mixtures. Behavior and killing rate were examined. At the same time, 2 broilers per trial equipped with brain electrodes were observed for behavior and brain activity. Ten percent of the 2-wk-old broilers survived the increasing CO2 percentage due to the injection of 30% O2 + 40% CO2 + 30% N2 mixture, therefore this mixture was excluded for further testing at 6 wk of age. At 6 wk of age, 30% of the broilers survived in the 50% N2 + 50% CO2 group. The highest level of CO2 in the breathing air (42%) was reached by the injection of the 100% CO2 mixture, vs. 25% for the other 2 mixtures. In all 3 gas mixtures, head shaking, gasping, and convulsions were observed before loss of posture. Loss of posture and suppression of electrical activity of the brain (n = 7) occurred almost simultaneously. The results of this experiment indicate that euthanasia of groups of 2- and 6-wk-old broilers by gradually increasing the percentage of CO2 in the breathing air up to 40% is possible.

Diffuse traumatic brain injury initially attenuates and later expands activation of the rat somatosensory whisker circuit concomitant with neuroplastic responses.

PubMed

Hall, Kelley D; Lifshitz, Jonathan

2010-04-06

Traumatic brain injury can initiate an array of chronic neurological deficits, effecting executive function, language and sensorimotor integration. Mechanical forces produce the diffuse pathology that disrupts neural circuit activation across vulnerable brain regions. The present manuscript explores the hypothesis that the extent of functional activation of brain-injured circuits is a consequence of initial disruption and consequent reorganization. In the rat, enduring sensory sensitivity to whisker stimulation directs regional analysis to the whisker barrel circuit. Adult, male rats were subjected to midline fluid percussion brain or sham injury and evaluated between 1day and 42days post-injury. Whisker somatosensory regions of the cortex and thalamus maintained cellular composition as visualized by Nissl stain. Within the first week post-injury, quantitatively less cFos activation was elicited by whisker stimulation, potentially due to axotomy within and surrounding the whisker circuit as visualized by amyloid precursor protein immunohistochemistry. Over six weeks post-injury, cFos activation after whisker stimulation showed a significant linear correlation with time in the cortex (r(2)=0.545; p=0.015), non-significant correlation in the thalamus (r(2)=0.326) and U-shaped correlation in the dentate gyrus (r(2)=0.831), all eventually exceeding sham levels. Ongoing neuroplastic responses in the cortex are evidenced by accumulating growth associated protein and synaptophysin gene expression. In the thalamus, the delayed restoration of plasticity markers may explain the broad distribution of neuronal activation extending into the striatum and hippocampus with whisker stimulation. The sprouting of diffuse-injured circuits into diffuse-injured tissue likely establishes maladaptive circuits responsible for behavioral morbidity. Therapeutic interventions to promote adaptive circuit restructuring may mitigate post-traumatic morbidity. Copyright 2010 Elsevier B.V. All rights reserved.

Attentional control activation relates to working memory in attention-deficit/hyperactivity disorder.

PubMed

Burgess, Gregory C; Depue, Brendan E; Ruzic, Luka; Willcutt, Erik G; Du, Yiping P; Banich, Marie T

2010-04-01

Attentional control difficulties in individuals with attention-deficit/hyperactivity disorder (ADHD) might reflect poor working memory (WM) ability, especially because WM ability and attentional control rely on similar brain regions. The current study examined whether WM ability might explain group differences in brain activation between adults with ADHD and normal control subjects during attentional demand. Participants were 20 adults with ADHD combined subtype with no comorbid psychiatric or learning disorders and 23 control subjects similar in age, IQ, and gender. The WM measures were obtained from the Wechsler Adult Intelligence Scale-III and Wechsler Memory Scale-Revised. Brain activation was assessed with functional magnetic resonance imaging (fMRI) while performing a Color-Word Stroop task. Group differences in WM ability explained a portion of the activation in left dorsolateral prefrontal cortex (DLPFC), which has been related to the creation and maintenance of an attentional set for task-relevant information. In addition, greater WM ability predicted increased activation of brain regions related to stimulus-driven attention and response selection processes in the ADHD group but not in the control group. The inability to maintain an appropriate task set in young adults with combined type ADHD, associated with decreased activity in left DLPFC, might in part be due to poor WM ability. Furthermore, in individuals with ADHD, higher WM ability might relate to increased recruitment of stimulus-driven attention and response selection processes, perhaps as a compensatory strategy. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip.

PubMed

Dauth, Stephanie; Maoz, Ben M; Sheehy, Sean P; Hemphill, Matthew A; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M; Budnik, Bogdan; Parker, Kevin Kit

2017-03-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. Copyright © 2017 the American Physiological Society.

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip

PubMed Central

Dauth, Stephanie; Maoz, Ben M.; Sheehy, Sean P.; Hemphill, Matthew A.; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M.; Budnik, Bogdan

2017-01-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the connection and communication of several brain regions, underlining the importance of developing multiregional brain in vitro models. We introduced a novel brain-on-a-chip model, implementing essential in vivo features, such as different brain areas and their functional connections. PMID:28031399

Language Lateralization Shifts with Learning by Adults

PubMed Central

Plante, Elena; Almryde, Kyle; Patterson, Dianne K.; Vance, Christopher J.; Asbjørnsen, Arve E.

2014-01-01

For the majority of the population, language is a left hemisphere lateralized function. During childhood, a pattern of increasing left lateralization for language has been described in brain imaging studies, suggesting this trait develops. This development could reflect change due to brain maturation or change due to skill acquisition, given that children acquire and refine language skills as they mature. We test the possibility that skill acquisition, independent of age-associated maturation can result in shifts in language lateralization in classic language cortex. We imaged adults exposed to unfamiliar language during three successive fMRI scans. Participants were then asked to identify specific words embedded in Norwegian sentences. Exposure to these sentences, relative to complex tones, resulted in consistent activation in the left and right superior temporal gyrus. Activation in this region became increasingly left lateralized with repeated exposure to the unfamiliar language. These results demonstrate that shifts in lateralization can be produced in the short-term within a learning context, independent of maturation. PMID:25285756

sAPP modulates iron efflux from brain microvascular endothelial cells by stabilizing the ferrous iron exporter ferroportin

PubMed Central

McCarthy, Ryan C; Park, Yun-Hee; Kosman, Daniel J

2014-01-01

A sequence within the E2 domain of soluble amyloid precursor protein (sAPP) stimulates iron efflux. This activity has been attributed to a ferroxidase activity suggested for this motif. We demonstrate that the stimulation of efflux supported by this peptide and by sAPPα is due to their stabilization of the ferrous iron exporter, ferroportin (Fpn), in the plasma membrane of human brain microvascular endothelial cells (hBMVEC). The peptide does not bind ferric iron explaining why it does not and thermodynamically cannot promote ferrous iron autoxidation. This peptide specifically pulls Fpn down from the plasma membrane of hBMVEC; based on these results, FTP, for ferroportin-targeting peptide, correctly identifies the function of this peptide. The data suggest that in stabilizing Fpn via the targeting due to the FTP sequence, sAPP will increase the flux of iron into the cerebral interstitium. This inference correlates with the observation of significant iron deposition in the amyloid plaques characteristic of Alzheimer’s disease. PMID:24867889

Multivariate Heteroscedasticity Models for Functional Brain Connectivity.

PubMed

Seiler, Christof; Holmes, Susan

2017-01-01

Functional brain connectivity is the co-occurrence of brain activity in different areas during resting and while doing tasks. The data of interest are multivariate timeseries measured simultaneously across brain parcels using resting-state fMRI (rfMRI). We analyze functional connectivity using two heteroscedasticity models. Our first model is low-dimensional and scales linearly in the number of brain parcels. Our second model scales quadratically. We apply both models to data from the Human Connectome Project (HCP) comparing connectivity between short and conventional sleepers. We find stronger functional connectivity in short than conventional sleepers in brain areas consistent with previous findings. This might be due to subjects falling asleep in the scanner. Consequently, we recommend the inclusion of average sleep duration as a covariate to remove unwanted variation in rfMRI studies. A power analysis using the HCP data shows that a sample size of 40 detects 50% of the connectivity at a false discovery rate of 20%. We provide implementations using R and the probabilistic programming language Stan.

Docosahexaenoic acid (DHA), a fundamental fatty acid for the brain: New dietary sources.

PubMed

Echeverría, Francisca; Valenzuela, Rodrigo; Catalina Hernandez-Rodas, María; Valenzuela, Alfonso

2017-09-01

Docosahexaenoic acid (C22: 6n-3, DHA) is a long-chain polyunsaturated fatty acid of marine origin fundamental for the formation and function of the nervous system, particularly the brain and the retina of humans. It has been proposed a remarkable role of DHA during human evolution, mainly on the growth and development of the brain. Currently, DHA is considered a critical nutrient during pregnancy and breastfeeding due their active participation in the development of the nervous system in early life. DHA and specifically one of its derivatives known as neuroprotectin D-1 (NPD-1), has neuroprotective properties against brain aging, neurodegenerative diseases and injury caused after brain ischemia-reperfusion episodes. This paper discusses the importance of DHA in the human brain given its relevance in the development of the tissue and as neuroprotective agent. It is also included a critical view about the ways to supply this noble fatty acid to the population. Copyright © 2017 Elsevier Ltd. All rights reserved.

Arterial Spin Labeling: a one-stop-shop for measurement of brain perfusion in the clinical settings.

PubMed

Golay, Xavier; Petersen, Esben T; Zimine, Ivan; Lim, Tchoyoson C C

2007-01-01

Arterial Spin Labeling (ASL) has opened a unique window into the human brain function and perfusion physiology. Altogether fast and of intrinsic high spatial resolution, ASL is a technique very appealing not only for the diagnosis of vascular diseases, but also in basic neuroscience for the follow-up of small perfusion changes occurring during brain activation. However, due to limited signal-to-noise ratio and complex flow kinetics, ASL is one of the more challenging disciplines within magnetic resonance imaging. In this paper, the theoretical background and main implementations of ASL are revisited. In particular, the different uses of ASL, the pitfalls and possibilities are described and illustrated using clinical cases.

Neural correlates of motor-cognitive dual-tasking in young and old adults

PubMed Central

Papegaaij, Selma; Hortobágyi, Tibor; Godde, Ben; Kaan, Wim A.; Erhard, Peter; Voelcker-Rehage, Claudia

2017-01-01

When two tasks are performed simultaneously, performance often declines in one or both tasks. These so-called dual-task costs are more pronounced in old than in young adults. One proposed neurological mechanism of the dual-task costs is that old compared with young adults tend to execute single-tasks with higher brain activation. In the brain regions that are needed for both tasks, the reduced residual capacity may interfere with performance of the dual-task. This competition for shared brain regions has been called structural interference. The purpose of the study was to determine whether structural interference indeed plays a role in the age-related decrease in dual-task performance. Functional magnetic resonance imaging (fMRI) was used to investigate 23 young adults (20–29 years) and 32 old adults (66–89 years) performing a calculation (serial subtraction by seven) and balance-simulation (plantar flexion force control) task separately or simultaneously. Behavioral performance decreased during the dual-task compared with the single-tasks in both age groups, with greater dual-task costs in old compared with young adults. Brain activation was significantly higher in old than young adults during all conditions. Region of interest analyses were performed on brain regions that were active in both tasks. Structural interference was apparent in the right insula, as quantified by an age-related reduction in upregulation of brain activity from single- to dual-task. However, the magnitude of upregulation did not correlate with dual-task costs. Therefore, we conclude that the greater dual-task costs in old adults were probably not due to increased structural interference. PMID:29220349

Reduced brain response to a sweet taste in Hispanic young adults.

PubMed

Szajer, Jacquelyn; Jacobson, Aaron; Green, Erin; Murphy, Claire

2017-11-01

Hispanics have an increased risk for metabolic disorders, which evidence suggests may be due to interactions between lifespan biological, genetic, and lifestyle factors. Studies show the diet of many U.S. Hispanic groups have high sugar consumption, which has been shown to influence future preference for and consumption of high-sugar foods, and is associated with increased risk for insulin-related disorders and obesity. Taste is a primary determinant of food preference and selection. Differences in neural response to taste have been associated with obesity. Understanding brain response to sweet taste stimuli in healthy Hispanic adults is an important first step in characterizing the potential neural mechanisms for this behavior. We used fMRI to examine brain activation during the hedonic evaluation of sucrose as a function of ethnicity in Hispanic and non-Hispanic young adults. Taste stimuli were administered orally while subjects were scanned at 3T. Data were analyzed with AFNI via 3dROIstats and 3dMEMA, a mixed effects multi-level analysis of whole brain activation. The Hispanic group had significantly lower ROI activation in the left amygdala and significantly lower whole brain activation in regions critical for reward processing, and hedonic evaluation (e.g. frontal, orbitofrontal, and anterior cingulate cortices) than the non-Hispanic group. Differences in processing of sweet tastes have important clinical and public health implications, especially considering increased risk of metabolic syndrome and cognitive decline in Hispanic populations. Future research to better understanding relationships between health risk and brain function in Hispanic populations is warranted to better conceptualize and develop interventions for these populations. Copyright © 2017. Published by Elsevier B.V.

Neurophysiological effects of modafinil on cue-exposure in cocaine dependence: a randomized placebo-controlled cross-over study using pharmacological fMRI.

PubMed

Goudriaan, Anna E; Veltman, Dick J; van den Brink, Wim; Dom, Geert; Schmaal, Lianne

2013-02-01

Enhanced reactivity to substance related cues is a central characteristic of addiction and has been associated with increased activity in motivation, attention, and memory related brain circuits and with a higher probability of relapse. Modafinil was promising in the first clinical trials in cocaine dependence, and was able to reduce craving in addictive disorders. However, its mechanism of action remains to be elucidated. In this functional magnetic resonance imaging (fMRI) study therefore, cue reactivity in cocaine dependent patients was compared to cue reactivity in healthy controls (HCs) under modafinil and placebo conditions. An fMRI cue reactivity study, with a double-blind, placebo-controlled cross-over challenge with a single dose of modafinil (200mg) was employed in 13 treatment seeking cocaine dependent patients and 16 HCs. In the placebo condition, watching cocaine-related pictures (versus neutral pictures) resulted in higher brain activation in the medial frontal cortex, anterior cingulate cortex, angular gyrus, left orbitofrontal cortex, and ventral tegmental area (VTA) in the cocaine dependent group compared to HCs. However, in the modafinil condition, no differences in brain activation patterns were found between cocaine dependent patients and HCs. Group interactions revealed decreased activity in the VTA and increased activity in the right ACC and putamen in the modafinil condition relative to the placebo condition in cocaine dependent patients, whereas such changes were not present in healthy controls. Decreases in self-reported craving when watching cocaine-related cues after modafinil administration compared to the placebo condition were associated with modafinil-induced increases in ACC and putamen activation. Enhanced cue reactivity in the cocaine dependent group compared to healthy controls was found in brain circuitries related to reward, motivation, and autobiographical memory processes. In cocaine dependent patients, these enhanced brain responses were attenuated by modafinil, mainly due to decreases in cue- reactivity in reward-related brain areas (VTA) and increases in cue reactivity in cognitive control areas (ACC). These modafinil-induced changes in brain activation in response to cocaine-related visual stimuli were associated with diminished self-reported craving. These findings imply that in cocaine dependent patients, modafinil, although mainly known as a cognitive enhancer, acts on both the motivational and the cognitive brain circuitry. Copyright © 2012 Elsevier Ltd. All rights reserved.

Increased Oxidative Metabolism and Neurotransmitter Cycling in the Brain of Mice Lacking the Thyroid Hormone Transporter Slc16a2 (Mct8)

PubMed Central

Rodrigues, Tiago B.; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-13C) glucose and brain extracts prepared and analyzed by 13C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood. PMID:24098341

Increased oxidative metabolism and neurotransmitter cycling in the brain of mice lacking the thyroid hormone transporter SLC16A2 (MCT8).

PubMed

Rodrigues, Tiago B; Ceballos, Ainhoa; Grijota-Martínez, Carmen; Nuñez, Barbara; Refetoff, Samuel; Cerdán, Sebastian; Morte, Beatriz; Bernal, Juan

2013-01-01

Mutations of the monocarboxylate transporter 8 (MCT8) cause a severe X-linked intellectual deficit and neurological impairment. MCT8 is a specific thyroid hormone (T4 and T3) transporter and the patients also present unusual abnormalities in the serum profile of thyroid hormone concentrations due to altered secretion and metabolism of T4 and T3. Given the role of thyroid hormones in brain development, it is thought that the neurological impairment is due to restricted transport of thyroid hormones to the target neurons. In this work we have investigated cerebral metabolism in mice with Mct8 deficiency. Adult male mice were infused for 30 minutes with (1-(13)C) glucose and brain extracts prepared and analyzed by (13)C nuclear magnetic resonance spectroscopy. Genetic inactivation of Mct8 resulted in increased oxidative metabolism as reflected by increased glutamate C4 enrichment, and of glutamatergic and GABAergic neurotransmissions as observed by the increases in glutamine C4 and GABA C2 enrichments, respectively. These changes were distinct to those produced by hypothyroidism or hyperthyroidism. Similar increments in glutamate C4 enrichment and GABAergic neurotransmission were observed in the combined inactivation of Mct8 and D2, indicating that the increased neurotransmission and metabolic activity were not due to increased production of cerebral T3 by the D2-encoded type 2 deiodinase. In conclusion, Mct8 deficiency has important metabolic consequences in the brain that could not be correlated with deficiency or excess of thyroid hormone supply to the brain during adulthood.

GM2 gangliosidosis in an adult pet rabbit.

PubMed

Rickmeyer, T; Schöniger, S; Petermann, A; Harzer, K; Kustermann-Kuhn, B; Fuhrmann, H; Schoon, H-A

2013-02-01

A 1.5-year-old neutered male rabbit was presented with chronic nasal discharge and ataxia. Rapid progression of neurological signs was noted subsequent to general anaesthesia and the rabbit was humanely destroyed due to the poor prognosis. At necropsy examination there were no gross changes affecting the brain or spinal cord. Microscopical examination revealed that the perikarya of numerous neurons in the brain and spinal cord were distended by the intracytoplasmic accumulation of pale, finely granular to vacuolar material. Transmission electron microscopy showed this to be composed of concentric membranous cytoplasmic bodies. Thin layer chromatography revealed elevation of GM2 ganglioside in the brain of this rabbit compared with that of an unaffected control rabbit. Enzymatically, there was markedly reduced activity of tissue β-hexosaminidase A in brain and liver tissue from the rabbit. This was a result of an almost complete absence of the enzymatic activity of the α-subunit of that enzyme. These findings are consistent with sphingolipidosis comparable with human GM2 gangliosidosis variant B1. Copyright © 2012 Elsevier Ltd. All rights reserved.

[Inflammation and oxidation: predictive and/or causative factors].

PubMed

Fernández-Viadero, Carlos; Jiménez-Sanz, Magdalena; Fernández-Pérez, Anzu; Verduga Vélez, Rosario; Crespo Santiago, Dámaso

2016-06-01

Brain ageing leads to a series of changes that reduce the processes of adaptation and response. These transformations can end in cognitive impairment and/or dementia. Although the cause of these changes is diverse, inflammation and oxidative stress explain some of the pathophysiological mechanisms of these anomalies of brain functioning. Neuroinflammation triggers neuronal injury through the presence of inflammatory cytokines and the activation of microglia through membrane receptors and nuclear activation factors. This neuroinflammatory phenomenon also affects neuron plasticity, altering the genesis and maintenance of long-term potentiation, leading to impairment of hippocampus-dependent memory. Oxidative stress and the production of free oxygen radicals also cause toxic effects in aged brains, largely due to lipid peroxidation and DNA damage. The identification of the molecular mechanisms involved in the pathogenesis of these events could shed new light on possible therapeutic targets and offer strategies for the prevention of diseases related to brain ageing, cognitive impairment and dementia. Copyright © 2016 Sociedad Española de Geriatría y Gerontología. Publicado por Elsevier España, S.L.U. All rights reserved.

[MRI for brain structure and function in patients with first-episode panic disorder].

PubMed

Zhang, Yan; Duan, Lian; Liao, Mei; Yang, Fan; Liu, Jun; Shan, Baoci; Li, Lingjiang

2011-12-01

To determine the brain function and structure in patinets with first-episode panic disorder (PD). All subjects (24 PD patients and 24 healthy subjects) received MRI scan and emotional counting Stroop task during the functional magnetic resonance imaging. Blood oxygenation level dependent functional magnetic resonance imaging and voxel-based morphometric technology were used to detect the gray matter volume. Compared with the healthy controls, left thalamus, left medial frontal gyrus, left anterior cingulate gyrus, left inferior frontal gyrus, left insula (panic-related words vs. neutral words) lacked activation in PD patients, but the over-activation were found in right brain stem, right occipital lobe/lingual gyrus in PD patients. Compared with the healthy controls, the gray matter volume in the PD patients significantly decreased in the left superior temporal gyrus, right medial frontal gyrus, left medial occipital gyrus, dorsomedial nucleus of left thalamus and right anterior cingulate gyrus. There was no significantly increased gray matter volume in any brain area in PD patients. PD patients have selective attentional bias in processing threatening information due to the depression and weakening of the frontal cingulated gyrus.

Licorice Pretreatment Protects Against Brain Damage Induced by Middle Cerebral Artery Occlusion in Mice.

PubMed

Lim, Chiyeon; Lim, Sehyun; Lee, Byoungho; Kim, Buyeo; Cho, Suin

2018-05-01

Licorice is extracted from the roots of plants in the Glycyrrhiza genus, especially Glycyrrhiza uralensis in China and Korea. It has several pharmacological activities, including neuro-protective, anti-fungal, and anti-cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause of adult disability and death; thus, the identification of anti-apoptotic, neuro-protective therapeutic agents is viewed as an attractive drug development strategy. Infarct volumes and the expression of several apoptosis-related proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by western blotting in the brains of mice subjected to middle cerebral artery occlusion (MCAO). Three consecutive days of oral pretreatment with the methanol extract of licorice (GRex) significantly reduced infarct volumes 24 h after MCAO. In addition, GRex effectively inhibited the activation of caspase-9 by upregulating protein expression of Bcl-xL and Bcl-2. The neuro-protective effect of licorice was due to its regulation of apoptosis-related proteins. These data suggest that licorice could be a potential candidate for the treatment of ischemia-induced brain damage.

The Role of the PI3K Pathway in the Regeneration of the Damaged Brain by Neural Stem Cells after Cerebral Infarction.

PubMed

Koh, Seong Ho; Lo, Eng H

2015-10-01

Neurologic deficits resulting from stroke remain largely intractable, which has prompted thousands of studies aimed at developing methods for treating these neurologic sequelae. Endogenous neurogenesis is also known to occur after brain damage, including that due to cerebral infarction. Focusing on this process may provide a solution for treating neurologic deficits caused by cerebral infarction. The phosphatidylinositol-3-kinase (PI3K) pathway is known to play important roles in cell survival, and many studies have focused on use of the PI3K pathway to treat brain injury after stroke. Furthermore, since the PI3K pathway may also play key roles in the physiology of neural stem cells (NSCs), eliciting the appropriate activation of the PI3K pathway in NSCs may help to improve the sequelae of cerebral infarction. This review describes the PI3K pathway, its roles in the brain and NSCs after cerebral infarction, and the therapeutic possibility of activating the pathway to improve neurologic deficits after cerebral infarction.

Computational Modeling of Resting-State Activity Demonstrates Markers of Normalcy in Children with Prenatal or Perinatal Stroke

PubMed Central

Raja Beharelle, Anjali; Griffa, Alessandra; Hagmann, Patric; Solodkin, Ana; McIntosh, Anthony R.; Small, Steven L.; Deco, Gustavo

2015-01-01

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere “take over” their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children. PMID:26063923

Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury.

PubMed

Liu, Yan-Yun; Brent, Gregory A

2018-06-01

Thyroid hormone (TH) is essential for normal brain development and may also promote recovery and neuronal regeneration after brain injury. TH acts predominantly through the nuclear receptors, TH receptor alpha (THRA) and beta (THRB). Additional factors that impact TH action in the brain include metabolism, activation of thyroxine (T4) to triiodothyronine (T3) by the enzyme 5'-deiodinase Type 2 (Dio2), inactivation by the enzyme 5-deiodinase Type 3 (Dio3) to reverse T3 (rT3), which occurs in glial cells, and uptake by the Mct8 transporter in neurons. Traumatic brain injury (TBI) is associated with inflammation, metabolic alterations and neural death. In clinical studies, central hypothyroidism, due to hypothalamic and pituitary dysfunction, has been found in some individuals after brain injury. TH has been shown, in animal models, to be protective for the damage incurred from brain injury and may have a role to limit injury and promote recovery. Although clinical trials have not yet been reported, findings from in vitro and in vivo models inform potential treatment strategies utilizing TH for protection and promotion of recovery after brain injury. Published by Elsevier Inc.

Circulating neprilysin clears brain amyloid.

PubMed

Liu, Yinxing; Studzinski, Christa; Beckett, Tina; Murphy, M Paul; Klein, Ronald L; Hersh, Louis B

2010-10-01

The use of the peptidase neprilysin (NEP) as a therapeutic for lowering brain amyloid burden is receiving increasing attention. We have previously demonstrated that peripheral expression of NEP on the surface of hindlimb muscle lowers brain amyloid burden in a transgenic mouse model of Alzheimer's disease. In this study we now show that using adeno-associated virus expressing a soluble secreted form of NEP (secNEP-AAV8), NEP secreted into plasma is effective in clearing brain Abeta. Soluble NEP expression in plasma was sustained over the 3-month time period it was measured. Secreted NEP decreased plasma Abeta by 30%, soluble brain Abeta by approximately 28%, insoluble brain Abeta by approximately 55%, and Abeta oligomersby 12%. This secNEP did not change plasma levels of substance P or bradykinin, nor did it alter blood pressure. No NEP was detected in CSF, nor did the AAV virus produce brain expression of NEP. Thus the lowering of brain Abeta was due to plasma NEP which altered blood-brain Abeta transport dynamics. Expressing NEP in plasma provides a convenient way to monitor enzyme activity during the course of its therapeutic testing. Copyright 2010 Elsevier Inc. All rights reserved.

Neurotoxic effects and biomarkers of lead exposure: a review.

PubMed

Sanders, Talia; Liu, Yiming; Buchner, Virginia; Tchounwou, Paul B

2009-01-01

Lead, a systemic toxicant affecting virtually every organ system, primarily affects the central nervous system, particularly the developing brain. Consequently, children are at a greater risk than adults of suffering from the neurotoxic effects of lead. To date, no safe lead-exposure threshold has been identified. The ability of lead to pass through the blood-brain barrier is due in large part to its ability to substitute for calcium ions. Within the brain, lead-induced damage in the prefrontal cerebral cortex, hippocampus, and cerebellum can lead to a variety of neurologic disorders. At the molecular level, lead interferes with the regulatory action of calcium on cell functions and disrupts many intracellular biological activities. Experimental studies have also shown that lead exposure may have genotoxic effects, especially in the brain, bone marrow, liver, and lung cells. Knowledge of the neurotoxicology of lead has advanced in recent decades due to new information on its toxic mechanisms and cellular specificity. This paper presents an overview, updated to January 2009, of the neurotoxic effects of lead with regard to children, adults, and experimental animals at both cellular and molecular levels, and discusses the biomarkers of lead exposure that are useful for risk assessment in the field of environmental health.

Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates.

PubMed

Roche-Labarbe, Nadege; Fenoglio, Angela; Radhakrishnan, Harsha; Kocienski-Filip, Marcia; Carp, Stefan A; Dubb, Jay; Boas, David A; Grant, P Ellen; Franceschini, Maria Angela

2014-01-15

The hemodynamic functional response is used as a reliable marker of neuronal activity in countless studies of brain function and cognition. In newborns and infants, however, conflicting results have appeared in the literature concerning the typical response, and there is little information on brain metabolism and functional activation. Measurement of all hemodynamic components and oxygen metabolism is critical for understanding neurovascular coupling in the developing brain. To this end, we combined multiple near infrared spectroscopy techniques to measure oxy- and deoxy-hemoglobin concentrations, cerebral blood volume (CBV), and relative cerebral blood flow (CBF) in the somatosensory cortex of 6 preterm neonates during passive tactile stimulation of the hand. By combining these measures we estimated relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO2). CBF starts increasing immediately after stimulus onset, and returns to baseline before blood volume. This is consistent with the model of pre-capillary arteriole active dilation driving the CBF response, with a subsequent CBV increase influenced by capillaries and veins dilating passively to accommodate the extra blood. rCMRO2 estimated using the steady-state formulation shows a biphasic pattern: an increase immediately after stimulus onset, followed by a post-stimulus undershoot due to blood flow returning faster to baseline than oxygenation. However, assuming a longer mean transit time from the arterial to the venous compartment, due to the immature vascular system of premature infants, reduces the post-stimulus undershoot and increases the flow/consumption ratio to values closer to adult values reported in the literature. We are the first to report changes in local rCBF and rCMRO2 during functional activation in preterm infants. The ability to measure these variables in addition to hemoglobin concentration changes is critical for understanding neurovascular coupling in the developing brain, and for using this coupling as a reliable functional imaging marker in neonates. Copyright © 2013 Elsevier Inc. All rights reserved.

Neural bases of human mate choice: multiple value dimensions, sex difference, and self-assessment system.

PubMed

Funayama, Risa; Sugiura, Motoaki; Sassa, Yuko; Jeong, Hyeonjeong; Wakusawa, Keisuke; Horie, Kaoru; Sato, Shigeru; Kawashima, Ryuta

2012-01-01

Mate choice is an example of sophisticated daily decision making supported by multiple componential processes. In mate-choice literature, different characteristics of the value dimensions, including the sex difference in the value dimensions, and the involvement of self-assessment due to the mutual nature of the choice, have been suggested. We examined whether the brain-activation pattern during virtual mate choice would be congruent with these characteristics in terms of stimulus selectivity and activated brain regions. In measuring brain activity, young men and women were shown two pictures of either faces or behaviors, and they indicated which person they would choose either as a spouse or as a friend. Activation selective to spouse choice was observed face-selectively in men's amygdala and behavior-selectively in women's motor system. During both partner-choice conditions, behavior-selective activation was observed in the temporoparietal regions. Taking the available knowledge of these regions into account, these results are congruent with the suggested characteristics of value dimensions for physical attractiveness, parenting resources, and beneficial personality traits for a long-lasting relationship, respectively. The medial prefrontal and posterior cingulate cortices were nonselectively activated during the partner choices, suggesting the involvement of a self-assessment process. The results thus provide neuroscientific support for the multi-component mate-choice mechanism.

Predicting risky choices from brain activity patterns

PubMed Central

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

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

Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning

PubMed Central

Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

2015-01-01

Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory. PMID:26179231

CORRELATION INDICES OF CEREBRAL HEMODYNAMICS AND ELECTRICAL ACTIVITY IN CHILDREN WITH IMPAIRED MOTOR SKILLS.

PubMed

Golovchenko, I V; Hayday, M I

The correlations between the indicators of cerebral hemodynamics and electrical activity in children with impaired motor skills of central origin (children with cerebral palsy) were investigated. There is established a high number of links between indicators of rheoencephalogram (REG) and electroencephalogram (EEG) in the left cerebral hemisphere than in the right. In frontomastoidal allocation 19 correlations and in occipitomastoidal - 59 links. We suppose that poor circulation in vertebroplasty-basilar system leads to the defeat of the brain stem, which, with afferent pathways of the reticular formation, connects the thalamus with the cortex. In the reticular formation there is an inhibition of ascending activators influences, which eland to decreasing of the cortex is tonus. You can talk about the functional immaturity of the system of nonspecific activation by the reticular formation of the brain stem. Children with violation of motor activity had significantly more negative and positive significant and high correlation among the existing indicators of electric brain activity and cerebral hemodynamics, in our opinion, is due to the development of interconnection compensation that is carried out by adjustment of the functional systems and the formation of new forms of adaptive responses in conditions of disontogenetik. Feature correlation pattern of the EEG, of children with disorders of motor activity, is associated with a significantly great number of high and significant correlations between measures of electrical brain activity in the δ- and q- rhythms, especially in the temporal areas of the cerebral cortex. According to visual analysis of EEG there is revealed a common manifestation of changes of bioelectric brain activity in children with disorders of motor activity. This is manifested in the development of paroxysmal activity of action potentials of θ- and δ-rhythms with the focus of activity in the anterior areas of the cerebral cortex; the formation of a mosaic representation of the θ-rhythms in temporal areas; the presence of hypersynchronous a-paroxysms in the posterior areas of the cerebral cortex. The given facts testify to activation of mechanisms of limbic-neocortical systems and synchronizing influences of the reticular formation of the stem and diencephalic structures. There is also detected greater number of correlations when occipitomastoidal registration was lone it reflects compensatory redistribution of cerebral blood flow over the affected structures of brain stem structures that are associated with the provision of cortical functions.

Breast Cancer Resistance Protein and P-glycoprotein in Brain Cancer: Two Gatekeepers Team Up

PubMed Central

Agarwal, Sagar; Hartz, Anika M.S.; Elmquist, William F.; Bauer, Björn

2012-01-01

Brain cancer is a devastating disease. Despite extensive research, treatment of brain tumors has been largely ineffective and the diagnosis of brain cancer remains uniformly fatal. Failure of brain cancer treatment may be in part due to limitations in drug delivery, influenced by the ABC drug efflux transporters P-gp and BCRP at the blood-brain and blood-tumor barriers, in brain tumor cells, as well as in brain tumor stem-like cells. P-gp and BCRP limit various anti-cancer drugs from entering the brain and tumor tissues, thus rendering chemotherapy ineffective. To overcome this obstacle, two strategies – targeting transporter regulation and direct transporter inhibition – have been proposed. In this review, we focus on these strategies. We first introduce the latest findings on signaling pathways that could potentially be targeted to down-regulate P-gp and BCRP expression and/or transport activity. We then highlight in detail the new paradigm of P-gp and BCRP working as a “cooperative team of gatekeepers” at the blood-brain barrier, discuss its ramifications for brain cancer therapy, and summarize the latest findings on dual P-gp/BCRP inhibitors. Finally, we provide a brief summary with conclusions and outline the perspectives for future research endeavors in this field. PMID:21827403

Pro-2-PAM Therapy for Central and Peripheral Cholinesterases

PubMed Central

DeMar, James C.; Clarkson, Edward D.; Ratcliffe, Ruthie H.; Campbell, Amy J.; Thangavelu, Sonia G.; Herdman, Christine A.; Leader, Haim; Schulz, Susan M.; Marek, Elizabeth; Medynets, Marie A.; Ku, Theresa C.; Evans, Sarah A.; Khan, Farhat A.; Owens, Roberta R.; Nambiar, Madhusoodana P.; Gordon, Richard K.

2010-01-01

Novel therapeutics to overcome the toxic effects of organophosphorus (OP) chemical agents are needed due to the documented use of OPs in warfare (e.g. 1980–1988 Iran/Iraq war) and terrorism (e.g. 1995 Tokyo subway attacks). Standard OP exposure therapy in the United States consists of atropine sulfate (to block muscarinic receptors), the acetylcholinesterase (AChE) reactivator (oxime) pralidoxime chloride (2-PAM), and a benzodiazepine anticonvulsant to ameliorate seizures. A major disadvantage is that quaternary nitrogen charged oximes, including 2-PAM, do not cross the blood brain barrier (BBB) to treat brain AChE. Therefore, we have synthesized and evaluated pro-2-PAM (a lipid permeable 2-PAM derivative) that can enter the brain and reactivate CNS AChE, preventing seizures in guinea pigs after exposure to OPs. The protective effects of the pro-2-PAM after OP exposure were shown using a) surgically-implanted radiotelemetry probes for electroencephalogram (EEG) b) neurohistopathology of brain, c) cholinesterase activities in the PNS and CNS, and d) survivability. The PNS oxime 2-PAM was ineffective at reducing seizures/status epilepticus (SE) in diisopropyl-fluorophosphate (DFP)-exposed animals. In contrast, pro-2-PAM significantly suppressed and then eliminated seizure activity. In OP-exposed guinea pigs, there was a significant reduction in neurological damage with pro-2-PAM, but not 2-PAM. Distinct regional areas of the brains showed significantly higher AChE activity 1.5 h after OP exposure in pro-2-PAM treated animals compared to the 2-PAM treated ones. However, blood and diaphragm showed similar AChE activities in animals treated with either oxime, as both 2-PAM and pro 2-PAM are PNS active oximes. In conclusion, pro-2-PAM can cross the BBB, is rapidly metabolized inside the brain to 2-PAM, and protects against OP-induced SE through restoration of brain AChE activity. Pro-2-PAM represents the first non-invasive means of administering a CNS therapeutic for the deleterious effects of OP poisoning by reactivating CNS AChE. PMID:20156430

Electro-mechanical response of a 3D nerve bundle model to mechanical loads leading to axonal injury.

PubMed

Cinelli, I; Destrade, M; Duffy, M; McHugh, P

2018-03-01

Traumatic brain injuries and damage are major causes of death and disability. We propose a 3D fully coupled electro-mechanical model of a nerve bundle to investigate the electrophysiological impairments due to trauma at the cellular level. The coupling is based on a thermal analogy of the neural electrical activity by using the finite element software Abaqus CAE 6.13-3. The model includes a real-time coupling, modulated threshold for spiking activation, and independent alteration of the electrical properties for each 3-layer fibre within a nerve bundle as a function of strain. Results of the coupled electro-mechanical model are validated with previously published experimental results of damaged axons. Here, the cases of compression and tension are simulated to induce (mild, moderate, and severe) damage at the nerve membrane of a nerve bundle, made of 4 fibres. Changes in strain, stress distribution, and neural activity are investigated for myelinated and unmyelinated nerve fibres, by considering the cases of an intact and of a traumatised nerve membrane. A fully coupled electro-mechanical modelling approach is established to provide insights into crucial aspects of neural activity at the cellular level due to traumatic brain injury. One of the key findings is the 3D distribution of residual stresses and strains at the membrane of each fibre due to mechanically induced electrophysiological impairments, and its impact on signal transmission. Copyright © 2017 John Wiley & Sons, Ltd.

Brain Processing of Contagious Itch in Patients with Atopic Dermatitis

PubMed Central

Schut, Christina; Mochizuki, Hideki; Grossman, Shoshana K.; Lin, Andrew C.; Conklin, Christopher J.; Mohamed, Feroze B.; Gieler, Uwe; Kupfer, Joerg; Yosipovitch, Gil

2017-01-01

Several studies show that itch and scratching cannot only be induced by pruritogens like histamine or cowhage, but also by the presentation of certain (audio-) visual stimuli like pictures on crawling insects or videos showing other people scratching. This phenomenon is coined “Contagious itch” (CI). Due to the fact that CI is more profound in patients with the chronic itchy skin disease atopic dermatitis (AD), we believe that it is highly relevant to study brain processing of CI in this group. Knowledge on brain areas involved in CI in AD-patients can provide us with useful hints regarding non-invasive treatments that AD-patients could profit from when they are confronted with itch-inducing situations in daily life. Therefore, this study investigated the brain processing of CI in AD-patients. 11 AD-patients underwent fMRI scans during the presentation of an itch inducing experimental video (EV) and a non-itch inducing control video (CV). Perfusion based brain activity was measured using arterial spin labeling functional MRI. As expected, the EV compared to the CV led to an increase in itch and scratching (p < 0.05). CI led to a significant increase in brain activity in the supplementary motor area, left ventral striatum and right orbitofrontal cortex (threshold: p < 0.001; cluster size k > 50). Moreover, itch induced by watching the EV was by trend correlated with activity in memory-related regions including the temporal cortex and the (pre-) cuneus as well as the posterior operculum, a brain region involved in itch processing (threshold: p < 0.005; cluster size k > 50). These findings suggest that the fronto-striatal circuit, which is associated with the desire to scratch, might be a target region for non-invasive treatments in AD patients. PMID:28790959

Oral supplements of inulin during gestation offsets rotenone-induced oxidative impairments and neurotoxicity in maternal and prenatal rat brain.

PubMed

Krishna, Gokul; Muralidhara

2018-05-25

Environmental insults including pesticide exposure and their entry into the immature brain are of increased concern due to their developmental neurotoxicity. Several lines of evidence suggest that maternal gut microbiota influences in utero fetal development via modulation of host's microbial composition with prebiotics. Hence we examined the hypothesis if inulin (IN) supplements during pregnancy in rats possess the potential to alleviate brain oxidative response and mitochondrial deficits employing a developmental model of rotenone (ROT) neurotoxicity. Initially, pregnant Sprague-Dawley rats were gavaged during gestational days (GDs) 6-19 with 0 (control), 10 (low), 30 (mid) or 50 (high) mg/kg bw/day of ROT to recapitulate developmental effects on general fetotoxicity (assessed by the number of fetuses, fetal body and placental weights), markers of oxidative stress and cholinergic activities in maternal brain regions and whole fetal-brain. Secondly, dams orally supplemented with inulin (2×/day, 2 g/kg/bw) on GD 0-21 were administered ROT (50 mg/kg, GD 6-19). IN supplements increased maternal cecal bacterial numbers that significantly corresponded with improved exploratory-related behavior among ROT administered rats. In addition, IN supplements improved fetal and placental weight on GD 19. IN diminished gestational ROT-induced increased reactive oxygen species levels, protein and lipid peroxidation biomarkers, and cholinesterase activity in maternal brain regions (cortex, cerebellum, and striatum) and fetal brain. Moreover, in the maternal cortex, mitochondrial assessment revealed IN protected against ROT-induced reduction in NADH cytochrome c oxidoreductase and ATPase activities. These data suggest a potential role for indigestible oligosaccharides in reducing oxidative stress-mediated developmental origins of neurodegenerative disorders. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Regional Delivery of Chimeric Antigen Receptor-Engineered T Cells Effectively Targets HER2+ Breast Cancer Metastasis to the Brain.

PubMed

Priceman, Saul J; Tilakawardane, Dileshni; Jeang, Brook; Aguilar, Brenda; Murad, John P; Park, Anthony K; Chang, Wen-Chung; Ostberg, Julie R; Neman, Josh; Jandial, Rahul; Portnow, Jana; Forman, Stephen J; Brown, Christine E

2018-01-01

Purpose: Metastasis to the brain from breast cancer remains a significant clinical challenge, and may be targeted with CAR-based immunotherapy. CAR design optimization for solid tumors is crucial due to the absence of truly restricted antigen expression and potential safety concerns with "on-target off-tumor" activity. Here, we have optimized HER2-CAR T cells for the treatment of breast to brain metastases, and determined optimal second-generation CAR design and route of administration for xenograft mouse models of breast metastatic brain tumors, including multifocal and leptomeningeal disease. Experimental Design: HER2-CAR constructs containing either CD28 or 4-1BB intracellular costimulatory signaling domains were compared for functional activity in vitro by measuring cytokine production, T-cell proliferation, and tumor killing capacity. We also evaluated HER2-CAR T cells delivered by intravenous, local intratumoral, or regional intraventricular routes of administration using in vivo human xenograft models of breast cancer that have metastasized to the brain. Results: Here, we have shown that HER2-CARs containing the 4-1BB costimulatory domain confer improved tumor targeting with reduced T-cell exhaustion phenotype and enhanced proliferative capacity compared with HER2-CARs containing the CD28 costimulatory domain. Local intracranial delivery of HER2-CARs showed potent in vivo antitumor activity in orthotopic xenograft models. Importantly, we demonstrated robust antitumor efficacy following regional intraventricular delivery of HER2-CAR T cells for the treatment of multifocal brain metastases and leptomeningeal disease. Conclusions: Our study shows the importance of CAR design in defining an optimized CAR T cell, and highlights intraventricular delivery of HER2-CAR T cells for treating multifocal brain metastases. Clin Cancer Res; 24(1); 95-105. ©2017 AACR . ©2017 American Association for Cancer Research.

Spatial Frequency Domain Imaging: Applications in Preclinical Models of Alzheimer's Disease

NASA Astrophysics Data System (ADS)

Lin, Alexander Justin

A clinical challenge in Alzheimer's disease (AD) is diagnosing and treating patients earlier, before symptoms of cognitive dysfunction occur. A good screening test would be sensitive to the AD brain pathology, safe, and cost-effective. Diffuse optical imaging, which measures how non-ionizing light is absorbed and scattered in tissue, may fulfill these three parameters. We imaged the brains of transgenic AD mouse models in vivo with a quantitative, camera-based, diffuse optical imaging technology called spatial frequency domain imaging (SFDI) to characterize near-infrared (650-970nm) optical biomarkers of AD. Compared to age-matched control mice, we found a decrease in light absorption --- due to lower oxygenated and total hemoglobin concentrations in the brain --- correlating to decreased blood vessel volume and density in histology. Light scattering also increased in AD mice, correlating to brain structural changes caused by neuron loss and activation of inflammatory cells. Furthermore, inhaled gas challenges revealed brain vascular function was diminished. To investigate how AD affects the small changes in blood perfusion caused by increased brain activity, we built a new SFDI system from a commercial light-emitting diode microprojector and off-the-shelf optical components and cameras to measure optical properties in the visible range (460-632nm). Our measurements showed a reduced amplitude and duration of blood vessel dilation to increased brain activity in the AD mice. Altogether, this work increased our understanding of AD pathogenesis, explored optical biomarkers of AD, and improved technology access to other research labs. These results and technologies can further be used to facilitate longitudinal drug therapy trials in mice and provide a roadmap to diffuse optical spectroscopy studies in humans.

Cytophotometric study of ATPase activity in brain neurons and gliocytes of paradoxical sleep-deprived rats.

PubMed

Klenikova, V A; Taranova, N P

1989-01-01

Conditions were chosen for optimal demonstration of ATPases in brain slices by a modified method of Wachstein and Meisel, and the reaction was shown to obey the Bouguer-Beer laws, confirming that ATPase activity can be determined quantitatively in single cells by cytophotometry. In rats in a state of relative physiological rest specific activity of both Na+, K+-ATPase and Mg++-ATPase in gliocytes of the hippocampus and dorsal raphe was found to be considerably higher than in neurons. Deprivation of the paradoxical phase of sleep of the rats for 24 h led to a significant increase in Na+, K+-ATPase activity in hippocampal neurons and to a decrease in its activity in gliocytes of the hippocampus and dorsal nucleus raphe. It is suggested that these changes in Na+, K+-ATPase activity may be due to some extent to a change in excitability of neurons and depolarization of the glia when sleep is disturbed.

