EFFECTS OF CONTINUOUS-WAVE, PULSED, AND SINUSOIDAL-AMPLITUDE-MODULATED MICROWAVES ON BRAIN ENERGY METABOLISM

EPA Science Inventory

A comparison of the effects of continuous wave, sinusoidal-amplitude modulated, and pulsed square-wave-modulated 591-MHz microwave exposures on brain energy metabolism was made in male Sprague Dawley rats (175-225g). Brain NADH fluorescence, adensine triphosphate (ATP) concentrat...

Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition

PubMed Central

Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J

2016-01-01

The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota–inflammasome–brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota–inflammasome–brain axis may offer novel therapeutic targets for psychiatric disorders. PMID:27090302

Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition.

PubMed

Wong, M-L; Inserra, A; Lewis, M D; Mastronardi, C A; Leong, L; Choo, J; Kentish, S; Xie, P; Morrison, M; Wesselingh, S L; Rogers, G B; Licinio, J

2016-06-01

The inflammasome is hypothesized to be a key mediator of the response to physiological and psychological stressors, and its dysregulation may be implicated in major depressive disorder. Inflammasome activation causes the maturation of caspase-1 and activation of interleukin (IL)-1β and IL-18, two proinflammatory cytokines involved in neuroimmunomodulation, neuroinflammation and neurodegeneration. In this study, C57BL/6 mice with genetic deficiency or pharmacological inhibition of caspase-1 were screened for anxiety- and depressive-like behaviors, and locomotion at baseline and after chronic stress. We found that genetic deficiency of caspase-1 decreased depressive- and anxiety-like behaviors, and conversely increased locomotor activity and skills. Caspase-1 deficiency also prevented the exacerbation of depressive-like behaviors following chronic stress. Furthermore, pharmacological caspase-1 antagonism with minocycline ameliorated stress-induced depressive-like behavior in wild-type mice. Interestingly, chronic stress or pharmacological inhibition of caspase-1 per se altered the fecal microbiome in a very similar manner. When stressed mice were treated with minocycline, the observed gut microbiota changes included increase in relative abundance of Akkermansia spp. and Blautia spp., which are compatible with beneficial effects of attenuated inflammation and rebalance of gut microbiota, respectively, and the increment in Lachnospiracea abundance was consistent with microbiota changes of caspase-1 deficiency. Our results suggest that the protective effect of caspase-1 inhibition involves the modulation of the relationship between stress and gut microbiota composition, and establishes the basis for a gut microbiota-inflammasome-brain axis, whereby the gut microbiota via inflammasome signaling modulate pathways that will alter brain function, and affect depressive- and anxiety-like behaviors. Our data also suggest that further elucidation of the gut microbiota-inflammasome-brain axis may offer novel therapeutic targets for psychiatric disorders.

Of Microbes and Minds: A Narrative Review on the Second Brain Aging.

PubMed

Calvani, Riccardo; Picca, Anna; Lo Monaco, Maria Rita; Landi, Francesco; Bernabei, Roberto; Marzetti, Emanuele

2018-01-01

In recent years, an extensive body of literature focused on the gut-brain axis and the possible role played by the gut microbiota in modulating brain morphology and function from birth to old age. Gut microbiota has been proposed as a relevant player during the early phases of neurodevelopment, with possible long-standing effects in later life. The reduction in gut microbiota diversity has also become one of the hallmarks of aging, and disturbances in its composition are associated with several (age-related) neurological conditions, including depression, Alzheimer's disease, and Parkinson's disease. Several pathways have been evoked for gut microbiota-brain communication, including neural connections (vagus nerve), circulating mediators derived by host-bacteria cometabolism, as well as the influence exerted by gut microbiota on host gut function, metabolism, and immune system. Although the most provoking data emerged from animal studies and despite the huge debate around the possible epiphenomenal nature of those findings, the gut microbiota-brain axis still remains a fascinating target to be exploited to attenuate some of the most burdensome consequences of aging.

Contrasting effects of Bifidobacterium breve NCIMB 702258 and Bifidobacterium breve DPC 6330 on the composition of murine brain fatty acids and gut microbiota.

PubMed

Wall, Rebecca; Marques, Tatiana M; O'Sullivan, Orla; Ross, R Paul; Shanahan, Fergus; Quigley, Eamonn M; Dinan, Timothy G; Kiely, Barry; Fitzgerald, Gerald F; Cotter, Paul D; Fouhy, Fiona; Stanton, Catherine

2012-05-01

We previously showed that microbial metabolism in the gut influences the composition of bioactive fatty acids in host adipose tissue. This study compared the effect of dietary supplementation for 8 wk with human-derived Bifidobacterium breve strains on fat distribution and composition and the composition of the gut microbiota in mice. C57BL/6 mice (n = 8 per group) received B. breve DPC 6330 or B. breve NCIMB 702258 (10(9) microorganisms) daily for 8 wk or no supplement (controls). Tissue fatty acid composition was assessed by gas-liquid chromatography while 16S rRNA pyrosequencing was used to investigate microbiota composition. Visceral fat mass and brain stearic acid, arachidonic acid, and DHA were higher in mice supplemented with B. breve NCIMB 702258 than in mice in the other 2 groups (P < 0.05). In addition, both B. breve DPC 6330 and B. breve NCIMB 702258 supplementation resulted in higher propionate concentrations in the cecum than did no supplementation (P < 0.05). Compositional sequencing of the gut microbiota showed a tendency for greater proportions of Clostridiaceae (25%, 12%, and 18%; P = 0.08) and lower proportions of Eubacteriaceae (3%, 12%, and 13%; P = 0.06) in mice supplemented with B. breve DPC 6330 than in mice supplemented with B. breve NCIMB 702258 and unsupplemented controls, respectively. The response of fatty acid metabolism to administration of bifidobacteria is strain-dependent, and strain-strain differences are important factors that influence modulation of the gut microbial community by ingested microorganisms.

Concerted and mosaic evolution of functional modules in songbird brains

PubMed Central

DeVoogd, Timothy J.

2017-01-01

Vertebrate brains differ in overall size, composition and functional capacities, but the evolutionary processes linking these traits are unclear. Two leading models offer opposing views: the concerted model ascribes major dimensions of covariation in brain structures to developmental events, whereas the mosaic model relates divergent structures to functional capabilities. The models are often cast as incompatible, but they must be unified to explain how adaptive changes in brain structure arise from pre-existing architectures and developmental mechanisms. Here we show that variation in the sizes of discrete neural systems in songbirds, a species-rich group exhibiting diverse behavioural and ecological specializations, supports major elements of both models. In accordance with the concerted model, most variation in nucleus volumes is shared across functional domains and allometry is related to developmental sequence. Per the mosaic model, residual variation in nucleus volumes is correlated within functional systems and predicts specific behavioural capabilities. These comparisons indicate that oscine brains evolved primarily as a coordinated whole but also experienced significant, independent modifications to dedicated systems from specific selection pressures. Finally, patterns of covariation between species and brain areas hint at underlying developmental mechanisms. PMID:28490627

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia.

PubMed

Mayurasakorn, Korapat; Williams, Jill J; Ten, Vadim S; Deckelbaum, Richard J

2011-03-01

With important effects on neuronal lipid composition, neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent against cerebrovascular disease. This paper examines pathways for DHA accretion in brain and evidence for possible roles of DHA in prophylactic and therapeutic approaches for cerebrovascular disease. DHA is a major n-3 fatty acid in the mammalian central nervous system and enhances synaptic activities in neuronal cells. DHA can be obtained through diet or to a limited extent via conversion from its precursor, α-linolenic acid (α-LNA). DHA attenuates brain necrosis after hypoxic ischemic injury, principally by modulating membrane biophysical properties and maintaining integrity in functions between presynaptic and postsynaptic areas, resulting in better stabilizing intracellular ion balance in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by inducing antiapoptotic activities such as decreasing responses to reactive oxygen species, upregulating antiapoptotic protein expression, downregulating apoptotic protein expression, and maintaining mitochondrial integrity and function. DHA in brain relates to a number of efficient delivery and accretion pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic injury by regulating multiple molecular pathways and gene expression.

The hydroxylated form of docosahexaenoic acid (DHA-H) modifies the brain lipid composition in a model of Alzheimer's disease, improving behavioral motor function and survival.

PubMed

Mohaibes, Raheem J; Fiol-deRoque, María A; Torres, Manuel; Ordinas, Margarita; López, David J; Castro, José A; Escribá, Pablo V; Busquets, Xavier

2017-09-01

We have compared the effect of the commonly used ω-3 fatty acid, docosahexaenoic acid ethyl ester (DHA-EE), and of its 2-hydroxylated DHA form (DHA-H), on brain lipid composition, behavior and lifespan in a new human transgenic Drosophila melanogaster model of Alzheimer's disease (AD). The transgenic flies expressed human Aβ42 and tau, and the overexpression of these human transgenes in the CNS of these flies produced progressive defects in motor function (antigeotaxic behavior) while reducing the animal's lifespan. Here, we demonstrate that both DHA-EE and DHA-H increase the longer chain fatty acids (≥18C) species in the heads of the flies, although only DHA-H produced an unknown chromatographic peak that corresponded to a non-hydroxylated lipid. In addition, only treatment with DHA-H prevented the abnormal climbing behavior and enhanced the lifespan of these transgenic flies. These benefits of DHA-H were confirmed in the well characterized transgenic PS1/APP mouse model of familial AD (5xFAD mice), mice that develop defects in spatial learning and in memory, as well as behavioral deficits. Hence, it appears that the modulation of brain lipid composition by DHA-H could have remedial effects on AD associated neurodegeneration. This article is part of a Special Issue entitled: Membrane Lipid Therapy: Drugs Targeting Biomembranes edited by Pablo V. Escribá. Copyright © 2017. Published by Elsevier B.V.

Comparison of individual and composite field analysis using array detector for Intensity Modulated Radiotherapy dose verification.

PubMed

Saminathan, Sathiyan; Chandraraj, Varatharaj; Sridhar, C H; Manickam, Ravikumar

2012-01-01

To compare the measured and calculated individual and composite field planar dose distribution of Intensity Modulated Radiotherapy plans. The measurements were performed in Clinac DHX linear accelerator with 6 MV photons using Matrixx device and a solid water phantom. The 20 brain tumor patients were selected for this study. The IMRT plan was carried out for all the patients using Eclipse treatment planning system. The verification plan was produced for every original plan using CT scan of Matrixx embedded in the phantom. Every verification field was measured by the Matrixx. The TPS calculated and measured dose distributions were compared for individual and composite fields. The percentage of gamma pixel match for the dose distribution patterns were evaluated using gamma histogram. The gamma pixel match was 95-98% for 41 fields (39%) and 98% for 59 fields (61%) with individual fields. The percentage of gamma pixel match was 95-98% for 5 patients and 98% for other 12 patients with composite fields. Three patients showed a gamma pixel match of less than 95%. The comparison of percentage gamma pixel match for individual and composite fields showed more than 2.5% variation for 6 patients, more than 1% variation for 4 patients, while the remaining 10 patients showed less than 1% variation. The individual and composite field measurements showed good agreement with TPS calculated dose distribution for the studied patients. The measurement and data analysis for individual fields is a time consuming process, the composite field analysis may be sufficient enough for smaller field dose distribution analysis with array detectors.