Uptake and bio-reactivity of polystyrene nanoparticles is affected by surface modifications, ageing and LPS adsorption: in vitro studies on neural tissue cells

NASA Astrophysics Data System (ADS)

Murali, Kumarasamy; Kenesei, Kata; Li, Yang; Demeter, Kornél; Környei, Zsuzsanna; Madarász, Emilia

2015-02-01

Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types. PS NPs within a size-range of 45-70 nm influenced the metabolic activity of cells depending on the cell-type, but caused toxicity only at extremely high particle concentrations. Neurons did not internalize particles, while microglial cells ingested a large amount of carboxylated but almost no PEGylated NPs. PEGylation reduced the protein adsorption, toxicity and cellular uptake of NPs. After storage (shelf-life >6 months), the toxicity and cellular uptake of NPs increased. The altered biological activity of ``aged'' NPs was due to particle aggregation and due to the adsorption of bioactive compounds on NP surfaces. Aggregation by increasing the size and sedimentation velocity of NPs results in increased cell-targeted NP doses. The ready endotoxin adsorption which cannot be prevented by PEG coating, can render the particles toxic. The age-dependent changes in otherwise harmless NPs could be the important sources for variability in the effects of NPs, and could explain the contradictory data obtained with ``identical'' NPs.Because of their capacity of crossing an intact blood-brain barrier and reaching the brain through an injured barrier or via the nasal epithelium, nanoparticles have been considered as vehicles to deliver drugs and as contrast materials for brain imaging. The potential neurotoxicity of nanoparticles, however, is not fully explored. Using particles with a biologically inert polystyrene core material, we investigated the role of the chemical composition of particle surfaces in the in vitro interaction with different neural cell types. PS NPs within a size-range of 45-70 nm influenced the metabolic activity of cells depending on the cell-type, but caused toxicity only at extremely high particle concentrations. Neurons did not internalize particles, while microglial cells ingested a large amount of carboxylated but almost no PEGylated NPs. PEGylation reduced the protein adsorption, toxicity and cellular uptake of NPs. After storage (shelf-life >6 months), the toxicity and cellular uptake of NPs increased. The altered biological activity of ``aged'' NPs was due to particle aggregation and due to the adsorption of bioactive compounds on NP surfaces. Aggregation by increasing the size and sedimentation velocity of NPs results in increased cell-targeted NP doses. The ready endotoxin adsorption which cannot be prevented by PEG coating, can render the particles toxic. The age-dependent changes in otherwise harmless NPs could be the important sources for variability in the effects of NPs, and could explain the contradictory data obtained with ``identical'' NPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr06849a

Stabilization of superoxide dismutase by acetyl-l-carnitine in human brain endothelium during alcohol exposure: novel protective approach.

PubMed

Haorah, James; Floreani, Nicholas A; Knipe, Bryan; Persidsky, Yuri

2011-10-15

Oxidative damage of the endothelium disrupts the integrity of the blood-brain barrier (BBB). We have shown before that alcohol exposure increases the levels of reactive oxygen species (ROS; superoxide and hydroxyl radical) and nitric oxide (NO) in brain endothelial cells by activating NADPH oxidase and inducible nitric oxide synthase. We hypothesize that impairment of antioxidant systems, such as a reduction in catalase and superoxide dismutase (SOD) activity, by ethanol exposure may elevate the levels of ROS/NO in endothelium, resulting in BBB damage. This study examines whether stabilization of antioxidant enzyme activity results in suppression of ROS levels by anti-inflammatory agents. To address this idea, we determined the effects of ethanol on the kinetic profile of SOD and catalase activity and ROS/NO generation in primary human brain endothelial cells (hBECs). We observed an enhanced production of ROS and NO levels due to the metabolism of ethanol in hBECs. Similar increases were found after exposure of hBECs to acetaldehyde, the major metabolite of ethanol. Ethanol simultaneously augmented ROS generation and the activity of antioxidative enzymes. SOD activity was increased for a much longer period of time than catalase activity. A decline in SOD activity and protein levels preceded elevation of oxidant levels. SOD stabilization by the antioxidant and mitochondria-protecting agent acetyl-L-carnitine (ALC) and the anti-inflammatory agent rosiglitazone suppressed ROS levels, with a marginal increase in NO levels. Mitochondrial membrane protein damage and decreased membrane potential after ethanol exposure indicated mitochondrial injury. These changes were prevented by ALC. Our findings suggest the counteracting mechanisms of oxidants and antioxidants during alcohol-induced oxidative stress at the BBB. The presence of enzymatic stabilizers favors the ROS-neutralizing antioxidant redox of the BBB, suggesting an underlying protective mechanism of NO for brain vascular tone and vasodilation. Published by Elsevier Inc.

Neurotrophin-3 provides neuroprotection via TrkC receptor dependent pErk5 activation in a rat surgical brain injury model.

PubMed

Akyol, Onat; Sherchan, Prativa; Yilmaz, Gokce; Reis, Cesar; Ho, Wingi Man; Wang, Yuechun; Huang, Lei; Solaroglu, Ihsan; Zhang, John H

2018-06-05

Surgical brain injury (SBI) which occurs due to the inadvertent injury inflicted to surrounding brain tissue during neurosurgical procedures can potentiate blood brain barrier (BBB) permeability, brain edema and neurological deficits. This study investigated the role of neurotrophin 3 (NT-3) and tropomyosin related kinase receptor C (TrkC) against brain edema and neurological deficits in a rat SBI model. SBI was induced in male Sprague Dawley rats by partial right frontal lobe resection. Temporal expression of endogenous NT-3 and TrkC was evaluated at 6, 12, 24 and 72 h after SBI. SBI rats received recombinant NT-3 which was directly applied to the brain surgical injury site using gelfoam. Brain edema and neurological function was evaluated at 24 and 72 h after SBI. Small interfering RNA (siRNA) for TrkC and Rap1 was administered via intracerebroventricular injection 24 h before SBI. BBB permeability assay and western blot was performed at 24 h after SBI. Endogenous NT-3 was decreased and TrkC expression increased after SBI. Topical administration of recombinant NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. Recombinant NT-3 administration increased the expression of phosphorylated Rap1 and Erk5. The protective effect of NT-3 was reversed with TrkC siRNA but not Rap1 siRNA. Topical application of NT-3 reduced brain edema, BBB permeability and improved neurological function after SBI. The protective effect of NT-3 was possibly mediated via TrkC dependent activation of Erk5. Copyright © 2018 Elsevier Inc. All rights reserved.

Non-invasive MRI measurements of venous oxygenation, oxygen extraction fraction and oxygen consumption in neonates.

PubMed

De Vis, J B; Petersen, E T; Alderliesten, T; Groenendaal, F; de Vries, L S; van Bel, F; Benders, M J N L; Hendrikse, J

2014-07-15

Brain oxygen consumption reflects neuronal activity and can therefore be used to investigate brain development or neuronal injury in neonates. In this paper we present the first results of a non-invasive MRI method to evaluate whole brain oxygen consumption in neonates. For this study 51 neonates were included. The T1 and T2 of blood in the sagittal sinus were fitted using the 'T2 prepared tissue relaxation inversion recovery' pulse sequence (T2-TRIR). From the T1 and the T2 of blood, the venous oxygenation and the oxygen extraction fraction (OEF) were calculated. The cerebral metabolic rate of oxygen (CMRO2) was the resultant of the venous oxygenation and arterial spin labeling whole brain cerebral blood flow (CBF) measurements. Venous oxygenation was 59±14% (mean±sd), OEF was 40±14%, CBF was 14±5ml/100g/min and CMRO2 was 30±12μmol/100g/min. The OEF in preterms at term-equivalent age was higher than in the preterms and in the infants with hypoxic-ischemic encephalopathy (p<0.01). The OEF, CBF and CMRO2 increased (p<0.01, <0.05 and <0.01, respectively) with postnatal age. We presented an MRI technique to evaluate whole-brain oxygen consumption in neonates non-invasively. The measured values are in line with reference values found by invasive measurement techniques. Preterms and infants with HIE demonstrated significant lower oxygen extraction fraction than the preterms at term-equivalent age. This could be due to decreased neuronal activity as a reflection of brain development or as a result of tissue damage, increased cerebral blood flow due to immature or impaired autoregulation, or could be caused by differences in postnatal age. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

PubMed

Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

2014-06-01

Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

Using human extra-cortical local field potentials to control a switch

NASA Astrophysics Data System (ADS)

Kennedy, Philip; Andreasen, Dinal; Ehirim, Princewill; King, Brandon; Kirby, Todd; Mao, Hui; Moore, Melody

2004-06-01

Individuals with profound paralysis and mutism require a communication channel. Traditional assistive technology devices eventually fail, especially in the case of amyotrophic lateral sclerosis (ALS) subjects who gradually become totally locked-in. A direct brain-to-computer interface that provides switch functions can provide a direct communication channel to the external world. Electroencephalographic (EEG) signals recorded from scalp electrodes are significantly degraded due to skull and scalp attenuation and ambient noise. The present system using conductive skull screws allows more reliable access to cortical local field potentials (LFPs) without entering the brain itself. We describe an almost locked-in human subject with ALS who activated a switch using online time domain detection techniques. Frequency domain analysis of his LFP activity demonstrates this to be an alternative method of detecting switch activation intentions. With this brain communicator system it is reasonable to expect that locked-in, but cognitively intact, humans will always be able to communicate. Financial disclosure. Authors PK and DA may derive some financial gain from the sale of this device. A patent has been applied under US and international law: 10/675,703.

Reduced cerebellar brain activity during reward processing in adolescent binge drinkers

PubMed Central

Cservenka, Anita; Jonesb, Scott A.; Nagel, Bonnie J.

2015-01-01

Due to ongoing development, adolescence may be a period of heightened vulnerability to the neurotoxic effects of alcohol. Binge drinking may alter reward-driven behavior and neurocircuitry, thereby increasing risk for escalating alcohol use. Therefore, we compared reward processing in adolescents with and without a history of recent binge drinking. At their baseline study visit, all participants (age = 14.86 ± 0.88) were free of heavy alcohol use and completed a modified version of the Wheel of Fortune (WOF) functional magnetic resonance imaging task. Following this visit, 17 youth reported binge drinking on ≥3 occasions within a 90 day period and were matched to 17 youth who remained alcohol and substance-naïve. All participants repeated the WOF task during a second visit (age = 16.83 ± 1.22). No significant effects were found in a region of interest analysis of the ventral striatum, but whole-brain analyses showed significant group differences in reward response at the second study visit in the left cerebellum, controlling for baseline visit brain activity (p/α<0.05), which was negatively correlated with mean number of drinks consumed/drinking day in the last 90 days. These findings suggest that binge drinking during adolescence may alter brain activity during reward processing in a dose-dependent manner. PMID:26190276

Curcumin micelles improve mitochondrial function in neuronal PC12 cells and brains of NMRI mice - Impact on bioavailability.

PubMed

Hagl, Stephanie; Kocher, Alexa; Schiborr, Christina; Kolesova, Natalie; Frank, Jan; Eckert, Gunter P

2015-10-01

Curcumin, a polyphenolic compound abundant in the rhizome of Curcuma longa, has been reported to have various beneficial biological and pharmacological activities. Recent research revealed that curcumin might be valuable in the prevention and therapy of numerous disorders including neurodegenerative diseases like Alzheimer's disease. Due to its low absorption and quick elimination from the body, curcumin bioavailability is rather low which poses major problems for the use of curcumin as a therapeutic agent. There are several approaches to ameliorate curcumin bioavailability after oral administration, amongst them simultaneous administration with secondary plant compounds, micronization and micellation. We examined bioavailability in vivo in NMRI mice and the effects of native curcumin and a newly developed curcumin micelles formulation on mitochondrial function in vitro in PC12 cells and ex vivo in isolated mouse brain mitochondria. We found that curcumin micelles improved bioavailability of native curcumin around 10- to 40-fold in plasma and brain of mice. Incubation with native curcumin and curcumin micelles prevented isolated mouse brain mitochondria from swelling, indicating less mitochondrial permeability transition pore (mPTP) opening and prevention of injury. Curcumin micelles proved to be more efficient in preventing mitochondrial swelling in isolated mouse brain mitochondria and protecting PC12 cells from nitrosative stress than native curcumin. Due to their improved effectivity, curcumin micelles might be a suitable formulation for the prevention of mitochondrial dysfunction in brain aging and neurodegeneration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Altered blood-brain barrier transport in neuro-inflammatory disorders.

PubMed

Schenk, Geert J; de Vries, Helga E

2016-06-01

During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood-brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, the delivery and disposition of drugs to the brain will be altered and may influence the treatment efficiency of such diseases. Altered BBB transport of drugs into the CNS during diseases may be the result of changes in both specific transport and non-specific transport pathways. Potential alterations in transport routes like adsorptive mediated endocytosis and receptor-mediated endocytosis may affect drug delivery to the brain. As such, drugs that normally are unable to traverse the BBB may reach their target in the diseased brain due to increased permeability. In contrast, the delivery of (targeted) drugs could be hampered during inflammatory conditions due to disturbed transport mechanisms. Therefore, the inventory of the neuro-inflammatory status of the neurovasculature (or recovery thereof) is of utmost importance in choosing and designing an adequate drug targeting strategy under disease conditions. Within this review we will briefly discuss how the function of the BBB can be affected during disease and how this may influence the delivery of drugs into the diseased CNS. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of ebselen on ischemia/reperfusion injury in rat brain.

PubMed

Aras, M; Altaş, M; Meydan, S; Nacar, E; Karcıoğlu, M; Ulutaş, K T; Serarslan, Y

2014-10-01

Interruption of blood flow may result in considerable tissue damage via ischemia/reperfusion (I/R) injury-induced oxidative stress in brain tissues. The aim of the present study was to investigate the effects of Ebselen treatment in short-term global brain I/R injury in rats. The study was carried out on 27 Wistar-albino rats, divided into three groups including Sham group (n = 11), I/R group (n = 8) and I/R+Ebselen group (n = 8). Malondialdehyde (MDA) levels were significantly increased in I/R group in comparison with the Sham group and I/R+Ebselen group (p < 0.001 and p < 0.01). Superoxide dismutase (SOD) activity was significantly lower in I/R group in comparison to both Sham (p < 0.001) and I/R+Ebselen (p < 0.01) groups. Similarly, SOD activity was decreased in I/R+Ebselen group when compared with Sham group (p < 0.001). Sham and I/R groups were similar in terms of nitric oxide (NO) levels. In contrast, the NO level was lower in I/R+Ebselen group when compared with Sham (p < 0.001) and I/R (p < 0.01) groups. There was no significant difference among the groups in terms of glutathione peroxidase and catalase activities. In histopathological examination, the brain tissues of rats that received Ebselen showed morphological improvement. Ebselen has neuron-protective effects due to its antioxidant properties as shown by the decrease in MDA overproduction, increase in SOD activity and the histological improvement after administration of Ebselen to I/R in brain tissue.

Bimanual Motor Coordination in Older Adults Is Associated with Increased Functional Brain Connectivity – A Graph-Theoretical Analysis

PubMed Central

Heitger, Marcus H.; Goble, Daniel J.; Dhollander, Thijs; Dupont, Patrick; Caeyenberghs, Karen; Leemans, Alexander; Sunaert, Stefan; Swinnen, Stephan P.

2013-01-01

In bimanual coordination, older and younger adults activate a common cerebral network but the elderly also have additional activation in a secondary network of brain areas to master task performance. It remains unclear whether the functional connectivity within these primary and secondary motor networks differs between the old and the young and whether task difficulty modulates connectivity. We applied graph-theoretical network analysis (GTNA) to task-driven fMRI data in 16 elderly and 16 young participants using a bimanual coordination task including in-phase and anti-phase flexion/extension wrist movements. Network nodes for the GTNA comprised task-relevant brain areas as defined by fMRI activation foci. The elderly matched the motor performance of the young but showed an increased functional connectivity in both networks across a wide range of connectivity metrics, i.e., higher mean connectivity degree, connection strength, network density and efficiency, together with shorter mean communication path length between the network nodes and also a lower betweenness centrality. More difficult movements showed an increased connectivity in both groups. The network connectivity of both groups had “small world” character. The present findings indicate (a) that bimanual coordination in the aging brain is associated with a higher functional connectivity even between areas also activated in young adults, independently from task difficulty, and (b) that adequate motor coordination in the context of task-driven bimanual control in older adults may not be solely due to additional neural recruitment but also to aging-related changes of functional relationships between brain regions. PMID:23637982

Planar implantable sensor for in vivo measurement of cellular oxygen metabolism in brain tissue.

PubMed

Tsytsarev, Vassiliy; Akkentli, Fatih; Pumbo, Elena; Tang, Qinggong; Chen, Yu; Erzurumlu, Reha S; Papkovsky, Dmitri B

2017-04-01

Brain imaging methods are continually improving. Imaging of the cerebral cortex is widely used in both animal experiments and charting human brain function in health and disease. Among the animal models, the rodent cerebral cortex has been widely used because of patterned neural representation of the whiskers on the snout and relative ease of activating cortical tissue with whisker stimulation. We tested a new planar solid-state oxygen sensor comprising a polymeric film with a phosphorescent oxygen-sensitive coating on the working side, to monitor dynamics of oxygen metabolism in the cerebral cortex following sensory stimulation. Sensory stimulation led to changes in oxygenation and deoxygenation processes of activated areas in the barrel cortex. We demonstrate the possibility of dynamic mapping of relative changes in oxygenation in live mouse brain tissue with such a sensor. Oxygenation-based functional magnetic resonance imaging (fMRI) is very effective method for functional brain mapping but have high costs and limited spatial resolution. Optical imaging of intrinsic signal (IOS) does not provide the required sensitivity, and voltage-sensitive dye optical imaging (VSDi) has limited applicability due to significant toxicity of the voltage-sensitive dye. Our planar solid-state oxygen sensor imaging approach circumvents these limitations, providing a simple optical contrast agent with low toxicity and rapid application. The planar solid-state oxygen sensor described here can be used as a tool in visualization and real-time analysis of sensory-evoked neural activity in vivo. Further, this approach allows visualization of local neural activity with high temporal and spatial resolution. Copyright © 2017 Elsevier B.V. All rights reserved.

Reproducibility of proton MR spectroscopic imaging (PEPSI): comparison of dyslexic and normal-reading children and effects of treatment on brain lactate levels during language tasks.

PubMed

Richards, Todd L; Berninger, Virginia W; Aylward, Elizabeth H; Richards, Anne L; Thomson, Jennifer B; Nagy, William E; Carlisle, Joanne F; Dager, Stephen R; Abbott, Robert D

2002-01-01

We repeated a proton echo-planar spectroscopic imaging (PEPSI) study to test the hypothesis that children with dyslexia and good readers differ in brain lactate activation during a phonologic judgment task before but not after instructional treatment. We measured PEPSI brain lactate activation (TR/TE, 4000/144; 1.5 T) at two points 1-2 months apart during two language tasks (phonologic and lexical) and a control task (passive listening). Dyslexic participants (n = 10) and control participants (n = 8) (boys and girls aged 9-12 years) were matched in age, verbal intelligence quotients, and valid PEPSI voxels. In contrast to patients in past studies who received combined treatment, our patients were randomly assigned to either phonologic or morphologic (meaning-based) intervention between the scanning sessions. Before treatment, the patients showed significantly greater lactate elevation in the left frontal regions (including the inferior frontal gyrus) during the phonologic task. Both patients and control subjects differed significantly in the right parietal and occipital regions during both tasks. After treatment, the two groups did not significantly differ in any brain region during either task, but individuals given morphologic treatment were significantly more likely to have reduced left frontal lactate activation during the phonologic task. The previous finding of greater left frontal lactate elevation in children with dyslexia during a phonologic judgment task was replicated, and brain activation changed as a result of treatment. However, the treatment effect was due to the morphologic component rather than the phonologic component.

[Successful treatment with anti-epileptic-drug of an 83-year-old man with musical hallucinosis].

PubMed

Futamura, Akinori; Katoh, Hirotaka; Kawamura, Mitsuru

2014-05-01

An 83-year-old man with 3 years symptomatic hearing loss suddenly experienced musical hallucinosis. He heard children's songs, folk songs, military songs, and the Japanese national anthem for seven months every day. He sometime had paroxysmal nausea, dull headaches and depressive mood. On examination he had no psychosis or neurological symptoms except sensorineural hearing loss in both ears. MRI brain imaging and electroencephalography showed no significant abnormalities, however ¹²³I-IMP brain SPECT showed decreased activity in the right temporal lobe and increased activity in the left temporal and parietal lobes. Late phase ¹²³I-iomazenil brain SPECT showed decreased accumulation in the right temporal lobe compared to the early phase. This indicates right temporal lobe epilepsy. He was diagnosed with epilepsy because of paroxysmal nausea and headache and the laterality of ¹²³I-IMP brain SPECT and ¹²³I-iomazenil brain SPECT. The musical hallucinosis was much reduced by carbamazepine 200mg per day. Nine months after beginning carbamazepine we detected decreased activity in the right temporal lobe and increased activity in left temporal and parietal lobes was improved. We do not believe he had epileptogenic musical hallucinosis because his musical hallusinosis was neither paroxysmal nor lateral. We diagnosed auditory Charles Bonnet syndrome with onset 3 years after sensorineural hearing loss due to reversible epileptic like discharge in temporal and parietal lobes. There is no established treatment for musical hallucinosis, but anti-epileptic drugs may be of some help.

[Traumatic brain injuries--forensic and expertise aspects].

PubMed

Vuleković, Petar; Simić, Milan; Misić-Pavkov, Gordana; Cigić, Tomislav; Kojadinović, Zeljko; Dilvesi, Dula

2008-01-01

Traumatic brain injuries have major socio-economic importance due to their frequency, high mortality and serious consequences. According to their nature the consequences of these injuries may be classified as neurological, psychiatric and esthetic. Various lesions of brain structures cause neurological consequences such as disturbance of motor functions, sensibility, coordination or involuntary movements, speech disturbances and other deviations, as well as epilepsy. Psychiatric consequences include cognitive deficit, emotional disturbances and behavior disturbances. CRIMINAL-LEGAL ASPECT OF TRAUMATIC BRAIN INJURIES AND LITIGATION: Criminal-legal aspect of traumatic brain injuries expertise understands the qualification of these injuries as mild, serious and qualified serious body injuries as well as the expertise about the mechanisms of their occurrence. Litigation expertise includes the estimation of pain, fear, diminished, i.e. lost vital activity and disability, esthetic marring, and psychological suffer based on the diminished general vital activity and esthetic marring. Evaluation of consequences of traumatic brain injuries should be performed only when it can be positively confirmed that they are permanent, i.e. at least one year after the injury. Expertise of these injuries is interdisciplinary. Among clinical doctors the most competent medical expert is the one who is in charge for diagnostics and injury treatment, with the recommendation to avoid, if possible, the doctor who conducted treatment. For the estimation of general vital activity, the neurological consequences, pain and esthetic marring expertise, the most competent doctors are neurosurgeon and neurologist. Psychological psychiatric consequences and fear expertise have to be performed by the psychiatrist. Specialists of forensic medicine contribute with knowledge of criminal low and legal expertise.

Source Space Estimation of Oscillatory Power and Brain Connectivity in Tinnitus

PubMed Central

Zobay, Oliver; Palmer, Alan R.; Hall, Deborah A.; Sereda, Magdalena; Adjamian, Peyman

2015-01-01

Tinnitus is the perception of an internally generated sound that is postulated to emerge as a result of structural and functional changes in the brain. However, the precise pathophysiology of tinnitus remains unknown. Llinas’ thalamocortical dysrhythmia model suggests that neural deafferentation due to hearing loss causes a dysregulation of coherent activity between thalamus and auditory cortex. This leads to a pathological coupling of theta and gamma oscillatory activity in the resting state, localised to the auditory cortex where normally alpha oscillations should occur. Numerous studies also suggest that tinnitus perception relies on the interplay between auditory and non-auditory brain areas. According to the Global Brain Model, a network of global fronto—parietal—cingulate areas is important in the generation and maintenance of the conscious perception of tinnitus. Thus, the distress experienced by many individuals with tinnitus is related to the top—down influence of this global network on auditory areas. In this magnetoencephalographic study, we compare resting-state oscillatory activity of tinnitus participants and normal-hearing controls to examine effects on spectral power as well as functional and effective connectivity. The analysis is based on beamformer source projection and an atlas-based region-of-interest approach. We find increased functional connectivity within the auditory cortices in the alpha band. A significant increase is also found for the effective connectivity from a global brain network to the auditory cortices in the alpha and beta bands. We do not find evidence of effects on spectral power. Overall, our results provide only limited support for the thalamocortical dysrhythmia and Global Brain models of tinnitus. PMID:25799178

Attenuation of Oxidative Damage by Boerhaavia diffusa L. Against Different Neurotoxic Agents in Rat Brain Homogenate.

PubMed

Ayyappan, Prathapan; Palayyan, Salin Raj; Kozhiparambil Gopalan, Raghu

2016-01-01

Due to a high rate of oxidative metabolic activity in the brain, intense production of reactive oxygen metabolite occurs, and the subsequent generation of free radicals is implicated in the pathogenesis of traumatic brain injury, epilepsy, and ischemia as well as chronic neurodegenerative diseases. In the present study, protective effects of polyphenol rich ethanolic extract of Boerhaavia diffusa (BDE), a neuroprotective edible medicinal plant against oxidative stress induced by different neurotoxic agents, were evaluated. BDE was tested against quinolinic acid (QA), 3-nitropropionic acid (NPA), sodium nitroprusside (SNP), and Fe (II)/EDTA complex induced oxidative stress in rat brain homogenates. QA, NPA, SNP, and Fe (II)/EDTA treatment caused an increased level of thiobarbituric acid reactive substances (TBARS) in brain homogenates along with a decline in the activities of antioxidant enzymes. BDE treatment significantly decreased the production of TBARS (p < .05) and increased the activities of antioxidant enzymes like catalase and superoxide dismutase along with increased concentration of non-enzymatic antioxidant, reduced glutathione (GSH). Similarly, BDE caused a significant decrease in the lipid peroxidation (LPO) in the cerebral cortex. Inhibitory potential of BDE against deoxyribose degradation (IC50 value 38.91 ± 0.12 μg/ml) shows that BDE can protect hydroxyl radical induced DNA damage in the tissues. Therefore, B. diffusa had high antioxidant potential that could inhibit the oxidative stress induced by different neurotoxic agents in brain. Since many of the neurological disorders are associated with free radical injury, these data may imply that B. diffusa, functioning as an antioxidant agent, may be beneficial for reducing various neurodegenerative complications.

Neural representation of anxiety and personality during exposure to anxiety-provoking and neutral scenes from scary movies.

PubMed

Straube, Thomas; Preissler, Sandra; Lipka, Judith; Hewig, Johannes; Mentzel, Hans-Joachim; Miltner, Wolfgang H R

2010-01-01

Some people search for intense sensations such as being scared by frightening movies while others do not. The brain mechanisms underlying such inter-individual differences are not clear. Testing theoretical models, we investigated neural correlates of anxiety and the personality trait sensation seeking in 40 subjects who watched threatening and neutral scenes from scary movies during functional magnetic resonance imaging. Threat versus neutral scenes induced increased activation in anterior cingulate cortex, insula, thalamus, and visual areas. Movie-induced anxiety correlated positively with activation in dorsomedial prefrontal cortex, indicating a role for this area in the subjective experience of being scared. Sensation seeking-scores correlated positively with brain activation to threat versus neutral scenes in visual areas and in thalamus and anterior insula, i.e. regions involved in the induction and representation of arousal states. For the insula and thalamus, these outcomes were partly due to an inverse relation between sensation seeking scores and brain activation during neutral film clips. These results support models predicting cerebral hypoactivation in high sensation seekers during neutral stimulation, which may be compensated by more intense sensations such as watching scary movies. 2009 Wiley-Liss, Inc.

[Streptomycin--an activator of persisting tick-borne encephalitis virus].

PubMed

Malenko, G V; Pogodina, V V; Karmysheva, V Ia

1984-01-01

The effect of streptomycin (C) on persistence of tick-borne encephalitis (TBE) virus in Syrian hamsters infected with 3 strains of the virus (41/65, Aina/1448, Vasilchenko ) intracerebrally or subcutaneously was studied. In the animals not given C the infectious virus could be detected in the brain for 8-14 days but not later although their organs (mostly brains and spleens) contained the hemagglutinating antigen and viral antigen detectable by immunofluorescence. Intramuscularly C was given twice daily for 13-35 days in a daily dose of 200 mg/kg. The C-treated hamsters yielded 7 virulent TBE virus strains: 3 from the brain, 3 from the spleen, and one from the blood. No virus could be isolated from the liver, kidneys, or lungs despite the use of various methods for isolation including tissue explantation. The activating effect of C was observed against the background of 4-fold decrease in the titre of complement-fixing and antihemagglutinating antibodies. C exerted its activating effect both at early (70 days) and late (9 months) stages of TBE virus persistence. The activating effect of C appears to be due to its immunosuppressive properties and neurotoxic action on the CNS.

Baicalin Attenuates Subarachnoid Hemorrhagic Brain Injury by Modulating Blood-Brain Barrier Disruption, Inflammation, and Oxidative Damage in Mice

PubMed Central

Fu, Yongjian; Zhang, SongSong; Ding, Hao; Chen, Jin

2017-01-01

In subarachnoid hemorrhagic brain injury, the early crucial events are edema formation due to inflammatory responses and blood-brain barrier disruption. Baicalin, a flavone glycoside, has antineuroinflammatory and antioxidant properties. We examined the effect of baicalin in subarachnoid hemorrhagic brain injury. Subarachnoid hemorrhage was induced through filament perforation and either baicalin or vehicle was administered 30 min prior to surgery. Brain tissues were collected 24 hours after surgery after evaluation of neurological scores. Brain tissues were processed for water content, real-time PCR, and immunoblot analyses. Baicalin improved neurological score and brain water content. Decreased levels of tight junction proteins (occludin, claudin-5, ZO-1, and collagen IV) required for blood-brain barrier function were restored to normal level by baicalin. Real-time PCR data demonstrated that baicalin attenuated increased proinflammatory cytokine (IL-1β, IL-6, and CXCL-3) production in subarachnoid hemorrhage mice. In addition to that, baicalin attenuated microglial cell secretion of IL-1β and IL-6 induced by lipopolysaccharide (100 ng/ml) dose dependently. Finally, baicalin attenuated induction of NOS-2 and NOX-2 in SAH mice at the mRNA and protein level. Thus, we demonstrated that baicalin inhibited microglial cell activation and reduced inflammation, oxidative damage, and brain edema. PMID:28912935

Antitumor activity of the selective ALK inhibitor alectinib in models of intracranial metastases.

PubMed

Kodama, Tatsushi; Hasegawa, Masami; Takanashi, Kenji; Sakurai, Yuji; Kondoh, Osamu; Sakamoto, Hiroshi

2014-11-01

The clinical efficacy of the anaplastic lymphoma kinase (ALK) inhibitor crizotinib has been demonstrated in ALK fusion-positive non-small cell lung cancer (NSCLC); however, brain metastases are frequent sites of initial failure in patients due to poor penetration of the central nervous system by crizotinib. Here, we examined the efficacy of a selective ALK inhibitor alectinib/CH5424802 in preclinical models of intracranial tumors. We established intracranial tumor implantation mouse models of EML4-ALK-positive NSCLC NCI-H2228 and examined the antitumor activity of alectinib in this model. Plasma distribution and brain distribution of alectinib were examined by quantitative whole-body autoradiography administrating a single oral dose of (14)C-labeled alectinib to rats. The drug permeability of alectinib was evaluated in Caco-2 cell. Alectinib resulted in regression of NCI-H2228 tumor in mouse brain and provided a survival benefit. In a pharmacokinetic study using rats, alectinib showed a high brain-to-plasma ratio, and in an in vitro drug permeability study using Caco-2 cells, alectinib was not transported by P-glycoprotein efflux transporter that is a key factor in blood-brain barrier penetration. We established intracranial tumor implantation models of EML4-ALK-positive NSCLC. Alectinib showed potent efficacy against intracranial EML4-ALK-positive tumor. These results demonstrated that alectinib might provide therapeutic opportunities for crizotinib-treated patients with brain metastases.

Listening to Brain Microcircuits for Interfacing With External World—Progress in Wireless Implantable Microelectronic Neuroengineering Devices

PubMed Central

Nurmikko, Arto V.; Donoghue, John P.; Hochberg, Leigh R.; Patterson, William R.; Song, Yoon-Kyu; Bull, Christopher W.; Borton, David A.; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

2011-01-01

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature’s amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic “brain-interfaces” within the body, a point of special emphasis of this paper. PMID:21654935

Increases in Brain 1H-MR Glutamine and Glutamate Signals Following Acute Exhaustive Endurance Exercise in the Rat

PubMed Central

Świątkiewicz, Maciej; Fiedorowicz, Michał; Orzeł, Jarosław; Wełniak-Kamińska, Marlena; Bogorodzki, Piotr; Langfort, Józef; Grieb, Paweł

2017-01-01

Objective: Proton magnetic resonance spectroscopy (1H-MRS) in ultra-high magnetic field can be used for non-invasive quantitative assessment of brain glutamate (Glu) and glutamine (Gln) in vivo. Glu, the main excitatory neurotransmitter in the central nervous system, is efficiently recycled between synapses and presynaptic terminals through Glu-Gln cycle which involves glutamine synthase confined to astrocytes, and uses 60–80% of energy in the resting human and rat brain. During voluntary or involuntary exercise many brain areas are significantly activated, which certainly intensifies Glu-Gln cycle. However, studies on the effects of exercise on 1H-MRS Glu and/or Gln signals from the brain provided divergent results. The present study on rats was performed to determine changes in 1H-MRS signals from three brain regions engaged in motor activity consequential to forced acute exercise to exhaustion. Method: After habituation to treadmill running, rats were subjected to acute treadmill exercise continued to exhaustion. Each animal participating in the study was subject to two identical imaging sessions performed under light isoflurane anesthesia, prior to, and following the exercise bout. In control experiments, two imaging sessions separated by the period of rest instead of exercise were performed. 1H-NMR spectra were recorded from the cerebellum, striatum, and hippocampus using a 7T small animal MR scanner. Results: Following exhaustive exercise statistically significant increases in the Gln and Glx signals were found in all three locations, whereas increases in the Glu signal were found in the cerebellum and hippocampus. In control experiments, no changes in 1H-MRS signals were found. Conclusion: Increase in glutamine signals from the brain areas engaged in motor activity may reflect a disequilibrium caused by increased turnover in the glutamate-glutamine cycle and a delay in the return of glutamine from astrocytes to neurons. Increased turnover of Glu-Gln cycle may be a result of functional activation caused by forced endurance exercise; the increased rate of ammonia detoxification may also contribute. Increases in glutamate in the cerebellum and hippocampus are suggestive of an anaplerotic increase in glutamate synthesis due to exercise-related stimulation of brain glucose uptake. The disequilibrium in the glutamate-glutamine cycle in brain areas activated during exercise may be a significant contributor to the central fatigue phenomenon. PMID:28197103

Monocrotophos Induces the Expression and Activity of Xenobiotic Metabolizing Enzymes in Pre-Sensitized Cultured Human Brain Cells

PubMed Central

Tripathi, Vinay K.; Kumar, Vivek; Singh, Abhishek K.; Kashyap, Mahendra P.; Jahan, Sadaf; Pandey, Ankita; Alam, Sarfaraz; Khan, Feroz; Khanna, Vinay K.; Yadav, Sanjay; Lohani, Mohtshim; Pant, Aditya B.

2014-01-01

The expression and metabolic profile of cytochrome P450s (CYPs) is largely missing in human brain due to non-availability of brain tissue. We attempted to address the issue by using human brain neuronal (SH-SY5Y) and glial (U373-MG) cells. The expression and activity of CYP1A1, 2B6 and 2E1 were carried out in the cells exposed to CYP inducers viz., 3-methylcholanthrene (3-MC), cyclophosphamide (CPA), ethanol and known neurotoxicant- monocrotophos (MCP), a widely used organophosphorous pesticide. Both the cells show significant induction in the expression and CYP-specific activity against classical inducers and MCP. The induction level of CYPs was comparatively lower in MCP exposed cells than cells exposed to classical inducers. Pre-exposure (12 h) of cells to classical inducers significantly added the MCP induced CYPs expression and activity. The findings were concurrent with protein ligand docking studies, which show a significant modulatory capacity of MCP by strong interaction with CYP regulators-CAR, PXR and AHR. Similarly, the known CYP inducers- 3-MC, CPA and ethanol have also shown significantly high docking scores with all the three studied CYP regulators. The expression of CYPs in neuronal and glial cells has suggested their possible association with the endogenous physiology of the brain. The findings also suggest the xenobiotic metabolizing capabilities of these cells against MCP, if received a pre-sensitization to trigger the xenobiotic metabolizing machinery. MCP induced CYP-specific activity in neuronal cells could help in explaining its effect on neurotransmission, as these CYPs are known to involve in the synthesis/transport of the neurotransmitters. The induction of CYPs in glial cells is also of significance as these cells are thought to be involved in protecting the neurons from environmental insults and safeguard them from toxicity. The data provide better understanding of the metabolizing capability of the human brain cells against xenobiotics. PMID:24663500

Role of Caspase-8 and Fas in Cell Death After Spinal Cord Injury

PubMed Central

Sobrido-Cameán, Daniel; Barreiro-Iglesias, Antón

2018-01-01

Spinal cord injury (SCI) causes the death of neurons and glial cells due to the initial mechanical forces (i.e., primary injury) and through a cascade of secondary molecular events (e.g., inflammation or excitotoxicity) that exacerbate cell death. The loss of neurons and glial cells that are not replaced after the injury is one of the main causes of disability after SCI. Evidence accumulated in last decades has shown that the activation of apoptotic mechanisms is one of the factors causing the death of intrinsic spinal cord (SC) cells following SCI. Although this is not as clear for brain descending neurons, some studies have also shown that apoptosis can be activated in the brain following SCI. There are two main apoptotic pathways, the extrinsic and the intrinsic pathways. Activation of caspase-8 is an important step in the initiation of the extrinsic pathway. Studies in rodents have shown that caspase-8 is activated in SC glial cells and neurons and that the Fas receptor plays a key role in its activation following a traumatic SCI. Recent work in the lamprey model of SCI has also shown the retrograde activation of caspase-8 in brain descending neurons following SCI. Here, we review our current knowledge on the role of caspase-8 and the Fas pathway in cell death following SCI. We also provide a perspective for future work on this process, like the importance of studying the possible contribution of Fas/caspase-8 signaling in the degeneration of brain neurons after SCI in mammals. PMID:29666570

Activation of the endoplasmic reticulum stress response by the amyloid-beta 1-40 peptide in brain endothelial cells.

PubMed

Fonseca, Ana Catarina R G; Ferreiro, Elisabete; Oliveira, Catarina R; Cardoso, Sandra M; Pereira, Cláudia F

2013-12-01

Neurovascular dysfunction arising from endothelial cell damage is an early pathogenic event that contributes to the neurodegenerative process occurring in Alzheimer's disease (AD). Since the mechanisms underlying endothelial dysfunction are not fully elucidated, this study was aimed to explore the hypothesis that brain endothelial cell death is induced upon the sustained activation of the endoplasmic reticulum (ER) stress response by amyloid-beta (Aβ) peptide, which deposits in the cerebral vessels in many AD patients and transgenic mice. Incubation of rat brain endothelial cells (RBE4 cell line) with Aβ1-40 increased the levels of several markers of ER stress-induced unfolded protein response (UPR), in a time-dependent manner, and affected the Ca(2+) homeostasis due to the release of Ca(2+) from this intracellular store. Finally, Aβ1-40 was shown to activate both mitochondria-dependent and -independent apoptotic cell death pathways. Enhanced release of cytochrome c from mitochondria and activation of the downstream caspase-9 were observed in cells treated with Aβ1-40 concomitantly with caspase-12 activation. Furthermore, Aβ1-40 activated the apoptosis effectors' caspase-3 and promoted the translocation of apoptosis-inducing factor (AIF) to the nucleus demonstrating the involvement of caspase-dependent and -independent mechanisms during Aβ-induced endothelial cell death. In conclusion, our data demonstrate that ER stress plays a significant role in Aβ1-40-induced apoptotic cell death in brain endothelial cells suggesting that ER stress-targeted therapeutic strategies might be useful in AD to counteract vascular defects and ultimately neurodegeneration. © 2013.

Electrostatic Microactuators for Precise Positioning of Neural Microelectrodes

PubMed Central

Muthuswamy, Jit; Okandan, Murat; Jain, Tilak; Gilletti, Aaron

2006-01-01

Microelectrode arrays used for monitoring single and multineuronal action potentials often fail to record from the same population of neurons over a period of time likely due to micromotion of neurons away from the microelectrode, gliosis around the recording site and also brain movement due to behavior. We report here novel electrostatic microactuated microelectrodes that will enable precise repositioning of the microelectrodes within the brain tissue. Electrostatic comb-drive microactuators and associated microelectrodes are fabricated using the SUMMiT V™ (Sandia's Ultraplanar Multilevel MEMS Technology) process, a five-layer polysilicon micromachining technology of the Sandia National labs, NM. The microfabricated microactuators enable precise bidirectional positioning of the microelectrodes in the brain with accuracy in the order of 1 μm. The microactuators allow for a linear translation of the microelectrodes of up to 5 mm in either direction making it suitable for positioning microelectrodes in deep structures of a rodent brain. The overall translation was reduced to approximately 2 mm after insulation of the microelectrodes with epoxy for monitoring multiunit activity. The microactuators are capable of driving the microelectrodes in the brain tissue with forces in the order of several micro-Newtons. Single unit recordings were obtained from the somatosensory cortex of adult rats in acute experiments demonstrating the feasibility of this technology. Further optimization of the insulation, packaging and interconnect issues will be necessary before this technology can be validated in long-term experiments. PMID:16235660

Multiscale neural connectivity during human sensory processing in the brain

NASA Astrophysics Data System (ADS)

Maksimenko, Vladimir A.; Runnova, Anastasia E.; Frolov, Nikita S.; Makarov, Vladimir V.; Nedaivozov, Vladimir; Koronovskii, Alexey A.; Pisarchik, Alexander; Hramov, Alexander E.

2018-05-01

Stimulus-related brain activity is considered using wavelet-based analysis of neural interactions between occipital and parietal brain areas in alpha (8-12 Hz) and beta (15-30 Hz) frequency bands. We show that human sensory processing related to the visual stimuli perception induces brain response resulted in different ways of parieto-occipital interactions in these bands. In the alpha frequency band the parieto-occipital neuronal network is characterized by homogeneous increase of the interaction between all interconnected areas both within occipital and parietal lobes and between them. In the beta frequency band the occipital lobe starts to play a leading role in the dynamics of the occipital-parietal network: The perception of visual stimuli excites the visual center in the occipital area and then, due to the increase of parieto-occipital interactions, such excitation is transferred to the parietal area, where the attentional center takes place. In the case when stimuli are characterized by a high degree of ambiguity, we find greater increase of the interaction between interconnected areas in the parietal lobe due to the increase of human attention. Based on revealed mechanisms, we describe the complex response of the parieto-occipital brain neuronal network during the perception and primary processing of the visual stimuli. The results can serve as an essential complement to the existing theory of neural aspects of visual stimuli processing.

Listening to Brain Microcircuits for Interfacing With External World-Progress in Wireless Implantable Microelectronic Neuroengineering Devices: Experimental systems are described for electrical recording in the brain using multiple microelectrodes and short range implantable or wearable broadcasting units.

PubMed

Nurmikko, Arto V; Donoghue, John P; Hochberg, Leigh R; Patterson, William R; Song, Yoon-Kyu; Bull, Christopher W; Borton, David A; Laiwalla, Farah; Park, Sunmee; Ming, Yin; Aceros, Juan

2010-01-01

Acquiring neural signals at high spatial and temporal resolution directly from brain microcircuits and decoding their activity to interpret commands and/or prior planning activity, such as motion of an arm or a leg, is a prime goal of modern neurotechnology. Its practical aims include assistive devices for subjects whose normal neural information pathways are not functioning due to physical damage or disease. On the fundamental side, researchers are striving to decipher the code of multiple neural microcircuits which collectively make up nature's amazing computing machine, the brain. By implanting biocompatible neural sensor probes directly into the brain, in the form of microelectrode arrays, it is now possible to extract information from interacting populations of neural cells with spatial and temporal resolution at the single cell level. With parallel advances in application of statistical and mathematical techniques tools for deciphering the neural code, extracted populations or correlated neurons, significant understanding has been achieved of those brain commands that control, e.g., the motion of an arm in a primate (monkey or a human subject). These developments are accelerating the work on neural prosthetics where brain derived signals may be employed to bypass, e.g., an injured spinal cord. One key element in achieving the goals for practical and versatile neural prostheses is the development of fully implantable wireless microelectronic "brain-interfaces" within the body, a point of special emphasis of this paper.

Functional connectivity of the rodent brain using optical imaging

NASA Astrophysics Data System (ADS)

Guevara Codina, Edgar

The aim of this thesis is to apply functional connectivity in a variety of animal models, using several optical imaging modalities. Even at rest, the brain shows high metabolic activity: the correlation in slow spontaneous fluctuations identifies remotely connected areas of the brain; hence the term "functional connectivity". Ongoing changes in spontaneous activity may provide insight into the neural processing that takes most of the brain metabolic activity, and so may provide a vast source of disease related changes. Brain hemodynamics may be modified during disease and affect resting-state activity. The thesis aims to better understand these changes in functional connectivity due to disease, using functional optical imaging. The optical imaging techniques explored in the first two contributions of this thesis are Optical Imaging of Intrinsic Signals and Laser Speckle Contrast Imaging, together they can estimate the metabolic rate of oxygen consumption, that closely parallels neural activity. They both have adequate spatial and temporal resolution and are well adapted to image the convexity of the mouse cortex. In the last article, a depth-sensitive modality called photoacoustic tomography was used in the newborn rat. Optical coherence tomography and laminar optical tomography were also part of the array of imaging techniques developed and applied in other collaborations. The first article of this work shows the changes in functional connectivity in an acute murine model of epileptiform activity. Homologous correlations are both increased and decreased with a small dependence on seizure duration. These changes suggest a potential decoupling between the hemodynamic parameters in resting-state networks, underlining the importance to investigate epileptic networks with several independent hemodynamic measures. The second study examines a novel murine model of arterial stiffness: the unilateral calcification of the right carotid. Seed-based connectivity analysis showed a decreasing trend of homologous correlation in the motor and cingulate cortices. Graph analyses showed a randomization of the cortex functional networks, suggesting a loss of connectivity, more specifically in the motor cortex ipsilateral to the treated carotid; however these changes are not reflected in differentiated metabolic estimates. Confounds remain due to the fact that carotid rigidification gives rise to neural decline in the hippocampus as well as unilateral alteration of vascular pulsatility; however the results support the need to look at several hemodynamic parameters when imaging the brain after arterial remodeling. The third article of this thesis studies a model of inflammatory injury on the newborn rat. Oxygen saturation and functional connectivity were assessed with photoacoustic tomography. Oxygen saturation was decreased in the site of the lesion and on the cortex ipsilateral to the injury; however this decrease is not fully explained by hypovascularization revealed by histology. Seed-based functional connectivity analysis showed that inter-hemispheric connectivity is not affected by inflammatory injury.