Tracking the Reorganization of Module Structure in Time-Varying Weighted Brain Functional Connectivity Networks.

PubMed

Schmidt, Christoph; Piper, Diana; Pester, Britta; Mierau, Andreas; Witte, Herbert

2018-05-01

Identification of module structure in brain functional networks is a promising way to obtain novel insights into neural information processing, as modules correspond to delineated brain regions in which interactions are strongly increased. Tracking of network modules in time-varying brain functional networks is not yet commonly considered in neuroscience despite its potential for gaining an understanding of the time evolution of functional interaction patterns and associated changing degrees of functional segregation and integration. We introduce a general computational framework for extracting consensus partitions from defined time windows in sequences of weighted directed edge-complete networks and show how the temporal reorganization of the module structure can be tracked and visualized. Part of the framework is a new approach for computing edge weight thresholds for individual networks based on multiobjective optimization of module structure quality criteria as well as an approach for matching modules across time steps. By testing our framework using synthetic network sequences and applying it to brain functional networks computed from electroencephalographic recordings of healthy subjects that were exposed to a major balance perturbation, we demonstrate the framework's potential for gaining meaningful insights into dynamic brain function in the form of evolving network modules. The precise chronology of the neural processing inferred with our framework and its interpretation helps to improve the currently incomplete understanding of the cortical contribution for the compensation of such balance perturbations.

Oxytocin And Vasopressin Modulation Of The Neural Correlates Of Motivation And Emotion: Results From Functional MRI Studies In Awake Rats

PubMed Central

Febo, Marcelo; Ferris, Craig F.

2014-01-01

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. PMID:24486356

Persistency and flexibility of complex brain networks underlie dual-task interference.

PubMed

Alavash, Mohsen; Hilgetag, Claus C; Thiel, Christiane M; Gießing, Carsten

2015-09-01

Previous studies on multitasking suggest that performance decline during concurrent task processing arises from interfering brain modules. Here, we used graph-theoretical network analysis to define functional brain modules and relate the modular organization of complex brain networks to behavioral dual-task costs. Based on resting-state and task fMRI we explored two organizational aspects potentially associated with behavioral interference when human subjects performed a visuospatial and speech task simultaneously: the topological overlap between persistent single-task modules, and the flexibility of single-task modules in adaptation to the dual-task condition. Participants showed a significant decline in visuospatial accuracy in the dual-task compared with single visuospatial task. Global analysis of topological similarity between modules revealed that the overlap between single-task modules significantly correlated with the decline in visuospatial accuracy. Subjects with larger overlap between single-task modules showed higher behavioral interference. Furthermore, lower flexible reconfiguration of single-task modules in adaptation to the dual-task condition significantly correlated with larger decline in visuospatial accuracy. Subjects with lower modular flexibility showed higher behavioral interference. At the regional level, higher overlap between single-task modules and less modular flexibility in the somatomotor cortex positively correlated with the decline in visuospatial accuracy. Additionally, higher modular flexibility in cingulate and frontal control areas and lower flexibility in right-lateralized nodes comprising the middle occipital and superior temporal gyri supported dual-tasking. Our results suggest that persistency and flexibility of brain modules are important determinants of dual-task costs. We conclude that efficient dual-tasking benefits from a specific balance between flexibility and rigidity of functional brain modules. © 2015 Wiley Periodicals, Inc.

Insulin Action in Brain Regulates Systemic Metabolism and Brain Function

PubMed Central

Kleinridders, André; Ferris, Heather A.; Cai, Weikang

2014-01-01

Insulin receptors, as well as IGF-1 receptors and their postreceptor signaling partners, are distributed throughout the brain. Insulin acts on these receptors to modulate peripheral metabolism, including regulation of appetite, reproductive function, body temperature, white fat mass, hepatic glucose output, and response to hypoglycemia. Insulin signaling also modulates neurotransmitter channel activity, brain cholesterol synthesis, and mitochondrial function. Disruption of insulin action in the brain leads to impairment of neuronal function and synaptogenesis. In addition, insulin signaling modulates phosphorylation of tau protein, an early component in the development of Alzheimer disease. Thus, alterations in insulin action in the brain can contribute to metabolic syndrome, and the development of mood disorders and neurodegenerative diseases. PMID:24931034

Modulation of Gut Microbiota-Brain Axis by Probiotics, Prebiotics, and Diet.

PubMed

Liu, Xiaofei; Cao, Shangqing; Zhang, Xuewu

2015-09-16

There exists a bidirectional communication system between the gastrointestinal tract and the brain. Increasing evidence shows that gut microbiota can play a critical role in this communication; thus, the concept of a gut microbiota and brain axis is emerging. Here, we review recent findings in the relationship between intestinal microbes and brain function, such as anxiety, depression, stress, autism, learning, and memory. We highlight the advances in modulating brain development and behavior by probiotics, prebiotics, and diet through the gut microbiota-brain axis. A variety of mechanisms including immune, neural, and metabolic pathways may be involved in modulation of the gut microbiota-brain axis. We also discuss some future challenges. A deeper understanding of the relationship between the gut bacteria and their hosts is implicated in developing microbial-based therapeutic strategies for brain disorders.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex.

PubMed

Herrera, Jose L; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M; Alonso, Rafael; Wandosell, Francisco G

2018-01-01

Different dietary ratios of n -6/ n -3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n -6/ n -3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n -3 and n -6 LC-PUFAs.

Ovarian Function Modulates the Effects of Long-Chain Polyunsaturated Fatty Acids on the Mouse Cerebral Cortex

PubMed Central

Herrera, Jose L.; Ordoñez-Gutierrez, Lara; Fabrias, Gemma; Casas, Josefina; Morales, Araceli; Hernandez, Guadalberto; Acosta, Nieves G.; Rodriguez, Covadonga; Prieto-Valiente, Luis; Garcia-Segura, Luis M.; Alonso, Rafael; Wandosell, Francisco G.

2018-01-01

Different dietary ratios of n−6/n−3 long-chain polyunsaturated fatty acids (LC-PUFAs) may alter brain lipid profile, neural activity, and brain cognitive function. To determine whether ovarian hormones influence the effect of diet on the brain, ovariectomized and sham-operated mice continuously treated with placebo or estradiol were fed for 3 months with diets containing low or high n−6/n−3 LC-PUFA ratios. The fatty acid (FA) profile and expression of key neuronal proteins were analyzed in the cerebral cortex, with intact female mice on standard diet serving as internal controls of brain lipidome composition. Diets containing different concentrations of LC-PUFAs greatly modified total FAs, sphingolipids, and gangliosides in the cerebral cortex. Some of these changes were dependent on ovarian hormones, as they were not detected in ovariectomized animals, and in the case of complex lipids, the effect of ovariectomy was partially or totally reversed by continuous administration of estradiol. However, even though differential dietary LC-PUFA content modified the expression of neuronal proteins such as synapsin and its phosphorylation level, PSD-95, amyloid precursor protein (APP), or glial proteins such as glial fibrillary acidic protein (GFAP), an effect also dependent on the presence of the ovary, chronic estradiol treatment was unable to revert the dietary effects on brain cortex synaptic proteins. These results suggest that, in addition to stable estradiol levels, other ovarian hormones such as progesterone and/or cyclic ovarian secretory activity could play a physiological role in the modulation of dietary LC-PUFAs on the cerebral cortex, which may have clinical implications for post-menopausal women on diets enriched with different proportions of n−3 and n−6 LC-PUFAs. PMID:29740285

Pain perception and hypnosis: findings from recent functional neuroimaging studies.

PubMed

Del Casale, Antonio; Ferracuti, Stefano; Rapinesi, Chiara; Serata, Daniele; Caltagirone, Saverio Simone; Savoja, Valeria; Piacentino, Daria; Callovini, Gemma; Manfredi, Giovanni; Sani, Gabriele; Kotzalidis, Georgios D; Girardi, Paolo

2015-01-01

Hypnosis modulates pain perception and tolerance by affecting cortical and subcortical activity in brain regions involved in these processes. By reviewing functional neuroimaging studies focusing on pain perception under hypnosis, the authors aimed to identify brain activation-deactivation patterns occurring in hypnosis-modulated pain conditions. Different changes in brain functionality occurred throughout all components of the pain network and other brain areas. The anterior cingulate cortex appears to be central in modulating pain circuitry activity under hypnosis. Most studies also showed that the neural functions of the prefrontal, insular, and somatosensory cortices are consistently modified during hypnosis-modulated pain conditions. Functional neuroimaging studies support the clinical use of hypnosis in the management of pain conditions.

Oxytocin and vasopressin modulation of the neural correlates of motivation and emotion: results from functional MRI studies in awake rats.

PubMed

Febo, Marcelo; Ferris, Craig F

2014-09-11

Oxytocin and vasopressin modulate a range of species typical behavioral functions that include social recognition, maternal-infant attachment, and modulation of memory, offensive aggression, defensive fear reactions, and reward seeking. We have employed novel functional magnetic resonance mapping techniques in awake rats to explore the roles of these neuropeptides in the maternal and non-maternal brain. Results from the functional neuroimaging studies that are summarized here have directly and indirectly confirmed and supported previous findings. Oxytocin is released within the lactating rat brain during suckling stimulation and activates specific subcortical networks in the maternal brain. Both vasopressin and oxytocin modulate brain regions involved unconditioned fear, processing of social stimuli and the expression of agonistic behaviors. Across studies there are relatively consistent brain networks associated with internal motivational drives and emotional states that are modulated by oxytocin and vasopressin. This article is part of a Special Issue entitled Oxytocin and Social Behav. Copyright © 2014 Elsevier B.V. All rights reserved.

Increased Global Interaction Across Functional Brain Modules During Cognitive Emotion Regulation.

PubMed

Brandl, Felix; Mulej Bratec, Satja; Xie, Xiyao; Wohlschläger, Afra M; Riedl, Valentin; Meng, Chun; Sorg, Christian

2017-07-13

Cognitive emotion regulation (CER) enables humans to flexibly modulate their emotions. While local theories of CER neurobiology suggest interactions between specialized local brain circuits underlying CER, e.g., in subparts of amygdala and medial prefrontal cortices (mPFC), global theories hypothesize global interaction increases among larger functional brain modules comprising local circuits. We tested the global CER hypothesis using graph-based whole-brain network analysis of functional MRI data during aversive emotional processing with and without CER. During CER, global between-module interaction across stable functional network modules increased. Global interaction increase was particularly driven by subregions of amygdala and cuneus-nodes of highest nodal participation-that overlapped with CER-specific local activations, and by mPFC and posterior cingulate as relevant connector hubs. Results provide evidence for the global nature of human CER, complementing functional specialization of embedded local brain circuits during successful CER. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Brain-gut-microbiota axis in Parkinson's disease.