[Are subcortical signs in the EEG a reliable indication of brain stem displacement and impaction processes by intracranial space-occupying processes? A comparative computer tomography-electroencephalography study].

PubMed

Zettler, H; Järisch, M; Leonhard, T

1985-01-01

Within the scope of an elektroencephalographic-computertomographic comperative study carried out in 430 patients, the concurrence of secondary brain stem damage due to mass displacement and herniation processes and parroxysmal generalised slow activity in the EEG ("intermittant frontal delta rhythms", "projected discharges", "subcortical signs") in intracranial space-occupying processes were studied among others. The occurrence of the EEG pattern was independent of the presence of brain stem displacements in about 20 and 25 per cent, respectively, of the 152 patients with supratentorial space occupations. The absence of the characteristics on 80 per cent of the patients with clear CT criteria for a secondary brain stem impairment shows that it is not suitable as a warning sign of an imminent intracranial decompensation and that in particular from the non-occurrence in the EEG no contribution to the operative risk and to the choice of the time of the operation can be derived. A relation between the occurrence of paroxysmal slow activity and the acuity of the course of the disease or the degree of malignity of cerebral tumours could not be verified. Possible causes of the inconstant occurrence of this EEG pattern in brain stem alterations are discussed.

Art, energy, and the brain.

PubMed

Pepperell, Robert

2018-01-01

Recent years have seen a growing interest among neuroscientists and vision scientists in art and aesthetics, exemplifying a more general trend toward interdisciplinary integration in the arts, humanities, and sciences. However, true art-science integration remains a distant prospect due to fundamental differences in outlook and approach between disciplines. I consider two great challenges for any project designed to explain the role of the brain in art appreciation. First, scientists and artists need to identify common ground, common questions, and a shared motivation for inquiry. Second, the neuroscience of art must transcend its current goal of correlating brain functions to behavior and begin to explain the connection between activity in the brain and the phenomenology of art appreciation. I propose that both challenges can be tackled using an energy-based approach. The concept of "energy" is clearly of central importance to the physical sciences, and to neuroscience in particular. Meanwhile, energy is a concept that artists and art historians have consistently referred to when trying to articulate how artworks are made and appreciated. I survey the role of energy in art, philosophical and psychological aesthetics, and neuroscience, and suggest how this approach could help to further integrate art and neuroscience, and explain how brain activity contributes to aesthetic experience. © 2018 Elsevier B.V. All rights reserved.

Influence of chronobiology on the nanoparticle-mediated drug uptake into the brain.

PubMed

Kreuter, Jörg

2015-02-03

Little attention so-far has been paid to the influence of chronobiology on the processes of nanoparticle uptake and transport into the brain, even though this transport appears to be chronobiologically controlled to a significant degree. Nanoparticles with specific surface properties enable the transport across the blood-brain barrier of many drugs that normally cannot cross this barrier. A clear dependence of the central antinociceptive (analgesic) effects of a nanoparticle-bound model drug, i.e., the hexapeptide dalargin, on the time of day was observable after intravenous injection in mice. In addition to the strongly enhanced antinociceptive effect due to the binding to the nanoparticles, the minima and maxima of the pain reaction with the nanoparticle-bound drug were shifted by almost half a day compared to the normal circadian nociception: The maximum in the pain reaction after i.v. injection of the nanoparticle-bound dalargin occurred during the later rest phase of the animals whereas the normal pain reaction and that of a dalargin solution was highest during the active phase of the mice in the night. This important shift could be caused by an enhanced endo- and exocytotic particulates transport activity of the brain capillary endothelial cells or within the brain during the rest phase.

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks

PubMed Central

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention. PMID:25745395

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks.

PubMed

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention.

Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A serial functional MRI activation pilot-study.

PubMed

Bokde, Arun L W; Cavedo, Enrica; Lopez-Bayo, Patricia; Lista, Simone; Meindl, Thomas; Born, Christine; Galluzzi, Samantha; Faltraco, Frank; Dubois, Bruno; Teipel, Stefan J; Reiser, Maximilian; Möller, Hans-Jürgen; Hampel, Harald

2016-03-30

A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm. The face matching task showed higher activation of visual areas after three months of treatment but no differences compared to baseline at six months. The location matching task showed a higher activation along the dorsal visual pathway at both three and six months follow ups. Treatment with rivastigmine demonstrates a significant effect on brain activation of the dorsal visual pathway during a location matching task in patients with aMCI. Our data support the potential use of task fMRI to map specific treatment effects of cholinergic drugs during prodromal stages of Alzheimer's disease (AD). Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Disrupting the brain to validate hypotheses on the neurobiology of language

PubMed Central

Papeo, Liuba; Pascual-Leone, Alvaro; Caramazza, Alfonso

2013-01-01

Comprehension of words is an important part of the language faculty, involving the joint activity of frontal and temporo-parietal brain regions. Transcranial Magnetic Stimulation (TMS) enables the controlled perturbation of brain activity, and thus offers a unique tool to test specific predictions about the causal relationship between brain regions and language understanding. This potential has been exploited to better define the role of regions that are classically accepted as part of the language-semantic network. For instance, TMS has contributed to establish the semantic relevance of the left anterior temporal lobe, or to solve the ambiguity between the semantic vs. phonological function assigned to the left inferior frontal gyrus (LIFG). We consider, more closely, the results from studies where the same technique, similar paradigms (lexical-semantic tasks) and materials (words) have been used to assess the relevance of regions outside the classically-defined language-semantic network—i.e., precentral motor regions—for the semantic analysis of words. This research shows that different aspects of the left precentral gyrus (primary motor and premotor sites) are sensitive to the action-non action distinction of words' meanings. However, the behavioral changes due to TMS over these sites are incongruent with what is expected after perturbation of a task-relevant brain region. Thus, the relationship between motor activity and language-semantic behavior remains far from clear. A better understanding of this issue could be guaranteed by investigating functional interactions between motor sites and semantically-relevant regions. PMID:23630480

Ethanolic extracts of Alstonia Scholaris and Bacopa Monniera possess neuroleptic activity due to anti-dopaminergic effect

PubMed Central

Jash, Rajiv; Chowdary, K. Appana

2014-01-01

Background: An increased inclination has been observed for the use of herbal drugs in chronic and incurable diseases. Treatment of psychiatric diseases like schizophrenia is largely palliative and more importantly, a prominent adverse effect prevails with the majority of anti-psychotic drugs, which are the extrapyramidal motor disorders. Existing anti-psychotic drug therapy is not so promising, and their adverse effect is a matter of concern for continuing the therapy for long duration. Objective: This experimental study was done to evaluate the neuroleptic activity of the ethanolic extracts of two plants Alstonia Scholaris and Bacopa Monnieri with different anti-psychotic animal models with a view that these plant extracts shall have no or at least reduced adverse effect so that it can be used for long duration. Materials and Methods: Two doses of both the extracts (100 and 200 mg/kg) and also standard drug haloperidol (0.2 mg/kg) were administered to their respective groups once daily with 5 different animal models. After that, the concentration of the dopamine neurotransmitter was estimated in two different regions of the brain viz. frontal cortex and striatum. Results: The result of the study indicated a significant reduction of amphetamine-induced stereotype and conditioned avoidance response for both the extracts compared with the control group, but both did not have any significant effect in phencyclidine-induced locomotor activity and social interaction activity. However, both the extracts showed minor signs of catalepsy compared to the control group. The study also revealed that the neuroleptic effect was due to the reduction of the dopamine concentration in the frontal cortex region of the rat brain. The results largely pointed out the fact that both the extract may be having the property to alleviate the positive symptoms of schizophrenia by reducing the dopamine levels of dopaminergic neurons of the brain. Conclusion: The estimation of dopamine in the two major regions of brain indicated the alteration of dopamine levels was the reason for the anti-psychotic activity as demonstrated by the different animal models. PMID:24497742

Computational modeling of resting-state activity demonstrates markers of normalcy in children with prenatal or perinatal stroke.

PubMed

Adhikari, Mohit H; Raja Beharelle, Anjali; Griffa, Alessandra; Hagmann, Patric; Solodkin, Ana; McIntosh, Anthony R; Small, Steven L; Deco, Gustavo

2015-06-10

Children who sustain a prenatal or perinatal brain injury in the form of a stroke develop remarkably normal cognitive functions in certain areas, with a particular strength in language skills. A dominant explanation for this is that brain regions from the contralesional hemisphere "take over" their functions, whereas the damaged areas and other ipsilesional regions play much less of a role. However, it is difficult to tease apart whether changes in neural activity after early brain injury are due to damage caused by the lesion or by processes related to postinjury reorganization. We sought to differentiate between these two causes by investigating the functional connectivity (FC) of brain areas during the resting state in human children with early brain injury using a computational model. We simulated a large-scale network consisting of realistic models of local brain areas coupled through anatomical connectivity information of healthy and injured participants. We then compared the resulting simulated FC values of healthy and injured participants with the empirical ones. We found that the empirical connectivity values, especially of the damaged areas, correlated better with simulated values of a healthy brain than those of an injured brain. This result indicates that the structural damage caused by an early brain injury is unlikely to have an adverse and sustained impact on the functional connections, albeit during the resting state, of damaged areas. Therefore, these areas could continue to play a role in the development of near-normal function in certain domains such as language in these children. Copyright © 2015 the authors 0270-6474/15/358914-11$15.00/0.

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats

PubMed Central

Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

2014-01-01

Background & objectives: Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Methods: Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. Results: SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. Interpretation & conclusions: The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney. PMID:24927349

Safety evaluation of mercury based Ayurvedic formulation (Sidh Makardhwaj) on brain cerebrum, liver & kidney in rats.

PubMed

Kumar, Gajendra; Srivastava, Amita; Sharma, Surinder Kumar; Gupta, Yogendra Kumar

2014-04-01

Sidh Makardhwaj (SM) is a mercury based Ayurvedic formulation used in rheumatoid arthritis and neurological disorders. However, toxicity concerns due to mercury content are often raised. Therefore, the present study was carried out to evaluate the effect of SM on brain cerebrum, liver and kidney in rats. Graded doses of SM (10, 50, 100 mg/kg), mercuric chloride (1 mg/kg) and normal saline were administered orally to male Wistar rats for 28 days. Behavioural parameters were assessed on days 1, 7, 14 and 28 using Morris water maze, passive avoidance, elevated plus maze and rota rod. Liver and kidney function tests were done on day 28. Animals were sacrificed and brain cerebrum acetylcholinesterase activity, levels of malondialdehyde (MDA), reduced glutathione (GSH) in brain cerebrum, liver, kidney were estimated. The levels of mercury in brain cerebrum, liver and kidney were estimated and histopathology of these tissues was also performed. SM in the doses used did not cause significant change in neurobehavioural parameters, brain cerebrum AChE activity, liver (ALT, AST, ALP bilirubin) and kidney (serum urea and creatinine) function tests as compared to control. The levels of mercury in brain cerebrum, liver, and kidney were found to be raised in dose dependent manner. However, the levels of MDA and GSH in these tissues did not show significant changes at doses of 10 and 50 mg/kg. Also, there was no histopathological change in cytoarchitecture of brain cerebrum, liver, and kidney tissues at doses of 10 and 50 mg/kg. The findings of the present study suggest that Sidh Makardhwaj upto five times the equivalent human dose administered for 28 days did not show any toxicological effects on rat brain cerebrum, liver and kidney.

Computing moment to moment BOLD activation for real-time neurofeedback

PubMed Central

Hinds, Oliver; Ghosh, Satrajit; Thompson, Todd W.; Yoo, Julie J.; Whitfield-Gabrieli, Susan; Triantafyllou, Christina; Gabrieli, John D.E.

2013-01-01

Estimating moment to moment changes in blood oxygenation level dependent (BOLD) activation levels from functional magnetic resonance imaging (fMRI) data has applications for learned regulation of regional activation, brain state monitoring, and brain-machine interfaces. In each of these contexts, accurate estimation of the BOLD signal in as little time as possible is desired. This is a challenging problem due to the low signal-to-noise ratio of fMRI data. Previous methods for real-time fMRI analysis have either sacrificed the ability to compute moment to moment activation changes by averaging several acquisitions into a single activation estimate or have sacrificed accuracy by failing to account for prominent sources of noise in the fMRI signal. Here we present a new method for computing the amount of activation present in a single fMRI acquisition that separates moment to moment changes in the fMRI signal intensity attributable to neural sources from those due to noise, resulting in a feedback signal more reflective of neural activation. This method computes an incremental general linear model fit to the fMRI timeseries, which is used to calculate the expected signal intensity at each new acquisition. The difference between the measured intensity and the expected intensity is scaled by the variance of the estimator in order to transform this residual difference into a statistic. Both synthetic and real data were used to validate this method and compare it to the only other published real-time fMRI method. PMID:20682350

Pathogenesis of Alzheimer disease: role of oxidative stress, amyloid-β peptides, systemic ammonia and erythrocyte energy metabolism.

PubMed

Kosenko, Elena A; Solomadin, Iliya N; Tikhonova, Lyudmila A; Reddy, V Prakash; Aliev, Gjumrakch; Kaminsky, Yury G

2014-02-01

Aβ exerts prooxidant or antioxidant effects based on the metal ion concentrations that it sequesters from the cytosol; at low metal ion concentrations, it is an antioxidant, whereas at relatively higher concentration it is a prooxidant. Thus Alzheimer disease (AD) treatment strategies based solely on the amyloid-β clearance should be re-examined in light of the vast accumulating evidence that increased oxidative stress in the human brains is the key causative factor for AD. Accumulating evidence indicates that the reduced brain glucose availability and brain hypoxia, due to the relatively lower concentration of ATP and 2,3-diphosphoglycerate, may be associated with increased concentration of endogenous ammonia, a potential neurotoxin in the AD brains. In this review, we summarize the progress in this area, and present some of our ongoing research activities with regard to brain Amyloid-β, systemic ammonia, erythrocyte energy metabolism and the role of 2,3-diphosphoglycerate in AD pathogenesis.

Whole brain radiotherapy for brain metastasis

PubMed Central

McTyre, Emory; Scott, Jacob; Chinnaiyan, Prakash

2013-01-01

Whole brain radiotherapy (WBRT) is a mainstay of treatment in patients with both identifiable brain metastases and prophylaxis for microscopic disease. The use of WBRT has decreased somewhat in recent years due to both advances in radiation technology, allowing for a more localized delivery of radiation, and growing concerns regarding the late toxicity profile associated with WBRT. This has prompted the development of several recent and ongoing prospective studies designed to provide Level I evidence to guide optimal treatment approaches for patients with intracranial metastases. In addition to defining the role of WBRT in patients with brain metastases, identifying methods to improve WBRT is an active area of investigation, and can be classified into two general categories: Those designed to decrease the morbidity of WBRT, primarily by reducing late toxicity, and those designed to improve the efficacy of WBRT. Both of these areas of research show diversity and promise, and it seems feasible that in the near future, the efficacy/toxicity ratio may be improved, allowing for a more diverse clinical application of WBRT. PMID:23717795

Successful Contextual Integration of Loose Mental Associations As Evidenced by Emotional Conflict-Processing

PubMed Central

Zimmer, Ulrike; Koschutnig, Karl; Ebner, Franz; Ischebeck, Anja

2014-01-01

Often we cannot resist emotional distraction, because emotions capture our attention. For example, in TV-commercials, tempting emotional voices add an emotional expression to a formerly neutral product. Here, we used a Stroop-like conflict paradigm as a tool to investigate whether emotional capture results in contextual integration of loose mental associations. Specifically, we tested whether the associatively connected meaning of an ignored auditory emotion with a non-emotional neutral visual target would yield a modulation of activation sensitive to emotional conflict in the brain. In an fMRI-study, nineteen participants detected the presence or absence of a little worm hidden in the picture of an apple, while ignoring a voice with an emotional sound of taste (delicious/disgusting). Our results indicate a modulation due to emotional conflict, pronounced most strongly when processing conflict in the context of disgust (conflict: disgust/no-worm vs. no conflict: disgust/worm). For conflict in the context of disgust, insula activity was increased, with activity correlating positively with reaction time in the conflict case. Conflict in the context of deliciousness resulted in increased amygdala activation, possibly due to the resulting “negative” emotion in incongruent versus congruent combinations. These results indicate that our associative stimulus-combinations showed a conflict-dependent modulation of activity in emotional brain areas. This shows that the emotional sounds were successfully contextually integrated with the loosely associated neutral pictures. PMID:24618674

Successful contextual integration of loose mental associations as evidenced by emotional conflict-processing.

PubMed

Zimmer, Ulrike; Koschutnig, Karl; Ebner, Franz; Ischebeck, Anja

2014-01-01

Often we cannot resist emotional distraction, because emotions capture our attention. For example, in TV-commercials, tempting emotional voices add an emotional expression to a formerly neutral product. Here, we used a Stroop-like conflict paradigm as a tool to investigate whether emotional capture results in contextual integration of loose mental associations. Specifically, we tested whether the associatively connected meaning of an ignored auditory emotion with a non-emotional neutral visual target would yield a modulation of activation sensitive to emotional conflict in the brain. In an fMRI-study, nineteen participants detected the presence or absence of a little worm hidden in the picture of an apple, while ignoring a voice with an emotional sound of taste (delicious/disgusting). Our results indicate a modulation due to emotional conflict, pronounced most strongly when processing conflict in the context of disgust (conflict: disgust/no-worm vs. no conflict: disgust/worm). For conflict in the context of disgust, insula activity was increased, with activity correlating positively with reaction time in the conflict case. Conflict in the context of deliciousness resulted in increased amygdala activation, possibly due to the resulting "negative" emotion in incongruent versus congruent combinations. These results indicate that our associative stimulus-combinations showed a conflict-dependent modulation of activity in emotional brain areas. This shows that the emotional sounds were successfully contextually integrated with the loosely associated neutral pictures.

Thyroid hormones and fetal brain development.

PubMed

Pemberton, H N; Franklyn, J A; Kilby, M D

2005-08-01

Thyroid hormones are intricately involved in the developing fetal brain. The fetal central nervous system is sensitive to the maternal thyroid status. Critical amounts of maternal T3 and T4 must be transported across the placenta to the fetus to ensure the correct development of the brain throughout ontogeny. Severe mental retardation of the child can occur due to compromised iodine intake or thyroid disease. This has been reported in areas of the world with iodine insufficiency, New Guinea, and also in mother with thyroid complications such as hypothyroxinaemia and hyperthyroidism. The molecular control of thyroid hormones by deiodinases for the activation of thyroid hormones is critical to ensure the correct amount of active thyroid hormones are temporally supplied to the fetus. These hormones provide timing signals for the induction of programmes for differentiation and maturation at specific stages of development. Understanding these molecular mechanisms further will have profound implications in the clinical management of individuals affected by abnormal maternal of fetal thyroid status.

Analysis of brain activity and response during monoscopic and stereoscopic visualization

NASA Astrophysics Data System (ADS)

Calore, Enrico; Folgieri, Raffaella; Gadia, Davide; Marini, Daniele

2012-03-01

Stereoscopic visualization in cinematography and Virtual Reality (VR) creates an illusion of depth by means of two bidimensional images corresponding to different views of a scene. This perceptual trick is used to enhance the emotional response and the sense of presence and immersivity of the observers. An interesting question is if and how it is possible to measure and analyze the level of emotional involvement and attention of the observers during a stereoscopic visualization of a movie or of a virtual environment. The research aims represent a challenge, due to the large number of sensorial, physiological and cognitive stimuli involved. In this paper we begin this research by analyzing possible differences in the brain activity of subjects during the viewing of monoscopic or stereoscopic contents. To this aim, we have performed some preliminary experiments collecting electroencephalographic (EEG) data of a group of users using a Brain- Computer Interface (BCI) during the viewing of stereoscopic and monoscopic short movies in a VR immersive installation.

Nouns, verbs, objects, actions, and abstractions: Local fMRI activity indexes semantics, not lexical categories

PubMed Central

Moseley, Rachel L.; Pulvermüller, Friedemann

2014-01-01

Noun/verb dissociations in the literature defy interpretation due to the confound between lexical category and semantic meaning; nouns and verbs typically describe concrete objects and actions. Abstract words, pertaining to neither, are a critical test case: dissociations along lexical-grammatical lines would support models purporting lexical category as the principle governing brain organisation, whilst semantic models predict dissociation between concrete words but not abstract items. During fMRI scanning, participants read orthogonalised word categories of nouns and verbs, with or without concrete, sensorimotor meaning. Analysis of inferior frontal/insula, precentral and central areas revealed an interaction between lexical class and semantic factors with clear category differences between concrete nouns and verbs but not abstract ones. Though the brain stores the combinatorial and lexical-grammatical properties of words, our data show that topographical differences in brain activation, especially in the motor system and inferior frontal cortex, are driven by semantics and not by lexical class. PMID:24727103

Evaluation of evidenced-based radioprotective efficacy of Gymnema sylvestre leaves in mice brain.

PubMed

Sharma, K; Singh, Umang; Vats, Sharad; Priyadarsini, K; Bhatia, A; Kamal, Raka

2009-01-01

A Gymnema sylvestre leaves extract (GSE) rich in gymnemic acids was examined for its antioxidant activities through various in vitro assays, along with its radioprotective efficacy in mice brain. The IC(50) values of GSE for 2,2-diphenyl-1-picryl-hydrazyl scavenging assays, superoxide radical scavenging assays, inhibition of in vitro lipid peroxidation assays, and protein carbonyl formation assay were 238, 140, 99.46, and 28.03 microg/mL, respectively. Furthermore, the total phenolic content in GSE was equivalent to 18.06 microg/mL of Gallic acid. The rate of *OH radical scavenging activity of GSE is 0.46 times slower than SCN- derived from nanosecond pulse radiolysis studies. Results of in vivo studies showed that radiation (8 Gy)-induced augmentation in the levels of lipid peroxidation and depletion in glutathione and protein levels in mice brain were significantly ameliorated by GSE pretreatment. Results suggest that the radioprotective efficacy of GSE may be due to its antioxidant properties.

Nouns, verbs, objects, actions, and abstractions: local fMRI activity indexes semantics, not lexical categories.

PubMed

Moseley, Rachel L; Pulvermüller, Friedemann

2014-05-01

Noun/verb dissociations in the literature defy interpretation due to the confound between lexical category and semantic meaning; nouns and verbs typically describe concrete objects and actions. Abstract words, pertaining to neither, are a critical test case: dissociations along lexical-grammatical lines would support models purporting lexical category as the principle governing brain organisation, whilst semantic models predict dissociation between concrete words but not abstract items. During fMRI scanning, participants read orthogonalised word categories of nouns and verbs, with or without concrete, sensorimotor meaning. Analysis of inferior frontal/insula, precentral and central areas revealed an interaction between lexical class and semantic factors with clear category differences between concrete nouns and verbs but not abstract ones. Though the brain stores the combinatorial and lexical-grammatical properties of words, our data show that topographical differences in brain activation, especially in the motor system and inferior frontal cortex, are driven by semantics and not by lexical class. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Neuronal chronometry of target detection: fusion of hemodynamic and event-related potential data.

PubMed

Calhoun, V D; Adali, T; Pearlson, G D; Kiehl, K A

2006-04-01

Event-related potential (ERP) studies of the brain's response to infrequent, target (oddball) stimuli elicit a sequence of physiological events, the most prominent and well studied being a complex, the P300 (or P3) peaking approximately 300 ms post-stimulus for simple stimuli and slightly later for more complex stimuli. Localization of the neural generators of the human oddball response remains challenging due to the lack of a single imaging technique with good spatial and temporal resolution. Here, we use independent component analyses to fuse ERP and fMRI modalities in order to examine the dynamics of the auditory oddball response with high spatiotemporal resolution across the entire brain. Initial activations in auditory and motor planning regions are followed by auditory association cortex and motor execution regions. The P3 response is associated with brainstem, temporal lobe, and medial frontal activity and finally a late temporal lobe "evaluative" response. We show that fusing imaging modalities with different advantages can provide new information about the brain.

Prodigiosin inhibits gp91{sup phox} and iNOS expression to protect mice against the oxidative/nitrosative brain injury induced by hypoxia-ischemia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chang, Chia-Che; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan; Agricultural Biotechnology Center, National Chung-Hsing University, Taichung, Taiwan

2011-11-15

This study aimed to explore the mechanisms by which prodigiosin protects against hypoxia-induced oxidative/nitrosative brain injury induced by middle cerebral artery occlusion/reperfusion (MCAo/r) injury in mice. Hypoxia in vitro was modeled using oxygen-glucose deprivation (OGD) followed by reoxygenation of BV-2 microglial cells. Our results showed that treatment of mice that have undergone MCAo/r injury with prodigiosin (10 and 100 {mu}g/kg, i.v.) at 1 h after hypoxia ameliorated MCAo/r-induced oxidative/nitrosative stress, brain infarction, and neurological deficits in the mice, and enhanced their survival rate. MCAo/r induced a remarkable production in the mouse brains of reactive oxygen species (ROS) and a significantmore » increase in protein nitrosylation; this primarily resulted from enhanced expression of NADPH oxidase 2 (gp91{sup phox}), inducible nitric oxide synthase (iNOS), and the infiltration of CD11b leukocytes due to breakdown of blood-brain barrier (BBB) by activation of nuclear factor-kappa B (NF-{kappa}B). All these changes were significantly diminished by prodigiosin. In BV-2 cells, OGD induced ROS and nitric oxide production by up-regulating gp91{sup phox} and iNOS via activation of the NF-{kappa}B pathway, and these changes were suppressed by prodigiosin. In conclusion, our results indicate that prodigiosin reduces gp91{sup phox} and iNOS expression possibly by impairing NF-{kappa}B activation. This compromises the activation of microglial and/or inflammatory cells, which then, in turn, mediates prodigiosin's protective effect in the MCAo/r mice. -- Highlights: Black-Right-Pointing-Pointer Prodigiosin ameliorated brain infarction and deficits. Black-Right-Pointing-Pointer Prodigiosin protected against hypoxia/reperfusion-induced brain injury. Black-Right-Pointing-Pointer Prodigiosin diminished oxidative/nitrosativestress and leukocytes infiltration. Black-Right-Pointing-Pointer Prodigiosin reduced BBB breakdown. Black-Right-Pointing-Pointer Prodigiosin down-regulated gp91{sup phox} and iNOS by inhibiting NF-{kappa}B activation.« less

FGF21 maintains glucose homeostasis by mediating the cross talk between liver and brain during prolonged fasting.

PubMed

Liang, Qingning; Zhong, Ling; Zhang, Jialiang; Wang, Yu; Bornstein, Stefan R; Triggle, Chris R; Ding, Hong; Lam, Karen S L; Xu, Aimin

2014-12-01

Hepatic gluconeogenesis is a main source of blood glucose during prolonged fasting and is orchestrated by endocrine and neural pathways. Here we show that the hepatocyte-secreted hormone fibroblast growth factor 21 (FGF21) induces fasting gluconeogenesis via the brain-liver axis. Prolonged fasting induces activation of the transcription factor peroxisome proliferator-activated receptor α (PPARα) in the liver and subsequent hepatic production of FGF21, which enters into the brain to activate the hypothalamic-pituitary-adrenal (HPA) axis for release of corticosterone, thereby stimulating hepatic gluconeogenesis. Fasted FGF21 knockout (KO) mice exhibit severe hypoglycemia and defective hepatic gluconeogenesis due to impaired activation of the HPA axis and blunted release of corticosterone, a phenotype similar to that observed in PPARα KO mice. By contrast, intracerebroventricular injection of FGF21 reverses fasting hypoglycemia and impairment in hepatic gluconeogenesis by restoring corticosterone production in both FGF21 KO and PPARα KO mice, whereas all these central effects of FGF21 were abrogated by blockage of hypothalamic FGF receptor-1. FGF21 acts directly on the hypothalamic neurons to activate the mitogen-activated protein kinase extracellular signal-related kinase 1/2 (ERK1/2), thereby stimulating the expression of corticotropin-releasing hormone by activation of the transcription factor cAMP response element binding protein. Therefore, FGF21 maintains glucose homeostasis during prolonged fasting by fine tuning the interorgan cross talk between liver and brain. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Caffeine and adenosine.

PubMed

Ribeiro, Joaquim A; Sebastião, Ana M

2010-01-01

Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.

Percutaneous endoscopic gastrostomy in neurological rehabilitation: a report of six cases.

PubMed

Annoni, J M; Vuagnat, H; Frischknecht, R; Uebelhart, D

1998-08-01

This study reports the cases of six patients with severe chronic neurological disability and swallowing difficulties due to traumatic brain injury (TBI), anoxia and multiple sclerosis (MS). The patients required nutritional supplement through percutaneous endoscopic gastrostomy (PEG). Their clinical follow-up showed a decrease of intercurrent medical complications, especially pressure sores. In addition, an improvement of oropharyngeal function was observed in some patients, also accompanied by slightly better basic psychomotor functions such as vigilance, sustained attention and tone or motor control. However, not every patient did improve with this procedure. The two MS patients benefited most, while the improvement was less homogenous in the three TBI patients. The advantages of PEG over nasogastric tube on oropharyngeal function can be related to the absence of pharyngeal irritation and its role in overall recovery could be due to an increase in social activities, a control of infections, a better rehabilitation schedule and a long-term effect on brain function due to better nutritional support.

Functional Geometry Alignment and Localization of Brain Areas.

PubMed

Langs, Georg; Golland, Polina; Tie, Yanmei; Rigolo, Laura; Golby, Alexandra J

2010-01-01

Matching functional brain regions across individuals is a challenging task, largely due to the variability in their location and extent. It is particularly difficult, but highly relevant, for patients with pathologies such as brain tumors, which can cause substantial reorganization of functional systems. In such cases spatial registration based on anatomical data is only of limited value if the goal is to establish correspondences of functional areas among different individuals, or to localize potentially displaced active regions. Rather than rely on spatial alignment, we propose to perform registration in an alternative space whose geometry is governed by the functional interaction patterns in the brain. We first embed each brain into a functional map that reflects connectivity patterns during a fMRI experiment. The resulting functional maps are then registered, and the obtained correspondences are propagated back to the two brains. In application to a language fMRI experiment, our preliminary results suggest that the proposed method yields improved functional correspondences across subjects. This advantage is pronounced for subjects with tumors that affect the language areas and thus cause spatial reorganization of the functional regions.

Cross-linked polyhemoglobin-superoxide dismutase-catalase supplies oxygen without causing blood-brain barrier disruption or brain edema in a rat model of transient global brain ischemia-reperfusion.

PubMed

Powanda, D Douglas; Chang, Thomas M S

2002-01-01

In strokes, myocardial infarctions, severe sustained hemorrhagic shock, and donor organs, inadequate blood supply results in lack of oxygen to the tissue (ischemia). If ischemia is sustained, reperfusion with the needed oxygen can result in tissue injury (ischemia-reperfusion injury) due to formation of reactive oxygen species. We are studying an oxygen-carrying solution with anitoxidant activity formed by cross-linking hemoglobin, superoxide dismutase, and catalase to form PolyHb-SOD-CAT. The present report studies its effect on the blood-brain barrier and cerebral edema when used in a transient global brain ischemia-reperfusion rat model. We compare this solution to sham-control, oxygenated saline, stroma-free hemoglobin (SF-Hb), polymerized hemoglobin (PolyHb), and a mixture of SF-Hb, SOD, and CAT in free solution. The results show that the cross-linked PolyHb-SOD-CAT solution, unlike the other solutions, can supply oxygen to ischemic tissues without causing reperfusion injury in the transient global brain ischemia-reperfusion model.

Tissue plasminogen activator followed by antioxidant-loaded nanoparticle delivery promotes activation/mobilization of progenitor cells in infarcted rat brain.

PubMed

Petro, Marianne; Jaffer, Hayder; Yang, Jun; Kabu, Shushi; Morris, Viola B; Labhasetwar, Vinod

2016-03-01

Inherent neuronal and circulating progenitor cells play important roles in facilitating neuronal and functional recovery post stroke. However, this endogenous repair process is rather limited, primarily due to unfavorable conditions in the infarcted brain involving reactive oxygen species (ROS)-mediated oxidative stress and inflammation following ischemia/reperfusion injury. We hypothesized that during reperfusion, effective delivery of antioxidants to ischemic brain would create an environment without such oxidative stress and inflammation, thus promoting activation and mobilization of progenitor cells in the infarcted brain. We administered recombinant human tissue-type plasminogen activator (tPA) via carotid artery at 3 h post stroke in a thromboembolic rat model, followed by sequential administration of the antioxidants catalase (CAT) and superoxide dismutase (SOD), encapsulated in biodegradable nanoparticles (nano-CAT/SOD). Brains were harvested at 48 h post stroke for immunohistochemical analysis. Ipsilateral brain slices from animals that had received tPA + nano-CAT/SOD showed a widespread distribution of glial fibrillary acidic protein-positive cells (with morphology resembling radial glia-like neural precursor cells) and nestin-positive cells (indicating the presence of immature neurons); such cells were considerably fewer in untreated animals or those treated with tPA alone. Brain sections from animals receiving tPA + nano-CAT/SOD also showed much greater numbers of SOX2- and nestin-positive progenitor cells migrating from subventricular zone of the lateral ventricle and entering the rostral migratory stream than in t-PA alone treated group or untreated control. Further, animals treated with tPA + nano-CAT/SOD showed far fewer caspase-positive cells and fewer neutrophils than did other groups, as well as an inhibition of hippocampal swelling. These results suggest that the antioxidants mitigated the inflammatory response, protected neuronal cells from undergoing apoptosis, and inhibited edema formation by protecting the blood-brain barrier from ROS-mediated reperfusion injury. A longer-term study would enable us to determine if our approach would assist progenitor cells to undergo neurogenesis and to facilitate neurological and functional recovery following stroke and reperfusion injury. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neural activity during interoceptive awareness and its associations with alexithymia—An fMRI study in major depressive disorder and non-psychiatric controls

PubMed Central

Wiebking, Christine; Northoff, Georg

2015-01-01

Objective: Alexithymia relates to difficulties recognizing and describing emotions. It has been linked to subjectively increased interoceptive awareness (IA) and to psychiatric illnesses such as major depressive disorder (MDD) and somatization. MDD in turn is characterized by aberrant emotion processing and IA on the subjective as well as on the neural level. However, a link between neural activity in response to IA and alexithymic traits in health and depression remains unclear. Methods: A well-established fMRI task was used to investigate neural activity during IA (heartbeat counting) and exteroceptive awareness (tone counting) in non-psychiatric controls (NC) and MDD. Firstly, comparing MDD and NC, a linear relationship between IA-related activity and scores of the Toronto Alexithymia Scale (TAS) was investigated through whole-brain regression. Secondly, NC were divided by median-split of TAS scores into groups showing low (NC-low) or high (NC-high) alexithymia. MDD and NC-high showed equally high TAS scores. Subsequently, IA-related neural activity was compared on a whole-brain level between the three independent samples (MDD, NC-low, NC-high). Results: Whole-brain regressions between MDD and NC revealed neural differences during IA as a function of TAS-DD (subscale difficulty describing feelings) in the supragenual anterior cingulate cortex (sACC; BA 24/32), which were due to negative associations between TAS-DD and IA-related activity in NC. Contrasting NC subgroups after median-split on a whole-brain level, high TAS scores were associated with decreased neural activity during IA in the sACC and increased insula activity. Though having equally high alexithymia scores, NC-high showed increased insula activity during IA compared to MDD, whilst both groups showed decreased activity in the sACC. Conclusions: Within the context of decreased sACC activity during IA in alexithymia (NC-high and MDD), increased insula activity might mirror a compensatory mechanism in NC-high, which is disrupted in MDD. PMID:26074827

T-cell reconstitution during murine acquired immunodeficiency syndrome (MAIDS) produces neuroinflammation and mortality in animals harboring opportunistic viral brain infection.

PubMed

Mutnal, Manohar B; Schachtele, Scott J; Hu, Shuxian; Lokensgard, James R

2013-07-31

Highly active antiretroviral therapy (HAART) restores inflammatory immune responses in AIDS patients which may unmask previous subclinical infections or paradoxically exacerbate symptoms of opportunistic infections. In resource-poor settings, 25% of patients receiving HAART may develop CNS-related immune reconstitution inflammatory syndrome (IRIS). Here we describe a reliable mouse model to study underlying immunopathological mechanisms of CNS-IRIS. Utilizing our HSV brain infection model and mice with MAIDS, we investigated the effect of immune reconstitution on MAIDS mice harboring opportunistic viral brain infection. Using multi-color flow cytometry, we quantitatively measured the cellular infiltrate and microglial activation. Infection with the LP-BM5 retroviral mixture was found to confer susceptibility to herpes simplex virus (HSV)-1 brain infection to normally-resistant C57BL/6 mice. Increased susceptibility to brain infection was due to severe immunodeficiency at 8 wks p.i. and a marked increase in programmed death-1 (PD-1) expression on CD4+ and CD8+ T-cells. Both T-cell loss and opportunistic brain infection were associated with high level PD-1 expression because PD-1-knockout mice infected with LP-BM5 did not exhibit lymphopenia and retained resistance to HSV-1. In addition, HSV-infection of MAIDS mice stimulated peripheral immune cell infiltration into the brain and its ensuing microglial activation. Interestingly, while opportunistic herpes virus brain infection of C57BL/6 MAIDS mice was not itself lethal, when T-cell immunity was reconstituted through adoptive transfer of virus-specific CD3+ T-cells, it resulted in significant mortality among recipients. This immune reconstitution-induced mortality was associated with exacerbated neuroinflammation, as determined by MHC class II expression on resident microglia and elevated levels of Th1 cytokines in the brain. Taken together, these results indicate development of an immune reconstitution disease within the central nervous system (CNS-IRD). Experimental immune reconstitution disease of the CNS using T-cell repopulation of lymphopenic murine hosts harboring opportunistic brain infections may help elucidate neuroimmunoregulatory networks that produce CNS-IRIS in patients initiating HAART.

Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

PubMed Central

Lenoir, Magalie

2012-01-01

Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological fluctuations in glucose levels. PMID:22723672

Transcranial cavitation-mediated ultrasound therapy at sub-MHz frequency via temporal interference modulation

NASA Astrophysics Data System (ADS)

Sun, Tao; Sutton, Jonathan T.; Power, Chanikarn; Zhang, Yongzhi; Miller, Eric L.; McDannold, Nathan J.

2017-10-01

Sub-megahertz transmission is not usually adopted in pre-clinical small animal experiments for focused ultrasound (FUS) brain therapy due to the large focal size. However, low frequency FUS is vital for preclinical evaluations due to the frequency-dependence of cavitation behavior. To maximize clinical relevance, a dual-aperture FUS system was designed for low-frequency (274.3 kHz) cavitation-mediated FUS therapy. Combining two spherically curved transducers provides significantly improved focusing in the axial direction while yielding an interference pattern with strong side lobes, leading to inhomogeneously distributed cavitation activities. By operating the two transducers at slightly offset frequencies to modulate this interference pattern over the period of sonication, the acoustic energy was redistributed and resulted in a spatially homogenous treatment profile. Simulation and pressure field measurements in water were performed to assess the beam profiles. In addition, the system performance was demonstrated in vivo in rats via drug delivery through microbubble-mediated blood-brain barrier disruption. This design resulted in a homogenous treatment profile that was fully contained within the rat brain at a clinically relevant acoustic frequency.

Xenobiotic Kinetics and Toxicity among Fish and Mammals

DTIC Science & Technology

1992-02-29

infusion studies similar to those described in the previous progress report for rat have been initiated. Due to its limited water solubility and lesser...potency in fish than rat, a solubilizing agent is needed and we have determined that 5% polysorbate 80 in water can be administered to fish without...affecting acetylcholinesterase (ACHE) activity. We have infused three fish and measured AChE activity in brain, heart, and jaw muscle after the fish

[The role of neurotrophic factors in adaptational processes in the nervous system].

PubMed

Akoev, G N; Chalisova, N I

1995-08-01

Many of neurotrophic factors (NTF) promote the survival during development, growth and neurite differentiation of neurons. The most known NTF are nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophins-3,4,5. These factors increase the survival of peripheral sensory neurons and some central neurons. The NTF are produced by the target of neuronal proections including brain tissues. So the process of adaptation in the nervous system may be also connected with level of the NTF. Recently it is shown that the NTF level in the brain is changed by central nervous system deseases--epilepsy, Parcinson and Alcgeimer deseases. In this conditions NGF and BDNF mRNC expression and their receptors mRNC are increased. So NTF diffusion in intracellular space can provide the brain function regulation in normal and pathological conditions. Model of chronic epileptogenesis was in vitro. The organotypic coculture was used--the rat newborn hippocampus and chick embryo dorsal root ganglia. Veratridine (30 nM) added in culture media induced neuronal activity in hippocampus explants and the level of NTF in media cosequently rised. It was shown that neurite-stimulating effect was mediated by veratridine. This action was blocked by NGF-antybody treatment and due to NGF activity.

Functional neuroimaging of normal aging: Declining brain, adapting brain.

PubMed

Sugiura, Motoaki

2016-09-01

Early functional neuroimaging research on normal aging brain has been dominated by the interest in cognitive decline. In this framework the age-related compensatory recruitment of prefrontal cortex, in terms of executive system or reduced lateralization, has been established. Further details on these compensatory mechanisms and the findings reflecting cognitive decline, however, remain the matter of intensive investigations. Studies in another framework where age-related neural alteration is considered adaptation to the environmental change are recently burgeoning and appear largely categorized into three domains. The age-related increase in activation of the sensorimotor network may reflect the alteration of the peripheral sensorimotor systems. The increased susceptibility of the network for the mental-state inference to the socioemotional significance may be explained by the age-related motivational shift due to the altered social perception. The age-related change in activation of the self-referential network may be relevant to the focused positive self-concept of elderly driven by a similar motivational shift. Across the domains, the concept of the self and internal model may provide the theoretical bases of this adaptation framework. These two frameworks complement each other to provide a comprehensive view of the normal aging brain. Copyright © 2016 Elsevier B.V. All rights reserved.

Vagus-brain communication in atherosclerosis-related inflammation: a neuroimmunomodulation perspective of CAD.

PubMed

Gidron, Yori; Kupper, Nina; Kwaijtaal, Martijn; Winter, Jobst; Denollet, Johan

2007-12-01

The current understanding of the pathophysiology of atherosclerosis leading to coronary artery disease (CAD) emphasizes the role of inflammatory mediators. Given the bidirectional communication between the immune and central nervous systems, an important question is whether the brain can be "informed" about and modulate CAD-related inflammation. A candidate communicator and modulator is the vagus nerve. Until now, the vagus nerve has received attention in cardiology mainly due to its role in the parasympathetic cardiovascular response. However, the vagus nerve can also "inform" the brain about peripheral inflammation since its paraganglia have receptors for interleukin-1. Furthermore, its efferent branch has a local anti-inflammatory effect. These effects have not been considered in research on the vagus nerve in CAD or in vagus nerve stimulation trials in CAD. In addition, various behavioural interventions, including relaxation, may influence CAD prognosis by affecting vagal activity. Based on this converging evidence, we propose a neuroimmunomodulation approach to atherogenesis. In this model, the vagus nerve "informs" the brain about CAD-related cytokines; in turn, activation of the vagus (via vagus nerve stimulation, vagomimetic drugs or relaxation) induces an anti-inflammatory response that can slow down the chronic process of atherogenesis.

Food-induced changes of lipids in rat neuronal tissue visualized by ToF-SIMS imaging.

PubMed

Dowlatshahi Pour, Masoumeh; Jennische, Eva; Lange, Stefan; Ewing, Andrew G; Malmberg, Per

2016-09-06

Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to image the lipid localization in brain tissue sections from rats fed specially processed cereals (SPC). An IonTof 5 instrument equipped with a Bi cluster ion gun was used to analyze the tissue sections. Data from 15 brain samples from control and cereal-fed rats were recorded and exported to principal components analysis (PCA). The data clearly show changes of certain lipids in the brain following cereal feeding. PCA score plots show a good separation in lipid distribution between the control and the SPC-fed group. The loadings plot reveal that the groups separated mainly due to changes in cholesterol, vitamin E and c18:2, c16:0 fatty acid distribution as well as some short chain monocarboxylic fatty acid compositions. These insights relate to the working mechanism of SPC as a dietary supplement. SPC is thought to activate antisecretory factor (AF), an endogenous protein with regulatory function for inflammation and fluid secretion. These data provide insights into lipid content in brain following SPC feeding and suggest a relation to activating AF.

Susceptibility-based functional brain mapping by 3D deconvolution of an MR-phase activation map.

PubMed

Chen, Zikuan; Liu, Jingyu; Calhoun, Vince D

2013-05-30

The underlying source of T2*-weighted magnetic resonance imaging (T2*MRI) for brain imaging is magnetic susceptibility (denoted by χ). T2*MRI outputs a complex-valued MR image consisting of magnitude and phase information. Recent research has shown that both the magnitude and the phase images are morphologically different from the source χ, primarily due to 3D convolution, and that the source χ can be reconstructed from complex MR images by computed inverse MRI (CIMRI). Thus, we can obtain a 4D χ dataset from a complex 4D MR dataset acquired from a brain functional MRI study by repeating CIMRI to reconstruct 3D χ volumes at each timepoint. Because the reconstructed χ is a more direct representation of neuronal activity than the MR image, we propose a method for χ-based functional brain mapping, which is numerically characterised by a temporal correlation map of χ responses to a stimulant task. Under the linear imaging conditions used for T2*MRI, we show that the χ activation map can be calculated from the MR phase map by CIMRI. We validate our approach using numerical simulations and Gd-phantom experiments. We also analyse real data from a finger-tapping visuomotor experiment and show that the χ-based functional mapping provides additional activation details (in the form of positive and negative correlation patterns) beyond those generated by conventional MR-magnitude-based mapping. Copyright © 2013 Elsevier B.V. All rights reserved.

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

DOE PAGES

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.; ...

2016-03-02

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. Here we show that the hypoxia-inducible factor prolyl-hydroxylase (HIF- PHD) family of iron-dependent oxygen sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in mouse striatum improved functional recovery following ICH. A low molecular weight hydroxyquinoline inhibitor of the HIF-PHDs, adaptaquin, reduced neuronal death and behavioral deficitsmore » following ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of expression of the prodeath factor ATF4 rather than activation of a HIF-dependent prosurvival pathway. In conclusion, together these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier permeable inhibitor adaptaquin can improve functional outcomes following ICH in multiple rodent species.« less

Therapeutic targeting of oxygen-sensing prolyl hydroxylases abrogates ATF4-dependent neuronal death and improves outcomes after brain hemorrhage in several rodent models

DOE Office of Scientific and Technical Information (OSTI.GOV)

Karuppagounder, Saravanan S.; Alim, Ishraq; Khim, Soah J.

Disability or death due to intracerebral hemorrhage (ICH) is attributed to blood lysis, liberation of iron and consequent oxidative stress. Iron chelators bind to free iron and prevent neuronal death induced by oxidative stress and disability due to ICH, but the mechanisms for this effect remain unclear. Here we show that the hypoxia-inducible factor prolyl-hydroxylase (HIF- PHD) family of iron-dependent oxygen sensing enzymes are effectors of iron chelation. Molecular reduction of the three HIF-PHD enzyme isoforms in mouse striatum improved functional recovery following ICH. A low molecular weight hydroxyquinoline inhibitor of the HIF-PHDs, adaptaquin, reduced neuronal death and behavioral deficitsmore » following ICH in several rodent models without affecting total iron or zinc distribution in the brain. Unexpectedly, protection from oxidative death in vitro or from ICH in vivo by adaptaquin was associated with suppression of expression of the prodeath factor ATF4 rather than activation of a HIF-dependent prosurvival pathway. In conclusion, together these findings demonstrate that brain-specific inactivation of the HIF-PHD metalloenzymes with the blood-brain barrier permeable inhibitor adaptaquin can improve functional outcomes following ICH in multiple rodent species.« less

Blood-brain barrier permeability during the development of experimental bacterial meningitis in the rat.

PubMed

Kim, K S; Wass, C A; Cross, A S

1997-05-01

In an attempt to examine whether routes of bacterial entry into the central nervous system have any bearing on subsequent changes in blood-brain barrier permeability, we examined cerebrospinal fluid (CSF) penetration of circulating 125I-albumin in two different models of experimental meningitis due to K1 Escherichia coli, type III group B streptococcus, or Haemophilus influenzae type b in infant rats: hematogenous meningitis subsequent to subcutaneous inoculation of bacteria vs meningitis induced by direct inoculation of bacteria into the CSF via the cisterna magna. In the model of hematogenous meningitis, the mean CSF penetration was significantly greater in animals with H. influenzae type b meningitis than in those with meningitis due to K1 E. coli or type III group B streptococcus. In contrast, the mean CSF penetration was significantly enhanced in all animals with meningitis induced by intracisternal inoculation regardless of infecting pathogens. Tumor necrosis factor activity in CSF appeared to correlate with the functional penetration of circulating albumin across the blood-brain barrier in both models of experimental meningitis. These findings suggest that the alterations of blood-brain barrier permeability during development of experimental meningitis may vary for different models of inducing meningitis and that the mechanisms responsible for these different permeability changes may be multifactorial.

Brain Tumor Epidemiology: Consensus from the Brain Tumor Epidemiology Consortium (BTEC)

PubMed Central

Bondy, Melissa L.; Scheurer, Michael E.; Malmer, Beatrice; Barnholtz-Sloan, Jill S.; Davis, Faith G.; Il’yasova, Dora; Kruchko, Carol; McCarthy, Bridget J.; Rajaraman, Preetha; Schwartzbaum, Judith A.; Sadetzki, Siegal; Schlehofer, Brigitte; Tihan, Tarik; Wiemels, Joseph L.; Wrensch, Margaret; Buffler, Patricia A.

2010-01-01

Epidemiologists in the Brain Tumor Epidemiology Consortium (BTEC) have prioritized areas for further research. Although many risk factors have been examined over the past several decades, there are few consistent findings possibly due to small sample sizes in individual studies and differences between studies in subjects, tumor types, and methods of classification. Individual studies have generally lacked sufficient sample size to examine interactions. A major priority based on available evidence and technologies includes expanding research in genetics and molecular epidemiology of brain tumors. BTEC has taken an active role in promoting understudied groups such as pediatric brain tumors, the etiology of rare glioma subtypes, such as oligodendroglioma, and meningioma, which not uncommon, has only recently been systematically registered in the US. There is also a pressing need to bring more researchers, especially junior investigators, to study brain tumor epidemiology. However, relatively poor funding for brain tumor research has made it difficult to encourage careers in this area. We review the group’s consensus on the current state of scientific findings and present a consensus on research priorities to identify the important areas the science should move to address. PMID:18798534

Peptidomics of Cpefat/fat mouse brain regions: Implications for neuropeptide processing

PubMed Central

Zhang, Xin; Che, Fa-Yun; Berezniuk, Iryna; Sonmez, Kemal; Toll, Lawrence; Fricker, Lloyd D.

2009-01-01

SUMMARY Quantitative peptidomics was used to compare levels of peptides in wild type and Cpefat/fat mice, which lack carboxypeptidase E (CPE) activity due to a point mutation. Six different brain regions were analyzed: amygdala, hippocampus, hypothalamus, prefrontal cortex, striatum, and thalamus. Altogether, 111 neuropeptides or other peptides derived from secretory pathway proteins were identified in wild type mouse brain extracts by tandem mass spectrometry, and another 47 peptides were tentatively identified based on mass and other criteria. Most secretory pathway peptides were much lower in Cpefat/fat mouse brain, relative to wild type mouse brain, indicating that CPE plays a major role in their biosynthesis. Other peptides were only partially reduced in the Cpefat/fat mice, indicating that another enzyme (presumably carboxypeptidase D) contributes to their biosynthesis. Approximately 10% of the secretory pathway peptides were present in the Cpefat/fat mouse brain at levels similar to those in wild type mouse brain. Many peptides were greatly elevated in the Cpefat/fat mice; these peptide processing intermediates with C-terminal Lys and/or Arg were generally not detectable in wild type mice. Taken together, these results indicate that CPE contributes, either directly or indirectly, to the production of the majority of neuropeptides. PMID:19014391

Thyroid Hormone Availability and Action during Brain Development in Rodents.

PubMed

Bárez-López, Soledad; Guadaño-Ferraz, Ana

2017-01-01

Thyroid hormones (THs) play an essential role in the development of all vertebrates; in particular adequate TH content is crucial for proper neurodevelopment. TH availability and action in the brain are precisely regulated by several mechanisms, including the secretion of THs by the thyroid gland, the transport of THs to the brain and neural cells, THs activation and inactivation by the metabolic enzymes deiodinases and, in the fetus, transplacental passage of maternal THs. Although these mechanisms have been extensively studied in rats, in the last decade, models of genetically modified mice have been more frequently used to understand the role of the main proteins involved in TH signaling in health and disease. Despite this, there is little knowledge about the mechanisms underlying THs availability in the mouse brain. This mini-review article gathers information from findings in rats, and the latest findings in mice regarding the ontogeny of TH action and the sources of THs to the brain, with special focus on neurodevelopmental stages. Unraveling TH economy and action in the mouse brain may help to better understand the physiology and pathophysiology of TH signaling in brain and may contribute to addressing the neurological alterations due to hypo and hyperthyroidism and TH resistance syndromes.

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

PubMed

Toth, Marton; Faludi, Bela; Kondakor, Istvan

2012-10-01

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

Brain activity associated with selective attention, divided attention and distraction.

PubMed

Salo, Emma; Salmela, Viljami; Salmi, Juha; Numminen, Jussi; Alho, Kimmo

2017-06-01

Top-down controlled selective or divided attention to sounds and visual objects, as well as bottom-up triggered attention to auditory and visual distractors, has been widely investigated. However, no study has systematically compared brain activations related to all these types of attention. To this end, we used functional magnetic resonance imaging (fMRI) to measure brain activity in participants performing a tone pitch or a foveal grating orientation discrimination task, or both, distracted by novel sounds not sharing frequencies with the tones or by extrafoveal visual textures. To force focusing of attention to tones or gratings, or both, task difficulty was kept constantly high with an adaptive staircase method. A whole brain analysis of variance (ANOVA) revealed fronto-parietal attention networks for both selective auditory and visual attention. A subsequent conjunction analysis indicated partial overlaps of these networks. However, like some previous studies, the present results also suggest segregation of prefrontal areas involved in the control of auditory and visual attention. The ANOVA also suggested, and another conjunction analysis confirmed, an additional activity enhancement in the left middle frontal gyrus related to divided attention supporting the role of this area in top-down integration of dual task performance. Distractors expectedly disrupted task performance. However, contrary to our expectations, activations specifically related to the distractors were found only in the auditory and visual cortices. This suggests gating of the distractors from further processing perhaps due to strictly focused attention in the current demanding discrimination tasks. Copyright © 2017 Elsevier B.V. All rights reserved.

Cerebral activations during viewing of food stimuli in adult patients with acquired structural hypothalamic damage: a functional neuroimaging study.

PubMed

Steele, C A; Powell, J L; Kemp, G J; Halford, J C G; Wilding, J P; Harrold, J A; Kumar, S V D; Cuthbertson, D J; Cross, A A; Javadpour, M; MacFarlane, I A; Stancak, A A; Daousi, C

2015-09-01

Obesity is common following hypothalamic damage due to tumours. Homeostatic and non-homeostatic brain centres control appetite and energy balance but their interaction in the presence of hypothalamic damage remains unknown. We hypothesized that abnormal appetite in obese patients with hypothalamic damage results from aberrant brain processing of food stimuli. We sought to establish differences in activation of brain food motivation and reward neurocircuitry in patients with hypothalamic obesity (HO) compared with patients with hypothalamic damage whose weight had remained stable. In a cross-sectional study at a University Clinical Research Centre, we studied 9 patients with HO, 10 age-matched obese controls, 7 patients who remained weight-stable following hypothalamic insult (HWS) and 10 non-obese controls. Functional magnetic resonance imaging was performed in the fasted state, 1 h and 3 h after a test meal, while subjects were presented with images of high-calorie foods, low-calorie foods and non-food objects. Insulin, glucagon-like peptide-1, Peptide YY and ghrelin were measured throughout the experiment, and appetite ratings were recorded. Mean neural activation in the posterior insula and lingual gyrus (brain areas linked to food motivation and reward value of food) in HWS were significantly lower than in the other three groups (P=0.001). A significant negative correlation was found between insulin levels and posterior insula activation (P=0.002). Neural pathways associated with food motivation and reward-related behaviour, and the influence of insulin on their activation may be involved in the pathophysiology of HO.

In Vivo Visualization of Active Polysynaptic Circuits With Longitudinal Manganese-Enhanced MRI (MEMRI).

PubMed

Almeida-Corrêa, Suellen; Czisch, Michael; Wotjak, Carsten T

2018-01-01

Manganese-enhanced magnetic resonance imaging (MEMRI) is a powerful tool for in vivo non-invasive whole-brain mapping of neuronal activity. Mn 2+ enters active neurons via voltage-gated calcium channels and increases local contrast in T 1 -weighted images. Given the property of Mn 2+ of axonal transport, this technique can also be used for tract tracing after local administration of the contrast agent. However, MEMRI is still not widely employed in basic research due to the lack of a complete description of the Mn 2+ dynamics in the brain. Here, we sought to investigate how the activity state of neurons modulates interneuronal Mn 2+ transport. To this end, we injected mice with low dose MnCl 2 2. (i.p., 20 mg/kg; repeatedly for 8 days) followed by two MEMRI scans at an interval of 1 week without further MnCl 2 injections. We assessed changes in T 1 contrast intensity before (scan 1) and after (scan 2) partial sensory deprivation (unilateral whisker trimming), while keeping the animals in a sensory enriched environment. After correcting for the general decay in Mn 2+ content, whole brain analysis revealed a single cluster with higher signal in scan 1 compared to scan 2: the left barrel cortex corresponding to the right untrimmed whiskers. In the inverse contrast (scan 2 > scan 1), a number of brain structures, including many efferents of the left barrel cortex were observed. These results suggest that continuous neuronal activity elicited by ongoing sensory stimulation accelerates Mn 2+ transport from the uptake site to its projection terminals, while the blockage of sensory-input and the resulting decrease in neuronal activity attenuates Mn 2+ transport. The description of this critical property of Mn 2+ dynamics in the brain allows a better understanding of MEMRI functional mechanisms, which will lead to more carefully designed experiments and clearer interpretation of the results.

Physical principles for scalable neural recording

PubMed Central

Zamft, Bradley M.; Maguire, Yael G.; Shapiro, Mikhail G.; Cybulski, Thaddeus R.; Glaser, Joshua I.; Amodei, Dario; Stranges, P. Benjamin; Kalhor, Reza; Dalrymple, David A.; Seo, Dongjin; Alon, Elad; Maharbiz, Michel M.; Carmena, Jose M.; Rabaey, Jan M.; Boyden, Edward S.; Church, George M.; Kording, Konrad P.

2013-01-01

Simultaneously measuring the activities of all neurons in a mammalian brain at millisecond resolution is a challenge beyond the limits of existing techniques in neuroscience. Entirely new approaches may be required, motivating an analysis of the fundamental physical constraints on the problem. We outline the physical principles governing brain activity mapping using optical, electrical, magnetic resonance, and molecular modalities of neural recording. Focusing on the mouse brain, we analyze the scalability of each method, concentrating on the limitations imposed by spatiotemporal resolution, energy dissipation, and volume displacement. Based on this analysis, all existing approaches require orders of magnitude improvement in key parameters. Electrical recording is limited by the low multiplexing capacity of electrodes and their lack of intrinsic spatial resolution, optical methods are constrained by the scattering of visible light in brain tissue, magnetic resonance is hindered by the diffusion and relaxation timescales of water protons, and the implementation of molecular recording is complicated by the stochastic kinetics of enzymes. Understanding the physical limits of brain activity mapping may provide insight into opportunities for novel solutions. For example, unconventional methods for delivering electrodes may enable unprecedented numbers of recording sites, embedded optical devices could allow optical detectors to be placed within a few scattering lengths of the measured neurons, and new classes of molecularly engineered sensors might obviate cumbersome hardware architectures. We also study the physics of powering and communicating with microscale devices embedded in brain tissue and find that, while radio-frequency electromagnetic data transmission suffers from a severe power–bandwidth tradeoff, communication via infrared light or ultrasound may allow high data rates due to the possibility of spatial multiplexing. The use of embedded local recording and wireless data transmission would only be viable, however, given major improvements to the power efficiency of microelectronic devices. PMID:24187539

Abnormal interactions of verbal- and spatial-memory networks in young people at familial high-risk for schizophrenia.

PubMed

Li, Xiaobo; Thermenos, Heidi W; Wu, Ziyan; Momura, Yoko; Wu, Kai; Keshavan, Matcheri; Seidman, Lawrence; DeLisi, Lynn E

2016-10-01

Working memory impairment (especially in verbal and spatial domains) is the core neurocognitive impairment in schizophrenia and the familial high-risk (FHR) population. Inconsistent results have been reported in clinical and neuroimaging studies examining the verbal- and spatial-memory deficits in the FHR subjects, due to sample differences and lack of understanding on interactions of the brain regions for processing verbal- and spatial-working memory. Functional MRI data acquired during a verbal- vs. spatial-memory task were included from 51 young adults [26 FHR and 25 controls]. Group comparisons were conducted in brain activation patterns responding to 1) verbal-memory condition (A), 2) spatial-memory condition (B), 3) verbal higher than spatial (A-B), 4) spatial higher than verbal (B-A), 5) conjunction of brain regions that were activated during both A and B (A∧B). Group difference of the laterality index (LI) in inferior frontal lobe for condition A was also assessed. Compared to controls, the FHR group exhibited significantly decreased brain activity in left inferior frontal during A, and significantly stronger involvement of ACC, PCC, paracentral gyrus for the contrast of A-B. The LI showed a trend of reduced left-higher-than-right pattern for verbal-memory processing in the HR group. Our findings suggest that in the entire functional brain network for working-memory processing, verbal information processing associated brain pathways are significantly altered in people at familial high risk for developing schizophrenia. Future studies will need to examine whether these alterations may indicate vulnerability for predicting the onset of Schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of argan oil on the mitochondrial function, antioxidant system and the activity of NADPH- generating enzymes in acrylamide treated rat brain.

PubMed

Aydın, Birsen

2017-03-01

Argan oil (AO) is rich in minor compounds such as polyphenols and tocopherols which are powerful antioxidants. Acrylamide (ACR) has been classified as a neurotoxic agent in animals and humans. Mitochondrial oxidative stress and dysfunction is one of the most probable molecular mechanisms of neurodegenerative diseases. Female Sprague Dawley rats were exposed to ACR (50mg/kg i.p. three times a week), AO (6ml/kg,o.p, per day) or together for 30days. The activities of cytosolic enzymes such as xanthine oxidase (XO), glucose 6-phosphate dehydrogenase (G6PDH), glutathione-S-transferase (GST), mitochondrial oxidative stress, oxidative phosphorylation (OXPHOS) and tricarboxylic acid cycle (TCA) enzymes, mitochondrial metabolic function, adenosine triphosphate (ATP) level and acetylcholinesterase (AChE) activity were assessed in rat brain. Cytosolic and mitochondrial antioxidant enzymes were significantly diminished in the brains of rats treated with ACR compared to those in control. Besides, ACR treatment resulted in a significant reduction in brain ATP level, mitochondrial metabolic function, OXPHOS and TCA enzymes. Administration of AO restored both the cytosolic and mitochondrial oxidative stress by normalizing nicotinamide adenine dinucleotide phosphate (NADPH) generating enzymes. In addition, improved mitochondrial function primarily enhancing nicotinamide adenine dinucleotide (NADH) generated enzymes activities and ATP level in the mitochondria. The reason for AO's obvious beneficial effects in this study may be due to synergistic effects of its different bioactive compounds which is especially effective on mitochondria. Modulation of the brain mitochondrial functions and antioxidant systems by AO may lead to the development of new mitochondria-targeted antioxidants in the future. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Functional Magnetic Resonance Imaging Networks Induced by Intracranial Stimulation May Help Defining the Epileptogenic Zone

PubMed Central

Zhang, Myron; Avitsian, Rafi; Bhattacharyya, Pallab; Bulacio, Juan; Cendes, Fernando; Enatsu, Rei; Lowe, Mark; Najm, Imad; Nair, Dileep; Phillips, Michael; Gonzalez-Martinez, Jorge

2014-01-01

Abstract Patients with medically intractable epilepsy often undergo invasive evaluation and surgery, with a 50% success rate. The low success rate is likely due to poor identification of the epileptogenic zone (EZ), the brain area causing seizures. This work introduces a new method using functional magnetic resonance imaging (fMRI) with simultaneous direct electrical stimulation of the brain that could help localize the EZ, performed in five patients with medically intractable epilepsy undergoing invasive evaluation with intracranial depth electrodes. Stimulation occurred in a location near the hypothesized EZ and a location away. Electrical recordings in response to stimulation were recorded and compared to fMRI. Multiple stimulation parameters were varied, like current and frequency. The brain areas showing fMRI response were compared with the areas resected and the success of surgery. Robust fMRI maps of activation networks were easily produced, which also showed a significant but weak positive correlation between quantitative measures of blood-oxygen-level-dependent (BOLD) activity and measures of electrical activity in response to direct electrical stimulation (mean correlation coefficient of 0.38 for all acquisitions that produced a strong BOLD response). For four patients with outcome data at 6 months, successful surgical outcome is consistent with the resection of brain areas containing high local fMRI activity. In conclusion, this method demonstrates the feasibility of simultaneous direct electrical stimulation and fMRI in humans, which allows the study of brain connectivity with high resolution and full spatial coverage. This innovative technique could be used to better define the localization and extension of the EZ in intractable epilepsies, as well as for other functional neurosurgical procedures. PMID:24735069

Absolute activity quantitation from projections using an analytical approach: comparison with iterative methods in Tc-99m and I-123 brain SPECT

NASA Astrophysics Data System (ADS)

Fakhri, G. El; Kijewski, M. F.; Moore, S. C.

2001-06-01

Estimates of SPECT activity within certain deep brain structures could be useful for clinical tasks such as early prediction of Alzheimer's disease with Tc-99m or Parkinson's disease with I-123; however, such estimates are biased by poor spatial resolution and inaccurate scatter and attenuation corrections. We compared an analytical approach (AA) of more accurate quantitation to a slower iterative approach (IA). Monte Carlo simulated projections of 12 normal and 12 pathologic Tc-99m perfusion studies, as well as 12, normal and 12 pathologic I-123 neurotransmission studies, were generated using a digital brain phantom and corrected for scatter by a multispectral fitting procedure. The AA included attenuation correction by a modified Metz-Fan algorithm and activity estimation by a technique that incorporated Metz filtering to compensate for variable collimator response (VCR), IA-modeled attenuation, and VCR in the projector/backprojector of an ordered subsets-expectation maximization (OSEM) algorithm. Bias and standard deviation over the 12 normal and 12 pathologic patients were calculated with respect to the reference values in the corpus callosum, caudate nucleus, and putamen. The IA and AA yielded similar quantitation results in both Tc-99m and I-123 studies in all brain structures considered in both normal and pathologic patients. The bias with respect to the reference activity distributions was less than 7% for Tc-99m studies, but greater than 30% for I-123 studies, due to partial volume effect in the striata. Our results were validated using I-123 physical acquisitions of an anthropomorphic brain phantom. The IA yielded quantitation accuracy comparable to that obtained with IA, while requiring much less processing time. However, in most conditions, IA yielded lower noise for the same bias than did AA.

Abnormal brain activation during emotion processing of euthymic bipolar patients taking different mood stabilizers.

PubMed

Li, Linling; Ji, Erni; Tang, Fei; Qiu, Yunhai; Han, Xue; Zhang, Shengli; Zhang, Zhiguo; Yang, Haichen

2018-06-16

Numerous functional magnetic resonance imaging studies have been conducted to elucidate emotion processing of patients with bipolar disorder (BD), but due to different inclusion criteria used, especially for the history of medication use, the results for euthymic BD patients are inconsistent. For this reason, brain functional effects of psychopharmacological treatments on BD patients have been investigated by numerous fMRI studies, but there is no existing report for brain functional effects of different mood stabilizers. In this study, we compared the emotion processing in BD patients treated by two popularly used mood stabilizer, lithium (N = 13; 30 ± 9 years) and valproate (N = 16; 33 ± 8 years), as well as healthy controls (HC; N = 16; 29 ± 7 years). Two emotional tasks were applied in this study: one used emotional pictures of everyday objects and scenes, and another used emotional facial expression pictures. The main findings were that BD on lithium showed increased fMRI activation in the right dorsal anterior cingulate cortex and bilateral lingual gyrus in response to the positive pictures relative to neutral pictures compared with BD on valproate and HC. Besides, no abnormal activation was observed in the amygdala. Limitations of this study comprise the small sample size and the cross-sectional design. Therefore, the results were suggestive of a different effect of lithium and valproate on brain activities during emotion processing but no causal role can be proposed. The enduring impairments in euthymic state could provide clues to the brain regions involved in the primary pathology of BD.

Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain.

PubMed

Rastogi, R B; Singhal, R L

1976-09-01

In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats. Whereas administration of l-triiodothyronine (10 mug/100 g/day) for 30 days to 120-day-old rats increased the levels of tyrosine by 23% and of tryptophan by 43%, no appreciable change was noted in tryptophan hydroxylase activity. In contrast to neonatal hyperthyroidism, excess of thyroid hormone in adult rats failed to produce any change in motor activity and tended to decrease striatal tyrosine hydroxylase activity only slightly. The concentration of dopamine remained unchanged in all regions of the brain except in midbrain where it rose by 19%. Whereas norepinephrine concentration was altered in hypothalamus, pons-medulla and midbrain, the levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, were significantly decreased in striatum and cerebellum. Since dopaminergic and noradrenergic neurons are the critical components of the motor system, the possibility exists that elevated behavioral activity in young L-triiodothyronine-treated animals might be associated with increased turnover of catecholamines in neuronal tissue.

Combined effects of caffeine and zinc in the maternal diet on fetal brains

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakamoto, T.; Gottschalk, S.B.; Yazdani, M.

1991-03-15

The authors have reported that caffeine (C) intake during the lactational period by dams decreases the Zn content of the brain in their offspring. The objective of the present study is to determine how C plus Zn supplementation to the maternal diet during gestation affects the fetal brains. Timed-pregnant rats at day 3 of gestation were randomly divided into 4 groups (G). G1 was fed a 20% protein diet as a control, G2 was fed a diet supplemented with Zn, G3 was fed a diet with C and G4 was fed a diet with C and Zn. At day 22more » of gestation, fetuses were taken out surgically. Fetal brains were removed. Their weights, DNA, Zn, protein, cholesterol, caffeine concentration, and alkaline phosphatase activity were determined. Body and brain weights and cholesterol contents in G4 were greater than in G1, whereas Zn concentration and alkaline phosphatase activity were less. Zn concentration and Zn/DNA in G2 were greater than in G1. Cholesterol content in G4 was higher than in G3. Although mean caffeine concentration in brain and plasma in G4 was greater than in G3, there was no statistical significance between the G due to the wide fluctuation among the pups. It is concluded that supplementation of C and Zn in the maternal diet during gestation could influence fetal brain composition differently than C supplementation alone. Supplementation of Zn alone showed minor effects.« less

Hybrid Brain-Computer Interface Techniques for Improved Classification Accuracy and Increased Number of Commands: A Review.

PubMed

Hong, Keum-Shik; Khan, Muhammad Jawad

2017-01-01

In this article, non-invasive hybrid brain-computer interface (hBCI) technologies for improving classification accuracy and increasing the number of commands are reviewed. Hybridization combining more than two modalities is a new trend in brain imaging and prosthesis control. Electroencephalography (EEG), due to its easy use and fast temporal resolution, is most widely utilized in combination with other brain/non-brain signal acquisition modalities, for instance, functional near infrared spectroscopy (fNIRS), electromyography (EMG), electrooculography (EOG), and eye tracker. Three main purposes of hybridization are to increase the number of control commands, improve classification accuracy and reduce the signal detection time. Currently, such combinations of EEG + fNIRS and EEG + EOG are most commonly employed. Four principal components (i.e., hardware, paradigm, classifiers, and features) relevant to accuracy improvement are discussed. In the case of brain signals, motor imagination/movement tasks are combined with cognitive tasks to increase active brain-computer interface (BCI) accuracy. Active and reactive tasks sometimes are combined: motor imagination with steady-state evoked visual potentials (SSVEP) and motor imagination with P300. In the case of reactive tasks, SSVEP is most widely combined with P300 to increase the number of commands. Passive BCIs, however, are rare. After discussing the hardware and strategies involved in the development of hBCI, the second part examines the approaches used to increase the number of control commands and to enhance classification accuracy. The future prospects and the extension of hBCI in real-time applications for daily life scenarios are provided.

Environmentally relevant mixtures in cumulative assessments: an acute study of toxicokinetics and effects on motor activity in rats exposed to a mixture of pyrethroids.

PubMed

Starr, James M; Scollon, Edward J; Hughes, Michael F; Ross, David G; Graham, Stephen E; Crofton, Kevin M; Wolansky, Marcelo J; Devito, Michael J; Tornero-Velez, Rogelio

2012-12-01

Due to extensive use, human exposure to multiple pyrethroid insecticides occurs frequently. Studies of pyrethroid neurotoxicity suggest a common mode of toxicity and that pyrethroids should be considered cumulatively to model risk. The objective of this work was to use a pyrethroid mixture that reflects human exposure to common pyrethroids to develop comparative toxicokinetic profiles in rats, and then model the relationship between brain concentration and motor activity. Data from a national survey of child care centers were used to make a mixture reflecting proportions of the most prevalent pyrethroids: permethrin, cypermethrin, β-cyfluthrin, deltamethrin, and esfenvalerate. The mixture was administered orally at one of two concentrations (11.2 and 27.4 mg/kg) to adult male rats. At intervals from 1 to 24h, motor activity was assessed and the animals were sacrificed. Pyrethroid concentrations were measured in the blood, liver, fat, and brain. After controlling for dose, there were no differences in any tissue concentrations, except blood at the initial time point. Elimination half-lives for all pyrethroids in all tissues were < 7h. Brain concentrations of all pyrethroids (when cis- and trans-permethrin were pooled) at the initial time point were proportional to their relative doses. Decreases in motor activity indicated dose additivity, and the relationship between pyrethroid brain concentration and motor activity was described by a four-parameter sigmoidal E(max) model. This study links environmental data with toxicokinetic and neurobehavioral assays to support cumulative risk assessments of pyrethroid pesticides. The results support the additive model of pyrethroid effect on motor activity and suggest that variation in the neurotoxicity of individual pyrethroids is related to toxicodynamic rather than toxicokinetic differences.

Neural responses to visual food stimuli after a normal vs. higher protein breakfast in breakfast-skipping teens: a pilot fMRI study.

PubMed

Leidy, Heather J; Lepping, Rebecca J; Savage, Cary R; Harris, Corey T

2011-10-01

This functional magnetic resonance imaging (fMRI) pilot study identified whether breakfast consumption would alter the neural activity in brain regions associated with food motivation and reward in overweight "breakfast skipping" (BS) adolescent girls and examined whether increased protein at breakfast would lead to additional alterations. Ten girls (Age: 15 ± 1 years; BMI percentile 93 ± 1%; BS 5 ± 1×/week) completed 3 testing days. Following the BS day, the participants were provided with, in randomized order, normal protein (NP; 18 ± 1 g protein) or higher protein (HP; 50 ± 1 g protein) breakfast meals to consume at home for 6 days. On day 7 of each pattern, the participants came to the laboratory to consume their respective breakfast followed by appetite questionnaires and an fMRI brain scan to identify brain activation responses to viewing food vs. nonfood images prior to lunch. Breakfast consumption led to enduring (i.e., 3-h post breakfast) reductions in neural activation in the hippocampus, amygdala, cingulate, and parahippocampus vs. BS. HP led to enduring reductions in insula and middle prefrontal cortex activation vs. NP. Hippocampal, amygdala, cingulate, and insular activations were correlated with appetite and inversely correlated with satiety. In summary, the addition of breakfast led to alterations in brain activation in regions previously associated with food motivation and reward with additional alterations following the higher-protein breakfast. These data suggest that increased dietary protein at breakfast might be a beneficial strategy to reduce reward-driven eating behavior in overweight teen girls. Due to the small sample size, caution is warranted when interpreting these preliminary findings.

Brain imaging with sup 123 I-IMP-SPECT in migraine between attacks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schlake, H.P.; Boettger, I.G.G.; Grotemeyer, K.H.

1989-06-01

{sup 123}I-IMP-SPECT brain imaging was performed in patients with classic migraine (n = 5) and migraine accompagnee (n = 18) during the headache-free interval. A regional reduction of tracer uptake into brain was observed in all patients with migraine accompagnee, while in patients with classic migraine only one case showed an area of decreased activity. The most marked alteration was found in a patient with persisting neurological symptoms (complicated migraine). In most cases the areas of decreased tracer uptake corresponded to headache localization as well as to topography of neurologic symptoms during migraine attacks. It may be concluded that migrainemore » attacks occur in connection with exacerbations of preexisting changes of cerebral autoregulation due to endogenous or exogenous factors.« less

Effect of mosquito mats (pyrethroid-based) vapor inhalation on rat brain cytochrome P450s.

PubMed

Vences-Mejía, Araceli; Gómez-Garduño, Josefina; Caballero-Ortega, Heriberto; Dorado-González, Víctor; Nosti-Palacios, Rosario; Labra-Ruíz, Norma; Espinosa-Aguirre, J Javier

2012-01-01

The effect of transfluthrin (TF) or D-allethrin (DA) pyrethroid (PYR) vapors, often contained as main ingredients in two commercially available mosquito repellent mats, on cytochrome P450 (CYP) enzymes of rat brain and liver was assessed. Immunodetection of CYP2E1 and CYP3A2 proteins revealed their induction in cerebrum and cerebellum, but not in liver microsomes of rats exposed by inhalation to TF or DA. This overexpression of proteins correlated with an increase of their catalytic activities. The specifically increased expression of CYP isoenzymes, due to PYR exposure in the rat brain, could perturb the normal metabolism of endogenous and xenobiotic compounds and leads to increased risks of neurotoxicity by bioactivation, lipid peroxidation and DNA damage.

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

PubMed Central

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

2013-01-01

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

Biochemical and hematological effects of lead ingestion in nestling American kestrels (Falco sparverius)

USGS Publications Warehouse

Hoffman, D.J.; Franson, J.C.; Pattee, O.H.; Bunck, C.M.; Murray, H.C.

1985-01-01

1. One-day old American kestrel (Faico sparverius) nestlings were orally dosed daily with 5 μl/g of corn oil (controls), 25, 125 or 625 mg/kg of metallic lead in corn oil for 10 days.2. Forty per cent of the nestlings receiving 625 mg/kg of lead died after 6 days and growth rates were significantly depressed in the two highest lead dosed groups. At 10 days hematocrit values were significantly lower in the two highest lead treated groups, and hemoglobin content and red blood cell (δ-aminolevulinic acid dehydratase (ALAD) activity was depressed in all lead treated groups. Plasma creatine phosphokinase decreased in the two highest treatment groups.3. Brain, liver and kidney ALAD activities, brain RNA to protein ratio and liver protein concentration decreased after lead exposure whereas liver DNA, DNA to RNA ratio and DNA to protein ratio increased. Brain monoamine oxidase and ATPase were not significantly altered.4. Measurements of the ontogeny of hematological variants and enzymes in normal development, using additional untreated nestlings, revealed decreases in red blood cell ALAD, plasma aspartate amino transferase, lactate dehydrogenase, brain DNA and RNA and liver DNA, whereas hematocrit, hemoglobin, plasma alkaline phosphatase, brain monoamine oxidase, brain ALAD and liver ALAD increased during the first 10 days of posthatching development.5. Biochemical and hematological alterations were more severe than those reported in adult kestrels or precocial young birds exposed to lead. Alterations may be due in part to delayed development.

Depletion of GGA3 stabilizes BACE and enhances β-secretase activity

PubMed Central

Tesco, Giuseppina; Koh, Young Ho; Kang, Eugene; Cameron, Andrew; Das, Shinjita; Sena-Esteves, Miguel; Hiltunen, Mikko; Yang, Shao-Hua; Zhong, Zhenyu; Shen, Yong; Simpkins, James; Tanzi, Rudolph E.

2007-01-01

Summary Beta-site APP-cleaving enzyme (BACE) is required for production of the Alzheimer's disease (AD)-associated Aβ protein. BACE levels are elevated in AD brain, and increasing evidence reveals BACE as a stress-related protease that is upregulated following cerebral ischemia. However, the molecular mechanism responsible is unknown. We show that increases in BACE and β-secretase activity are due to post-translational stabilization following caspase activation. We also found that during cerebral ischemia, levels of GGA3, an adaptor protein involved in BACE trafficking, are reduced, while BACE levels are increased. RNAi silencing of GGA3 also elevated levels of BACE and Aβ. Finally, in AD brain samples, GGA3 protein levels were significantly decreased and inversely correlated with increased levels of BACE. In summary, we have elucidated a novel GGA3-dependent mechanism regulating BACE levels and β-secretase activity. This mechanism may explain increased cerebral levels of BACE and Aβ following cerebral ischemia and in AD. PMID:17553422

Analysis of spontaneous EEG activity in Alzheimer's disease using cross-sample entropy and graph theory.

PubMed

Gomez, Carlos; Poza, Jesus; Gomez-Pilar, Javier; Bachiller, Alejandro; Juan-Cruz, Celia; Tola-Arribas, Miguel A; Carreres, Alicia; Cano, Monica; Hornero, Roberto

2016-08-01

The aim of this pilot study was to analyze spontaneous electroencephalography (EEG) activity in Alzheimer's disease (AD) by means of Cross-Sample Entropy (Cross-SampEn) and two local measures derived from graph theory: clustering coefficient (CC) and characteristic path length (PL). Five minutes of EEG activity were recorded from 37 patients with dementia due to AD and 29 elderly controls. Our results showed that Cross-SampEn values were lower in the AD group than in the control one for all the interactions among EEG channels. This finding indicates that EEG activity in AD is characterized by a lower statistical dissimilarity among channels. Significant differences were found mainly for fronto-central interactions (p <; 0.01, permutation test). Additionally, the application of graph theory measures revealed diverse neural network changes, i.e. lower CC and higher PL values in AD group, leading to a less efficient brain organization. This study suggests the usefulness of our approach to provide further insights into the underlying brain dynamics associated with AD.

Daidzein and its Effects on Brain.

PubMed

Ahmed, Touqeer; Javed, Sana; Tariq, Ameema; Budzyńska, Barbara; D'Onofrio, Grazia; Daglia, Maria; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad

2017-01-01

Among naturally occurring isoflavones, soy isoflavones are an important class with various biological activities. Due to their phytoestrogenic structure, their effects on the brain are profound thus making the neurobiological effects of these compounds an active area of research. One such compound is daidzein, which has been reported to affect various neurobiological regulatory mechanisms such as behavior, cognition, growth, development and reproduction. These effects are mainly elicited through the interaction of daidzein with different signaling molecules and receptors, thereby offering neuroprotection. In addition, daidzein has also been reported to possess activities against various neuropathological conditions mainly by its interaction with the cerebrovascular system. This review focuses on providing a comprehensive account on the bioavailability and metabolism of daidzein in vivo, and discusses its activities and mechanisms of action in detail, in both physiological and pathological conditions. In addition, the effects of daidzein on other disorders have also been examined briefly in this article. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning.

PubMed

Butler, Christopher W; Wilson, Yvette M; Gunnersen, Jenny M; Murphy, Mark

2015-08-01

Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory. © 2015 Butler et al.; Published by Cold Spring Harbor Laboratory Press.

Spontaneous sensorimotor cortical activity is suppressed by deep brain stimulation in patients with advanced Parkinson's disease.

PubMed

Luoma, Jarkko; Pekkonen, Eero; Airaksinen, Katja; Helle, Liisa; Nurminen, Jussi; Taulu, Samu; Mäkelä, Jyrki P

2018-06-22

Advanced Parkinson's disease (PD) is characterized by an excessive oscillatory beta band activity in the subthalamic nucleus (STN). Deep brain stimulation (DBS) of STN alleviates motor symptoms in PD and suppresses the STN beta band activity. The effect of DBS on cortical sensorimotor activity is more ambiguous; both increases and decreases of beta band activity have been reported. Non-invasive studies with simultaneous DBS are problematic due to DBS-induced artifacts. We recorded magnetoencephalography (MEG) from 16 advanced PD patients with and without STN DBS during rest and wrist extension. The strong magnetic artifacts related to stimulation were removed by temporal signal space separation. MEG oscillatory activity at 5-25 Hz was suppressed during DBS in a widespread frontoparietal region, including the sensorimotor cortex identified by the cortico-muscular coherence. The strength of suppression did not correlate with clinical improvement. Our results indicate that alpha and beta band oscillations are suppressed at the frontoparietal cortex by STN DBS in PD. Copyright © 2018. Published by Elsevier B.V.

Copper exposure induces oxidative injury, disturbs the antioxidant system and changes the Nrf2/ARE (CuZnSOD) signaling in the fish brain: protective effects of myo-inositol.

PubMed

Jiang, Wei-Dan; Liu, Yang; Hu, Kai; Jiang, Jun; Li, Shu-Hong; Feng, Lin; Zhou, Xiao-Qiu

2014-10-01

The brain is the center of the nervous system in all vertebrates, and homeostasis of the brain is crucial for fish survival. Copper (Cu) is essential for normal cellular processes in most eukaryotic organisms but is toxic in excess. Although Cu is indicated as a potent neurotoxicant, information regarding its threat to fish brain and underlying mechanisms is still scarce. In accordance, the objective of this study was to assess the effects and the potential mechanism of Cu toxicity by evaluating brain oxidative status, the enzymatic and mRNA levels of antioxidant genes, as well as the Nrf2/ARE signaling in the brain of fish after Cu exposure. The protective effects of myo-inositol (MI) against subsequent Cu exposure were also investigated. The results indicate that induction of oxidative stress by Cu is shown by increases in brain ROS production, lipid peroxidation and protein oxidation, which are accompanied by depletions of antioxidants, including total superoxide dismutase (T-SOD), CuZnSOD, glutathione-S-transferase (GST) and glutathione reductase (GR) activities and glutathione (GSH) content. Cu exposure increased the catalase (CAT) and glutathione peroxidase (GPx) activities. Further molecular results showed that Cu exposure up-regulated CuZnSOD, GPx1a and GR mRNA levels, suggesting an adaptive mechanism against stress. Moreover, Cu exposure increased fish brain Nrf2 nuclear accumulation and increased its ability of binding to ARE (CuZnSOD), which supported the increased CuZnSOD mRNA levels. In addition, Cu exposure caused increases of the expression of the Nrf2, Maf G1 (rather than Maf G2 gene) and PKCd genes, suggesting that de novo synthesis of those factors is required for the protracted induction of such antioxidant genes. However, the modulation of Keap1a (rather than Keap1b) of fish brain under Cu exposure might be used to turn off of the signaling cascade and avoid harmful effects. Interestingly, pre-treatment of fish with MI prevented the fish brain from Cu-induced oxidative damages mainly by increasing the GSH content and CuZnSOD and GST activities. Summarily, this study indicates that although Cu stimulates adaptive increases in the expression of some antioxidant enzyme genes through Nrf2/ARE signaling, it also induces oxidation and the depletion of most of antioxidant enzyme activities and GSH content due to the increase of ROS production, and MI protects the fish brain against Cu toxicity. Copyright © 2014 Elsevier B.V. All rights reserved.

Applications of bioactive material from snakehead fish (Channa striata) for repairing of learning-memory capability and motoric activity: a case study of physiological aging and aging-caused oxidative stress in rats

NASA Astrophysics Data System (ADS)

Sunarno, Sunarno; Muflichatun Mardiati, Siti; Rahadian, Rully

2018-05-01

Physiological aging and aging due to oxidative stress are a major factor cause accelerated brain aging. Aging is characterized by a decrease of brain function of the hippocampus which is linked to the decline in the capability of learning-memory and motoric activity. The objective of this research is to obtain the important information about the mechanisms of brain antiaging associated with the improvement of hippocampus function, which includes aspects of learning-memory capability and motoric activity as well as mitochondrial ultrastructure profile of hippocampus cornu ammonis cells after treated by fish snakehead fish extract. Snakehead fish in Rawa Pening Semarang District allegedly holds the potential of endemic, which contains bioactive antiaging material that can prevent aging or improve the function of the hippocampus. This research has been conducted using a completely randomized design consisting of four treatments with five replications. The treatments were including rats with physiological aging or aging due to oxidative stress which was treated and without treated with meat extract of snakehead fish. The research was divided into two stages, i.e., determining of learning-memory capability, and determining motoric activity. The measured-parameters are time response to find feed, distance travel, time stereotypes, ambulatory time, and resting time. The result showed that the snakehead fish meat extract might improve function hippocampus, both in physiological aging or aging due to oxidative stress. The capability of learning and memory showed that the rats in both conditions of aging after getting treatment of meat extract of snakehead fish could get a feed in the fourth arm maze faster than rats untreated snakehead fish meat extract. Similarly, the measurement of the distance traveled, time stereotypes, ambulatory time, and resting time showed that rats which received treatment of meat extract of snakehead fish were better than the untreated rats. To conclude, the meat extract of snakehead fish can be used as antiaging material to improve the function of the hippocampus, to improve the capability of learning and memory, to improve motoric activity, and to prevent aging. These findings are expected to provide comprehensive information for the development of antiaging research as an effort to improve public health and to improve learning-memory capability and motoric activity.

Altered resting-state whole-brain functional networks of neonates with intrauterine growth restriction.

PubMed

Batalle, Dafnis; Muñoz-Moreno, Emma; Tornador, Cristian; Bargallo, Nuria; Deco, Gustavo; Eixarch, Elisenda; Gratacos, Eduard

2016-04-01

The feasibility to use functional MRI (fMRI) during natural sleep to assess low-frequency basal brain activity fluctuations in human neonates has been demonstrated, although its potential to characterise pathologies of prenatal origin has not yet been exploited. In the present study, we used intrauterine growth restriction (IUGR) as a model of altered neurodevelopment due to prenatal condition to show the suitability of brain networks to characterise functional brain organisation at neonatal age. Particularly, we analysed resting-state fMRI signal of 20 neonates with IUGR and 13 controls, obtaining whole-brain functional networks based on correlations of blood oxygen level-dependent (BOLD) signal in 90 grey matter regions of an anatomical atlas (AAL). Characterisation of the networks obtained with graph theoretical features showed increased network infrastructure and raw efficiencies but reduced efficiency after normalisation, demonstrating hyper-connected but sub-optimally organised IUGR functional brain networks. Significant association of network features with neurobehavioral scores was also found. Further assessment of spatiotemporal dynamics displayed alterations into features associated to frontal, cingulate and lingual cortices. These findings show the capacity of functional brain networks to characterise brain reorganisation from an early age, and their potential to develop biomarkers of altered neurodevelopment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Anticholinesterase exposure of white-winged doves breeding in lower Rio Grande valley, Texas

USGS Publications Warehouse

Tacha, T.C.; Schacht, S.J.; George, R.R.; Hill, E.F.

1994-01-01

We studied exposure of breeding white-winged doves (Zenaida asiatica) to anticholinesterase compounds (organophosphorus and carbamate pesticides) in the Lower Rio Grande Valley (LRGV), Texas. Widespread use of organophosphorus pesticides and dove population declines prompted the study. We collected breeding adult doves in May and July 1991 (n = 28) and July 1992 (n = 33) at 6 locations. We used depression of whole-brain cholinesterase (ChE) activity (2 SD below control mean) to detect exposure; values from 4 hand-reared doves fed commercial pigeon chow served as the control. Mean brain ChE activity was lower (P lt 0.027) than the control sample at all 6 locations in 1991; 79% of the birds were diagnostic of exposure ( gt 16.1% ChE depression). Pooled 1992 field samples also were lower (P lt 0.036) than were control samples; doves from 4 of the 6 locations had brain ChE activity below (P lt 0.088) controls. Overall, 39% of 1992 doves were diagnostic of exposure to anticholinesterase compounds. Higher exposure rates in 1991 were probably due to increased use of organophosphorus pesticides. Research is needed documenting effects of sublethal exposure on white-winged dove productivity.