PubMed

Mulak, Agata; Bonaz, Bruno

2015-10-07

Parkinson's disease (PD) is characterized by alpha-synucleinopathy that affects all levels of the brain-gut axis including the central, autonomic, and enteric nervous systems. Recently, it has been recognized that the brain-gut axis interactions are significantly modulated by the gut microbiota via immunological, neuroendocrine, and direct neural mechanisms. Dysregulation of the brain-gut-microbiota axis in PD may be associated with gastrointestinal manifestations frequently preceding motor symptoms, as well as with the pathogenesis of PD itself, supporting the hypothesis that the pathological process is spread from the gut to the brain. Excessive stimulation of the innate immune system resulting from gut dysbiosis and/or small intestinal bacterial overgrowth and increased intestinal permeability may induce systemic inflammation, while activation of enteric neurons and enteric glial cells may contribute to the initiation of alpha-synuclein misfolding. Additionally, the adaptive immune system may be disturbed by bacterial proteins cross-reacting with human antigens. A better understanding of the brain-gut-microbiota axis interactions should bring a new insight in the pathophysiology of PD and permit an earlier diagnosis with a focus on peripheral biomarkers within the enteric nervous system. Novel therapeutic options aimed at modifying the gut microbiota composition and enhancing the intestinal epithelial barrier integrity in PD patients could influence the initial step of the following cascade of neurodegeneration in PD.

Docosahexaenoic acid: brain accretion and roles in neuroprotection after brain hypoxia and ischemia

PubMed Central

Mayurasakorn, Korapat; Williams, Jill J.; Ten, Vadim S.; Deckelbaum, Richard J.

2014-01-01

Purpose of review With important effects on neuronal lipid composition, neurochemical signaling and cerebrovascular pathobiology, docosahexaenoic acid (DHA), a n-3 polyunsaturated fatty acid, may emerge as a neuroprotective agent against cerebrovascular disease. This paper examines pathways for DHA accretion in brain and evidence for possible roles of DHA in prophylactic and therapeutic approaches for cerebrovascular disease. Recent findings DHA is a major n-3 fatty acid in the mammalian central nervous system and enhances synaptic activities in neuronal cells. DHA can be obtained through diet or to a limited extent via conversion from its precursor, α-linolenic acid (α-LNA). DHA attenuates brain necrosis after hypoxic ischemic injury, principally by modulating membrane biophysical properties and maintaining integrity in functions between pre-and post-synaptic areas, resulting in better stabilizing intracellular ion balance in hypoxic-ischemic insult. Additionally, DHA alleviates brain apoptosis, by inducing anti-apoptotic activities such as decreasing responses to reactive oxygen species, up-regulating anti-apoptotic protein expression, down-regulating apoptotic protein expression, and maintaining mitochondrial integrity and function. Summary DHA in brain relates to a number of efficient delivery and accretion pathways. In animal models DHA renders neuroprotection after hypoxic-ischemic injury by regulating multiple molecular pathways and gene expression. PMID:21178607

Brain-specific Crmp2 deletion leads to neuronal development deficits and behavioural impairments in mice.

PubMed

Zhang, Hongsheng; Kang, Eunchai; Wang, Yaqing; Yang, Chaojuan; Yu, Hui; Wang, Qin; Chen, Zheyu; Zhang, Chen; Christian, Kimberly M; Song, Hongjun; Ming, Guo-Li; Xu, Zhiheng

2016-06-01

Several genome- and proteome-wide studies have associated transcription and translation changes of CRMP2 (collapsing response mediator protein 2) with psychiatric disorders, yet little is known about its function in the developing or adult mammalian brain in vivo. Here we show that brain-specific Crmp2 knockout (cKO) mice display molecular, cellular, structural and behavioural deficits, many of which are reminiscent of neural features and symptoms associated with schizophrenia. cKO mice exhibit enlarged ventricles and impaired social behaviour, locomotor activity, and learning and memory. Loss of Crmp2 in the hippocampus leads to reduced long-term potentiation, abnormal NMDA receptor composition, aberrant dendrite development and defective synapse formation in CA1 neurons. Furthermore, knockdown of crmp2 specifically in newborn neurons results in stage-dependent defects in their development during adult hippocampal neurogenesis. Our findings reveal a critical role for CRMP2 in neuronal plasticity, neural function and behavioural modulation in mice.

Network-dependent modulation of brain activity during sleep.

PubMed

Watanabe, Takamitsu; Kan, Shigeyuki; Koike, Takahiko; Misaki, Masaya; Konishi, Seiki; Miyauchi, Satoru; Miyahsita, Yasushi; Masuda, Naoki

2014-09-01

Brain activity dynamically changes even during sleep. A line of neuroimaging studies has reported changes in functional connectivity and regional activity across different sleep stages such as slow-wave sleep (SWS) and rapid-eye-movement (REM) sleep. However, it remains unclear whether and how the large-scale network activity of human brains changes within a given sleep stage. Here, we investigated modulation of network activity within sleep stages by applying the pairwise maximum entropy model to brain activity obtained by functional magnetic resonance imaging from sleeping healthy subjects. We found that the brain activity of individual brain regions and functional interactions between pairs of regions significantly increased in the default-mode network during SWS and decreased during REM sleep. In contrast, the network activity of the fronto-parietal and sensory-motor networks showed the opposite pattern. Furthermore, in the three networks, the amount of the activity changes throughout REM sleep was negatively correlated with that throughout SWS. The present findings suggest that the brain activity is dynamically modulated even in a sleep stage and that the pattern of modulation depends on the type of the large-scale brain networks. Copyright © 2014 Elsevier Inc. All rights reserved.