Music and the nucleus accumbens.

PubMed

Mavridis, Ioannis N

2015-03-01

Music is a universal feature of human societies over time, mainly because it allows expression and regulation of strong emotions, thus influencing moods and evoking pleasure. The nucleus accumbens (NA), the most important pleasure center of the human brain (dominates the reward system), is the 'king of neurosciences' and dopamine (DA) can be rightfully considered as its 'crown' due to the fundamental role that this neurotransmitter plays in the brain's reward system. Purpose of this article was to review the existing literature regarding the relation between music and the NA. Studies have shown that reward value for music can be coded by activity levels in the NA, whose functional connectivity with auditory and frontal areas increases as a function of increasing musical reward. Listening to music strongly modulates activity in a network of mesolimbic structures involved in reward processing including the NA. The functional connectivity between brain regions mediating reward, autonomic and cognitive processing provides insight into understanding why listening to music is one of the most rewarding and pleasurable human experiences. Musical stimuli can significantly increase extracellular DA levels in the NA. NA DA and serotonin were found significantly higher in animals exposed to music. Finally, passive listening to unfamiliar although liked music showed activations in the NA.

Circulating Estradiol Regulates Brain-Derived Estradiol via Actions at GnRH Receptors to Impact Memory in Ovariectomized Rats.

PubMed

Nelson, Britta S; Black, Katelyn L; Daniel, Jill M

2016-01-01

Systemic estradiol treatment enhances hippocampus-dependent memory in ovariectomized rats. Although these enhancements are traditionally thought to be due to circulating estradiol, recent data suggest these changes are brought on by hippocampus-derived estradiol, the synthesis of which depends on gonadotropin-releasing hormone (GnRH) activity. The goal of the current work is to test the hypothesis that peripheral estradiol affects hippocampus-dependent memory through brain-derived estradiol regulated via hippocampal GnRH receptor activity. In the first experiment, intracerebroventricular infusion of letrozole, which prevents the synthesis of estradiol, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory in a radial-maze task. In the second experiment, hippocampal infusion of antide, a long-lasting GnRH receptor antagonist, blocked the ability of peripheral estradiol administration in ovariectomized rats to enhance hippocampus-dependent memory. In the third experiment, hippocampal infusion of GnRH enhanced hippocampus-dependent memory, the effects of which were blocked by letrozole infusion. Results indicate that peripheral estradiol-induced enhancement of cognition is mediated by brain-derived estradiol via hippocampal GnRH receptor activity.

Structural covariance mapping delineates medial and medio-lateral temporal networks in déjà vu.

PubMed

Shaw, Daniel Joel; Mareček, Radek; Brázdil, Milan

2016-12-01

Déjà vu (DV) is an eerie phenomenon experienced frequently as an aura of temporal lobe epilepsy, but also reported commonly by healthy individuals. The former pathological manifestation appears to result from aberrant neural activity among brain structures within the medial temporal lobes. Recent studies also implicate medial temporal brain structures in the non-pathological experience of DV, but as one element of a diffuse neuroanatomical correlate; it remains to be seen if neural activity among the medial temporal lobes also underlies this benign manifestation. The present study set out to investigate this. Due to its unpredictable and infrequent occurrence, however, non-pathological DV does not lend itself easily to functional neuroimaging. Instead, we draw on research showing that brain structure covaries among regions that interact frequently as nodes of functional networks. Specifically, we assessed whether grey-matter covariance among structures implicated in non-pathological DV differs according to the frequency with which the phenomenon is experienced. This revealed two diverging patterns of structural covariation: Among the first, comprised primarily of medial temporal structures and the caudate, grey-matter volume becomes more positively correlated with higher frequency of DV experience. The second pattern encompasses medial and lateral temporal structures, among which greater DV frequency is associated with more negatively correlated grey matter. Using a meta-analytic method of co-activation mapping, we demonstrate a higher probability of functional interactions among brain structures constituting the former pattern, particularly during memory-related processes. Our findings suggest that altered neural signalling within memory-related medial temporal brain structures underlies both pathological and non-pathological DV.

The chemokine CCL2 protects against methylmercury neurotoxicity.

PubMed

Godefroy, David; Gosselin, Romain-Daniel; Yasutake, Akira; Fujimura, Masatake; Combadière, Christophe; Maury-Brachet, Régine; Laclau, Muriel; Rakwal, Randeep; Melik-Parsadaniantz, Stéphane; Bourdineaud, Jean-Paul; Rostène, William

2012-01-01

Industrial pollution due to heavy metals such as mercury is a major concern for the environment and public health. Mercury, in particular methylmercury (MeHg), primarily affects brain development and neuronal activity, resulting in neurotoxic effects. Because chemokines can modulate brain functions and are involved in neuroinflammatory and neurodegenerative diseases, we tested the possibility that the neurotoxic effect of MeHg may interfere with the chemokine CCL2. We have used an original protocol in young mice using a MeHg-contaminated fish-based diet for 3 months relevant to human MeHg contamination. We observed that MeHg induced in the mice cortex a decrease in CCL2 concentrations, neuronal cell death, and microglial activation. Knock-out (KO) CCL2 mice fed with a vegetal control food already presented a decrease in cortical neuronal cell density in comparison with wild-type animals under similar diet conditions, suggesting that the presence of CCL2 is required for normal neuronal survival. Moreover, KO CCL2 mice showed a pronounced neuronal cell death in response to MeHg. Using in vitro experiments on pure rat cortical neurons in culture, we observed by blockade of the CCL2/CCR2 neurotransmission an increased neuronal cell death in response to MeHg neurotoxicity. Furthermore, we showed that sod genes are upregulated in brain of wild-type mice fed with MeHg in contrast to KO CCL2 mice and that CCL2 can blunt in vitro the decrease in glutathione levels induced by MeHg. These original findings demonstrate that CCL2 may act as a neuroprotective alarm system in brain deficits due to MeHg intoxication.

Fumaric Acid Esters Do Not Reduce Inflammatory NF-κB/p65 Nuclear Translocation, ICAM-1 Expression and T-Cell Adhesiveness of Human Brain Microvascular Endothelial Cells.

PubMed

Haarmann, Axel; Nehen, Mathias; Deiß, Annika; Buttmann, Mathias

2015-08-13

Dimethyl fumarate (DMF) is approved for disease-modifying treatment of patients with relapsing-remitting multiple sclerosis. Animal experiments suggested that part of its therapeutic effect is due to a reduction of T-cell infiltration of the central nervous system (CNS) by uncertain mechanisms. Here we evaluated whether DMF and its primary metabolite monomethyl fumarate (MMF) modulate pro-inflammatory intracellular signaling and T-cell adhesiveness of nonimmortalized single donor human brain microvascular endothelial cells at low passages. Neither DMF nor MMF at concentrations of 10 or 50 µM blocked the IL-1β-induced nuclear translocation of NF-κB/p65, whereas the higher concentration of DMF inhibited the nuclear entry of p65 in human umbilical vein endothelium cultured in parallel. DMF and MMF also did not alter the IL-1β-stimulated activation of p38 MAPK in brain endothelium. Furthermore, neither DMF nor MMF reduced the basal or IL-1β-inducible expression of ICAM-1. In accordance, both fumaric acid esters did not reduce the adhesion of activated Jurkat T cells to brain endothelium under basal or inflammatory conditions. Therefore, brain endothelial cells probably do not directly mediate a potential blocking effect of fumaric acid esters on the inflammatory infiltration of the CNS by T cells.

In vitro and In vivo Antioxidant Evaluation and Estimation of Total Phenolic, Flavonoidal Content of Mimosa pudica L

PubMed Central

Patro, Ganesh; Bhattamisra, Subrat Kumar; Mohanty, Bijay Kumar; Sahoo, Himanshu Bhusan

2016-01-01

Objective: Mimosa pudica Linn. (Mimosaceae) is traditionally used as a folk medicine to treat various ailments including convulsions, alopecia, diarrhea, dysentery, insomnia, tumor, wound healing, snake bite, etc., Here, the study was aimed to evaluate the antioxidant potential of M. pudica leaves extract against 2, 2-diphenyl-1-picrylhydrazyl (DPPH) (in vitro) and its modulatory effect on rat brain enzymes. Materials and Methods: Total phenolic, flavonoid contents, and in vitro antioxidant potential against DPPH radical were evaluated from various extracts of M. pudica leaves. In addition, ethyl acetate extract of Mimosa pudica leaves (EAMP) in doses of 100, 200, and 400 mg/kg/day were administered orally for 7 consecutive days to albino rats and evaluated for the oxidative stress markers as thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) from rat brain homogenate. Results: The ethyl acetate extract showed the highest total phenolic content and total flavonoid content among other extracts of M. pudica leaves. The percentage inhibition and IC50 value of all the extracts were followed dose-dependency and found significant (P < 0.01) as compared to standard (ascorbic acid). The oxidative stress markers as SOD, CAT, and GSH were increased significantly (P < 0.01) at 200 and 400 mg/kg of EAMP treated animals and decreased significantly the TBARS level at 400 mg/kg of EAMP as compared to control group. Conclusion: These results revealed that the ethyl acetate extract of M. pudica exhibits both in vitro antioxidant activity against DPPH and in vivo antioxidant activity by modulating brain enzymes in the rat. This could be further correlated with its potential to neuroprotective activity due to the presence of flavonoids and phenolic contents in the extract. SUMMARY Total phenolic, flavonoid contents and in-vitro antioxidant potential were evaluated from various extracts of M. pudica leaves. Again, in-vivo antioxidant evaluation from brain homogenate on oxidative stress markers as TBARS, SOD, CAT and GSH from rat was investigated. Our findings revealed that M. pudica possesses both in-vitro and in-vivo antioxidant activity due to presence of phenolics and flavonoids. PMID:26941532

Neuroprotective Effect of TAT-14-3-3ε Fusion Protein against Cerebral Ischemia/Reperfusion Injury in Rats

PubMed Central

Liu, Xiaoyan; Hu, Wenhui; Wang, Yinye

2014-01-01

Stroke is the major cause of death and disability worldwide, and the thrombolytic therapy currently available was unsatisfactory. 14-3-3ε is a well characterized member of 14-3-3 family, and has been reported to protect neurons against apoptosis in cerebral ischemia. However, it cannot transverse blood brain barrier (BBB) due to its large size. A protein transduction domain (PTD) of HIV TAT protein, is capable of delivering a large variety of proteins into the brain. In this study, we generated a fusion protein TAT-14-3-3ε, and evaluated its potential neuroprotective effect in rat focal ischemia/reperfusion (I/R) model. Western blot analysis validated the efficient transduction of TAT-14-3-3ε fusion protein into brain via a route of intravenous injection. TAT-14-3-3ε pre-treatment 2 h before ischemia significantly reduced cerebral infarction volume and improved neurologic score, while post-treatment 2 h after ischemia was less effective. Importantly, pre- or post-ischemic treatment with TAT-14-3-3ε significantly increased the number of surviving neurons as determined by Nissl staining, and attenuated I/R-induced neuronal apoptosis as showed by the decrease in apoptotic cell numbers and the inhibition of caspase-3 activity. Moreover, the introduction of 14-3-3ε into brain by TAT-mediated delivering reduced the formation of autophagosome, attenuated LC3B-II upregulation and reversed p62 downregulation induced by ischemic injury. Such inhibition of autophagy was reversed by treatment with an autophagy inducer rapamycin (RAP), which also attenuated the neuroprotective effect of TAT-14-3-3ε. Conversely, autophagy inhibitor 3-methyladenine (3-MA) inhibited I/R-induced the increase in autophagic activity, and attenuated I/R-induced brain infarct. These results suggest that TAT-14-3-3ε can be efficiently transduced into brain and exert significantly protective effect against brain ischemic injury through inhibiting neuronal apoptosis and autophagic activation. PMID:24671253

SUSPECTED CARBARYL TOXICITY IN A CAPTIVE COLONY OF STRAW-COLORED FRUIT BATS ( EIDOLON HELVUM).

PubMed

Selig, Michael; Lewandowski, Albert

2017-12-01

Carbaryl was the first carbamate insecticide produced and remains the most widely used due to its perceived low level of toxicity in nontarget species. This report describes the management and evaluation of a group of straw-colored fruit bats, Eidolon helvum, that were exposed to carbaryl. Cholinesterase activity of blood, retina, and brain was evaluated to further investigate whether carbaryl was the causative agent. Decreased whole blood and retinal cholinesterase activity coupled with the response to atropine suggests that the cause of the clinical signs in this bat colony was due to carbaryl exposure. Whole blood and retinal tissue may be the best samples for confirming carbamate exposure in this species.

Propagation of damage in the rat brain following sarin exposure: Differential progression of early processes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lazar, Shlomi; Egoz, Inbal; Brandeis, Rachel

Sarin is an irreversible organophosphate cholinesterase inhibitor and a highly toxic warfare agent. Following the overt, dose-dependent signs (e.g. tremor, hyper secretion, seizures, respiratory depression and eventually death), brain damage is often reported. The goal of the present study was to characterize the early histopathological and biochemical events leading to this damage. Rats were exposed to 1LD50 of sarin (80 μg/kg, i.m.). Brains were removed at 1, 2, 6, 24 and 48 h and processed for analysis. Results showed that TSPO (translocator protein) mRNA increased at 6 h post exposure while TSPO receptor density increased only at 24 h. Inmore » all brain regions tested, bax mRNA decreased 1 h post exposure followed by an increase 24 h later, with only minor increase in bcl2 mRNA. At this time point a decrease was seen in both anti-apoptotic protein Bcl2 and pro-apoptotic Bax, followed by a time and region specific increase in Bax. An immediate elevation in ERK1/2 activity with no change in JNK may indicate an endogenous “first response” mechanism used to attenuate the forthcoming apoptosis. The time dependent increase in the severity of brain damage included an early bi-phasic activation of astrocytes, a sharp decrease in intact neuronal cells, a time dependent reduction in MAP2 and up to 15% of apoptosis. Thus, neuronal death is mostly due to necrosis and severe astrocytosis. The data suggests that timing of possible treatments should be determined by early events following exposure. For example, the biphasic changes in astrocytes activity indicate a possible beneficial effects of delayed anti-inflammatory intervention. - Highlights: • The severity of brain damage post 1LD50 sarin exposure is time dependent. • Sarin induce differential progression of early processes in the rat brain. • Potential treatments should be timed according to early events following exposure. • The biphasic astrocytes activity suggests a delay in anti-inflammatory intervention.« less

Downregulation of the expression of mitochondrial electron transport complex genes in autism brains.

PubMed

Anitha, Ayyappan; Nakamura, Kazuhiko; Thanseem, Ismail; Matsuzaki, Hideo; Miyachi, Taishi; Tsujii, Masatsugu; Iwata, Yasuhide; Suzuki, Katsuaki; Sugiyama, Toshiro; Mori, Norio

2013-05-01

Mitochondrial dysfunction (MtD) and abnormal brain bioenergetics have been implicated in autism, suggesting possible candidate genes in the electron transport chain (ETC). We compared the expression of 84 ETC genes in the post-mortem brains of autism patients and controls. Brain tissues from the anterior cingulate gyrus, motor cortex, and thalamus of autism patients (n = 8) and controls (n = 10) were obtained from Autism Tissue Program, USA. Quantitative real-time PCR arrays were used to quantify gene expression. We observed reduced expression of several ETC genes in autism brains compared to controls. Eleven genes of Complex I, five genes each of Complex III and Complex IV, and seven genes of Complex V showed brain region-specific reduced expression in autism. ATP5A1 (Complex V), ATP5G3 (Complex V) and NDUFA5 (Complex I) showed consistently reduced expression in all the brain regions of autism patients. Upon silencing ATP5A1, the expression of mitogen-activated protein kinase 13 (MAPK13), a p38 MAPK responsive to stress stimuli, was upregulated in HEK 293 cells. This could have been induced by oxidative stress due to impaired ATP synthesis. We report new candidate genes involved in abnormal brain bioenergetics in autism, supporting the hypothesis that mitochondria, critical for neurodevelopment, may play a role in autism. © 2012 The Authors; Brain Pathology © 2012 International Society of Neuropathology.

Enhancement of brain-targeting delivery of danshensu in rat through conjugation with pyrazine moiety to form danshensu-pyrazine ester.

PubMed

Hui, Ailing; Yin, Huayang; Zhang, Zheng; Zhou, An; Chen, Jingchao; Yang, Li; Wu, Zeyu; Zhang, Wencheng

2018-06-01

Tetramethylpyrazine was introduced to the structure of danshensu (DSS) as P-glycoprotein (P-gp)-inhibiting carrier, designing some novel brain-targeting DSS-pyrazine derivatives via prodrug delivery strategy. Following the virtual screening, three DSS-pyrazine esters (DT1, DT2, DT3) were selected because of their better prediction parameters related to brain-targeting. Among them, DT3 was thought to be a promising candidate due to its appropriate bioreversible property in vitro release assay. Further investigation with regard to DT3's brain-targeting effects in vivo was also reported in this study. High-performance liquid chromatography-diode array detection (HPLC-DAD) method was established for the quantitative determination of DT3 and DSS in rat plasma, brain homogenate after intravenous injection. In vivo metabolism of DT3 indicated that it was first converted into DT1, DT2, then the generation of DSS, which could be the result of carboxylesterase activity in rat blood and brain tissue. Moreover, the brain pharmacokinetics of DT3 was significantly altered with 2.16 times increase in half-life compared with that of DSS, and its drug targeting index (DTI) was up to 16.95. Above these data demonstrated that DT3 had better tendency of brain-targeting delivery, which would be positive for the treatment of brain-related disorders.

Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid

PubMed Central

Kozela, Ewa; Juknat, Ana; Vogel, Zvi

2017-01-01

The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. Their precise regulation is still far from understood, although several candidate molecules/systems arise as promising targets for astrocyte-mediated neuroregulation and/or neuroprotection. The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes. Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from Cannabis. CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a number of important effects in the brain. Here, we attempt to sum up the current findings on the effects of CBD on astrocyte activity, and in this way on central nervous system (CNS) functions, across various tested models and neuropathologies. The collected data shows that increased astrocyte activity is suppressed in the presence of CBD in models of ischemia, Alzheimer-like and Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions and signaling in astrocytes. PMID:28788104

Cognitive slowing in Parkinson disease is accompanied by hypofunctioning of the striatum.

PubMed

Sawamoto, N; Honda, M; Hanakawa, T; Aso, T; Inoue, M; Toyoda, H; Ishizu, K; Fukuyama, H; Shibasaki, H

2007-03-27

To investigate whether cognitive slowing in Parkinson disease (PD) reflects disruption of the basal ganglia or dysfunction of the frontal lobe by excluding an influence of abnormal brain activity due to motor deficits. We measured neuronal activity during a verbal mental-operation task with H(2)(15)O PET. This task enabled us to evaluate brain activity change associated with an increase in the cognitive speed without an influence on motor deficits. As the speed of the verbal mental-operation task increased, healthy controls exhibited proportional increase in activities in the anterior striatum and medial premotor cortex, suggesting the involvement of the corticobasal ganglia circuit in normal performance of the task. By contrast, patients with PD lacked an increase in the striatal activity, whereas the medial premotor cortex showed a proportional increase. Although the present study chose a liberal threshold and needs subsequent confirmation, the findings suggest that striatal disruption resulting in abnormal processing in the corticobasal ganglia circuit may contribute to cognitive slowing in Parkinson disease, as is the case in motor slowing.

Modulation of Astrocyte Activity by Cannabidiol, a Nonpsychoactive Cannabinoid.

PubMed

Kozela, Ewa; Juknat, Ana; Vogel, Zvi

2017-07-31

The astrocytes have gained in recent decades an enormous interest as a potential target for neurotherapies, due to their essential and pleiotropic roles in brain physiology and pathology. Their precise regulation is still far from understood, although several candidate molecules/systems arise as promising targets for astrocyte-mediated neuroregulation and/or neuroprotection. The cannabinoid system and its ligands have been shown to interact and affect activities of astrocytes. Cannabidiol (CBD) is the main non-psychotomimetic cannabinoid derived from Cannabis . CBD is devoid of direct CB1 and CB2 receptor activity, but exerts a number of important effects in the brain. Here, we attempt to sum up the current findings on the effects of CBD on astrocyte activity, and in this way on central nervous system (CNS) functions, across various tested models and neuropathologies. The collected data shows that increased astrocyte activity is suppressed in the presence of CBD in models of ischemia, Alzheimer-like and Multiple-Sclerosis-like neurodegenerations, sciatic nerve injury, epilepsy, and schizophrenia. Moreover, CBD has been shown to decrease proinflammatory functions and signaling in astrocytes.

Brain-computer interfaces in the continuum of consciousness.

PubMed

Kübler, Andrea; Kotchoubey, Boris

2007-12-01

To summarize recent developments and look at important future aspects of brain-computer interfaces. Recent brain-computer interface studies are largely targeted at helping severely or even completely paralysed patients. The former are only able to communicate yes or no via a single muscle twitch, and the latter are totally nonresponsive. Such patients can control brain-computer interfaces and use them to select letters, words or items on a computer screen, for neuroprosthesis control or for surfing the Internet. This condition of motor paralysis, in which cognition and consciousness appear to be unaffected, is traditionally opposed to nonresponsiveness due to disorders of consciousness. Although these groups of patients may appear to be very alike, numerous transition states between them are demonstrated by recent studies. All nonresponsive patients can be regarded on a continuum of consciousness which may vary even within short time periods. As overt behaviour is lacking, cognitive functions in such patients can only be investigated using neurophysiological methods. We suggest that brain-computer interfaces may provide a new tool to investigate cognition in disorders of consciousness, and propose a hierarchical procedure entailing passive stimulation, active instructions, volitional paradigms, and brain-computer interface operation.

Loss of proteostasis induced by amyloid beta peptide in brain endothelial cells.

PubMed

Fonseca, Ana Catarina; Oliveira, Catarina R; Pereira, Cláudia F; Cardoso, Sandra M

2014-06-01

Abnormal accumulation of amyloid-β (Aβ) peptide in the brain is a pathological hallmark of Alzheimer's disease (AD). In addition to neurotoxic effects, Aβ also damages brain endothelial cells (ECs) and may thus contribute to the degeneration of cerebral vasculature, which has been proposed as an early pathogenic event in the course of AD and is able to trigger and/or potentiate the neurodegenerative process and cognitive decline. However, the mechanisms underlying Aβ-induced endothelial dysfunction are not completely understood. Here we hypothesized that Aβ impairs protein quality control mechanisms both in the secretory pathway and in the cytosol in brain ECs, leading cells to death. In rat brain RBE4 cells, we demonstrated that Aβ1-40 induces the failure of the ER stress-adaptive unfolded protein response (UPR), deregulates the ubiquitin-proteasome system (UPS) decreasing overall proteasome activity with accumulation of ubiquitinated proteins and impairs the autophagic protein degradation pathway due to failure in the autophagic flux, which culminates in cell demise. In conclusion, Aβ deregulates proteostasis in brain ECs and, as a consequence, these cells die by apoptosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Preliminary study of Alzheimer's Disease diagnosis based on brain electrical signals using wireless EEG

NASA Astrophysics Data System (ADS)

Handayani, N.; Akbar, Y.; Khotimah, S. N.; Haryanto, F.; Arif, I.; Taruno, W. P.

2016-03-01

This research aims to study brain's electrical signals recorded using EEG as a basis for the diagnosis of patients with Alzheimer's Disease (AD). The subjects consisted of patients with AD, and normal subjects are used as the control. Brain signals are recorded for 3 minutes in a relaxed condition and with eyes closed. The data is processed using power spectral analysis, brain mapping and chaos test to observe the level of complexity of EEG's data. The results show a shift in the power spectral in the low frequency band (delta and theta) in AD patients. The increase of delta and theta occurs in lobus frontal area and lobus parietal respectively. However, there is a decrease of alpha activity in AD patients where in the case of normal subjects with relaxed condition, brain alpha wave dominates the posterior area. This is confirmed by the results of brain mapping. While the results of chaos analysis show that the average value of MMLE is lower in AD patients than in normal subjects. The level of chaos associated with neural complexity in AD patients with lower neural complexity is due to neuronal damage caused by the beta amyloid plaques and tau protein in neurons.

WINCS Harmoni: Closed-loop dynamic neurochemical control of therapeutic interventions

NASA Astrophysics Data System (ADS)

Lee, Kendall H.; Lujan, J. Luis; Trevathan, James K.; Ross, Erika K.; Bartoletta, John J.; Park, Hyung Ook; Paek, Seungleal Brian; Nicolai, Evan N.; Lee, Jannifer H.; Min, Hoon-Ki; Kimble, Christopher J.; Blaha, Charles D.; Bennet, Kevin E.

2017-04-01

There has been significant progress in understanding the role of neurotransmitters in normal and pathologic brain function. However, preclinical trials aimed at improving therapeutic interventions do not take advantage of real-time in vivo neurochemical changes in dynamic brain processes such as disease progression and response to pharmacologic, cognitive, behavioral, and neuromodulation therapies. This is due in part to a lack of flexible research tools that allow in vivo measurement of the dynamic changes in brain chemistry. Here, we present a research platform, WINCS Harmoni, which can measure in vivo neurochemical activity simultaneously across multiple anatomical targets to study normal and pathologic brain function. In addition, WINCS Harmoni can provide real-time neurochemical feedback for closed-loop control of neurochemical levels via its synchronized stimulation and neurochemical sensing capabilities. We demonstrate these and other key features of this platform in non-human primate, swine, and rodent models of deep brain stimulation (DBS). Ultimately, systems like the one described here will improve our understanding of the dynamics of brain physiology in the context of neurologic disease and therapeutic interventions, which may lead to the development of precision medicine and personalized therapies for optimal therapeutic efficacy.

Optogenetic stimulation of cholinergic projection neurons as an alternative for deep brain stimulation for Alzheimer's treatment

NASA Astrophysics Data System (ADS)

Mancuso, James; Chen, Yuanxin; Zhao, Zhen; Li, Xuping; Xue, Zhong; Wong, Stephen T. C.

2013-03-01

Deep brain stimulation (DBS) of the cholinergic nuclei has emerged as a powerful potential treatment for neurodegenerative disease and is currently in a clinical trial for Alzheimer's therapy. While effective in treatment for a number of conditions from depression to epilepsy, DBS remains somewhat unpredictable due to the heterogeneity of the projection neurons that are activated, including glutamatergic, GABAergic, and cholinergic neurons, leading to unacceptable side effects ranging from apathy to depression or even suicidal behavior. It would be highly advantageous to confine stimulation to specific populations of neurons, particularly in brain diseases involving complex network interactions such as Alzheimer's. Optogenetics, now firmly established as an effective approach to render genetically-defined populations of cells sensitive to light activation including mice expressing Channelrhodopsin-2 specifically in cholinergic neurons, provides just this opportunity. Here we characterize the light activation properties and cell density of cholinergic neurons in healthy mice and mouse models of Alzheimer's disease in order to evaluate the feasibility of using optogenetic modulation of cholinergic synaptic activity to slow or reverse neurodegeneration. This paper is one of the very first reports to suggest that, despite the anatomical depth of their cell bodies, cholinergic projection neurons provide a better target for systems level optogenetic modulation than cholinergic interneurons found in various brain regions including striatum and the cerebral cortex. Additionally, basal forebrain channelrhodopsin-expressing cholinergic neurons are shown to exhibit normal distribution at 60 days and normal light activation at 40 days, the latest timepoints observed. The data collected form the basis of ongoing computational modeling of light stimulation of entire populations of cholinergic neurons.

Impact of a microRNA MIR137 Susceptibility Variant on Brain Function in People at High Genetic Risk of Schizophrenia or Bipolar Disorder

PubMed Central

Whalley, Heather C; Papmeyer, Martina; Romaniuk, Liana; Sprooten, Emma; Johnstone, Eve C; Hall, Jeremy; Lawrie, Stephen M; Evans, Kathryn L; Blumberg, Hilary P; Sussmann, Jessika E; McIntosh, Andrew M

2012-01-01

A recent ‘mega-analysis' combining genome-wide association study data from over 40 000 individuals identified novel genetic loci associated with schizophrenia (SCZ) at genome-wide significance level. The strongest finding was a locus within an intron of a putative primary transcript for microRNA MIR137. In the current study, we examine the impact of variation at this locus (rs1625579, G/T; where T is the common and presumed risk allele) on brain activation during a sentence completion task that differentiates individuals with SCZ, bipolar disorder (BD), and their relatives from controls. We examined three groups of individuals performing a sentence completion paradigm: (i) individuals at high genetic risk of SCZ (n=44), (ii) individuals at high genetic risk of BD (n=90), and (iii) healthy controls (n=81) in order to test the hypothesis that genotype at rs1625579 would influence brain activation. Genotype groups were assigned as ‘RISK−' for GT and GG individuals, and ‘RISK+' for TT homozygotes. The main effect of genotype was significantly greater activation in the RISK− individuals in the posterior right medial frontal gyrus, BA 6. There was also a significant genotype*group interaction in the left amygdala and left pre/postcentral gyrus. This was due to differences between the controls (where individuals with the RISK− genotype showed greater activation than RISK+ subjects) and the SCZ high-risk group, where the opposite genotype effect was seen. These results suggest that the newly identified SCZ locus may influence brain activation in a manner that is partly dependent on the presence of existing genetic susceptibility for SCZ. PMID:22850735

In vitro investigation of efficacy of new reactivators on OPC inhibited rat brain acetylcholinesterase.

PubMed

Atanasov, Vasil N; Petrova, Iskra; Dishovsky, Christophor

2013-03-25

Organophosphorus compounds (OPC) were developed as warfare nerve agents. They are also widely used as pesticides. The drug therapy of intoxication with OPC includes mainly combination of cholinesterase (ChE) reactivators and cholinolytics. There is no single ChE reactivator having an ability to reactivate sufficiently the inhibited enzyme due to the high variability of chemical structure of the inhibitors. The difficulties in reactivation of ChE activity and slight antidote effect regarding intoxication with some OPC are some of the reasons for continuous efforts to obtain new reactivators of ChE. The aim of the present study was to evaluate the efficacy of some ChE reactivators against OPC intoxication (tabun, paraoxon and dichlorvos) in in vitro experiments and to compare their activity to that known for some currently used oximes (obidoxime, HI-6, 2-PAM). Experiments were carried out using rat brain acetylcholinesterase (AChE). Reactivators showed different activity in the reactivation of rat brain AChE after dichlorvos, paraoxon and tabun inhibition. AChE was easier reactivated after paraoxon treatment. The best effect showed BT-07-4M, obidoxime, TMB-4 and BT-08 from the group of symmetric oximes, and Toxidin, BT-05 and BT-03 from asymmetric compounds. The reactivation of brain AChE inhibited with tabun demonstrated better activity of new compound BT-07-4M, TMB-4 and obidoxime from symmetric oximes, and BT-05 and BT-03 possessing asymmetric structure. All compounds showed low activity toward inhibition of AChE caused by dichlorvos. Comparison of two main structure types (symmetric/asymmetric) showed that the symmetric compounds reactivated better AChE, inhibited with this OPC, than asymmetric ones. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Temporally Specific Divided Attention Tasks in Young Adults Reveal the Temporal Dynamics of Episodic Encoding Failures in Elderly Adults

PubMed Central

Johnson, Ray; Nessler, Doreen; Friedman, David

2013-01-01

Nessler, Johnson, Bersick, and Friedman (D. Nessler, R. Johnson, Jr., M. Bersick, & D. Friedman, 2006, On why the elderly have normal semantic retrieval but deficient episodic encoding: A study of left inferior frontal ERP activity, NeuroImage, Vol. 30, pp. 299–312) found that, compared with young adults, older adults show decreased event-related brain potential (ERP) activity over posterior left inferior prefrontal cortex (pLIPFC) in a 400- to 1,400-ms interval during episodic encoding. This altered brain activity was associated with significantly decreased recognition performance and reduced recollection-related brain activity at retrieval (D. Nessler, D. Friedman, R. Johnson, Jr., & M. Bersick, 2007, Does repetition engender the same retrieval processes in young and older adults? NeuroReport, Vol. 18, pp. 1837–1840). To test the hypothesis that older adults’ well-documented episodic retrieval deficit is related to reduced pLIPFC activity at encoding, we used a novel divided attention task in healthy young adults that was specifically timed to disrupt encoding in either the 1st or 2nd half of a 300- to 1,400-ms interval. The results showed that diverting resources for 550 ms during either half of this interval reproduced the 4 characteristic aspects of the older participants’ retrieval performance: normal semantic retrieval during encoding, reduced subsequent episodic recognition and recall, reduced recollection-related ERP activity, and the presence of “compensatory” brain activity. We conclude that part of older adults’ episodic memory deficit is attributable to altered pLIPFC activity during encoding due to reduced levels of available processing resources. Moreover, the findings also provide insights into the nature and timing of the putative “compensatory” processes posited to be used by older adults in an attempt to compensate for age-related decline in cognitive function. These results support the scaffolding account of compensation, in which the recruitment of additional cognitive processes is an adaptive response across the life span. PMID:23276214

How structure sculpts function: Unveiling the contribution of anatomical connectivity to the brain's spontaneous correlation structure

NASA Astrophysics Data System (ADS)

Bettinardi, R. G.; Deco, G.; Karlaftis, V. M.; Van Hartevelt, T. J.; Fernandes, H. M.; Kourtzi, Z.; Kringelbach, M. L.; Zamora-López, G.

2017-04-01

Intrinsic brain activity is characterized by highly organized co-activations between different regions, forming clustered spatial patterns referred to as resting-state networks. The observed co-activation patterns are sustained by the intricate fabric of millions of interconnected neurons constituting the brain's wiring diagram. However, as for other real networks, the relationship between the connectional structure and the emergent collective dynamics still evades complete understanding. Here, we show that it is possible to estimate the expected pair-wise correlations that a network tends to generate thanks to the underlying path structure. We start from the assumption that in order for two nodes to exhibit correlated activity, they must be exposed to similar input patterns from the entire network. We then acknowledge that information rarely spreads only along a unique route but rather travels along all possible paths. In real networks, the strength of local perturbations tends to decay as they propagate away from the sources, leading to a progressive attenuation of the original information content and, thus, of their influence. Accordingly, we define a novel graph measure, topological similarity, which quantifies the propensity of two nodes to dynamically correlate as a function of the resemblance of the overall influences they are expected to receive due to the underlying structure of the network. Applied to the human brain, we find that the similarity of whole-network inputs, estimated from the topology of the anatomical connectome, plays an important role in sculpting the backbone pattern of time-average correlations observed at rest.

rTMS Induced Tinnitus Relief Is Related to an Increase in Auditory Cortical Alpha Activity

PubMed Central

Müller, Nadia; Lorenz, Isabel; Langguth, Berthold; Weisz, Nathan

2013-01-01

Chronic tinnitus, the continuous perception of a phantom sound, is a highly prevalent audiological symptom. A promising approach for the treatment of tinnitus is repetitive transcranial magnetic stimulation (rTMS) as this directly affects tinnitus-related brain activity. Several studies indeed show tinnitus relief after rTMS, however effects are moderate and vary strongly across patients. This may be due to a lack of knowledge regarding how rTMS affects oscillatory activity in tinnitus sufferers and which modulations are associated with tinnitus relief. In the present study we examined the effects of five different stimulation protocols (including sham) by measuring tinnitus loudness and tinnitus-related brain activity with Magnetoencephalography before and after rTMS. Changes in oscillatory activity were analysed for the stimulated auditory cortex as well as for the entire brain regarding certain frequency bands of interest (delta, theta, alpha, gamma). In line with the literature the effects of rTMS on tinnitus loudness varied strongly across patients. This variability was also reflected in the rTMS effects on oscillatory activity. Importantly, strong reductions in tinnitus loudness were associated with increases in alpha power in the stimulated auditory cortex, while an unspecific decrease in gamma and alpha power, particularly in left frontal regions, was linked to an increase in tinnitus loudness. The identification of alpha power increase as main correlate for tinnitus reduction sheds further light on the pathophysiology of tinnitus. This will hopefully stimulate the development of more effective therapy approaches. PMID:23390539

Prism adaptation enhances activity of intact fronto-parietal areas in both hemispheres in neglect patients.

PubMed

Saj, Arnaud; Cojan, Yann; Vocat, Roland; Luauté, Jacques; Vuilleumier, Patrik

2013-01-01

Unilateral spatial neglect involves a failure to report or orient to stimuli in the contralesional (left) space due to right brain damage, with severe handicap in everyday activities and poor rehabilitation outcome. Because behavioral studies suggest that prism adaptation may reduce spatial neglect, we investigated the neural mechanisms underlying prism effects on visuo-spatial processing in neglect patients. We used functional magnetic resonance imaging (fMRI) to examine the effect of (right-deviating) prisms on seven patients with left neglect, by comparing brain activity while they performed three different spatial tasks on the same visual stimuli (bisection, search, and memory), before and after a single prism-adaptation session. Following prism adaptation, fMRI data showed increased activation in bilateral parietal, frontal, and occipital cortex during bisection and visual search, but not during the memory task. These increases were associated with significant behavioral improvement in the same two tasks. Changes in neural activity and behavior were seen only after prism adaptation, but not attributable to mere task repetition. These results show for the first time the neural substrates underlying the therapeutic benefits of prism adaptation, and demonstrate that visuo-motor adaptation induced by prism exposure can restore activation in bilateral brain networks controlling spatial attention and awareness. This bilateral recruitment of fronto-parietal networks may counteract the pathological biases produced by unilateral right hemisphere damage, consistent with recent proposals that neglect may reflect lateralized deficits induced by bilateral hemispheric dysfunction. Copyright © 2011 Elsevier Ltd. All rights reserved.

Relationships between years of education, regional grey matter volumes, and working memory-related brain activity in healthy older adults.

PubMed

Boller, Benjamin; Mellah, Samira; Ducharme-Laliberté, Gabriel; Belleville, Sylvie

2017-04-01

The aim of this study was to examine the relationships between educational attainment, regional grey matter volume, and functional working memory-related brain activation in older adults. The final sample included 32 healthy older adults with 8 to 22 years of education. Structural magnetic resonance imaging (MRI) was used to measure regional volume and functional MRI was used to measure activation associated with performing an n-back task. A positive correlation was found between years of education and cortical grey matter volume in the right medial and middle frontal gyri, in the middle and posterior cingulate gyri, and in the right inferior parietal lobule. The education by age interaction was significant for cortical grey matter volume in the left middle frontal gyrus and in the right medial cingulate gyrus. In this region, the volume loss related to age was larger in the low than high-education group. The education by age interaction was also significant for task-related activity in the left superior, middle and medial frontal gyri due to the fact that activation increased with age in those with higher education. No correlation was found between regions that are structurally related with education and those that are functionally related with education and age. The data suggest a protective effect of education on cortical volume. Furthermore, the brain regions involved in the working memory network are getting more activated with age in those with higher educational attainment.

Effect of Dimethoate (Rogor 30% EC) on the brain neurosecretory cells of third instar grubs of Oryctes rhinoceros L. (Coleoptera : Scarabaeidae).

PubMed

Padmasheela, N C; Delvi, M R

2004-10-01

The brain neurosecretory cells of III instar grubs of Oryctes rhinoceros were exposed to insecticide Dimethoate (Rogor 30% EC) in the laboratory condition. The sublethal doses (0.125, 0.25 and 0.5%) of Rogor at time intervals of 8, 16 and 24 h have produced marked changes in the structure and the secretory activities of medial and lateral neurosecretory cells. Rogor stimulates the synthetic activity of these cells at the initial stages of its action and results in the accumulation of neurosecretory materials (NSM) in the cytoplasm. The decreased neurosecretion at later stages of the action was due to its transportation through the axons before the death of treated grubs. Similarly, vacuolization, shrinking and degeneration of cells were also observed in treated grubs.

Importance of Video-EEG Monitoring in the Diagnosis of Epilepsy in a Psychiatric Patient

PubMed Central

Kirmani, Batool F.

2013-01-01

Epilepsy is a chronic medical condition which is disabling to both patients and caregivers. The differential diagnosis of epilepsy includes psychogenic nonepileptic spells or “pseudoseizures.” Epilepsy is due to abnormal electrical activity in the brain, and pseudoseizure is a form of conversion disorder. The brain waves remain normal in pseudoseizures. The problem arises when a patient with significant psychiatric history presents with seizures. Pseudoseizures become high on the differential diagnosis without extensive work up. This is a case of woman with significant psychiatric issues which resulted in a delay in the diagnosis of epilepsy. PMID:23585974

Mind and Language Architecture

PubMed Central

Logan, Robert K

2010-01-01

A distinction is made between the brain and the mind. The architecture of the mind and language is then described within a neo-dualistic framework. A model for the origin of language based on emergence theory is presented. The complexity of hominid existence due to tool making, the control of fire and the social cooperation that fire required gave rise to a new level of order in mental activity and triggered the simultaneous emergence of language and conceptual thought. The mind is shown to have emerged as a bifurcation of the brain with the emergence of language. The role of language in the evolution of human culture is also described. PMID:20922045

Overview of non-pharmacological intervention for dementia and principles of brain-activating rehabilitation.

PubMed

Yamaguchi, Haruyasu; Maki, Yohko; Yamagami, Tetsuya

2010-12-01

Non-pharmacological interventions for dementia are likely to have an important role in delaying disease progression and functional decline. Research into non-pharmacological interventions has focused on the differentiation of each approach and a comparison of their effects. However, Cochrane Reviews on non-pharmacological interventions have noted the paucity of evidence regarding the effects of these interventions. The essence of non-pharmacological intervention is dependent of the patients, families, and therapists involved, with each situation inevitably being different. To obtain good results with non-pharmacological therapy, the core is not 'what' approach is taken but 'how' the therapists communicate with their patients. Here, we propose a new type of rehabilitation for dementia, namely brain-activating rehabilitation, that consists of five principles: (i) enjoyable and comfortable activities in an accepting atmosphere; (ii) activities associated with empathetic two-way communication between the therapist and patient, as well as between patients; (iii) therapists should praise patients to enhance motivation; (iv) therapists should try to offer each patient some social role that takes advantage of his/her remaining abilities; and (v) the activities should be based on errorless learning to ensure a pleasant atmosphere and to maintain a patient's dignity. The behavioral and cognitive status is not necessarily a reflection of pathological lesions in the brain; there is cognitive reserve for improvement. The aim of brain-activating rehabilitation is to enhance patients' motivation and maximize the use of their remaining function, recruiting a compensatory network, and preventing the disuse of brain function. The primary expected effect is that patients recover a desire for life, as well as their self-respect. Enhanced motivation can lead to improvements in cognitive function. Amelioration of the behavioral and psychological symptoms of dementia and improvements in activities of daily living can also be expected due to the renewed positive attitude towards life. In addition, improvements in the quality of life for both patients and caregivers is an expected outcome. To establish evidence for non-pharmacological interventions, research protocols and outcome measures should be standardized to facilitate comparison among studies, as well as meta-analysis. © 2010 The Authors. Journal compilation © 2010 Japanese Psychogeriatric Society.

Activation of PAF-synthesizing enzymes in rat brain stem slices after LTP induction in the medial vestibular nuclei.

PubMed

Francescangeli, Ermelinda; Grassi, Silvarosa; Pettorossi, Vito E; Goracci, Gianfrancesco

2002-11-01

LysoPAF acetyltransferase (lysoPAF-AT) and PAF-synthesizing phosphocholinetransferase (PAF-PCT) are the two enzymes which catalyze the final reactions for the synthesis of PAF. Their activities, assayed in the homogenate of rat brain stem slices and under their optimal conditions, increased 5 min after high frequency stimulation of vestibular afferents, inducing LTP in the medial vestibular nuclei. The activity of phosphatidylcholine-synthesizing phosphocholinetransferase, was not affected. Sixty minutes from the induction of LTP, PAF-PCT activity, but not that of lysoPAF-AT, was still significantly higher with respect to 5 min test stimulated control. We used AP-5 to verify whether this increase was strictly dependent upon LTP induction, which requires NMDA receptor activation. In AP-5 treated slices, lysoPAF-acetyltransferase and PAF-synthesizing phosphocholinetransferase activities increased, but they were reduced after high frequency stimulation under AP-5. In conclusion, we have demonstrated that the activities of PAF-synthesizing enzymes are activated soon after the induction of LTP and that this effect is linked to the activation of NMDA-receptors. We suggest that the enzyme activation by AP-5, preventing LTP, might be due to glutamate enhancement but, in neurons showing LTP and under normal conditions, the activation of potentiation mechanisms is critical for the enhancement of enzyme activities.

Automatic Speech Recognition from Neural Signals: A Focused Review.

PubMed

Herff, Christian; Schultz, Tanja

2016-01-01

Speech interfaces have become widely accepted and are nowadays integrated in various real-life applications and devices. They have become a part of our daily life. However, speech interfaces presume the ability to produce intelligible speech, which might be impossible due to either loud environments, bothering bystanders or incapabilities to produce speech (i.e., patients suffering from locked-in syndrome). For these reasons it would be highly desirable to not speak but to simply envision oneself to say words or sentences. Interfaces based on imagined speech would enable fast and natural communication without the need for audible speech and would give a voice to otherwise mute people. This focused review analyzes the potential of different brain imaging techniques to recognize speech from neural signals by applying Automatic Speech Recognition technology. We argue that modalities based on metabolic processes, such as functional Near Infrared Spectroscopy and functional Magnetic Resonance Imaging, are less suited for Automatic Speech Recognition from neural signals due to low temporal resolution but are very useful for the investigation of the underlying neural mechanisms involved in speech processes. In contrast, electrophysiologic activity is fast enough to capture speech processes and is therefor better suited for ASR. Our experimental results indicate the potential of these signals for speech recognition from neural data with a focus on invasively measured brain activity (electrocorticography). As a first example of Automatic Speech Recognition techniques used from neural signals, we discuss the Brain-to-text system.

The impact of symptomatic mild traumatic brain injury on complex everyday activities and the link with alterations in cerebral functioning: Exploratory case studies.

PubMed

Bottari, Carolina; Gosselin, Nadia; Chen, Jen-Kai; Ptito, Alain

2017-07-01

The objective of the study was to explore the neurophysiological correlates of altered functional independence using functional magnetic resonance imaging (fMRI) and event-related potentials (ERP) after a mild traumatic brain injury (mTBI). The participants consisted of three individuals with symptomatic mTBI (3.9 ± 3.6 months post-mTBI) and 12 healthy controls. The main measures used were the Instrumental Activities of Daily Living (IADL) Profile observation-based assessment; a visual externally ordered working memory task combined to event-related potentials (ERP) and fMRI recordings; neuropsychological tests; post-concussion symptoms questionnaires; and the Activities of Daily Living (ADL) Profile interview. Compared to normal controls, all three patients had difficulty with a real-world complex budgeting activity due to deficits in planning, ineffective strategy use and/or a prolonged time to detect and correct errors. Reduced activations in the right mid-dorsolateral prefrontal cortex on fMRI as well as abnormal frontal or parietal components of the ERP occurred alongside these deficits. Results of this exploratory study suggest that reduced independence in complex everyday activities in symptomatic mTBI may be at least partly explained by a decrease in brain activation in the prefrontal cortex, abnormal ERP, or slower reaction times on working memory tasks. The study presents an initial attempt at combining research in neuroscience with ecological real-world evaluation research to further our understanding of the difficulties in complex everyday activities experienced by individuals with mTBI.

Altered neural activity and emotions following right middle cerebral artery stroke.

PubMed

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

2011-01-01

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. Brain activity during presentation of emotional stimuli was measured in 6 patients with stable stroke, and in 12 age- and sex-matched nonlesion comparisons using positron emission tomography and the [(15)O]H(2)O autoradiographic method. 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. 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. Copyright © 2011 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Dual-slit confocal light sheet microscopy for in vivo whole-brain imaging of zebrafish

PubMed Central

Yang, Zhe; Mei, Li; Xia, Fei; Luo, Qingming; Fu, Ling; Gong, Hui

2015-01-01

In vivo functional imaging at single-neuron resolution is an important approach to visualize biological processes in neuroscience. Light sheet microscopy (LSM) is a cutting edge in vivo imaging technique that provides micron-scale spatial resolution at high frame rate. Due to the scattering and absorption of tissue, however, conventional LSM is inadequate to resolve cells because of the attenuated signal to noise ratio (SNR). Using dual-beam illumination and confocal dual-slit detection, here a dual-slit confocal LSM is demonstrated to obtain the SNR enhanced images with frame rate twice as high as line confocal LSM method. Through theoretical calculations and experiments, the correlation between the slit’s width and SNR was determined to optimize the image quality. In vivo whole brain structural imaging stacks and the functional imaging sequences of single slice were obtained for analysis of calcium activities at single-cell resolution. A two-fold increase in imaging speed of conventional confocal LSM makes it possible to capture the sequence of the neurons’ activities and help reveal the potential functional connections in the whole zebrafish’s brain. PMID:26137381

Identification of Cerebral Metal Ion Imbalance in the Brain of Aging Octodon degus

PubMed Central

Braidy, Nady; Poljak, Anne; Marjo, Chris; Rutlidge, Helen; Rich, Anne; Jugder, Bat-Erdene; Jayasena, Tharusha; Inestrosa, Nibaldo C.; Sachdev, Perminder S.

2017-01-01

The accumulation of redox-active transition metals in the brain and metal dyshomeostasis are thought to be associated with the etiology and pathogenesis of several neurodegenerative diseases, and Alzheimer’s disease (AD) in particular. As well, distinct biometal imaging and role of metal uptake transporters are central to understanding AD pathogenesis and aging but remain elusive, due inappropriate detection methods. We therefore hypothesized that Octodon degus develop neuropathological abnormalities in the distribution of redox active biometals, and this effect may be due to alterations in the expression of lysosomal protein, major Fe/Cu transporters, and selected Zn transporters (ZnTs and ZIPs). Herein, we report the distribution profile of biometals in the aged brain of the endemic Chilean rodent O. degus—a natural model to investigate the role of metals on the onset and progression of AD. Using laser ablation inductively coupled plasma mass spectrometry, our quantitative images of biometals (Fe, Ca, Zn, Cu, and Al) appear significantly elevated in the aged O. degus and show an age-dependent rise. The metals Fe, Ca, Zn, and Cu were specifically enriched in the cortex and hippocampus, which are the regions where amyloid plaques, tau phosphorylation and glial alterations are most commonly reported, whilst Al was enriched in the hippocampus alone. Using whole brain extracts, age-related deregulation of metal trafficking pathways was also observed in O. degus. More specifically, we observed impaired lysosomal function, demonstrated by increased cathepsin D protein expression. An age-related reduction in the expression of subunit B2 of V-ATPase, and significant increases in amyloid beta peptide 42 (Aβ42), and the metal transporter ATP13a2 were also observed. Although the protein expression levels of the zinc transporters, ZnT (1,3,4,6, and 7), and ZIP7,8 and ZIP14 increased in the brain of aged O. degus, ZnT10, decreased. Although no significant age-related change was observed for the major iron/copper regulator IRP2, we did find a significant increase in the expression of DMT1, a major transporter of divalent metal species, 5′-aminolevulinate synthase 2 (ALAS2), and the proto-oncogene, FOS. Collectively, our data indicate that transition metals may be enriched with age in the brains of O. degus, and metal dyshomeostasis in specific brain regions is age-related. PMID:28405187

Mapping social behavior-induced brain activation at cellular resolution in the mouse

PubMed Central

Kim, Yongsoo; Venkataraju, Kannan Umadevi; Pradhan, Kith; Mende, Carolin; Taranda, Julian; Turaga, Srinivas C.; Arganda-Carreras, Ignacio; Ng, Lydia; Hawrylycz, Michael J.; Rockland, Kathleen; Seung, H. Sebastian; Osten, Pavel

2014-01-01

Understanding how brain activation mediates behaviors is a central goal of systems neuroscience. Here we apply an automated method for mapping brain activation in the mouse in order to probe how sex-specific social behaviors are represented in the male brain. Our method uses the immediate early gene c-fos, a marker of neuronal activation, visualized by serial two-photon tomography: the c-fos-GFP-positive neurons are computationally detected, their distribution is registered to a reference brain and a brain atlas, and their numbers are analyzed by statistical tests. Our results reveal distinct and shared female and male interaction-evoked patterns of male brain activation representing sex discrimination and social recognition. We also identify brain regions whose degree of activity correlates to specific features of social behaviors and estimate the total numbers and the densities of activated neurons per brain areas. Our study opens the door to automated screening of behavior-evoked brain activation in the mouse. PMID:25558063

Thyroid Hormone Availability and Action during Brain Development in Rodents

PubMed Central

Bárez-López, Soledad; Guadaño-Ferraz, Ana

2017-01-01

Thyroid hormones (THs) play an essential role in the development of all vertebrates; in particular adequate TH content is crucial for proper neurodevelopment. TH availability and action in the brain are precisely regulated by several mechanisms, including the secretion of THs by the thyroid gland, the transport of THs to the brain and neural cells, THs activation and inactivation by the metabolic enzymes deiodinases and, in the fetus, transplacental passage of maternal THs. Although these mechanisms have been extensively studied in rats, in the last decade, models of genetically modified mice have been more frequently used to understand the role of the main proteins involved in TH signaling in health and disease. Despite this, there is little knowledge about the mechanisms underlying THs availability in the mouse brain. This mini-review article gathers information from findings in rats, and the latest findings in mice regarding the ontogeny of TH action and the sources of THs to the brain, with special focus on neurodevelopmental stages. Unraveling TH economy and action in the mouse brain may help to better understand the physiology and pathophysiology of TH signaling in brain and may contribute to addressing the neurological alterations due to hypo and hyperthyroidism and TH resistance syndromes. PMID:28855863

Functional brain networks for learning predictive statistics.

PubMed

Giorgio, Joseph; Karlaftis, Vasilis M; Wang, Rui; Shen, Yuan; Tino, Peter; Welchman, Andrew; Kourtzi, Zoe

2017-08-18

Making predictions about future events relies on interpreting streams of information that may initially appear incomprehensible. This skill relies on extracting regular patterns in space and time by mere exposure to the environment (i.e., without explicit feedback). Yet, we know little about the functional brain networks that mediate this type of statistical learning. Here, we test whether changes in the processing and connectivity of functional brain networks due to training relate to our ability to learn temporal regularities. By combining behavioral training and functional brain connectivity analysis, we demonstrate that individuals adapt to the environment's statistics as they change over time from simple repetition to probabilistic combinations. Further, we show that individual learning of temporal structures relates to decision strategy. Our fMRI results demonstrate that learning-dependent changes in fMRI activation within and functional connectivity between brain networks relate to individual variability in strategy. In particular, extracting the exact sequence statistics (i.e., matching) relates to changes in brain networks known to be involved in memory and stimulus-response associations, while selecting the most probable outcomes in a given context (i.e., maximizing) relates to changes in frontal and striatal networks. Thus, our findings provide evidence that dissociable brain networks mediate individual ability in learning behaviorally-relevant statistics. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Magnetite pollution nanoparticles in the human brain

NASA Astrophysics Data System (ADS)

Maher, Barbara A.; Ahmed, Imad A. M.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

2016-09-01

Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <˜200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

Magnetite pollution nanoparticles in the human brain.

PubMed

Maher, Barbara A; Ahmed, Imad A M; Karloukovski, Vassil; MacLaren, Donald A; Foulds, Penelope G; Allsop, David; Mann, David M A; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

2016-09-27

Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683-7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health.

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain

PubMed Central

Haider, Lukas; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang

2016-01-01

Abstract Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. PMID:26912645

Assembling the Puzzle: Pathways of Oxytocin Signaling in the Brain.

PubMed

Grinevich, Valery; Knobloch-Bollmann, H Sophie; Eliava, Marina; Busnelli, Marta; Chini, Bice

2016-02-01

Oxytocin (OT) is a neuropeptide, which can be seen to be one of the molecules of the decade due to its profound prosocial effects in nonvertebrate and vertebrate species, including humans. Although OT can be detected in various physiological fluids (blood, saliva, urine, cerebrospinal fluid) and brain tissue, it is unclear whether peripheral and central OT releases match and synergize. Moreover, the pathways of OT delivery to brain regions involved in specific behaviors are far from clear. Here, we discuss the evolutionarily and ontogenetically determined pathways of OT delivery and OT signaling, which orchestrate activity of the mesolimbic social decision-making network. Furthermore, we speculate that both the alteration in OT delivery and OT receptor expression may cause behavioral abnormalities in patients afflicted with psychosocial diseases. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Evaluation of the antagonism of nicotine by mecamylamine and pempidine in the brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Martin, T.J.

1989-01-01

Antagonists have been crucial in the characterization of nicotine's pharmacology. Initial evidence for the existence of central nicotinic receptors was based on the fact that nicotine produced a number of behavioral effects that were antagonized by ganglionic blockers that crossed the blood-brain barrier, such as mecamylamine and pempidine. These compounds are thought to be noncompetitive antagonists due to the fact that they do not compete for agonist binding to brain homogenate in vitro. However, pharmacological evidence in support of noncompetitive antagonism is lacking. Dose-response curves for nicotine were determined in the presence of various doses of pempidine for depression ofmore » spontaneous activity and antinociception in mice. Pempidine was found to shift the dose response curves for these effects of nicotine in a manner consistent with noncompetitive antagonism. A number of mecamylamine analogs were investigated for antagonism of these central effects of nicotine as well. These studies revealed that the N-, 2-, and 3-methyls were crucial for optimal efficacy and potency and suggests that these compounds possess a specific mechanism of action, possibly involving a receptor. Furthermore, the structure-activity relationships for the mecamylamine analogs were found to be different than that previously reported for the agonists, suggesting that they do not act at the same site. The binding of ({sup 3} H)-L-nicotine and ({sup 3}H)-pempidine was studied in vitro to mouse brain homogentate and in situ to rat brain slices. The in situ binding of ({sup 3}H)-L-nicotine to rat brain slices was quantitated autoradiographically to discrete brain areas in the presence and absence of 1, 10 and 100 {mu}M nicotine and pempidine. Pempidine did not effectively displace ({sup 3}H)-L-nicotine binding.« less

Ketamine induces a robust whole-brain connectivity pattern that can be differentially modulated by drugs of different mechanism and clinical profile.

PubMed

Joules, R; Doyle, O M; Schwarz, A J; O'Daly, O G; Brammer, M; Williams, S C; Mehta, M A

2015-11-01

Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, has been studied in relation to the glutamate hypothesis of schizophrenia and increases dissociation, positive and negative symptom ratings. Ketamine effects brain function through changes in brain activity; these activity patterns can be modulated by pre-treatment of compounds known to attenuate the effects of ketamine on glutamate release. Ketamine also has marked effects on brain connectivity; we predicted that these changes would also be modulated by compounds known to attenuate glutamate release. Here, we perform task-free pharmacological magnetic resonance imaging (phMRI) to investigate the functional connectivity effects of ketamine in the brain and the potential modulation of these effects by pre-treatment of the compounds lamotrigine and risperidone, compounds hypothesised to differentially modulate glutamate release. Connectivity patterns were assessed by combining windowing, graph theory and multivariate Gaussian process classification. We demonstrate that ketamine has a robust effect on the functional connectivity of the human brain compared to saline (87.5 % accuracy). Ketamine produced a shift from a cortically centred, to a subcortically centred pattern of connections. This effect is strongly modulated by pre-treatment with risperidone (81.25 %) but not lamotrigine (43.75 %). Based on the differential effect of these compounds on ketamine response, we suggest the observed connectivity effects are primarily due to NMDAR blockade rather than downstream glutamatergic effects. The connectivity changes contrast with amplitude of response for which no differential effect between pre-treatments was detected, highlighting the necessity of these techniques in forming an informed view of the mechanistic effects of pharmacological compounds in the human brain.

Prefrontal Cortex Structure Predicts Training-Induced Improvements in Multitasking Performance.

PubMed

Verghese, Ashika; Garner, K G; Mattingley, Jason B; Dux, Paul E

2016-03-02

The ability to perform multiple, concurrent tasks efficiently is a much-desired cognitive skill, but one that remains elusive due to the brain's inherent information-processing limitations. Multitasking performance can, however, be greatly improved through cognitive training (Van Selst et al., 1999, Dux et al., 2009). Previous studies have examined how patterns of brain activity change following training (for review, see Kelly and Garavan, 2005). Here, in a large-scale human behavioral and imaging study of 100 healthy adults, we tested whether multitasking training benefits, assessed using a standard dual-task paradigm, are associated with variability in brain structure. We found that the volume of the rostral part of the left dorsolateral prefrontal cortex (DLPFC) predicted an individual's response to training. Critically, this association was observed exclusively in a task-specific training group, and not in an active-training control group. Our findings reveal a link between DLPFC structure and an individual's propensity to gain from training on a task that taps the limits of cognitive control. Cognitive "brain" training is a rapidly growing, multibillion dollar industry (Hayden, 2012) that has been touted as the panacea for a variety of disorders that result in cognitive decline. A key process targeted by such training is "cognitive control." Here, we combined an established cognitive control measure, multitasking ability, with structural brain imaging in a sample of 100 participants. Our goal was to determine whether individual differences in brain structure predict the extent to which people derive measurable benefits from a cognitive training regime. Ours is the first study to identify a structural brain marker-volume of left hemisphere dorsolateral prefrontal cortex-associated with the magnitude of multitasking performance benefits induced by training at an individual level. Copyright © 2016 the authors 0270-6474/16/362638-08$15.00/0.

A designed recombinant fusion protein for targeted delivery of siRNA to the mouse brain.

PubMed

Haroon, Mohamed Mohamed; Dar, Ghulam Hassan; Jeyalakshmi, Durga; Venkatraman, Uthra; Saba, Kamal; Rangaraj, Nandini; Patel, Anant Bahadur; Gopal, Vijaya

2016-04-28

RNA interference represents a novel therapeutic approach to modulate several neurodegenerative disease-related genes. However, exogenous delivery of siRNA restricts their transport into different tissues and specifically into the brain mainly due to its large size and the presence of the blood-brain barrier (BBB). To overcome these challenges, we developed here a strategy wherein a peptide known to target specific gangliosides was fused to a double-stranded RNA binding protein to deliver siRNA to the brain parenchyma. The designed fusion protein designated as TARBP-BTP consists of a double-stranded RNA-binding domain (dsRBD) of human Trans Activation response element (TAR) RNA Binding Protein (TARBP2) fused to a brain targeting peptide that binds to monosialoganglioside GM1. Conformation-specific binding of TARBP2 domain to siRNA led to the formation of homogenous serum-stable complex with targeting potential. Further, uptake of the complex in Neuro-2a, IMR32 and HepG2 cells analyzed by confocal microscopy and fluorescence activated cell sorting, revealed selective requirement of GM1 for entry. Remarkably, systemic delivery of the fluorescently labeled complex (TARBP-BTP:siRNA) in ΑβPP-PS1 mouse model of Alzheimer's disease (AD) led to distinctive localization in the cerebral hemisphere. Further, the delivery of siRNA mediated by TARBP-BTP led to significant knockdown of BACE1 in the brain, in both ΑβPP-PS1 mice and wild type C57BL/6. The study establishes the growing importance of fusion proteins in delivering therapeutic siRNA to brain tissues. Copyright © 2016 Elsevier B.V. All rights reserved.

Blood-brain barrier dysfunction in mice induced by lipopolysaccharide is attenuated by dapsone.

PubMed

Zhou, Ting; Zhao, Lei; Zhan, Rui; He, Qihua; Tong, Yawei; Tian, Xiaosheng; Wang, Hecheng; Zhang, Tao; Fu, Yaoyun; Sun, Yang; Xu, Feng; Guo, Xiangyang; Fan, Dongsheng; Han, Hongbin; Chui, Dehua

2014-10-24

Blood-brain barrier (BBB) dysfunction is a key event in the development of many central nervous system (CNS) diseases, such as septic encephalopathy and stroke. 4,4'-Diaminodiphenylsulfone (DDS, Dapsone) has displayed neuroprotective effect, but whether DDS has protective role on BBB integrity is not clear. This study was designed to examine the effect of DDS on lipopolysaccharide (LPS)-induced BBB disruption and oxidative stress in brain vessels. Using in vivo multiphoton imaging, we found that DDS administration significantly restored BBB integrity compromised by LPS. DDS also increased the expression of tight junction proteins occludin, zona occludens-1 (ZO-1) and claudin-5 in brain vessels. Level of reactive oxygen species (ROS) was reduced by DDS treatment, which may due to decreased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NOX2 expression. Our results showed that LPS-induced BBB dysfunction could be attenuated by DDS, indicated that DDS has a therapeutic potential for treating CNS infection and other BBB related diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

Effective Treatment of Solitary Pituitary Metastasis with Panhypopituitarism in HER2-Positive Breast Cancer by Lapatinib.

PubMed

Park, Youngmok; Kim, Hyemin; Kim, Eui-Hyun; Suh, Chang-Ok; Lee, Soohyeon

2016-01-01

Brain metastasis affects one third of patients with HER2-positive breast cancer after treatment with trastuzumab. Surgical resection and radiation therapy are often unsuccessful at accomplishing complete control of metastasis. Lapatinib is presumed to cross the blood-brain barrier, and exhibits clinical activities for treatment of HER2-positive breast cancer. A 43-year-old woman was treated for early breast carcinoma with total mastectomy, axillary lymph-node dissection, and adjuvant chemotherapy with cyclophosphamide plus doxorubicin. After the end of adjuvant trastuzumab therapy, she was diagnosed with panhypopituitarism due to pituitary metastasis. Surgical removal and whole brain radiation therapy were performed, but a portion of viable tumor remained. Only taking lapatinib, the size of the metastatic lesion began to shrink. Trastuzumab may have controlled the micro-metastasis of breast cancer, but it was unable to control its progression to the central nervous system. Lapatinib is a possible option for HER2-positive metastatic breast cancer patients with brain metastasis.

Neurobehavioral comorbidities of epilepsy: Role of inflammation.

PubMed

Mazarati, Andrey M; Lewis, Megan L; Pittman, Quentin J

2017-07-01

Epilepsy is associated with a high incidence of comorbid neurologic and psychiatric disorders. This review focuses on the association of epilepsy with autism spectrum disorder (ASD) and depression. There is high concordance of these behavioral pathologies with epilepsy. We review data that unambiguously reveal that epilepsy, ASD, and depression are associated with elevated brain inflammatory markers and that these may interact with serotoninergic pathways. Interference with inflammatory pathways or actions can reduce the severity of seizures, depression, and ASD-like behavior. Inflammation in the brain can be induced by seizure activity as well as by behavioral, environmental, and physiologic stressors. Furthermore, induction of inflammation at an early time point during gestation and in early neonatal life can precipitate both an ASD-like phenotype as well as a more excitable brain. It appears likely that priming of the brain due to early inflammation could provide a means by which subsequent inflammatory processes associated with epilepsy, ASD, and depression may lead to comorbidity. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

Aging exacerbates intracerebral hemorrhage-induced brain injury.

PubMed

Lee, Jae-Chul; Cho, Geum-Sil; Choi, Byung-Ok; Kim, Hyoung Chun; Kim, Won-Ki

2009-09-01

Aging may be an important factor affecting brain injury by intracerebral hemorrhage (ICH). In the present study, we investigated the responses of glial cells and monocytes to intracerebral hemorrhage in normal and aged rats. ICH was induced by microinjecting autologous whole blood (15 microL) into the striatum of young (4 month old) and aged (24 month old) Sprague-Dawley rats. Age-dependent relations of brain tissue damage with glial and macrophageal responses were evaluated. Three days after ICH, activated microglia/macrophages with OX42-positive processes and swollen cytoplasm were more abundantly distributed around and inside the hemorrhagic lesions. These were more dramatic in aged versus the young rats. Western blot and immunohistochemistry analyses showed that the expression of interleukin-1beta protein after ICH was greater in aged rats, whereas the expression of GFAP and ciliary neurotrophic factor protein after ICH was significantly lower in aged rats. These results suggest that ICH causes more severe brain injury in aged rats most likely due to overactivation of microglia/macrophages and concomitant repression of reactive astrocytes.

Deep brain stimulation macroelectrodes compared to multiple microelectrodes in rat hippocampus

PubMed Central

Arcot Desai, Sharanya; Gutekunst, Claire-Anne; Potter, Steve M.; Gross, Robert E.

2014-01-01

Microelectrode arrays (wire diameter <50 μm) were compared to traditional macroelectrodes for deep brain stimulation (DBS). Understanding the neuronal activation volume may help solve some of the mysteries associated with DBS, e.g., its mechanisms of action. We used c-fos immunohistochemistry to investigate neuronal activation in the rat hippocampus caused by multi-micro- and macroelectrode stimulation. At ± 1V stimulation at 25 Hz, microelectrodes (33 μm diameter) had a radius of activation of 100 μm, which is 50% of that seen with 150 μm diameter macroelectrode stimulation. Macroelectrodes activated about 5.8 times more neurons than a single microelectrode, but displaced ~20 times more neural tissue. The sphere of influence of stimulating electrodes can be significantly increased by reducing their impedance. By ultrasonic electroplating (sonicoplating) the microelectrodes with platinum to increase their surface area and reduce their impedance by an order of magnitude, the radius of activation increased by 50 μm and more than twice the number of neurons were activated within this increased radius compared to unplated microelectrodes. We suggest that a new approach to DBS, one that uses multiple high-surface area microelectrodes, may be more therapeutically effective due to increased neuronal activation. PMID:24971060

Manganese-induced effects on cerebral trace element and nitric oxide of Hyline cocks.

PubMed

Liu, Xiaofei; Zuo, Nan; Guan, Huanan; Han, Chunran; Xu, Shi Wen

2013-08-01

Exposure to Manganese (Mn) is a common phenomenon due to its environmental pervasiveness. To investigate the Mn-induced toxicity on cerebral trace element levels and crucial nitric oxide parameters on brain of birds, 50-day-old male Hyline cocks were fed either a commercial diet or a Mn-supplemented diet containing 600, 900, 1,800 mg kg(-1). After being treated with Mn for 30, 60, and 90 days, the following were determined: the changes in contents of copper (Cu), iron (Fe), zinc (Zn), calcium (Ca), selenium (Se) in brain; inducible nitric oxide synthase-nitric oxide (iNOS-NO) system activity in brain; and histopathology and ultrastructure changes of cerebral cortex. The results showed that Mn was accumulated in brain and the content of Cu and Fe increased. However, the levels of Zn and Se decreased and the Ca content presented no obvious regularity. Exposure to Mn significantly elevated the content of NO and the expression of iNOS mRNA. Activity of total NO synthase (T NOS) and iNOS appeared with an increased tendency. These findings suggested that Mn exposure resulted in the imbalance of cerebral trace elements and influenced iNOS in the molecular level, which are possible underlying nervous system injury mechanisms induced by Mn exposure.

Aromatic L-Amino Acid Decarboxylase (AADC) Is Crucial for Brain Development and Motor Functions

PubMed Central

Shih, De-Fen; Hsiao, Chung-Der; Min, Ming-Yuan; Lai, Wen-Sung; Yang, Chianne-Wen; Lee, Wang-Tso; Lee, Shyh-Jye

2013-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children. PMID:23940784

Aromatic L-amino acid decarboxylase (AADC) is crucial for brain development and motor functions.

PubMed

Shih, De-Fen; Hsiao, Chung-Der; Min, Ming-Yuan; Lai, Wen-Sung; Yang, Chianne-Wen; Lee, Wang-Tso; Lee, Shyh-Jye

2013-01-01

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare pediatric neuro-metabolic disease in children. Due to the lack of an animal model, its pathogenetic mechanism is poorly understood. To study the role of AADC in brain development, a zebrafish model of AADC deficiency was generated. We identified an aadc gene homolog, dopa decarboxylase (ddc), in the zebrafish genome. Whole-mount in situ hybridization analysis showed that the ddc gene is expressed in the epiphysis, locus caeruleus, diencephalic catecholaminergic clusters, and raphe nuclei of 36-h post-fertilization (hpf) zebrafish embryos. Inhibition of Ddc by AADC inhibitor NSD-1015 or anti-sense morpholino oligonucleotides (MO) reduced brain volume and body length. We observed increased brain cell apoptosis and loss of dipencephalic catecholaminergic cluster neurons in ddc morphants (ddc MO-injected embryos). Seizure-like activity was also detected in ddc morphants in a dose-dependent manner. ddc morphants had less sensitive touch response and impaired swimming activity that could be rescued by injection of ddc plasmids. In addition, eye movement was also significantly impaired in ddc morphants. Collectively, loss of Ddc appears to result in similar phenotypes as that of ADCC deficiency, thus zebrafish could be a good model for investigating pathogenetic mechanisms of AADC deficiency in children.

Cyclodextrins, blood-brain barrier, and treatment of neurological diseases.

PubMed

Vecsernyés, Miklós; Fenyvesi, Ferenc; Bácskay, Ildikó; Deli, Mária A; Szente, Lajos; Fenyvesi, Éva

2014-11-01

Biological barriers are the main defense systems of the homeostasis of the organism and protected organs. The blood-brain barrier (BBB), formed by the endothelial cells of brain capillaries, not only provides nutrients and protection to the central nervous system but also restricts the entry of drugs, emphasizing its importance in the treatment of neurological diseases. Cyclodextrins are increasingly used in human pharmacotherapy. Due to their favorable profile to form hydrophilic inclusion complexes with poorly soluble active pharmaceutical ingredients, they are present as excipients in many marketed drugs. Application of cyclodextrins is widespread in formulations for oral, parenteral, nasal, pulmonary, and skin delivery of drugs. Experimental and clinical data suggest that cyclodextrins can be used not only as excipients for centrally acting marketed drugs like antiepileptics, but also as active pharmaceutical ingredients to treat neurological diseases. Hydroxypropyl-β-cyclodextrin received orphan drug designation for the treatment of Niemann-Pick type C disease. In addition to this rare lysosomal storage disease with neurological symptoms, experimental research revealed the potential therapeutic use of cyclodextrins and cyclodextrin nanoparticles in neurodegenerative diseases, stroke, neuroinfections and brain tumors. In this context, the biological effects of cyclodextrins, their interaction with plasma membranes and extraction of different lipids are highly relevant at the level of the BBB. Copyright © 2015 IMSS. Published by Elsevier Inc. All rights reserved.

Neuroprotective pentapeptide CN-105 is associated with reduced sterile inflammation and improved functional outcomes in a traumatic brain injury murine model

PubMed Central

Laskowitz, Daniel T.; Wang, Haichen; Chen, Tony; Lubkin, David T.; Cantillana, Viviana; Tu, Tian Ming; Kernagis, Dawn; Zhou, Guanen; Macy, Gary; Kolls, Bradley J.; Dawson, Hana N.

2017-01-01

At present, there are no proven pharmacological treatments demonstrated to improve long term functional outcomes following traumatic brain injury(TBI). In the setting of non-penetrating TBI, sterile brain inflammatory responses are associated with the development of cerebral edema, intracranial hypertension, and secondary neuronal injury. There is increasing evidence that endogenous apolipoprotein E(apoE) modifies the neuroinflammatory response through its role in downregulating glial activation, however, the intact apoE holoprotein does not cross the blood-brain barrier due to its size. To address this limitation, we developed a small 5 amino acid apoE mimetic peptide(CN-105) that mimics the polar face of the apoE helical domain involved in receptor interactions. The goal of this study was to investigate the therapeutic potential of CN-105 in a murine model of closed head injury. Treatment with CN-105 was associated with a durable improvement in functional outcomes as assessed by Rotarod and Morris Water Maze and a reduction in positive Fluoro-Jade B stained injured neurons and microglial activation. Administration of CN-105 was also associated with reduction in mRNA expression of a subset of inflammatory and immune-related genes. PMID:28429734

A case of refractary epilepsy and related pain due to dysmenorrhea solved with loading dose of lacosamide: clinical and neurophysiological correlates.

PubMed

Marchitto, Nicolino; Ceratti, Umberto; Dalmaso, Serenella; Raimondi, Gianfranco

2017-10-23

 In most cases, the etiology of epilepsy is unknown, although some individuals may develop epilepsy as a result of certain brain injuries, following a stroke, a brain tumor or because of drugs and alcohol. Even some rare genetic mutations may be related to the onset of the condition. Seizures are the result of excessive and abnormal activity of neurons in the cerebral cortex. In this case report we show a clinical case of refractory epilepsy due to pain related to uncontrolled dysmenorrhea. The patient, 43 yrs old, had a history of epilepsy of 20 years and ovarian cancer. She was treated with lamotrigine, clonazepam and levomepromazina maleato. At admission the patient shew seizures due to pain related to dysmenorrhea. In emergency we treated with verapamil hydrochloride 10 mg ev, subsequently verapamil hydrochloride 20 mg in 250 ml of saline solution as maintenance dose. Then we decided to administer a loading dose of 100 mg cpr of Lacosamide to stop the treatment with verapamil hydrochloride. With Lacosamide we solved the seizures in 24 hours.

Evolutionary combinatorial chemistry, a novel tool for SAR studies on peptide transport across the blood-brain barrier. Part 2. Design, synthesis and evaluation of a first generation of peptides.

PubMed

Teixidó, Meritxell; Belda, Ignasi; Zurita, Esther; Llorà, Xavier; Fabre, Myriam; Vilaró, Senén; Albericio, Fernando; Giralt, Ernest

2005-12-01

The use of high-throughput methods in drug discovery allows the generation and testing of a large number of compounds, but at the price of providing redundant information. Evolutionary combinatorial chemistry combines the selection and synthesis of biologically active compounds with artificial intelligence optimization methods, such as genetic algorithms (GA). Drug candidates for the treatment of central nervous system (CNS) disorders must overcome the blood-brain barrier (BBB). This paper reports a new genetic algorithm that searches for the optimal physicochemical properties for peptide transport across the blood-brain barrier. A first generation of peptides has been generated and synthesized. Due to the high content of N-methyl amino acids present in most of these peptides, their syntheses were especially challenging due to over-incorporations, deletions and DKP formations. Distinct fragmentation patterns during peptide cleavage have been identified. The first generation of peptides has been studied by evaluation techniques such as immobilized artificial membrane chromatography (IAMC), a cell-based assay, log Poctanol/water calculations, etc. Finally, a second generation has been proposed. (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.

Effect of unilateral versus bilateral electrostimulation in subthalamic nucleus on speech in Parkinsons disease

NASA Astrophysics Data System (ADS)

Wang, Emily; Verhagen Metman, Leo; Bakay, Roy; Arzbaecher, Jean; Bernard, Bryan

2004-05-01

Previously, it was found that 16 right-handed patients with idiopathic Parkinsons disease who underwent unilateral implantation of deep brain stimulator in subthalamic nucleus (STN) showed significant improvement in their nonspeech motor functions. Eight of the 16 patients had stimulator in the left STN and eight in the right STN. In contrast, their speech function showed very mild improvement that was limited to the respiratory/phonotory subsystems. Further, there seemed a trend that the patients with right STN stimulation did better than those with left STN stimulation. It was speculated that the difference might be due to a micro lesion caused by the surgical procedure to the corticobulbar fibers run in the left internal capsule. This paper reports speech changes associated with bilateral DBS in STN in four of the 16 subjects who elected to have deep brain stimulator implanted in STN on the opposite side of the brain at a later time. Results show negative changes in speech after bilateral DBS in STN. The changes were not limited to the micro lesion effect due to the surgery itself, but also related to the active stimulation on the dominant hemisphere for speech processing. [Work supported by NIH.

The motivation and actions of Australians concerning brain health and dementia risk reduction.

PubMed

Smith, Ben J; Ali, Suha; Quach, Henry

2015-08-01

Alzheimer's disease and dementia are recognised as critical public health priorities. This study investigated intentions and behaviours concerning brain health and dementia risk reduction among Australians. A cross-sectional survey of 1000 persons aged 20-75 years measured knowledge, beliefs, intentions and behaviours concerning brain health and dementia. The demographic, experiential and cognitive factors associated with intentions and actions were examined. Around half of respondents were motivated to improve brain health. Behaviours most often reported were mental activity (19%), physical activity (9.6%) and dietary action (6.5%). Actions were most likely among women (OR 1.59, 95% CI 1.19-2.14), those aged 60 years and over (OR 3.07, 95% CI 2.01-2.58), with university education (OR 1.67, 95% CI 1.08-2.58) or with prior contact with a person with dementia (OR 1.99, 95% CI 1.12-3.56). Both intentions and actions were associated with moderate to high knowledge, and beliefs and confidence that favoured dementia risk reduction. A lower proportion of Australians reported taking action to improve brain health than who expressed intentions in this regard. Strategies are needed to improve knowledge about the range of behaviours that contribute to dementia risk reduction and to increase confidence that this outcome is personally achievable. SO WHAT? The burden of disease due to Alzheimer's disease and dementia is growing dramatically. It is essential to promote awareness that dementia is not an inevitable result of ageing and to increase understanding that action can be taken throughout the life course to promote brain health.

Real-Time fMRI in Neuroscience Research and Its Use in Studying the Aging Brain

PubMed Central

Rana, Mohit; Varan, Andrew Q.; Davoudi, Anis; Cohen, Ronald A.; Sitaram, Ranganatha; Ebner, Natalie C.

2016-01-01

Cognitive decline is a major concern in the aging population. It is normative to experience some deterioration in cognitive abilities with advanced age such as related to memory performance, attention distraction to interference, task switching, and processing speed. However, intact cognitive functioning in old age is important for leading an independent day-to-day life. Thus, studying ways to counteract or delay the onset of cognitive decline in aging is crucial. The literature offers various explanations for the decline in cognitive performance in aging; among those are age-related gray and white matter atrophy, synaptic degeneration, blood flow reduction, neurochemical alterations, and change in connectivity patterns with advanced age. An emerging literature on neurofeedback and Brain Computer Interface (BCI) reports exciting results supporting the benefits of volitional modulation of brain activity on cognition and behavior. Neurofeedback studies based on real-time functional magnetic resonance imaging (rtfMRI) have shown behavioral changes in schizophrenia and behavioral benefits in nicotine addiction. This article integrates research on cognitive and brain aging with evidence of brain and behavioral modification due to rtfMRI neurofeedback. We offer a state-of-the-art description of the rtfMRI technique with an eye towards its application in aging. We present preliminary results of a feasibility study exploring the possibility of using rtfMRI to train older adults to volitionally control brain activity. Based on these first findings, we discuss possible implementations of rtfMRI neurofeedback as a novel technique to study and alleviate cognitive decline in healthy and pathological aging. PMID:27803662

bFGF Protects Against Blood-Brain Barrier Damage Through Junction Protein Regulation via PI3K-Akt-Rac1 Pathway Following Traumatic Brain Injury.

PubMed

Wang, Zhou-Guang; Cheng, Yi; Yu, Xi-Chong; Ye, Li-Bing; Xia, Qing-Hai; Johnson, Noah R; Wei, Xiaojie; Chen, Da-Qing; Cao, Guodong; Fu, Xiao-Bing; Li, Xiao-Kun; Zhang, Hong-Yu; Xiao, Jian

2016-12-01

Many traumatic brain injury (TBI) survivors sustain neurological disability and cognitive impairments due to the lack of defined therapies to reduce TBI-induced blood-brain barrier (BBB) breakdown. Exogenous basic fibroblast growth factor (bFGF) has been shown to have neuroprotective function in brain injury. The present study therefore investigates the beneficial effects of bFGF on the BBB after TBI and the underlying mechanisms. In this study, we demonstrate that bFGF reduces neurofunctional deficits and preserves BBB integrity in a mouse model of TBI. bFGF suppresses RhoA and upregulates tight junction proteins, thereby mitigating BBB breakdown. In vitro, bFGF exerts a protective effect on BBB by upregulating tight junction proteins claudin-5, occludin, zonula occludens-1, p120-catenin, and β-catenin under oxygen glucose deprivation/reoxygenation (OGD) in human brain microvascular endothelial cells (HBMECs). Both the in vivo and in vitro effects are related to the activation of the downstream signaling pathway, PI3K/Akt/Rac-1. Inhibition of the PI3K/Akt or Rac-1 by specific inhibitors LY294002 or si-Rac-1, respectively, partially reduces the protective effect of bFGF on BBB integrity. Overall, our results indicate that the protective role of bFGF on BBB involves the regulation of tight junction proteins and RhoA in the TBI model and OGD-induced HBMECs injury, and that activation of the PI3K/Akt /Rac-1 signaling pathway underlies these effects.

Acetylcholine Esterase Activity and Behavioral Response in Hypoxia Induced Neonatal Rats: Effect of Glucose, Oxygen and Epinephrine Supplementation

ERIC Educational Resources Information Center

Chathu, Finla; Krishnakumar, Amee; Paulose, Cheramadathikudyil S.

2008-01-01

Brain damage due to an episode of hypoxia remains a major problem in infants causing deficit in motor and sensory function. Hypoxia leads to neuronal functional failure, cerebral palsy and neuro-developmental delay with characteristic biochemical and molecular alterations resulting in permanent or transitory neurological sequelae or even death.…

The Functional Organization of Trial-Related Activity in Lexical Processing after Early Left Hemispheric Brain Lesions: An Event-Related fMRI Study

ERIC Educational Resources Information Center

Fair, Damien A.; Choi, Alexander H.; Dosenbach, Yannic B. L.; Coalson, Rebecca S.; Miezin, Francis M.; Petersen, Steven E.; Schlaggar, Bradley L.

2010-01-01

Children with congenital left hemisphere damage due to perinatal stroke are capable of acquiring relatively normal language functions despite experiencing a cortical insult that in adults often leads to devastating lifetime disabilities. Although this observed phenomenon is accepted, its neurobiological mechanisms are not well characterized. In…

Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

PubMed

Mahncke, Henry W; Bronstone, Amy; Merzenich, Michael M

2006-01-01

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

The topograpy of demyelination and neurodegeneration in the multiple sclerosis brain.

PubMed

Haider, Lukas; Zrzavy, Tobias; Hametner, Simon; Höftberger, Romana; Bagnato, Francesca; Grabner, Günther; Trattnig, Siegfried; Pfeifenbring, Sabine; Brück, Wolfgang; Lassmann, Hans

2016-03-01

Multiple sclerosis is a chronic inflammatory disease with primary demyelination and neurodegeneration in the central nervous system. In our study we analysed demyelination and neurodegeneration in a large series of multiple sclerosis brains and provide a map that displays the frequency of different brain areas to be affected by these processes. Demyelination in the cerebral cortex was related to inflammatory infiltrates in the meninges, which was pronounced in invaginations of the brain surface (sulci) and possibly promoted by low flow of the cerebrospinal fluid in these areas. Focal demyelinated lesions in the white matter occurred at sites with high venous density and additionally accumulated in watershed areas of low arterial blood supply. Two different patterns of neurodegeneration in the cortex were identified: oxidative injury of cortical neurons and retrograde neurodegeneration due to axonal injury in the white matter. While oxidative injury was related to the inflammatory process in the meninges and pronounced in actively demyelinating cortical lesions, retrograde degeneration was mainly related to demyelinated lesions and axonal loss in the white matter. Our data show that accumulation of lesions and neurodegeneration in the multiple sclerosis brain does not affect all brain regions equally and provides the pathological basis for the selection of brain areas for monitoring regional injury and atrophy development in future magnetic resonance imaging studies. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

Brain Gym. Simple Activities for Whole Brain Learning.

ERIC Educational Resources Information Center

Dennison, Paul E.; Dennison, Gail E.

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

Recovery of brain and plasma cholinesterase activities in ducklings exposed to organophosphorus pesticides

USGS Publications Warehouse

Fleming, W.J.

1981-01-01

Brain and plasma cholinesterase (ChE) activities were determined for mallard ducklings (Anas platyrhynchos) exposed to dicrotophos and fenthion. Recovery rates of brain ChE did not differ between ducklings administered a single oral dose vs. a 2-week dietary dose of these organophosphates. Exposure to the organophosphates, followed by recovery of brain ChE, did not significantly affect the degree of brain ChE inhibition or the recovery of ChE activity at a subsequent exposure. Recovery of brain ChE activity followed the general model Y = a + b(logX) with rapid recovery to about 50% of normal, followed by a slower rate of recovery until normal ChE activity levels were attained. Fenthion and dicrotophos-inhibited brain ChE were only slightly reactivated in vitro by pyridine-2-aldoxime methiodide, which suggested that spontaneous reactivation was not a primary method of recovery of ChE activity. Recovery of brain ChE activity can be modeled for interpretation of sublethal inhibition of brain ChE activities in wild birds following environmental applications of organophosphates. Plasma ChE activity is inferior to brain ChE activity for environmental monitoring, because of its rapid recovery and large degree of variation among individuals.

The human body odor compound androstadienone increases neural conflict coupled to higher behavioral costs during an emotional Stroop task.

PubMed

Hornung, Jonas; Kogler, Lydia; Erb, Michael; Freiherr, Jessica; Derntl, Birgit

2018-05-01

The androgen derivative androstadienone (AND) is a substance found in human sweat and thus may act as human chemosignal. With the current experiment, we aimed to explore in which way AND affects interference processing during an emotional Stroop task which used human faces as target and emotional words as distractor stimuli. This was complemented by functional magnetic resonance imaging (fMRI) to unravel the neural mechanism of AND-action. Based on previous accounts we expected AND to increase neural activation in areas commonly implicated in evaluation of emotional face processing and to change neural activation in brain regions linked to interference processing. For this aim, a total of 80 healthy individuals (oral contraceptive users, luteal women, men) were tested twice on two consecutive days with an emotional Stroop task using fMRI. Our results suggest that AND increases interference processing in brain areas that are heavily recruited during emotional conflict. At the same time, correlation analyses revealed that this neural interference processing was paralleled by higher behavioral costs (response times) with higher interference related brain activation under AND. Furthermore, AND elicited higher activation in regions implicated in emotional face processing including right fusiform gyrus, inferior frontal gyrus and dorsomedial cortex. In this connection, neural activation was not coupled to behavioral outcome. Furthermore, despite previous accounts of increased hypothalamic activation under AND, we were not able to replicate this finding and discuss possible reasons for this discrepancy. To conclude, AND increased interference processing in regions heavily recruited during emotional conflict which was coupled to higher costs in resolving emotional conflicts with stronger interference-related brain activation under AND. At the moment it remains unclear whether these effects are due to changes in conflict detection or resolution. However, evidence most consistently suggests that AND does not draw attention to the most potent socio-emotional information (human faces) but rather highlights representations of emotional words. Copyright © 2018 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2014-01-01

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

Brain Stem Infarction Due to Basilar Artery Dissection in a Patient with Moyamoya Disease Four Years after Successful Bilateral Revascularization Surgeries.

PubMed

Abe, Takatsugu; Fujimura, Miki; Mugikura, Shunji; Endo, Hidenori; Tominaga, Teiji

2016-06-01

Moyamoya disease (MMD) is a rare cerebrovascular disease with an unknown etiology and is characterized by intrinsic fragility in the intracranial vascular walls such as the affected internal elastic lamina and thinning medial layer. The association of MMD with intracranial arterial dissection is extremely rare, whereas that with basilar artery dissection (BAD) has not been reported previously. A 46-year-old woman developed brain stem infarction due to BAD 4 years after successful bilateral superficial temporal artery-middle cerebral artery anastomosis with indirect pial synangiosis for ischemic-onset MMD. She presented with sudden occipitalgia and subsequently developed transient dysarthria and mild hemiparesis. Although a transient ischemic attack was initially suspected, her condition deteriorated in a manner that was consistent with left hemiplegia with severe dysarthria. Magnetic resonance (MR) imaging revealed brain stem infarction, and MR angiography delineated a double-lumen sign in the basilar artery, indicating BAD. She was treated conservatively and brain stem infarction did not expand. One year after the onset of brain stem infarction, her activity of daily living is still dependent (modified Rankin Scale of 4), and there were no morphological changes associated with BAD or recurrent cerebrovascular events during the follow-up period. The association of MMD with BAD is extremely rare. While considering the common underlying pathology such as an affected internal elastic lamina and fragile medial layer, the occurrence of BAD in a patient with MMD in a stable hemodynamic state is apparently unique. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Genetic, hormonal, and metabolomic influences on social behavior and sex preference of XXY mice

PubMed Central

Erkkila, Krista; Lue, YanHe; Jentsch, J. David; Schwarcz, Monica Dorin; Abuyounes, Deena; Hikim, Amiya Sinha; Wang, Christina; Lee, Paul W.-N.; Swerdloff, Ronald S.