Noninvasive transcranial focused ultrasonic-magnetic stimulation for modulating brain oscillatory activity

NASA Astrophysics Data System (ADS)

Yuan, Yi; Chen, Yudong; Li, Xiaoli

2016-02-01

A novel technique, transcranial focused ultrasonic-magnetic stimulation (tFUMS), has been developed for noninvasive brain modulation in vivo. tFUMS has a higher spatial resolution (<2 mm) and a higher penetration depth than other noninvasive neuromodulation methods. The in vivo animal experimental results show that tFUMS can not only increase the power of local field potentials and the firing rate of the neurons, but also enhance the effect of transcranial focused ultrasound stimulation on the neuromodulation. The results demonstrate that tFUMS can modulate brain oscillatory activities by stimulating brain tissues.

Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus

PubMed Central

Zhang, Jiyong; Sadowska, Grazyna B.; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A.; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G.; Gaitanis, John; Banks, William A.; Stonestreet, Barbara S.

2015-01-01

Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti–IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti–IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti–IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.—Zhang, J., Sadowska, G. B., Chen, X., Park, S. Y., Kim, J.-E., Bodge, C. A., Cummings, E., Lim, Y.-P., Makeyev, O., Besio, W. G., Gaitanis, J., Banks, W. A., Stonestreet, B. S. Anti–IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus. PMID:25609424

Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration

PubMed Central

Gerardy-Schahn, Rita; Hildebrandt, Herbert

2014-01-01

Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system. PMID:24692354

Towards better brain management: nootropics.

PubMed

Malik, Ruchi; Sangwan, Abhijeet; Saihgal, Ruchika; Jindal, Dharam Paul; Piplani, Poonam

2007-01-01

The learning and memory deficits have been recognized as severe and consistent neurological disorders associated with numerous neurodegenerative states. Research in this area has gained momentum only in the recent past after the biochemical and physiological basis of these processes have been understood. A considerable alteration in the neurotransmission is a consistent finding in cognitive disorders. Therefore, many therapeutic strategies to augment the concentration of neurotransmitters in brain such as cholinergic agents, biogenic amines and neuropeptides etc. have been evaluated in cognitive deficits. CNS modulators are the type of antiamnesics that act via modulation of the neurological processes underlying memory storage. These include psychostimulants, excitatory amino acids and most important of all "nootropics". Nootropics are a heterogeneous group of compounds of diverse chemical composition and biological function that allegedly facilitate learning and memory or overcome natural or induced cognitive impairments. The literature survey incorporated in this article hallmarks the success achieved in the design and development of potential nootropic agents. Additionally, this review is an attempt towards discussing various approaches available to enhance memory, along with the classification of the known memory enhancers, authors research work towards various structural modifications carried out and the biological screening.

Cytokines and cytokine networks target neurons to modulate long-term potentiation.

PubMed

Prieto, G Aleph; Cotman, Carl W

2017-04-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cytokines and cytokine networks target neurons to modulate long-term potentiation

PubMed Central

Prieto, G. Aleph; Cotman, Carl W.

2017-01-01

Cytokines play crucial roles in the communication between brain cells including neurons and glia, as well as in the brain-periphery interactions. In the brain, cytokines modulate long-term potentiation (LTP), a cellular correlate of memory. Whether cytokines regulate LTP by direct effects on neurons or by indirect mechanisms mediated by non-neuronal cells is poorly understood. Elucidating neuron-specific effects of cytokines has been challenging because most brain cells express cytokine receptors. Moreover, cytokines commonly increase the expression of multiple cytokines in their target cells, thus increasing the complexity of brain cytokine networks even after single-cytokine challenges. Here, we review evidence on both direct and indirect-mediated modulation of LTP by cytokines. We also describe novel approaches based on neuron- and synaptosome-enriched systems to identify cytokines able to directly modulate LTP, by targeting neurons and synapses. These approaches can test multiple samples in parallel, thus allowing the study of multiple cytokines simultaneously. Hence, a cytokine networks perspective coupled with neuron-specific analysis may contribute to delineation of maps of the modulation of LTP by cytokines. PMID:28377062

Brain composition and olfactory learning in honey bees

PubMed Central

Gronenberg, Wulfila; Couvillon, Margaret J.

2015-01-01

Correlations between brain or brain component size and behavioral measures are frequently studied by comparing different animal species, which sometimes introduces variables that complicate interpretation in terms of brain function. Here, we have analyzed the brain composition of honey bees (Apis mellifera) that have been individually tested in an olfactory learning paradigm. We found that the total brain size correlated with the bees’ learning performance. Among different brain components, only the mushroom body, a structure known to be involved in learning and memory, showed a positive correlation with learning performance. In contrast, visual neuropils were relatively smaller in bees that performed better in the olfactory learning task, suggesting modality-specific behavioral specialization of individual bees. This idea is also supported by inter-individual differences in brain composition. Some slight yet statistically significant differences in the brain composition of European and Africanized honey bees are reported. Larger bees had larger brains, and by comparing brains of different sizes, we report isometric correlations for all brain components except for a small structure, the central body. PMID:20060918

A comprehensive analysis on preservation patterns of gene co-expression networks during Alzheimer's disease progression.