2010-01-01

XXY men (Klinefelter syndrome) are testosterone deficient, socially isolated, exhibit impaired gender identity, and may experience more homosexual behaviors. Here, we characterize social behaviors in a validated XXY mouse model to understand mechanisms. Sociability and gender preference were assessed by three-chambered choice tasks before and after castration and after testosterone replacement. Metabolomic activities of brain and blood were quantified through fractional synthesis rates of palmitate and ribose (GC-MS). XXY mice exhibit greater sociability than XY littermates, particularly for male mice. The differences in sociability disappear after matching androgen exposure. Intact XXY, compared with XY, mice prefer male mice odors when the alternatives are ovariectomized female mice odors, but they prefer estrous over male mice odors, suggesting that preference for male mice may be due to social, not sexual, cues. Castration followed by testosterone treatment essentially remove these preferences. Fractional synthesis rates of palmitate are higher in the hypothalamus, amygdala, and hippocampus of XXY compared with XY mice but not with ribose in these brain regions or palmitate in blood. Androgen ablation in XY mice increases fractional synthesis rates of fatty acids in the brain to levels indistinguishable from those in XXY mice. We conclude that intact XXY mice exhibit increased sociability, differences in gender preference for mice and their odors are due to social rather than sexual cues and, these differences are mostly related to androgen deficiency rather than genetics. Specific metabolic changes in brain lipids, which are also regulated by androgens, are observed in brain regions that are involved in these behaviors. PMID:20570823

Gaming is related to enhanced working memory performance and task-related cortical activity.

PubMed

Moisala, M; Salmela, V; Hietajärvi, L; Carlson, S; Vuontela, V; Lonka, K; Hakkarainen, K; Salmela-Aro, K; Alho, K

2017-01-15

Gaming experience has been suggested to lead to performance enhancements in a wide variety of working memory tasks. Previous studies have, however, mostly focused on adult expert gamers and have not included measurements of both behavioral performance and brain activity. In the current study, 167 adolescents and young adults (aged 13-24 years) with different amounts of gaming experience performed an n-back working memory task with vowels, with the sensory modality of the vowel stream switching between audition and vision at random intervals. We studied the relationship between self-reported daily gaming activity, working memory (n-back) task performance and related brain activity measured using functional magnetic resonance imaging (fMRI). The results revealed that the extent of daily gaming activity was related to enhancements in both performance accuracy and speed during the most demanding (2-back) level of the working memory task. This improved working memory performance was accompanied by enhanced recruitment of a fronto-parietal cortical network, especially the dorsolateral prefrontal cortex. In contrast, during the less demanding (1-back) level of the task, gaming was associated with decreased activity in the same cortical regions. Our results suggest that a greater degree of daily gaming experience is associated with better working memory functioning and task difficulty-dependent modulation in fronto-parietal brain activity already in adolescence and even when non-expert gamers are studied. The direction of causality within this association cannot be inferred with certainty due to the correlational nature of the current study. Copyright © 2016 Elsevier B.V. All rights reserved.

The influence of caffeine on the activity of moclobemide, venlafaxine, bupropion and milnacipran in the forced swim test in mice.

PubMed

Poleszak, Ewa; Szopa, Aleksandra; Wyska, Elżbieta; Wośko, Sylwia; Serefko, Anna; Wlaź, Aleksandra; Pieróg, Mateusz; Wróbel, Andrzej; Wlaź, Piotr

2015-09-01

Worrying data indicate that excessive caffeine intake applies to patients suffering from mental disorders, including depression. It is thus possible to demonstrate the usefulness of caffeine and its derivatives in the treatment of depression. The main goal of the present studywas to evaluate the influence of caffeine (5mg/kg) on the activity of moclobemide (1.5 mg/kg), venlafaxine (1 mg/kg), bupropion (10 mg/kg), and milnacipran (1.25 mg/kg). Moreover, we assessed the influence of caffeine on their serum and brain levels using highperformance liquid chromatography. The experiment was carried out on naïve adult male Albino Swiss mice. Caffeine and tested drugs were administered intraperitoneally. The influence of caffeine on the activity of selected antidepressant drugs was evaluated in forced swim test (FST). Locomotor activity was estimated to verify and exclude false positive/negative results. To assess the influence of caffeine on the levels of studied antidepressant drugs, their concentrations were determined in murine serum and brains using high-performance liquid chromatography. Caffeine potentiated activity of all antidepressants examined in FST and the observed effects were not due to the increase in locomotor activity in the animals. Only in the case of co-administration of caffeine and milnacipran an increased milnacipran concentration in serum was observed without affecting its concentration in the brain. Caffeine potentiates the activity of antidepressant drugs from different chemical groups. The interactions of caffeine with venlafaxine, bupropion and moclobemide occur in pharmacodynamic phase, whereas the interaction of caffeine–milnacipran occurs, at least partially, in pharmacokinetic phase.

Citrus peel extract attenuates acute cyanide poisoning-induced seizures and oxidative stress in rats.

PubMed

Abdel Moneim, Ahmed E

2014-01-01

The primary aimed of this study was to investigate the potential protective effects of methanolic extract of citrus peel (MECP) on acute cyanide (KCN) poisoning-induced seizures and oxidative stress in rats. The intraperitoneal LD50 value of KCN (6.3 mg/Kg bwt), based on 24 hrs mortality, was significantly increased by 9, 52 or 113% by oral administration of MECP (500 mg/Kg bwt) pre-administered for 1, 2 and 3 days, respectively, in rats in a time-dependent manner. Intraperitoneal injection of the sublethal dose of KCN (3 mg/Kg bwt) into rats increased, 24 hrs later, lipid peroxidation (LPO), nitric oxide (NO), glutamate levels and acetylcholinesterase (AChE) activity in hippocampus, striatum and cerebral cortex. KCN also decreased brain glutathione (GSH) level and superoxide dismutase (SOD) and catalase (CAT) activities in these animals. Pre-treatment of rats with MECP inhibited KCN-induced increases in LPO, NO, and glutamate levels and AChE activity as well as decreases in brain GSH level and SOD and CAT activities. In addition, KCN significantly decreased norepinephrine, dopamine and serotonin levels in different brain regions which were resolved by MECP. From the present results, it can be concluded that the neuroprotective effects of MECP against KCN-induced seizures and oxidative stress may be due to the inhibition of oxidative stress overproduction and maintenance of antioxidant defense mechanisms.

Neural Activation During Mental Rotation in Complete Androgen Insensitivity Syndrome: The Influence of Sex Hormones and Sex Chromosomes.

PubMed

van Hemmen, Judy; Veltman, Dick J; Hoekzema, Elseline; Cohen-Kettenis, Peggy T; Dessens, Arianne B; Bakker, Julie

2016-03-01

Sex hormones, androgens in particular, are hypothesized to play a key role in the sexual differentiation of the human brain. However, possible direct effects of the sex chromosomes, that is, XX or XY, have not been well studied in humans. Individuals with complete androgen insensitivity syndrome (CAIS), who have a 46,XY karyotype but a female phenotype due to a complete androgen resistance, enable us to study the separate effects of gonadal hormones versus sex chromosomes on neural sex differences. Therefore, in the present study, we compared 46,XY men (n = 30) and 46,XX women (n = 29) to 46,XY individuals with CAIS (n = 21) on a mental rotation task using functional magnetic resonance imaging. Previously reported sex differences in neural activation during mental rotation were replicated in the control groups, with control men showing more activation in the inferior parietal lobe than control women. Individuals with CAIS showed a female-like neural activation pattern in the parietal lobe, indicating feminization of the brain in CAIS. Furthermore, this first neuroimaging study in individuals with CAIS provides evidence that sex differences in regional brain function during mental rotation are most likely not directly driven by genetic sex, but rather reflect gonadal hormone exposure. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Nootropic activity of Celastrus paniculatus seed.

PubMed

Bhanumathy, M; Harish, M S; Shivaprasad, H N; Sushma, G

2010-03-01

The effect of Celastrus paniculatus Willd. (Celastraceae) seed aqueous extract on learning and memory was studied using elevated plus maze and passive avoidance test (sodium nitrite induced amnesia rodent model). The aqueous seed extract was administered orally in two different doses to rats (350 and 1050 mg/kg) and to mice (500 and 1500 mg/kg). The results were compared to piracetam (100 mg/kg, p.o.) used as a standard drug. Chemical hypoxia was induced by subcutaneous administration of sodium nitrite (35 mg/kg), immediately after acquisition training. In elevated plus maze and sodium nitrite-induced amnesia model, Celastrus paniculatus extract has showed statistically significant improvement in memory process when compared to control. The estimation of acetylcholinesterase enzyme in rat brain supports the plus maze and passive avoidance test by reducing acetylcholinesterase activity which helps in memory performance. The study reveals that the aqueous extract of Celastrus paniculatus seed has dose-dependent cholinergic activity, thereby improving memory performance. The mechanism by which Celastrus paniculatus enhances cognition may be due to increased acetylcholine level in rat brain.

The impact of early-onset cannabis use on functional brain correlates of working memory.

PubMed

Becker, Benjamin; Wagner, Daniel; Gouzoulis-Mayfrank, Euphrosyne; Spuentrup, Elmar; Daumann, Jörg

2010-08-16

Cannabis is the most commonly used illicit drug. Prevalence rates are particularly high among adolescents. Neuropsychological studies have identified cannabis-associated memory deficits, particularly linked to an early onset of use. However, it remains unclear, whether the age of onset accounts for altered cortical activation patterns usually observed in cannabis users. Functional magnetic resonance imaging was used to examine cortical activation during verbal working memory challenge in (1) early-onset (onset before the age of sixteen; n=26) and (2) late-onset cannabis users (age at onset at least sixteen; n=17). Early-onset users showed increased activation in the left superior parietal lobe. Correlational analyses confirmed the association between an earlier start of use and increased activity. Contrariwise neither cumulative dose, frequency nor time since last use was significantly associated with cortical activity. Our findings suggest that an early start of cannabis use is associated with increased cortical activation in adult cannabis users, possibly reflecting suboptimal cortical efficiency during cognitive challenge. The maturing brain might be more vulnerable to the harmful effects of cannabis use. However, due to a lack of a non-using control group we cannot exclude alternative interpretations. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Automatic selection of localized region-based active contour models using image content analysis applied to brain tumor segmentation.

PubMed

Ilunga-Mbuyamba, Elisee; Avina-Cervantes, Juan Gabriel; Cepeda-Negrete, Jonathan; Ibarra-Manzano, Mario Alberto; Chalopin, Claire

2017-12-01

Brain tumor segmentation is a routine process in a clinical setting and provides useful information for diagnosis and treatment planning. Manual segmentation, performed by physicians or radiologists, is a time-consuming task due to the large quantity of medical data generated presently. Hence, automatic segmentation methods are needed, and several approaches have been introduced in recent years including the Localized Region-based Active Contour Model (LRACM). There are many popular LRACM, but each of them presents strong and weak points. In this paper, the automatic selection of LRACM based on image content and its application on brain tumor segmentation is presented. Thereby, a framework to select one of three LRACM, i.e., Local Gaussian Distribution Fitting (LGDF), localized Chan-Vese (C-V) and Localized Active Contour Model with Background Intensity Compensation (LACM-BIC), is proposed. Twelve visual features are extracted to properly select the method that may process a given input image. The system is based on a supervised approach. Applied specifically to Magnetic Resonance Imaging (MRI) images, the experiments showed that the proposed system is able to correctly select the suitable LRACM to handle a specific image. Consequently, the selection framework achieves better accuracy performance than the three LRACM separately. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cofilin Knockdown Attenuates Hemorrhagic Brain Injury-induced Oxidative Stress and Microglial Activation in Mice.

PubMed

Alhadidi, Qasim; Nash, Kevin M; Alaqel, Saleh; Sayeed, Muhammad Shahdaat Bin; Shah, Zahoor A

2018-05-08

Intracerebral hemorrhage (ICH) resulting from the rupture of the blood vessels in the brain is associated with significantly higher mortality and morbidity. Clinical studies focused on alleviating the primary injury, hematoma formation and expansion, were largely ineffective, suggesting that secondary injury-induced inflammation and the formation of reactive species also contribute to the overall injury process. In this study, we explored the effects of cofilin knockdown in a mouse model of ICH. Animals given stereotaxic injections of cofilin siRNA, 72-h prior to induction of ICH by collagenase injection within the area of siRNA administration showed significantly decreased cofilin expression levels and lower hemorrhage volume and edema, and the animals performed significantly better in neurobehavioral tasks i.e., rotarod, grip strength and neurologic deficit scores. Cofilin siRNA knocked-down mice had reduced ICH-induced DNA fragmentation, blood-brain barrier disruption and microglial activation, with a concomitant increase in astrocyte activation. Increased expression of pro-survival proteins and decreased markers of oxidative stress were also observed in cofilin siRNA-treated mice possibly due to the reduced levels of cofilin. Our results suggest that cofilin plays a major role in ICH-induced secondary injury, and could become a potential therapeutic target. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

The role of multidrug resistance protein (MRP-1) as an active efflux transporter on blood-brain barrier (BBB) permeability.

PubMed

Lingineni, Karthik; Belekar, Vilas; Tangadpalliwar, Sujit R; Garg, Prabha

2017-05-01

Drugs acting on central nervous system (CNS) may take longer duration to reach the market as these compounds have a higher attrition rate in clinical trials due to the complexity of the brain, side effects, and poor blood-brain barrier (BBB) permeability compared to non-CNS-acting compounds. The roles of active efflux transporters with BBB are still unclear. The aim of the present work was to develop a predictive model for BBB permeability that includes the MRP-1 transporter, which is considered as an active efflux transporter. A support vector machine model was developed for the classification of MRP-1 substrates and non-substrates, which was validated with an external data set and Y-randomization method. An artificial neural network model has been developed to evaluate the role of MRP-1 on BBB permeation. A total of nine descriptors were selected, which included molecular weight, topological polar surface area, ClogP, number of hydrogen bond donors, number of hydrogen bond acceptors, number of rotatable bonds, P-gp, BCRP, and MRP-1 substrate probabilities for model development. We identified 5 molecules that fulfilled all criteria required for passive permeation of BBB, but they all have a low logBB value, which suggested that the molecules were effluxed by the MRP-1 transporter.

Compelling Evidence that Exposure Therapy for PTSD Normalizes Brain Function.

PubMed

Roy, Michael J; Costanzo, Michelle E; Blair, James R; Rizzo, Albert A

2014-01-01

Functional magnetic resonance imaging (fMRI) is helping us better understand the neurologic pathways involved in posttraumatic stress disorder (PTSD). We previously reported that military service members with PTSD after deployment to Iraq or Afghanistan demonstrated significant improvement, or normalization, in the fMRI-measured activation of the amygdala, prefrontal cortex and anterior cingulate gyrus following exposure therapy for PTSD. However, our original study design did not include repeat scans of control participants, rendering it difficult to discern how much of the observed normalization in brain activity is attributable to treatment, rather than merely a practice effect. Using the same Affective Stroop task paradigm, we now report on a larger sample of PTSD-positive combat veterans that we treated with exposure therapy, as well as a combat-exposed control group of service members who completed repeat scans at 3-4 month intervals. Findings from the treatment group are similar to our prior report. Combat controls showed no significant change on repeat scanning, indicating that the observed differences in the intervention group were in fact due to treatment. We continue to scan additional study participants, in order to determine whether virtual reality exposure therapy has a different impact on regional brain activation than other therapies for PTSD.

Entropy is more resistant to artifacts than bispectral index in brain-dead organ donors.

PubMed

Wennervirta, Johanna; Salmi, Tapani; Hynynen, Markku; Yli-Hankala, Arvi; Koivusalo, Anna-Maria; Van Gils, Mark; Pöyhiä, Reino; Vakkuri, Anne

2007-01-01

To evaluate the usefulness of entropy and the bispectral index (BIS) in brain-dead subjects. A prospective, open, nonselective, observational study in the university hospital. 16 brain-dead organ donors. Time-domain electroencephalography (EEG), spectral entropy of the EEG, and BIS were recorded during solid organ harvest. State entropy differed significantly from 0 (isoelectric EEG) 28%, response entropy 29%, and BIS 68% of the total recorded time. The median values during the operation were state entropy 0.0, response entropy 0.0, and BIS 3.0. In four of 16 organ donors studied the EEG was not isoelectric, and nonreactive rhythmic activity was noted in time-domain EEG. After excluding the results from subjects with persistent residual EEG activity state entropy, response entropy, and BIS values differed from zero 17%, 18%, and 62% of the recorded time, respectively. Median values were 0.0, 0.0, and 2.0 for state entropy, response entropy, and BIS, respectively. The highest index values in entropy and BIS monitoring were recorded without neuromuscular blockade. The main sources of artifacts were electrocauterization, 50-Hz artifact, handling of the donor, ballistocardiography, electromyography, and electrocardiography. Both entropy and BIS showed nonzero values due to artifacts after brain death diagnosis. BIS was more liable to artifacts than entropy. Neither of these indices are diagnostic tools, and care should be taken when interpreting EEG and EEG-derived indices in the evaluation of brain death.

The brain's silent messenger: using selective attention to decode human thought for brain-based communication.

PubMed

Naci, Lorina; Cusack, Rhodri; Jia, Vivian Z; Owen, Adrian M

2013-05-29

The interpretation of human thought from brain activity, without recourse to speech or action, is one of the most provoking and challenging frontiers of modern neuroscience. In particular, patients who are fully conscious and awake, yet, due to brain damage, are unable to show any behavioral responsivity, expose the limits of the neuromuscular system and the necessity for alternate forms of communication. Although it is well established that selective attention can significantly enhance the neural representation of attended sounds, it remains, thus far, untested as a response modality for brain-based communication. We asked whether its effect could be reliably used to decode answers to binary (yes/no) questions. Fifteen healthy volunteers answered questions (e.g., "Do you have brothers or sisters?") in the fMRI scanner, by selectively attending to the appropriate word ("yes" or "no"). Ninety percent of the answers were decoded correctly based on activity changes within the attention network. The majority of volunteers conveyed their answers with less than 3 min of scanning, suggesting that this technique is suited for communication in a reasonable amount of time. Formal comparison with the current best-established fMRI technique for binary communication revealed improved individual success rates and scanning times required to detect responses. This novel fMRI technique is intuitive, easy to use in untrained participants, and reliably robust within brief scanning times. Possible applications include communication with behaviorally nonresponsive patients.

Objects tell us what action we can expect: dissociating brain areas for retrieval and exploitation of action knowledge during action observation in fMRI

PubMed Central

Schubotz, Ricarda I.; Wurm, Moritz F.; Wittmann, Marco K.; von Cramon, D. Yves

2014-01-01

Objects are reminiscent of actions often performed with them: knife and apple remind us on peeling the apple or cutting it. Mnemonic representations of object-related actions (action codes) evoked by the sight of an object may constrain and hence facilitate recognition of unrolling actions. The present fMRI study investigated if and how action codes influence brain activation during action observation. The average number of action codes (NAC) of 51 sets of objects was rated by a group of n = 24 participants. In an fMRI study, different volunteers were asked to recognize actions performed with the same objects presented in short videos. To disentangle areas reflecting the storage of action codes from those exploiting them, we showed object-compatible and object-incompatible (pantomime) actions. Areas storing action codes were considered to positively co-vary with NAC in both object-compatible and object-incompatible action; due to its role in tool-related tasks, we here hypothesized left anterior inferior parietal cortex (aIPL). In contrast, areas exploiting action codes were expected to show this correlation only in object-compatible but not incompatible action, as only object-compatible actions match one of the active action codes. For this interaction, we hypothesized ventrolateral premotor cortex (PMv) to join aIPL due to its role in biasing competition in IPL. We found left anterior intraparietal sulcus (IPS) and left posterior middle temporal gyrus (pMTG) to co-vary with NAC. In addition to these areas, action codes increased activity in object-compatible action in bilateral PMv, right IPS, and lateral occipital cortex (LO). Findings suggest that during action observation, the brain derives possible actions from perceived objects, and uses this information to shape action recognition. In particular, the number of expectable actions quantifies the activity level at PMv, IPL, and pMTG, but only PMv reflects their biased competition while observed action unfolds. PMID:25009519

Decreased activation along the dorsal visual pathway after a 3-month treatment with galantamine in mild Alzheimer disease: a functional magnetic resonance imaging study.

PubMed

Bokde, Arun L W; Karmann, Michaela; Teipel, Stefan J; Born, Christine; Lieb, Martin; Reiser, Maximilian F; Möller, Hans-Jürgen; Hampel, Harald

2009-04-01

Visual perception has been shown to be altered in Alzheimer disease (AD) patients, and it is associated with decreased cognitive function. Galantamine is an active cholinergic agent, which has been shown to lead to improved cognition in mild to moderate AD patients. This study examined brain activation in a group of mild AD patients after a 3-month open-label treatment with galantamine. The objective was to examine the changes in brain activation due to treatment. There were 2 tasks to visual perception. The first task was a face-matching task to test the activation along the ventral visual pathway, and the second task was a location-matching task to test neuronal function along the dorsal pathway. Brain activation was measured using functional magnetic resonance imaging. There were 5 mild AD patients in the study. There were no differences in the task performance and in the cognitive scores of the Consortium to Establish a Registry for Alzheimer's Disease battery before and after treatment. In the location-matching task, we found a statistically significant decrease in activation along the dorsal visual pathway after galantamine treatment. A previous study found that AD patients had higher activation in the location-matching task compared with healthy controls. There were no differences in activation for the face-matching task after treatment. Our data indicate that treatment with galantamine leads to more efficient visual processing of stimuli or changes the compensatory mechanism in the AD patients. A visual perception task recruiting the dorsal visual system may be useful as a biomarker of treatment effects.

Spatiotemporal Imaging of Glutamate-Induced Biophotonic Activities and Transmission in Neural Circuits

PubMed Central

Tang, Rendong; Dai, Jiapei

2014-01-01

The processing of neural information in neural circuits plays key roles in neural functions. Biophotons, also called ultra-weak photon emissions (UPE), may play potential roles in neural signal transmission, contributing to the understanding of the high functions of nervous system such as vision, learning and memory, cognition and consciousness. However, the experimental analysis of biophotonic activities (emissions) in neural circuits has been hampered due to technical limitations. Here by developing and optimizing an in vitro biophoton imaging method, we characterize the spatiotemporal biophotonic activities and transmission in mouse brain slices. We show that the long-lasting application of glutamate to coronal brain slices produces a gradual and significant increase of biophotonic activities and achieves the maximal effect within approximately 90 min, which then lasts for a relatively long time (>200 min). The initiation and/or maintenance of biophotonic activities by glutamate can be significantly blocked by oxygen and glucose deprivation, together with the application of a cytochrome c oxidase inhibitor (sodium azide), but only partly by an action potential inhibitor (TTX), an anesthetic (procaine), or the removal of intracellular and extracellular Ca2+. We also show that the detected biophotonic activities in the corpus callosum and thalamus in sagittal brain slices mostly originate from axons or axonal terminals of cortical projection neurons, and that the hyperphosphorylation of microtubule-associated protein tau leads to a significant decrease of biophotonic activities in these two areas. Furthermore, the application of glutamate in the hippocampal dentate gyrus results in increased biophotonic activities in its intrahippocampal projection areas. These results suggest that the glutamate-induced biophotonic activities reflect biophotonic transmission along the axons and in neural circuits, which may be a new mechanism for the processing of neural information. PMID:24454909

Spatiotemporal imaging of glutamate-induced biophotonic activities and transmission in neural circuits.

PubMed

Tang, Rendong; Dai, Jiapei

2014-01-01

The processing of neural information in neural circuits plays key roles in neural functions. Biophotons, also called ultra-weak photon emissions (UPE), may play potential roles in neural signal transmission, contributing to the understanding of the high functions of nervous system such as vision, learning and memory, cognition and consciousness. However, the experimental analysis of biophotonic activities (emissions) in neural circuits has been hampered due to technical limitations. Here by developing and optimizing an in vitro biophoton imaging method, we characterize the spatiotemporal biophotonic activities and transmission in mouse brain slices. We show that the long-lasting application of glutamate to coronal brain slices produces a gradual and significant increase of biophotonic activities and achieves the maximal effect within approximately 90 min, which then lasts for a relatively long time (>200 min). The initiation and/or maintenance of biophotonic activities by glutamate can be significantly blocked by oxygen and glucose deprivation, together with the application of a cytochrome c oxidase inhibitor (sodium azide), but only partly by an action potential inhibitor (TTX), an anesthetic (procaine), or the removal of intracellular and extracellular Ca(2+). We also show that the detected biophotonic activities in the corpus callosum and thalamus in sagittal brain slices mostly originate from axons or axonal terminals of cortical projection neurons, and that the hyperphosphorylation of microtubule-associated protein tau leads to a significant decrease of biophotonic activities in these two areas. Furthermore, the application of glutamate in the hippocampal dentate gyrus results in increased biophotonic activities in its intrahippocampal projection areas. These results suggest that the glutamate-induced biophotonic activities reflect biophotonic transmission along the axons and in neural circuits, which may be a new mechanism for the processing of neural information.

An Improved Ivermectin-activated Chloride Channel Receptor for Inhibiting Electrical Activity in Defined Neuronal Populations*

PubMed Central

Lynagh, Timothy; Lynch, Joseph W.

2010-01-01

The ability to silence the electrical activity of defined neuronal populations in vivo is dramatically advancing our understanding of brain function. This technology may eventually be useful clinically for treating a variety of neuropathological disorders caused by excessive neuronal activity. Several neuronal silencing methods have been developed, with the bacterial light-activated halorhodopsin and the invertebrate allatostatin-activated G protein-coupled receptor proving the most successful to date. However, both techniques may be difficult to implement clinically due to their requirement for surgically implanted stimulus delivery methods and their use of nonhuman receptors. A third silencing method, an invertebrate glutamate-gated chloride channel receptor (GluClR) activated by ivermectin, solves the stimulus delivery problem as ivermectin is a safe, well tolerated drug that reaches the brain following systemic administration. However, the limitations of this method include poor functional expression, possibly due to the requirement to coexpress two different subunits in individual neurons, and the nonhuman origin of GluClR. Here, we describe the development of a modified human α1 glycine receptor as an improved ivermectin-gated silencing receptor. The crucial development was the identification of a mutation, A288G, which increased ivermectin sensitivity almost 100-fold, rendering it similar to that of GluClR. Glycine sensitivity was eliminated via the F207A mutation. Its large unitary conductance, homomeric expression, and human origin may render the F207A/A288G α1 glycine receptor an improved silencing receptor for neuroscientific and clinical purposes. As all known highly ivermectin-sensitive GluClRs contain an endogenous glycine residue at the corresponding location, this residue appears essential for exquisite ivermectin sensitivity. PMID:20308070

Influence of ventral tegmental area input on cortico-subcortical networks underlying action control and decision making.

PubMed

Richter, Anja; Gruber, Oliver

2018-02-01

It is argued that the mesolimbic system has a more general function in processing all salient events, including and extending beyond rewards. Saliency was defined as an event that is unexpected due to its frequency of occurrence and elicits an attentional-behavioral switch. Using functional magnetic resonance imaging (fMRI), signals were measured in response to the modulation of salience of rewarding and nonrewarding events during a reward-based decision making task, the so called desire-reason dilemma paradigm (DRD). Replicating previous findings, both frequent and infrequent, and therefore salient, reward stimuli elicited reliable activation of the ventral tegmental area (VTA) and ventral striatum (vStr). When immediate reward desiring contradicted the superordinate task-goal, we found an increased activation of the VTA and vStr when the salient reward stimuli were presented compared to the nonsalient reward stimuli, indicating a boosting of activation in these brain regions. Furthermore, we found a significantly increased functional connectivity between the VTA and vStr, confirming the boosting of vStr activation via VTA input. Moreover, saliency per se without a reward association led to an increased activation of brain regions in the mesolimbic reward system as well as the orbitofrontal cortex (OFC), inferior frontal gyrus (IFG), and anterior cingulate cortex (ACC). Finally, findings uncovered multiple increased functional interactions between cortical saliency-processing brain areas and the VTA and vStr underlying detection and processing of salient events and adaptive decision making. © 2017 Wiley Periodicals, Inc.

[Immune dysfunction and cognitive deficit in stress and physiological aging (Part I): Pathogenesis and risk factors].

PubMed

Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets. The brain, immune and endocrine systems being the principal adaptive systems in the body permanently share information both in the form of neural impulses and soluble mediators. The CNS differs from other organs due to several peculiarities that affect local immune surveillance. The brain cells secluded from the blood flow by a specialized blood-brain-barrier (BBB) can endogenously express pro- and anti-inflammatory cytokines without the intervention of the immune system. In normal brain the cytokine signaling rather contributes to exclusive brain function (e.g. long-term potentiation, synaptic plasticity, adult neurogenesis) than serves as immune communicator. The stress of different origin increases the serum cytokine levels and disrupts BBB. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Mass intrusion of biologically active peptides having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. In addition owing to BBB disruption dendritic cells and T cells also penetrate into the brain where they take up a perivascular position. The changes observed in stressed subject may accumulate during repeated episodes of stress forming a picture typical of the aging brain. Moreover long-term stress as well as physiological aging result in hormonal and immunological disturbances including hypothalamic-pituitary-adrenal axis depletion, regulatory T-cell accumulation and dehydroepiandrosterone decrease.

Invisible Brain: Knowledge in Research Works and Neuron Activity.

PubMed

Segev, Aviv; Curtis, Dorothy; Jung, Sukhwan; Chae, Suhyun

2016-01-01

If the market has an invisible hand, does knowledge creation and representation have an "invisible brain"? While knowledge is viewed as a product of neuron activity in the brain, can we identify knowledge that is outside the brain but reflects the activity of neurons in the brain? This work suggests that the patterns of neuron activity in the brain can be seen in the representation of knowledge-related activity. Here we show that the neuron activity mechanism seems to represent much of the knowledge learned in the past decades based on published articles, in what can be viewed as an "invisible brain" or collective hidden neural networks. Similar results appear when analyzing knowledge activity in patents. Our work also tries to characterize knowledge increase as neuron network activity growth. The results propose that knowledge-related activity can be seen outside of the neuron activity mechanism. Consequently, knowledge might exist as an independent mechanism.

[Significant decrease in factor VII activity by tissue thromboplastin derived from rabbit brain in a patient with congenital factor VII deficiency (FVII Padua)].

PubMed

Sekiya, Akiko; Morishita, Eriko; Maruyama, Keiko; Asakura, Hidesaku; Nakao, Shinji; Ohtake, Shigeki

2012-03-01

Congenital factor VII (FVII) deficiency is a bleeding disorder that requires optimal hemostatic management for each case due to its wide variety of bleeding symptoms. We experienced a patient with inherited FVII deficiency who demonstrated different FVII activities depending on tissue thromboplastins used for assays. An 82-year-old woman without any episodes of abnormal bleeding was found to have different FVII activities of 1.4% and 32% when assayed using thromboplastins from rabbit brain and human placenta, respectively. DNA sequencing analysis revealed a homozygous missense mutation of G10828A (FVII Padua) that caused an amino acid substitution of Arg304 to Gln (R304Q). Carriers of 304Q alleles are usually clinically asymptomatic and do not require FVII replacement therapies even in cases of homozygotes. In case a prolonged prothrombin time or reduced FVII activity is detected, re-examination using thromboplastins of other sources can be helpful for preliminary diagnosis of R304Q, in order to prevent unnecessary FVII replacement therapies.

GLP-1 receptors exist in the parietal cortex, hypothalamus and medulla of human brains and the GLP-1 analogue liraglutide alters brain activity related to highly desirable food cues in individuals with diabetes: a crossover, randomised, placebo-controlled trial

PubMed Central

Farr, Olivia M.; Sofopoulos, Michail; Tsoukas, Michael A.; Dincer, Fadime; Thakkar, Bindiya; Sahin-Efe, Ayse; Filippaios, Andreas; Bowers, Jennifer; Srnka, Alexandra; Gavrieli, Anna; Ko, Byung-Joon; Liakou, Chrysoula; Kanyuch, Nickole; Tseleni-Balafouta, Sofia; Mantzoros, Christos S.

2016-01-01

Aims/hypothesis Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). Methods In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrollment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (fMRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Results Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide −0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. Conclusions/interpretation For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity. PMID:26831302

[Personality Change due to Brain Trauma Caused by Traffic Accidents and Its Assessment of Psychiatric Impairment].

PubMed

Fan, Hui-yu; Zhang, Qin-ting; Tang, Tao; Cai, Wei-xiong

2016-04-01

To explore the main performance of personality change in people with mild psychiatric impairments which due to the brain trauma caused by traffic accidents and its value in assessment of psychiatric impairment. The condition of personality change of patients with traumatic brain injury caused by traffic accident was evaluated by the Scale of Personality Change Post-traumatic Brain Injury (SPCPTBI). Furthermore, the correlation between the personality change and the degrees of traumatic brain injury and psychiatric impairment were explored. Results In 271 samples, 239 (88.2%) with personality changes. Among these 239 samples, 178 (65.7%), 46 (17.0%), 15 (5.5%) with mild, moderate and severe personality changes, respectively. The ratio based on the extent of personality changes to the degree of brain trauma was not significant (P > 0.05), but the total score difference between the groups was significant (P < 0.05). There was no statistical significance between the medium and high severity brain trauma groups. The higher degree of personality changes, the higher rank of mental disabilities. The total score difference of the scale of personality change among the different mild psychiatric impairment group was significant (P<0.05). The difference between other psychiatric impairment levels had statistical significance (P < 0.05) except level 7 and 8. The occurrence of personality change due to traumatic brain injury caused by traffic accident was high. Correlations exist between the personality change and the degree of psychiatric impairment. Personality change due to brain trauma caused by traffic accident can be assessed effectively by means of SPCPTBI, and the correlation between the total score and the extent of traumatic brain injury can be found.

Neuroimaging explanations of age-related differences in task performance.

PubMed

Steffener, Jason; Barulli, Daniel; Habeck, Christian; Stern, Yaakov

2014-01-01

Advancing age affects both cognitive performance and functional brain activity and interpretation of these effects has led to a variety of conceptual research models without always explicitly linking the two effects. However, to best understand the multifaceted effects of advancing age, age differences in functional brain activity need to be explicitly tied to the cognitive task performance. This work hypothesized that age-related differences in task performance are partially explained by age-related differences in functional brain activity and formally tested these causal relationships. Functional MRI data was from groups of young and old adults engaged in an executive task-switching experiment. Analyses were voxel-wise testing of moderated-mediation and simple mediation statistical path models to determine whether age group, brain activity and their interaction explained task performance in regions demonstrating an effect of age group. Results identified brain regions whose age-related differences in functional brain activity significantly explained age-related differences in task performance. In all identified locations, significant moderated-mediation relationships resulted from increasing brain activity predicting worse (slower) task performance in older but not younger adults. Findings suggest that advancing age links task performance to the level of brain activity. The overall message of this work is that in order to understand the role of functional brain activity on cognitive performance, analysis methods should respect theoretical relationships. Namely, that age affects brain activity and brain activity is related to task performance.

Effects of Insulin Detemir and NPH Insulin on Body Weight and Appetite-Regulating Brain Regions in Human Type 1 Diabetes: A Randomized Controlled Trial

PubMed Central

van Golen, Larissa W.; Veltman, Dick J.; IJzerman, Richard G.; Deijen, Jan Berend; Heijboer, Annemieke C.; Barkhof, Frederik; Drent, Madeleine L.; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. Trial Registration ClinicalTrials.gov NCT00626080. PMID:24739875

Effects of insulin detemir and NPH insulin on body weight and appetite-regulating brain regions in human type 1 diabetes: a randomized controlled trial.

PubMed

van Golen, Larissa W; Veltman, Dick J; IJzerman, Richard G; Deijen, Jan Berend; Heijboer, Annemieke C; Barkhof, Frederik; Drent, Madeleine L; Diamant, Michaela

2014-01-01

Studies in rodents have demonstrated that insulin in the central nervous system induces satiety. In humans, these effects are less well established. Insulin detemir is a basal insulin analog that causes less weight gain than other basal insulin formulations, including the current standard intermediate-long acting Neutral Protamine Hagedorn (NPH) insulin. Due to its structural modifications, which render the molecule more lipophilic, it was proposed that insulin detemir enters the brain more readily than other insulins. The aim of this study was to investigate whether insulin detemir treatment differentially modifies brain activation in response to food stimuli as compared to NPH insulin. In addition, cerebral spinal fluid (CSF) insulin levels were measured after both treatments. Brain responses to viewing food and non-food pictures were measured using functional Magnetic Resonance Imaging in 32 type 1 diabetic patients, after each of two 12-week treatment periods with insulin detemir and NPH insulin, respectively, both combined with prandial insulin aspart. CSF insulin levels were determined in a subgroup. Insulin detemir decreased body weight by 0.8 kg and NPH insulin increased weight by 0.5 kg (p = 0.02 for difference), while both treatments resulted in similar glycemic control. After treatment with insulin detemir, as compared to NPH insulin, brain activation was significantly lower in bilateral insula in response to visual food stimuli, compared to NPH (p = 0.02 for right and p = 0.05 for left insula). Also, CSF insulin levels were higher compared to those with NPH insulin treatment (p = 0.003). Our findings support the hypothesis that in type 1 diabetic patients, the weight sparing effect of insulin detemir may be mediated by its enhanced action on the central nervous system, resulting in blunted activation in bilateral insula, an appetite-regulating brain region, in response to food stimuli. ClinicalTrials.gov NCT00626080.

A Multimodal Imaging- and Stimulation-based Method of Evaluating Connectivity-related Brain Excitability in Patients with Epilepsy

PubMed Central

Shafi, Mouhsin M.; Whitfield-Gabrieli, Susan; Chu, Catherine J.; Pascual-Leone, Alvaro; Chang, Bernard S.

2017-01-01

Resting-state functional connectivity MRI (rs-fcMRI) is a technique that identifies connectivity between different brain regions based on correlations over time in the blood-oxygenation level dependent signal. rs-fcMRI has been applied extensively to identify abnormalities in brain connectivity in different neurologic and psychiatric diseases. However, the relationship among rs-fcMRI connectivity abnormalities, brain electrophysiology and disease state is unknown, in part because the causal significance of alterations in functional connectivity in disease pathophysiology has not been established. Transcranial Magnetic Stimulation (TMS) is a technique that uses electromagnetic induction to noninvasively produce focal changes in cortical activity. When combined with electroencephalography (EEG), TMS can be used to assess the brain's response to external perturbations. Here we provide a protocol for combining rs-fcMRI, TMS and EEG to assess the physiologic significance of alterations in functional connectivity in patients with neuropsychiatric disease. We provide representative results from a previously published study in which rs-fcMRI was used to identify regions with abnormal connectivity in patients with epilepsy due to a malformation of cortical development, periventricular nodular heterotopia (PNH). Stimulation in patients with epilepsy resulted in abnormal TMS-evoked EEG activity relative to stimulation of the same sites in matched healthy control patients, with an abnormal increase in the late component of the TMS-evoked potential, consistent with cortical hyperexcitability. This abnormality was specific to regions with abnormal resting-state functional connectivity. Electrical source analysis in a subject with previously recorded seizures demonstrated that the origin of the abnormal TMS-evoked activity co-localized with the seizure-onset zone, suggesting the presence of an epileptogenic circuit. These results demonstrate how rs-fcMRI, TMS and EEG can be utilized together to identify and understand the physiological significance of abnormal brain connectivity in human diseases. PMID:27911366

Behavioral and cellular consequences of increasing serotonergic activity during brain development: a role in autism?

PubMed

Whitaker-Azmitia, Patricia M

2005-02-01

The hypothesis explored in this review is that the high levels of serotonin in the blood seen in some autistic children (the so-called hyperserotonemia of autism) may lead to some of the behavioral and cellular changes also observed in the disorder. At early stages of development, when the blood-brain Barrier is not yet fully formed, the high levels of serotonin in the blood can enter the brain of a developing fetus and cause loss of serotonin terminals through a known negative feedback function of serotonin during development. The loss of serotonin innervation persists throughout subsequent development and the symptoms of autism appear. A review of the basic scientific literature on prenatal treatments affecting serotonin is given, in support of this hypothesis, with an emphasis on studies using the serotonin agonist, 5-methoxytryptamine (5-MT). In work using 5-MT to mimic hyperserotonemia, Sprague-Dawley rats are treated from gestational day 12 until postnatal 20. In published reports, these animals have been found to have a significant loss of serotonin terminals, decreased metabolic activity in cortex, changes in columnar development in cortex, changes in serotonin receptors, and "autistic-like" behaviors. In preliminary cellular findings given in this review, the animals have also been found to have cellular changes in two relevant brain regions: 1. Central nucleus of the amygdala, a brain region involved in fear-responding, where an increase in calcitonin gene related peptide (CGRP) was found 2. Paraventricular nucleus of the hypothalamus, a brain region involved in social memory and bonding, where a decrease in oxytocin was found. Both of these cellular changes could result from loss of serotonin innervation, possibly due to loss of terminal outgrowth from the same cells of the raphe nuclei. Thus, increased serotonergic activity during development could damage neurocircuitry involved in emotional responding to social stressors and may have relevance to the symptoms of autism.

[On factors that effect the variability of central mechanisms of bilingualism].

PubMed

Kruchinina, O V; Gal'perina, E I; Kats, E É; Shepoval'nikov, A N

2012-01-01

The article discusses the probable role of many factors that determine the individual variety of neurophysiological mechanisms, which provide the opportunity to learn and free use two or more languages. The formation of a speech functions is affected by both the general factors for bilinguals and monolinguals, as well as the specific characteristic of the situation of bilingualism. The general factors include genetic and environmental impact of explaining the diversity of individual options for the development of morphofunctional organization of speech functions. A bilinguals, obviously, have even more wide variance of the central maintenance of speech activity, due to the combination of different conditions that influence the language environment, which include the age of the second language acquisition, the language proficiency, linguistic closeness of the languages, the method of their acquisition, intensity of use and the scope of application of each of the languages. The influence of these factors can mediates in different ways by the individual characteristics of the bilingual's brain. Being exposed to two languages from the first days of life, the child uses for the development of speech skills of the unique features of the brain, which are available only in the initial stages of postnatal ontogenesis. In older age mastering a second language requires much more effort, when, as maturation, the brain acquires new additional possibilities, but permanently lose that special "bonus", which nature gives a small child only in the first months of life. Large individual variability patterns of activation of the cortex when verbal activity in late bilingual" compared with the "early", allows to assume, that the brain of "late bilingual", mastering a new language, forced to operate a large number of backup mechanisms, and this is reflected in the increase of variation in the cerebral processes, responsible for providing of speech functions. In addition, there is serious reason to believe that learning a second language contributes to the expansion of the functional capabilities of the brain and creates the basis for a successful cognitive activity.

Neurobiology of KB220Z-Glutaminergic-Dopaminergic Optimization Complex [GDOC] as a Liquid Nano: Clinical Activation of Brain in a Highly Functional Clinician Improving Focus, Motivation and Overall Sensory Input Following Chronic Intake.

PubMed

Duquette, Lucien L; Mattiace, Frank; Blum, Kenneth; Waite, Roger L; Boland, Teresa; McLaughlin, Thomas; Dushaj, Kristina; Febo, Marcelo; Badgaiyan, Rajendra D

2016-01-01

With neurogenetic and epigenetic tools utilized in research and neuroimaging, we are unraveling the mysteries of brain function, especially as it relates to Reward Deficiency (RDS). We encourage the development of pharmaceuticals or nutraceuticals that promote a reduction in dopamine resistance and balance brain neurochemistry, leading to dopamine homeostasis. We disclose self-assessment of a highly functional professional under work-related stress following KB220Z use, a liquid (aqua) nano glutaminergic-dopaminergic optimization complex (GDOC). Subject took GDOC for one month. Subject self-administered GDOC using one-half-ounce twice a day. During first three days, unique brain activation occurred; resembling white noise after 30 minutes and sensation was strong for 45 minutes and then dissipated. He described effect as if his eyesight improved slightly and pointed out that his sense of smell and sleep greatly improved. Subject experienced a calming effect similar to meditation that could be linked to dopamine release. He also reported control of going over the edge after a hard day's work, which was coupled with a slight increase in energy, increased motivation to work, increased focus and multi-tasking, with clearer purpose of task at hand. Subject felt less inhibited in a social setting and suggested Syndrome that GDOC increased his Behavior Activating System (reward), while having a decrease in the Behavior Inhibition System (caution). These results and other related studies reveal an improved mood, work-related focus, and sleep. These effects as a subjective feeling of brain activation maybe due to direct or indirect dopaminergic interaction. While this case is encouraging, we must await more research in a larger randomized placebo-controlled study to map the role of GDOC, especially in a nano-sized product, to determine the possible effects on circuit inhibitory control and memory banks and the induction of dopamine homeostasis independent of either hypo- or hyper-dopaminergic traits/states.

Decoding of Ankle Flexion and Extension from Cortical Current Sources Estimated from Non-invasive Brain Activity Recording Methods.

PubMed

Mejia Tobar, Alejandra; Hyoudou, Rikiya; Kita, Kahori; Nakamura, Tatsuhiro; Kambara, Hiroyuki; Ogata, Yousuke; Hanakawa, Takashi; Koike, Yasuharu; Yoshimura, Natsue

2017-01-01

The classification of ankle movements from non-invasive brain recordings can be applied to a brain-computer interface (BCI) to control exoskeletons, prosthesis, and functional electrical stimulators for the benefit of patients with walking impairments. In this research, ankle flexion and extension tasks at two force levels in both legs, were classified from cortical current sources estimated by a hierarchical variational Bayesian method, using electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) recordings. The hierarchical prior for the current source estimation from EEG was obtained from activated brain areas and their intensities from an fMRI group (second-level) analysis. The fMRI group analysis was performed on regions of interest defined over the primary motor cortex, the supplementary motor area, and the somatosensory area, which are well-known to contribute to movement control. A sparse logistic regression method was applied for a nine-class classification (eight active tasks and a resting control task) obtaining a mean accuracy of 65.64% for time series of current sources, estimated from the EEG and the fMRI signals using a variational Bayesian method, and a mean accuracy of 22.19% for the classification of the pre-processed of EEG sensor signals, with a chance level of 11.11%. The higher classification accuracy of current sources, when compared to EEG classification accuracy, was attributed to the high number of sources and the different signal patterns obtained in the same vertex for different motor tasks. Since the inverse filter estimation for current sources can be done offline with the present method, the present method is applicable to real-time BCIs. Finally, due to the highly enhanced spatial distribution of current sources over the brain cortex, this method has the potential to identify activation patterns to design BCIs for the control of an affected limb in patients with stroke, or BCIs from motor imagery in patients with spinal cord injury.

Transparent, Flexible, Low Noise Graphene Electrodes for Simultaneous Electrophysiology and Neuroimaging

PubMed Central

Kuzum, Duygu; Takano, Hajime; Shim, Euijae; Reed, Jason C; Juul, Halvor; Richardson, Andrew G.; de Vries, Julius; Bink, Hank; Dichter, Marc A.; Lucas, Timothy H.; Coulter, Douglas A.; Cubukcu, Ertugrul; Litt, Brian

2014-01-01

Calcium imaging is a versatile experimental approach capable of resolving single neurons with single-cell spatial resolution in the brain. Electrophysiological recordings provide high temporal, but limited spatial resolution, due to the geometrical inaccessibility of the brain. An approach that integrates the advantages of both techniques could provide new insights into functions of neural circuits. Here, we report a transparent, flexible neural electrode technology based on graphene, which enables simultaneous optical imaging and electrophysiological recording. We demonstrate that hippocampal slices can be imaged through transparent graphene electrodes by both confocal and two-photon microscopy without causing any light-induced artifacts in the electrical recordings. Graphene electrodes record high frequency bursting activity and slow synaptic potentials that are hard to resolve by multi-cellular calcium imaging. This transparent electrode technology may pave the way for high spatio-temporal resolution electrooptic mapping of the dynamic neuronal activity. PMID:25327632

Cannabinoids: between neuroprotection and neurotoxicity.

PubMed

Sarne, Yosef; Mechoulam, Raphael

2005-12-01

Cannabinoids, such as the delta9-tetrahydrocannabinol (THC), present in the cannabis plant, as well as anandamide and 2-arachidonoyl glycerol, produced by the mammalian body, have been shown to protect the brain from various insults and to improve several neurodegenerative diseases. The current review summarizes the evidence for cannabinoid neuroprotection in vivo, and refers to recent in vitro studies, which help elucidate possible molecular mechanisms underlying this protective effect. Some of these mechanisms involve the activation of CB1 and CB2 cannabinoid receptors, while others are not dependent on them. In some cases, protection is due to a direct effect of the cannabinoids on neuronal cells, while in others, it results from their effects on non-neuronal elements within the brain. In many experimental set-ups, cannabinoid neurotoxicity, particularly by THC, resides side by side with neuroprotection. The current review attempts to shed light on this dual activity, and to dissociate between the two contradictory effects.

Neuronal plasticity and thalamocortical sleep and waking oscillations

PubMed Central

Timofeev, Igor

2011-01-01

Throughout life, thalamocortical (TC) network alternates between activated states (wake or rapid eye movement sleep) and slow oscillatory state dominating slow-wave sleep. The patterns of neuronal firing are different during these distinct states. I propose that due to relatively regular firing, the activated states preset some steady state synaptic plasticity and that the silent periods of slow-wave sleep contribute to a release from this steady state synaptic plasticity. In this respect, I discuss how states of vigilance affect short-, mid-, and long-term synaptic plasticity, intrinsic neuronal plasticity, as well as homeostatic plasticity. Finally, I suggest that slow oscillation is intrinsic property of cortical network and brain homeostatic mechanisms are tuned to use all forms of plasticity to bring cortical network to the state of slow oscillation. However, prolonged and profound shift from this homeostatic balance could lead to development of paroxysmal hyperexcitability and seizures as in the case of brain trauma. PMID:21854960

[The neurobiology of autism].

PubMed

Kotsopoulos, S

2007-07-01

The research effort on autism has for several years been intensive. Recent progress in this field is due mainly to the development of increasingly sophisticated visualizing assessment methods of the brain. Most of the evidence reported in this review requires further replication and elaboration by ongoing research. Evidence from volumetric studies indicates that the brain of the child with autism deviates from normal paths at the early stages of development showing excessive growth during the first year and a half involving the hemispheres and the cerebellum. Post mortem studies have shown neuron abnormalities in the frontal and temporal cortex and the cerebellum. Studies using diffusion tensor imaging, an fMRI based method, have shown disruptions between white and grey matter in several areas of the hemispheres. Other studies investigating activation of the cortex showed lack of synchrony and coordination between anterior and posterior areas of the hemispheres. It has been suggested that the deviation in brain development in autism consists of excessive numbers of neurons which cause the cytoarchitectural deviation. A theory suggesting that the basic deficit in autism is due to dysfunction of the "mirror neuron system" requires further substantiation. The aetiology of autism is not known although risk factors have been identified. Predominant among them are genetic influences. The search is currently intensive for an understanding of the pathogenesis of the pathological deviation in the development of the brain in autism. Neurotrophic factors which determine the developmental steps of the brain are examined such as serotonin, brain-derived neurotrophic factor (BDNF), the neuropeptide reelin, neuroligines and others. There is evidence of some involvement of these factors with autism but it is still far from clear how they do interact with one another and how they lead to the pathological deviations observed in autism. The neurotrophic factors are evidently coded by genes which are being examined by geneticists. It has also been suggested that autoimmune responses while interacting with neurotrophic factors may be important for the autistic deviation in brain development. Limitations may exist in the interpretation of the study results on which the present review was based. These are probably due to inconsistencies among studies related to variability in the severity of the disorders and age among subjects, presence or not of mental retardation, differing assessment methods.

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

PubMed

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

2009-08-04

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

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

PubMed Central

Timms, Andrew E.; Conti, Valerio; Girisha, Katta M.; Martin, Beth; Olds, Carissa; Collins, Sarah; Park, Kaylee; Carter, Melissa; Krägeloh-Mann, Inge; Chitayat, David; Parikh, Aditi Shah; Bradshaw, Rachael; Torti, Erin; Braddock, Stephen; Burke, Leah; Ghedia, Sondhya; Stephan, Mark; Stewart, Fiona; Prasad, Chitra; Napier, Melanie; Saitta, Sulagna; Straussberg, Rachel; Gabbett, Michael; O’Connor, Bridget C.; Yin, Lim Jiin; Lai, Angeline Hwei Meeng; Martin, Nicole; McKinnon, Margaret; Addor, Marie-Claude; Schwartz, Charles E.; Lanoel, Agustina; Conway, Robert L.; Devriendt, Koenraad; Tatton-Brown, Katrina; Pierpont, Mary Ella; Painter, Michael; Worgan, Lisa; Reggin, James; Hennekam, Raoul; Pritchard, Colin C.; Aracena, Mariana; Gripp, Karen W.; Cordisco, Maria; Van Esch, Hilde; Garavelli, Livia; Curry, Cynthia; Goriely, Anne; Kayserilli, Hulya; Shendure, Jay; Graham, John; Guerrini, Renzo; Dobyns, William B.

2016-01-01

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations. PMID:27631024

Communication, concepts and grounding.

PubMed

van der Velde, Frank

2015-02-01

This article discusses the relation between communication and conceptual grounding. In the brain, neurons, circuits and brain areas are involved in the representation of a concept, grounding it in perception and action. In terms of grounding we can distinguish between communication within the brain and communication between humans or between humans and machines. In the first form of communication, a concept is activated by sensory input. Due to grounding, the information provided by this communication is not just determined by the sensory input but also by the outgoing connection structure of the conceptual representation, which is based on previous experiences and actions. The second form of communication, that between humans or between humans and machines, is influenced by the first form. In particular, a more successful interpersonal communication might require forms of situated cognition and interaction in which the entire representations of grounded concepts are involved. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Neurophysiological Foundations and Practical Realizations of the Brain-Machine Interfaces the Technology in Neurological Rehabilitation].

PubMed

Kaplan, A Ya

2016-01-01

Technology brain-computer interface (BCI) based on the registration and interpretation of EEG has recently become one of the most popular developments in neuroscience and psychophysiology. This is due not only to the intended future use of these technologies in many areas of practical human activity, but also to the fact that IMC--is a completely new paradigm in psychophysiology, allowing test hypotheses about the possibilities of the human brain to the development of skills of interaction with the outside world without the mediation of the motor system, i.e. only with the help of voluntary modulation of EEG generators. This paper examines the theoretical and experimental basis, the current state and prospects of development of training, communicational and assisting complexes based on BCI to control them without muscular effort on the basis of mental commands detected in the EEG of patients with severely impaired speech and motor system.

Neuronal overexpression of cyclooxygenase-2 does not alter the neuroinflammatory response during brain innate immune activation.

PubMed

Aid, Saba; Parikh, Nishant; Palumbo, Sara; Bosetti, Francesca

2010-07-12

Neuroinflammation is a critical component in the progression of several neurological and neurodegenerative diseases and cyclooxygenases (COX)-1 and -2 are key regulators of innate immune responses. We recently demonstrated that COX-1 deletion attenuates, whereas COX-2 deletion enhances, the neuroinflammatory response, blood-brain barrier permeability and leukocyte recruitment during lipopolysaccharide (LPS)-induced innate immune activation. Here, we used transgenic mice, which overexpressed human COX-2 via neuron-specific Thy-1 promoter (TgCOX-2), causing elevated prostaglandins (PGs) levels. We tested whether neuronal COX-2 overexpression affects the glial response to a single intracerebroventricular injection of LPS, which produces a robust neuroinflammatory reaction. Relative to non-transgenic controls (NTg), 7 month-old TgCOX-2 did not show any basal neuroinflammation, as assessed by gene expression of markers of inflammation and oxidative stress, neuronal damage, as assessed by Fluoro-JadeB staining, or systemic inflammation, as assessed by plasma levels of IL-1beta and corticosterone. Twenty-four hours after LPS injection, all mice showed increased microglial activation, as indicated by Iba1 immunostaining, neuronal damage, mRNA expression of cytokines (TNF-alpha, IL-6), reactive oxygen expressing enzymes (iNOS and NADPH oxidase subunits), endogenous COX-2, cPLA(2) and mPGES-1, and hippocampal and cortical IL-1beta levels. However, the increases were similar in TgCOX-2 and NTg. In NTg, LPS increased brain PGE(2) to the levels observed in TgCOX-2. These results suggest that PGs derived from neuronal COX-2 do not play a role in the neuroinflammatory response to acute activation of brain innate immunity. This is likely due to the direct effect of LPS on glial rather than neuronal cells. Published by Elsevier Ireland Ltd.

Age-dependent effects of esculetin on mood-related behavior and cognition from stressed mice are associated with restoring brain antioxidant status.

PubMed

Martín-Aragón, Sagrario; Villar, Ángel; Benedí, Juana

2016-02-04

Dietary antioxidants might exert an important role in the aging process by relieving oxidative damage, a likely cause of age-associated brain dysfunctions. This study aims to investigate the influence of esculetin (6,7-dihydroxycoumarin), a naturally occurring antioxidant in the diet, on mood-related behaviors and cognitive function and its relation with age and brain oxidative damage. Behavioral tests were employed in 11-, 17- and 22-month-old male C57BL/6J mice upon an oral 35day-esculetin treatment (25mg/kg). Activity of antioxidant enzymes, GSH and GSSG levels, GSH/GSSG ratio, and mitochondrial function were analyzed in brain cortex at the end of treatment in order to assess the oxidative status related to mouse behavior. Esculetin treatment attenuated the increased immobility time and enhanced the diminished climbing time in the forced swim task elicited by acute restraint stress (ARS) in the 11- and 17-month-old mice versus their counterpart controls. Furthermore, ARS caused an impairment of contextual memory in the step-through passive avoidance both in mature adult and aged mice which was partially reversed by esculetin only in the 11-month-old mice. Esculetin was effective to prevent the ARS-induced oxidative stress mostly in mature adult mice by restoring antioxidant enzyme activities, augmenting the GSH/GSSG ratio and increasing cytochrome c oxidase (COX) activity in cortex. Modulation of the mood-related behavior and cognitive function upon esculetin treatment in a mouse model of ARS depends on age and is partly due to the enhancement of redox status and levels of COX activity in cortex. Copyright © 2015. Published by Elsevier Inc.

Effects of chemical and thermal stress on acetylcholinesterase activity in the brain of the bank vole, Myodes glareolus.

PubMed

Świergosz-Kowalewska, Renata; Molenda, Patrycja; Halota, Anna

2014-08-01

One of the most important issues in ecotoxicology is better understanding the effects of interactions between chemical pollutants and physical environmental factors on animals. To fill this knowledge gap, changes in the activity of acetylcholinesterase (AChE) in the brain samples of bank voles Myodes (Clethrionomys) glareolus due to temperature effects, and two chemical stressors were studied in a full factorial laboratory experiment (27 treatments). The experiment was divided into three phases: acclimatisation (3 days), intoxication (42 days) and elimination (21 days). During the intoxication phase, animals were orally exposed to different concentrations of either nickel (0, 300 or 800 mg Ni/kg food), chlorpyrifos (CPF) (0, 50 or 350 mg CPF/kg food) or a mixture of both chemicals. During the acclimatisation and elimination phases, the bank voles were given uncontaminated food. The experiment was conducted at three different temperatures (10, 20 or 30 °C), and a 12 h:12 h light:dark regime. The animals were sacrificed at 0, 5, 10, 20, 42, 49 and 63 days after the beginning of the intoxication, and brain samples were obtained for chemical analysis. The nickel accumulation in the brain depended on the level of nickel exposure and on interactions between the temperature and other factors. Nickel exhibited no effect on AChE activity. In contrast, AChE was drastically inhibited by chlorpyrifos and low temperature, but interactions between all factors significantly influenced the enzyme activity during the elimination phase of the experiment. High mortality was observed in the groups exposed to high concentrations of nickel and chlorpyrifos. Copyright © 2014 Elsevier Inc. All rights reserved.

Human Brain Modeling with Its Anatomical Structure and Realistic Material Properties for Brain Injury Prediction.

PubMed

Atsumi, Noritoshi; Nakahira, Yuko; Tanaka, Eiichi; Iwamoto, Masami

2018-05-01

Impairments of executive brain function after traumatic brain injury (TBI) due to head impacts in traffic accidents need to be obviated. Finite element (FE) analyses with a human brain model facilitate understanding of the TBI mechanisms. However, conventional brain FE models do not suitably describe the anatomical structure in the deep brain, which is a critical region for executive brain function, and the material properties of brain parenchyma. In this study, for better TBI prediction, a novel brain FE model with anatomical structure in the deep brain was developed. The developed model comprises a constitutive model of brain parenchyma considering anisotropy and strain rate dependency. Validation was performed against postmortem human subject test data associated with brain deformation during head impact. Brain injury analyses were performed using head acceleration curves obtained from reconstruction analysis of rear-end collision with a human whole-body FE model. The difference in structure was found to affect the regions of strain concentration, while the difference in material model contributed to the peak strain value. The injury prediction result by the proposed model was consistent with the characteristics in the neuroimaging data of TBI patients due to traffic accidents.

Distinguishing rhythmic from non-rhythmic brain activity during rest in healthy neurocognitive aging.

PubMed

Caplan, Jeremy B; Bottomley, Monica; Kang, Pardeep; Dixon, Roger A

2015-05-15

Rhythmic brain activity at low frequencies (<12Hz) during rest are thought to increase in neurodegenerative disease, but findings in healthy neurocognitive aging are mixed. Here we address two reasons conventional spectral analyses may have led to inconsistent results. First, spectral-power measures are compared to a baseline condition; when resting activity is the signal of interest, it is unclear what the baseline should be. Second, conventional methods do not clearly differentiate power due to rhythmic versus non-rhythmic activity. The Better OSCillation detection method (BOSC; Caplan et al., 2001; Whitten et al., 2011) avoids these problems by using the signal's own spectral characteristics as a reference to detect elevations in power lasting a few cycles. We recorded electroencephalographic (EEG) signal during rest, alternating eyes open and closed, in healthy younger (18-25 years) and older (60-74 years) participants. Topographic plots suggested the conventional and BOSC analyses measured different sources of activity, particularly at frequencies, like delta (1-4Hz), at which rhythms are sporadic; topographies were more similar in the 8-12Hz alpha band. There was little theta-band activity meeting the BOSC method's criteria, suggesting prior findings of theta power in healthy aging may reflect non-rhythmic signal. In contrast, delta oscillations were present at higher levels than theta in both age groups. In summary, applying strict and standardized criteria for rhythmicity, slow rhythms appear present in the resting brain at delta and alpha, but not theta frequencies, and appear unchanged in healthy aging. Copyright © 2015 Elsevier Inc. All rights reserved.

A method for recording resistance changes non-invasively during neuronal depolarization with a view to imaging brain activity with electrical impedance tomography.

PubMed

Gilad, Ori; Ghosh, Anthony; Oh, Dongin; Holder, David S

2009-05-30

Electrical impedance tomography (EIT) is a recently developed medical imaging method which has the potential to produce images of fast neuronal depolarization in the brain. The principle is that current remains in the extracellular space at rest but passes into the intracellular space during depolarization through open ion channels. As current passes into the intracellular space across the capacitance of cell membranes at higher frequencies, applied current needs to be below 100 Hz. A method is presented for its measurement with subtraction of the contemporaneous evoked potentials which occur in the same frequency band. Neuronal activity is evoked by stimulation and resistance is recorded from the potentials resulting from injection of a constant current square wave at 1 Hz with amplitude less than 25% of the threshold for stimulating neuronal activity. Potentials due to the evoked activity and the injected square wave are removed by subtraction. The method was validated with compound action potentials in crab walking leg nerve. Resistance changes of -0.85+/-0.4% (mean+/-SD) occurred which decreased from -0.97+/-0.43% to -0.46+/-0.16% with spacing of impedance current application electrodes from 2 to 8 mm but did not vary significantly with applied currents of 1-10 microA. These tallied with biophysical modelling, and so were consistent with a genuine physiological origin. This method appears to provide a reproducible and artefact free means for recording resistance changes during neuronal activity which could lead to the long-term goal of imaging of fast neural activity in the brain.

Distinguishing rhythmic from non-rhythmic brain activity during rest in healthy neurocognitive aging

PubMed Central

Caplan, Jeremy B.; Bottomley, Monica; Kang, Pardeep; Dixon, Roger A.

2015-01-01

Rhythmic brain activity at low frequencies (<12 Hz) during rest are thought to increase in neurodegenerative disease, but findings in healthy neurocognitive aging are mixed. Here we address two reasons conventional spectral analyses may have led to inconsistent results. First, spectral-power measures are compared to a baseline condition; when resting activity is the signal of interest, it is unclear what the baseline should be. Second, conventional methods do not clearly differentiate power due to rhythmic versus non-rhythmic activity. The Better OSCillation detection method (BOSC; [10], [65]) avoids these problems by using the signal’s own spectral characteristics as a reference to detect elevations in power lasting a few cycles. We recorded electroencephalographic (EEG) signal during rest, alternating eyes open and closed, in healthy younger (18–25 years) and older (60–74 years) participants. Topographic plots suggested the conventional and BOSC analyses measured different sources of activity, particularly at frequencies, like delta (1–4 Hz), at which rhythms are sporadic (but topographies were more similar in the 8–12 Hz alpha band). There was little theta-band activity meeting the BOSC method’s criteria, suggesting prior findings of theta power in healthy aging may reflect non-rhythmic signal. In contrast, delta oscillations were present at higher levels than theta in both age groups. In sum, applying strict and standardized criteria for rhythmicity, slow rhythms appear present in the resting brain at delta and alpha, but not theta frequencies, and appear unchanged in healthy aging. PMID:25769279

Turning a cylindrical treadmill with feet: an MR-compatible device for assessment of the neural correlates of lower-limb movement.

PubMed

Toyomura, Akira; Yokosawa, Koichi; Shimojo, Atsushi; Fujii, Tetsunoshin; Kuriki, Shinya

2018-06-17

Locomotion, which is one of the most basic motor functions, is critical for performing various daily-life activities. Despite its essential function, assessment of brain activity during lower-limb movement is still limited because of the constraints of existing brain imaging methods. Here, we describe an MR-compatible, cylindrical treadmill device that allows participants to perform stepping movements on an MRI scanner table. The device was constructed from wood and all of the parts were handmade by the authors. We confirmed the MR-compatibility of the device by evaluating the temporal signal-to-noise ratio of 64 voxels of a phantom during scanning. Brain activity was measured while twenty participants turned the treadmill with feet in sync with metronome sounds. The rotary speed of the cylinder was encoded by optical fibers. The post/pre-central gyrus and cerebellum showed significant activity during the movements, which was comparable to the activity patterns reported in previous studies. Head movement on the y- and z-axes was influenced more by lower-limb movement than was head movement on the x-axis. Among the 60 runs (3 runs × 20 participants), head movement during two of the runs (3.3%) was excessive due to the lower-limb movement. Compared to MR-compatible devices proposed in the previous studies, the advantage of this device may be simple structure and replicability to realize stepping movement with a supine position. Collectively, our results suggest that the treadmill device is useful for evaluating lower-limb-related neural activity. Copyright © 2018. Published by Elsevier B.V.

The Bioelectromagnetics Society Annual Scientific Session (5th) Abstracts,

DTIC Science & Technology

1983-01-01

cm ) for one hour. Extended survival of hamsters from VSV injection could be due to activated macropha- ges destroying Injected virus and perhaps...to increased anti-VSV antibody production. These results are consistent with our previous work with vaccinia virus (Bloelectromagnetics, In press...guinea pigs and cats reflect intracranial rever- berations of a pressure pulse induced within the brain. Results from single-unit and psychophysical

Integrating EEG and fMRI in epilepsy.

PubMed

Formaggio, Emanuela; Storti, Silvia Francesca; Bertoldo, Alessandra; Manganotti, Paolo; Fiaschi, Antonio; Toffolo, Gianna Maria

2011-02-14

Integrating electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) studies enables to non-invasively investigate human brain function and to find the direct correlation of these two important measures of brain activity. Presurgical evaluation of patients with epilepsy is one of the areas where EEG and fMRI integration has considerable clinical relevance for localizing the brain regions generating interictal epileptiform activity. The conventional analysis of EEG-fMRI data is based on the visual identification of the interictal epileptiform discharges (IEDs) on scalp EEG. The convolution of these EEG events, represented as stick functions, with a model of the fMRI response, i.e. the hemodynamic response function, provides the regressor for general linear model (GLM) analysis of fMRI data. However, the conventional analysis is not automatic and suffers of some subjectivity in IEDs classification. Here, we present an easy-to-use and automatic approach for combined EEG-fMRI analysis able to improve IEDs identification based on Independent Component Analysis and wavelet analysis. EEG signal due to IED is reconstructed and its wavelet power is used as a regressor in GLM. The method was validated on simulated data and then applied on real data set consisting of 2 normal subjects and 5 patients with partial epilepsy. In all continuous EEG-fMRI recording sessions a good quality EEG was obtained allowing the detection of spontaneous IEDs and the analysis of the related BOLD activation. The main clinical finding in EEG-fMRI studies of patients with partial epilepsy is that focal interictal slow-wave activity was invariably associated with increased focal BOLD responses in a spatially related brain area. Our study extends current knowledge on epileptic foci localization and confirms previous reports suggesting that BOLD activation associated with slow activity might have a role in localizing the epileptogenic region even in the absence of clear interictal spikes. Copyright © 2010 Elsevier Inc. All rights reserved.

Coping with Brain Disorders using Neurotechnology.

PubMed

Pedro A, Valdes-Sosa

2012-01-01

Brain disorders account for more than 34% of the global burden of disease, crippling nations by decreasing their "mental capital"-with greater effect in developing countries. Early detection is the key to their management, but establishing such programmes seems nearly impossible due to the high prevalence of the dysfunctions as compared with the high cost of neuroimaging devices. Thus, at first sight, the research of the Decade of the Brain and the international Human Brain Mapping Project might seem to be condemned to benefit only a small elite. Cuba has shown that is not so by using neurotechnology for the last 3 decades to implement stratified active screening programmes for brain disorders at the population level. This experience has shown that, by the transformation of health indicators, an appropriate use of technology can be integrated with attention to the population at the primary levels of both health care and education. An essential component of neurotechnology is neuroinformatics, which-like its counterpart bioinformatics-combines databases, analysis tools, and theoretical models to craft tools for early disease diagnosis and management. Much work remains to be done and will depend critically on south-south cooperation to solve problems for countries with similar situations.

Coping with Brain Disorders using Neurotechnology

PubMed Central

Pedro A, Valdes-Sosa

2012-01-01

Brain disorders account for more than 34% of the global burden of disease, crippling nations by decreasing their “mental capital”—with greater effect in developing countries. Early detection is the key to their management, but establishing such programmes seems nearly impossible due to the high prevalence of the dysfunctions as compared with the high cost of neuroimaging devices. Thus, at first sight, the research of the Decade of the Brain and the international Human Brain Mapping Project might seem to be condemned to benefit only a small elite. Cuba has shown that is not so by using neurotechnology for the last 3 decades to implement stratified active screening programmes for brain disorders at the population level. This experience has shown that, by the transformation of health indicators, an appropriate use of technology can be integrated with attention to the population at the primary levels of both health care and education. An essential component of neurotechnology is neuroinformatics, which—like its counterpart bioinformatics—combines databases, analysis tools, and theoretical models to craft tools for early disease diagnosis and management. Much work remains to be done and will depend critically on south—south cooperation to solve problems for countries with similar situations. PMID:22977368

Brain Imaging and Human Nutrition: Which Measures to Use in Intervention Studies?12

PubMed Central

Sizonenko, Stéphane V.; Babiloni, Claudio; Sijben, John W.; Walhovd, Kristine B.

2013-01-01

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed. PMID:24038255

New Antioxidant Drugs for Neonatal Brain Injury

PubMed Central

Tataranno, Maria Luisa; Longini, Mariangela; Buonocore, Giuseppe

2015-01-01

The brain injury concept covers a lot of heterogeneity in terms of aetiology involving multiple factors, genetic, hemodynamic, metabolic, nutritional, endocrinological, toxic, and infectious mechanisms, acting in antenatal or postnatal period. Increased vulnerability of the immature brain to oxidative stress is documented because of the limited capacity of antioxidant enzymes and the high free radicals (FRs) generation in rapidly growing tissue. FRs impair transmembrane enzyme Na+/K+-ATPase activity resulting in persistent membrane depolarization and excessive release of FR and excitatory aminoacid glutamate. Besides being neurotoxic, glutamate is also toxic to oligodendroglia, via FR effects. Neuronal cells die of oxidative stress. Excess of free iron and deficient iron/binding metabolising capacity are additional features favouring oxidative stress in newborn. Each step in the oxidative injury cascade has become a potential target for neuroprotective intervention. The administration of antioxidants for suspected or proven brain injury is still not accepted for clinical use due to uncertain beneficial effects when treatments are started after resuscitation of an asphyxiated newborn. The challenge for the future is the early identification of high-risk babies to target a safe and not toxic antioxidant therapy in combination with standard therapies to prevent brain injury and long-term neurodevelopmental impairment. PMID:25685254

Apparent isotropic electrical property for electrical brain stimulation (EBS) using magnetic resonance diffusion weighted imaging (MR-DWI)

NASA Astrophysics Data System (ADS)

Lee, Mun Bae; Kwon, Oh-In

2018-04-01

Electrical brain stimulation (EBS) is an invasive electrotherapy and technique used in brain neurological disorders through direct or indirect stimulation using a small electric current. EBS has relied on computational modeling to achieve optimal stimulation effects and investigate the internal activations. Magnetic resonance diffusion weighted imaging (DWI) is commonly useful for diagnosis and investigation of tissue functions in various organs. The apparent diffusion coefficient (ADC) measures the intensity of water diffusion within biological tissues using DWI. By measuring trace ADC and magnetic flux density induced by the EBS, we propose a method to extract electrical properties including the effective extracellular ion-concentration (EEIC) and the apparent isotropic conductivity without any auxiliary additional current injection. First, the internal current density due to EBS is recovered using the measured one component of magnetic flux density. We update the EEIC by introducing a repetitive scheme called the diffusion weighting J-substitution algorithm using the recovered current density and the trace ADC. To verify the proposed method, we study an anesthetized canine brain to visualize electrical properties including electrical current density, effective extracellular ion-concentration, and effective isotropic conductivity by applying electrical stimulation of the brain.

Protein kinase C restricts transport of carnitine by amino acid transporter ATB(0,+) apically localized in the blood-brain barrier.

PubMed

Michalec, Katarzyna; Mysiorek, Caroline; Kuntz, Mélanie; Bérézowski, Vincent; Szczepankiewicz, Andrzej A; Wilczyński, Grzegorz M; Cecchelli, Roméo; Nałęcz, Katarzyna A

2014-07-15

Carnitine (3-hydroxy-4-trimethylammoniobutyrate) is necessary for transfer of fatty acids through the inner mitochondrial membrane. Carnitine, not synthesized in the brain, is delivered there through the strongly polarized blood-brain barrier (BBB). Expression and presence of two carnitine transporters - organic cation/carnitine transporter (OCTN2) and amino acid transporter B(0,+) (ATB(0,+)) have been demonstrated previously in an in vitro model of the BBB. Due to potential protein kinase C (PKC) phosphorylation sites within ATB(0,+) sequence, the present study verified effects of this kinase on transporter function and localization in the BBB. ATB(0,+) can be regulated by estrogen receptor α and up-regulated in vitro, therefore its presence in vivo was verified with the transmission electron microscopy. The analyses of brain slices demonstrated ATB(0,+) luminal localization in brain capillaries, confirmed by biotinylation experiments in an in vitro model of the BBB. Brain capillary endothelial cells were shown to control carnitine gradient. ATB(0,+) was phosphorylated by PKC, what correlated with inhibition of carnitine transport. PKC activation did not change the amount of ATB(0,+) present in the apical membrane of brain endothelial cells, but resulted in transporter exclusion from raft microdomains. ATB(0,+) inactivation by a lateral movement in plasma membrane after transporter phosphorylation has been postulated. Copyright © 2014 Elsevier Inc. All rights reserved.

Functional connectivity analysis of resting-state fMRI networks in nicotine dependent patients

NASA Astrophysics Data System (ADS)

Smith, Aria; Ehtemami, Anahid; Fratte, Daniel; Meyer-Baese, Anke; Zavala-Romero, Olmo; Goudriaan, Anna E.; Schmaal, Lianne; Schulte, Mieke H. J.

2016-03-01

Brain imaging studies identified brain networks that play a key role in nicotine dependence-related behavior. Functional connectivity of the brain is dynamic; it changes over time due to different causes such as learning, or quitting a habit. Functional connectivity analysis is useful in discovering and comparing patterns between functional magnetic resonance imaging (fMRI) scans of patients' brains. In the resting state, the patient is asked to remain calm and not do any task to minimize the contribution of external stimuli. The study of resting-state fMRI networks have shown functionally connected brain regions that have a high level of activity during this state. In this project, we are interested in the relationship between these functionally connected brain regions to identify nicotine dependent patients, who underwent a smoking cessation treatment. Our approach is on the comparison of the set of connections between the fMRI scans before and after treatment. We applied support vector machines, a machine learning technique, to classify patients based on receiving the treatment or the placebo. Using the functional connectivity (CONN) toolbox, we were able to form a correlation matrix based on the functional connectivity between different regions of the brain. The experimental results show that there is inadequate predictive information to classify nicotine dependent patients using the SVM classifier. We propose other classification methods be explored to better classify the nicotine dependent patients.

Magnetite pollution nanoparticles in the human brain

PubMed Central

Maher, Barbara A.; Karloukovski, Vassil; MacLaren, Donald A.; Foulds, Penelope G.; Allsop, David; Mann, David M. A.; Torres-Jardón, Ricardo; Calderon-Garciduenas, Lilian

2016-01-01

Biologically formed nanoparticles of the strongly magnetic mineral, magnetite, were first detected in the human brain over 20 y ago [Kirschvink JL, Kobayashi-Kirschvink A, Woodford BJ (1992) Proc Natl Acad Sci USA 89(16):7683–7687]. Magnetite can have potentially large impacts on the brain due to its unique combination of redox activity, surface charge, and strongly magnetic behavior. We used magnetic analyses and electron microscopy to identify the abundant presence in the brain of magnetite nanoparticles that are consistent with high-temperature formation, suggesting, therefore, an external, not internal, source. Comprising a separate nanoparticle population from the euhedral particles ascribed to endogenous sources, these brain magnetites are often found with other transition metal nanoparticles, and they display rounded crystal morphologies and fused surface textures, reflecting crystallization upon cooling from an initially heated, iron-bearing source material. Such high-temperature magnetite nanospheres are ubiquitous and abundant in airborne particulate matter pollution. They arise as combustion-derived, iron-rich particles, often associated with other transition metal particles, which condense and/or oxidize upon airborne release. Those magnetite pollutant particles which are <∼200 nm in diameter can enter the brain directly via the olfactory bulb. Their presence proves that externally sourced iron-bearing nanoparticles, rather than their soluble compounds, can be transported directly into the brain, where they may pose hazard to human health. PMID:27601646

A critical review of neonicotinoid insecticides for developmental neurotoxicity

PubMed Central

Sheets, Larry P.; Li, Abby A.; Minnema, Daniel J.; Collier, Richard H.; Creek, Moire R.; Peffer, Richard C.

2016-01-01

Abstract A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood–brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of action and potential exposure with agricultural and residential uses. This review identified in vitro, in vivo, and epidemiology studies in the literature and studies performed in rats in accordance with GLP standards and EPA guidelines with imidacloprid, acetamiprid, thiacloprid, clothianidin, thiamethoxam, and dinotefuran, which are all the neonicotinoids currently registered in major markets. For the guideline-based studies, treatment was administered via the diet or gavage to primiparous female rats at three dose levels, plus a vehicle control (≥20/dose level), from gestation day 0 or 6 to lactation day 21. F1 males and females were evaluated using measures of motor activity, acoustic startle response, cognition, brain morphometry, and neuropathology. The principal effects in F1 animals were associated with decreased body weight (delayed sexual maturation, decreased brain weight, and morphometric measurements) and acute toxicity (decreased activity during exposure) at high doses, without neuropathology or impaired cognition. No common effects were identified among the neonicotinoids that were consistent with DNT or the neurodevelopmental effects associated with nicotine. Findings at high doses were associated with evidence of systemic toxicity, which indicates that these insecticides do not selectively affect the developing nervous system. PMID:26513508

A critical review of neonicotinoid insecticides for developmental neurotoxicity.

PubMed

Sheets, Larry P; Li, Abby A; Minnema, Daniel J; Collier, Richard H; Creek, Moire R; Peffer, Richard C

2016-02-01

A comprehensive review of published and previously unpublished studies was performed to evaluate the neonicotinoid insecticides for evidence of developmental neurotoxicity (DNT). These insecticides have favorable safety profiles, due to their preferential affinity for nicotinic receptor (nAChR) subtypes in insects, poor penetration of the mammalian blood-brain barrier, and low application rates. Nevertheless, examination of this issue is warranted, due to their insecticidal mode of action and potential exposure with agricultural and residential uses. This review identified in vitro, in vivo, and epidemiology studies in the literature and studies performed in rats in accordance with GLP standards and EPA guidelines with imidacloprid, acetamiprid, thiacloprid, clothianidin, thiamethoxam, and dinotefuran, which are all the neonicotinoids currently registered in major markets. For the guideline-based studies, treatment was administered via the diet or gavage to primiparous female rats at three dose levels, plus a vehicle control (≥20/dose level), from gestation day 0 or 6 to lactation day 21. F1 males and females were evaluated using measures of motor activity, acoustic startle response, cognition, brain morphometry, and neuropathology. The principal effects in F1 animals were associated with decreased body weight (delayed sexual maturation, decreased brain weight, and morphometric measurements) and acute toxicity (decreased activity during exposure) at high doses, without neuropathology or impaired cognition. No common effects were identified among the neonicotinoids that were consistent with DNT or the neurodevelopmental effects associated with nicotine. Findings at high doses were associated with evidence of systemic toxicity, which indicates that these insecticides do not selectively affect the developing nervous system.

Distributed Neural Activity Patterns during Human-to-Human Competition

PubMed Central

Piva, Matthew; Zhang, Xian; Noah, J. Adam; Chang, Steve W. C.; Hirsch, Joy

2017-01-01

Interpersonal interaction is the essence of human social behavior. However, conventional neuroimaging techniques have tended to focus on social cognition in single individuals rather than on dyads or groups. As a result, relatively little is understood about the neural events that underlie face-to-face interaction. We resolved some of the technical obstacles inherent in studying interaction using a novel imaging modality and aimed to identify neural mechanisms engaged both within and across brains in an ecologically valid instance of interpersonal competition. Functional near-infrared spectroscopy was utilized to simultaneously measure hemodynamic signals representing neural activity in pairs of subjects playing poker against each other (human–human condition) or against computer opponents (human–computer condition). Previous fMRI findings concerning single subjects confirm that neural areas recruited during social cognition paradigms are individually sensitive to human–human and human–computer conditions. However, it is not known whether face-to-face interactions between opponents can extend these findings. We hypothesize distributed effects due to live processing and specific variations in across-brain coherence not observable in single-subject paradigms. Angular gyrus (AG), a component of the temporal-parietal junction (TPJ) previously found to be sensitive to socially relevant cues, was selected as a seed to measure within-brain functional connectivity. Increased connectivity was confirmed between AG and bilateral dorsolateral prefrontal cortex (dlPFC) as well as a complex including the left subcentral area (SCA) and somatosensory cortex (SS) during interaction with a human opponent. These distributed findings were supported by contrast measures that indicated increased activity at the left dlPFC and frontopolar area that partially overlapped with the region showing increased functional connectivity with AG. Across-brain analyses of neural coherence between the players revealed synchrony between dlPFC and supramarginal gyrus (SMG) and SS in addition to synchrony between AG and the fusiform gyrus (FG) and SMG. These findings present the first evidence of a frontal-parietal neural complex including the TPJ, dlPFC, SCA, SS, and FG that is more active during human-to-human social cognition both within brains (functional connectivity) and across brains (across-brain coherence), supporting a model of functional integration of socially and strategically relevant information during live face-to-face competitive behaviors. PMID:29218005

LC-MS/MS profiling and neuroprotective effects of Mentat® against transient global ischemia and reperfusion-induced brain injury in rats.

PubMed

Viswanatha, Gollapalle Lakshminarayanashastry; Kumar, Lakkavalli Mohan Sharath; Rafiq, Mohamed; Kavya, Kethaganahalli Jayaramaiah; Thippeswamy, Agadi Hiremath; Yuvaraj, Huvvinamadu Chandrashekarappa; Azeemuddin, Mohammed; Anturlikar, Suryakanth Dattatreya; Patki, Pralhad Sadashiv; Babu, Uddagiri Venkanna; Ramakrishnan, Shyam

2015-01-01

The aim of this study was to evaluate the possible beneficial effects of Mentat against transient global ischemia and reperfusion-induced brain injury in rats. The neuroprotective effects of Mentat were evaluated against transient global ischemia and reperfusion (I/R)-induced brain injury in rats. Various neurobehavioral and biochemical parameters were assessed, followed by morphologic and histopathologic evaluation of brain tissue to conclude the protective effect of Mentat. Additionally, in vitro antioxidant assays were performed to explore the antioxidant capacity of Mentat and detailed liquid chromatography-mass spectrometry (LC-MS/MS) profiling was carried out to identify the active phytoconstituents responsible for the protective effects of Mentat. Sixty minutes of transient global ischemia followed by 24 h reperfusion (I/R) caused significant alterations in the cognitive and neurologic functions in the ischemia control group (P < 0.01) compared with the sham control. Furthermore, 2,3,5-triphenyltetrazolium chloride staining of the ischemia control group showed 20.85% ± 0.39% of cerebral infarct area (P < 0.01), increased brain volume (% edema 17.81% ± 1.576%; P < 0.01), and increased lipid peroxidation (P < 0.01) in the brain homogenate. Additionally, the histopathology of the ischemia control group showed severe brain injury compared with the sham control group. Interestingly, pretreatment with Mentat (250 and 500 mg/kg, p.o.) and quercetin (20 mg/kg, p.o.) for 7 d has alleviated all pathological changes observed due to I/R injury. Mentat also showed very good antioxidant activity in in vitro assays (2,2-diphenyl-l-picrylhydrazyl, ferric-reducing antioxidant power, and oxygen radical absorbance capacity assays). Furthermore, the detailed LC-MS/MS analysis of Mentat was performed and enclosed for identifying the actives responsible for its protective effects. These findings suggest that Mentat is a neuroprotective agent that may be a useful adjunct in the management of ischemic stroke and its rehabilitation especially with respect to associated memory impairment and other related neurologic conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Cerebral Developmental Abnormalities in a Mouse with Systemic Pyruvate Dehydrogenase Deficiency

PubMed Central

Pliss, Lioudmila; Hausknecht, Kathryn A.; Stachowiak, Michal K.; Dlugos, Cynthia A.; Richards, Jerry B.; Patel, Mulchand S.

2013-01-01

Pyruvate dehydrogenase (PDH) complex (PDC) deficiency is an inborn error of pyruvate metabolism causing a variety of neurologic manifestations. Systematic analyses of development of affected brain structures and the cellular processes responsible for their impairment have not been performed due to the lack of an animal model for PDC deficiency. METHODS: In the present study we investigated a murine model of systemic PDC deficiency by interrupting the X-linked Pdha1 gene encoding the α subunit of PDH to study its role on brain development and behavioral studies. RESULTS: Male embryos died prenatally but heterozygous females were born. PDC activity was reduced in the brain and other tissues in female progeny compared to age-matched control females. Immunohistochemical analysis of several brain regions showed that approximately 40% of cells were PDH−. The oxidation of glucose to CO2 and incorporation of glucose-carbon into fatty acids were reduced in brain slices from 15 day-old PDC-deficient females. Histological analyses showed alterations in several structures in white and gray matters in 35 day-old PDC-deficient females. Reduction in total cell number and reduced dendritic arbors in Purkinje neurons were observed in PDC-deficient females. Furthermore, cell proliferation, migration and differentiation into neurons by newly generated cells were reduced in the affected females during pre- and postnatal periods. PDC-deficient mice had normal locomotor activity in a novel environment but displayed decreased startle responses to loud noises and there was evidence of abnormal pre-pulse inhibition of the startle reflex. CONCLUSIONS: The results show that a reduction in glucose metabolism resulting in deficit in energy production and fatty acid biosynthesis impairs cellular differentiation and brain development in PDC-deficient mice. PMID:23840713

The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats.

PubMed

Uzar, Ertuğrul; Acar, Abdullah; Evliyaoğlu, Osman; Fırat, Uğur; Kamasak, Kağan; Göçmez, Cüneyt; Alp, Harun; Tüfek, Adnan; Taşdemir, Nebahat; Ilhan, Atilla

2012-01-10

The aim of this experiment was to investigate whether nebivolol and zofenopril have protective effects against oxidative damage and apoptosis induced by cerebral ischemia/reperfusion (I/R). There were seven groups of rats, with each containing eight rats. The groups were: the control group, I/R group, I/R plus zofenopril, I/R plus nebivolol, I/R plus nebivolol and zofenopril, zofenopril only and nebivolol only. Cerebral I/R was induced by clamping the bilateral common carotid artery and through hypotension. The rats were sacrificed 1h after ischemia, and histopathological and biochemical analyses were carried out on their brains. The total antioxidant capacity was evaluated by using an automated and colorimetric measurement method developed by Erel. I/R produced a significant increase in the levels of total oxidant status and malondialdehyde levels, the number of caspase-3 immunopositive cells and activities of prolidase and paraoxonase in brain when compared with the control group (p<0.05). A significant decrease in brain total antioxidant capacity and nitric oxide levels were found in I/R group when compared with the control group (p<0.05). Both nebivolol and zofenopril treatment prevented decreasing of the total antioxidant capacity and nitric oxide levels, produced by I/R in the brain (p<0.05). Both nebivolol and zofenopril treatment prevented the total oxidant status, malondialdehyde levels, activities of paraoxonase and prolidase from increasing in brains of rats exposed to I/R (p<0.05). In conclusion, both nebivolol and zofenopril protected rats from ischemia-induced brain injury. The protection may be due to the indirect prevention of oxidative stress and apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Targeted drug delivery with focused ultrasound-induced blood-brain barrier opening using acoustically-activated nanodroplets.

PubMed

Chen, Cherry C; Sheeran, Paul S; Wu, Shih-Ying; Olumolade, Oluyemi O; Dayton, Paul A; Konofagou, Elisa E

2013-12-28

Focused ultrasound (FUS) in the presence of systemically administered microbubbles has been shown to locally, transiently and reversibly increase the permeability of the blood-brain barrier (BBB), thus allowing targeted delivery of therapeutic agents in the brain for the treatment of central nervous system diseases. Currently, microbubbles are the only agents that have been used to facilitate the FUS-induced BBB opening. However, they are constrained within the intravascular space due to their micron-size diameters, limiting the delivery effect at or near the microvessels. In the present study, acoustically-activated nanodroplets were used as a new class of contrast agents to mediate FUS-induced BBB opening in order to study the feasibility of utilizing these nanoscale phase-shift particles for targeted drug delivery in the brain. Significant dextran delivery was achieved in the mouse hippocampus using nanodroplets at clinically relevant pressures. Passive cavitation detection was used in the attempt to establish a correlation between the amount of dextran delivered in the brain and the acoustic emission recorded during sonication. Conventional microbubbles with the same lipid shell composition and perfluorobutane core as the nanodroplets were also used to compare the efficiency of an FUS-induced dextran delivery. It was found that nanodroplets had a higher BBB opening pressure threshold but a lower stable cavitation threshold than microbubbles, suggesting that contrast agent-dependent acoustic emission monitoring was needed. A more homogeneous dextran delivery within the targeted hippocampus was achieved using nanodroplets without inducing inertial cavitation or compromising safety. Our results offered a new means of developing the FUS-induced BBB opening technology for potential extravascular targeted drug delivery in the brain, extending the potential drug delivery region beyond the cerebral vasculature. © 2013.

Stage-specific regulation of juvenile hormone biosynthesis by ecdysteroid in Bombyx mori.

PubMed

Kaneko, Yu; Kinjoh, Terunori; Kiuchi, Makoto; Hiruma, Kiyoshi

2011-03-30

In the penultimate (4th) instar larvae of Bombyx mori, juvenile hormone (JH) synthesis by corpora allata (CA) fluctuates. When diet containing 20-hydroxyecdysone (20E) was fed, JH synthetic activity of the CA was first stimulated as the ecdysteroid titer increased, then suppressed slightly by the higher molting concentration of ecdysteroids (>250 ng/ml). The overall JH biosynthetic activity was modulated by the expression of JH biosynthetic enzymes in the CA: primarily JH acid O-methyltransferase (JHAMT), isopentenyl diphosphate isomerase, and farnesyl diphosphate synthase 1. After the last (5th) larval ecdysis, the artificially increased high ecdysteroid level due to the 20E diet activated JH synthesis by the CA, which required intact nervous connections with the brain. A factor(s) from the 20E-activated brain controls mainly JHAMT and HMG Co-A reductase expression to stimulate the JH synthesis. In the normal last instar larvae, the ecdysteroid titer declines so that these activation mechanisms are absent; therefore the decline of the ecdysteroid titer after the final larval ecdysis is one of the factors which induces the cessation of the JH synthesis by CA. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.