PubMed

Ray, Sumanta; Hossain, Sk Md Mosaddek; Khatun, Lutfunnesa; Mukhopadhyay, Anirban

2017-12-20

Alzheimer's disease (AD) is a chronic neuro-degenerative disruption of the brain which involves in large scale transcriptomic variation. The disease does not impact every regions of the brain at the same time, instead it progresses slowly involving somewhat sequential interaction with different regions. Analysis of the expression patterns of the genes in different regions of the brain influenced in AD surely contribute for a enhanced comprehension of AD pathogenesis and shed light on the early characterization of the disease. Here, we have proposed a framework to identify perturbation and preservation characteristics of gene expression patterns across six distinct regions of the brain ("EC", "HIP", "PC", "MTG", "SFG", and "VCX") affected in AD. Co-expression modules were discovered considering a couple of regions at once. These are then analyzed to know the preservation and perturbation characteristics. Different module preservation statistics and a rank aggregation mechanism have been adopted to detect the changes of expression patterns across brain regions. Gene ontology (GO) and pathway based analysis were also carried out to know the biological meaning of preserved and perturbed modules. In this article, we have extensively studied the preservation patterns of co-expressed modules in six distinct brain regions affected in AD. Some modules are emerged as the most preserved while some others are detected as perturbed between a pair of brain regions. Further investigation on the topological properties of preserved and non-preserved modules reveals a substantial association amongst "betweenness centrality" and "degree" of the involved genes. Our findings may render a deeper realization of the preservation characteristics of gene expression patterns in discrete brain regions affected by AD.

Central nervous system regulation of intestinal lipid and lipoprotein metabolism.

PubMed

Farr, Sarah; Taher, Jennifer; Adeli, Khosrow

2016-02-01

In response to nutrient availability, the small intestine and brain closely communicate to modulate energy homeostasis and metabolism. The gut-brain axis involves complex nutrient sensing mechanisms and an integration of neuronal and hormonal signaling. This review summarizes recent evidence implicating the gut-brain axis in regulating lipoprotein metabolism, with potential implications for the dyslipidemia of insulin resistant states. The intestine and brain possess distinct mechanisms for sensing lipid availability, which triggers subsequent regulation of feeding, glucose homeostasis, and adipose tissue metabolism. More recently, central receptors, neuropeptides, and gut hormones that communicate with the brain have been shown to modulate hepatic and intestinal lipoprotein metabolism via parasympathetic and sympathetic signaling. Gut-derived glucagon-like peptides appear to be particularly important in modulating the intestinal secretion of chylomicron particles via a novel brain-gut axis. Dysregulation of these pathways may contribute to postprandial diabetic dyslipidemia. Emerging evidence implicates the central and enteric nervous systems in controlling many aspects of lipid and lipoprotein metabolism. Bidirectional communication between the gut and brain involving neuronal pathways and gut peptides is critical for regulating feeding and metabolism, and forms a neuroendocrine circuit to modulate dietary fat absorption and intestinal production of atherogenic chylomicron particles.

SU-E-T-568: Improving Normal Brain Sparing with Increasing Number of Arc Beams for Volume Modulated Arc Beam Radiosurgery of Multiple Brain Metastases

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

Hossain, S; Hildebrand, K; Ahmad, S

Purpose: Intensity modulated arc beams have been newly reported for treating multiple brain metastases. The purpose of this study was to determine the variations in the normal brain doses with increasing number of arc beams for multiple brain metastases treatments via the TrueBeam Rapidarc system (Varian Oncology, Palo Alto, CA). Methods: A patient case with 12 metastatic brain lesions previously treated on the Leksell Gamma Knife Perfexion (GK) was used for the study. All lesions and organs at risk were contoured by a senior radiation oncologist and treatment plans for a subset of 3, 6, 9 and all 12 targetsmore » were developed for the TrueBeam Rapidarc system via 3 to 7 intensity modulated arc-beams with each target covered by at least 99% of the prescribed dose of 20 Gy. The peripheral normal brain isodose volumes as well as the total beam-on time were analyzed with increasing number of arc beams for these targets. Results: All intensisty modulated arc-beam plans produced efficient treatment delivery with the beam-on time averaging 0.6–1.5 min per lesion at an output of 1200 MU/min. With increasing number of arc beams, the peripheral normal brain isodose volumes such as the 12-Gy isodose line enclosed normal brain tissue volumes were on average decreased by 6%, 11%, 18%, and 28% for the 3-, 6-, 9-, 12-target treatment plans respectively. The lowest normal brain isodose volumes were consistently found for the 7-arc treatment plans for all the cases. Conclusion: With nearly identical beam-on times, the peripheral normal brain dose was notably decreased when the total number of intensity modulated arc beams was increased when treating multiple brain metastases. Dr Sahgal and Dr Ma are currently serving on the board of international society of stereotactic radiosurgery.« less

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

PubMed Central

Johanson, Conrad E; Duncan, John A; Klinge, Petra M; Brinker, Thomas; Stopa, Edward G; Silverberg, Gerald D

2008-01-01

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces. Outline 1 Overview 2 CSF formation 2.1 Transcription factors 2.2 Ion transporters 2.3 Enzymes that modulate transport 2.4 Aquaporins or water channels 2.5 Receptors for neuropeptides 3 CSF pressure 3.1 Servomechanism regulatory hypothesis 3.2 Ontogeny of CSF pressure generation 3.3 Congenital hydrocephalus and periventricular regions 3.4 Brain response to elevated CSF pressure 3.5 Advances in measuring CSF waveforms 4 CSF flow 4.1 CSF flow and brain metabolism 4.2 Flow effects on fetal germinal matrix 4.3 Decreasing CSF flow in aging CNS 4.4 Refinement of non-invasive flow measurements 5 CSF volume 5.1 Hemodynamic factors 5.2 Hydrodynamic factors 5.3 Neuroendocrine factors 6 CSF turnover rate 6.1 Adverse effect of ventriculomegaly 6.2 Attenuated CSF sink action 7 CSF composition 7.1 Kidney-like action of CP-CSF system 7.2 Altered CSF biochemistry in aging and disease 7.3 Importance of clearance transport 7.4 Therapeutic manipulation of composition 8 CSF recycling in relation to ISF dynamics 8.1 CSF exchange with brain interstitium 8.2 Components of ISF movement in brain 8.3 Compromised ISF/CSF dynamics and amyloid retention 9 CSF reabsorption 9.1 Arachnoidal outflow resistance 9.2 Arachnoid villi vs. olfactory drainage routes 9.3 Fluid reabsorption along spinal nerves 9.4 Reabsorption across capillary aquaporin channels 10 Developing translationally effective models for restoring CSF balance 11 Conclusion PMID:18479516

Cholesterol as a modifying agent of the neurovascular unit structure and function under physiological and pathological conditions.

PubMed

Czuba, Ewelina; Steliga, Aleksandra; Lietzau, Grażyna; Kowiański, Przemysław

2017-08-01

The brain, demanding constant level of cholesterol, precisely controls its synthesis and homeostasis. The brain cholesterol pool is almost completely separated from the rest of the body by the functional blood-brain barrier (BBB). Only a part of cholesterol pool can be exchanged with the blood circulation in the form of the oxysterol metabolites such, as 27-hydroxycholesterol (27-OHC) and 24S-hydroxycholesterol (24S-OHC). Not only neurons but also blood vessels and neuroglia, constituting neurovascular unit (NVU), are crucial for the brain cholesterol metabolism and undergo precise regulation by numerous modulators, metabolites and signal molecules. In physiological conditions maintaining the optimal cholesterol concentration is important for the energetic metabolism, composition of cell membranes and myelination. However, a growing body of evidence indicates the consequences of the cholesterol homeostasis dysregulation in several pathophysiological processes. There is a causal relationship between hypercholesterolemia and 1) development of type 2 diabetes due to long-term high-fat diet consumption, 2) significance of the oxidative stress consequences for cerebral amyloid angiopathy and neurodegenerative diseases, 3) insulin resistance on progression of the neurodegenerative brain diseases. In this review, we summarize the current state of knowledge concerning the cholesterol influence upon functioning of the NVU under physiological and pathological conditions.

Brain-gut-microbiota axis: challenges for translation in psychiatry.

PubMed

Kelly, John R; Clarke, Gerard; Cryan, John F; Dinan, Timothy G

2016-05-01

The accruing data linking the gut microbiome to the development and function of the central nervous system has been proposed as a paradigm shift in neuroscience. The gut microbiota can communicate with the brain via neuroimmune, neuroendocrine, and neural pathways comprising the brain-gut-microbiota axis. Dysfunctional neuroimmune pathways are implicated in stress-related psychiatric disorders. Using depression as our primary example, we review both the preclinical and clinical evidence supporting the possible role played by the gut microbiota in stress-related psychiatric disorders. We consider how this can inform future treatment strategies and outline the challenges and necessary studies for moving the field forward. The role played by the gut microbiota has not been fully elucidated in psychiatric populations. Although tempting to speculate that psychiatric patients may benefit from therapeutic modulation of the brain-gut-microbiota axis, the translational applications of the results obtained in rodent studies have yet to be demonstrated. Evidence of altered gut microbiota composition and function in psychiatric patients is limited and cannot be regarded as proven. Moreover the efficacy of targeting the gut microbiota has not yet been established, and needs further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

SU-F-T-349: Dosimetric Comparison of Three Different Simultaneous Integrated Boost Irradiation Techniques for Multiple Brain Metastases: Intensity-Modulatedradiotherapy, Hybrid Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy

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

Lin, X; Sun, T; Yin, Y

Purpose: To study the dosimetric impact of intensity-modulated radiotherapy (IMRT), hybrid intensity-modulated radiotherapy (h-IMRT) and volumetric modulated arc therapy(VMAT) for whole-brain radiotherapy (WBRT) with simultaneous integrated boost in patients with multiple brain metastases. Methods: Ten patients with multiple brain metastases were included in this analysis. The prescribed dose was 45 Gy to the whole brain (PTVWBRT) and 55 Gy to individual brain metastases (PTVboost) delivered simultaneously in 25 fractions. Three treatment techniques were designed: the 7 equal spaced fields IMRT plan, hybrid IMRT plan and VMAT with two 358°arcs. In hybrid IMRT plan, two fields(90°and 270°) were planned to themore » whole brain. This was used as a base dose plan. Then 5 fields IMRT plan was optimized based on the two fields plan. The dose distribution in the target, the dose to the organs at risk and total MU in three techniques were compared. Results: For the target dose, conformity and homogeneity in PTV, no statistically differences were observed in the three techniques. For the maximum dose in bilateral lens and the mean dose in bilateral eyes, IMRT and h-IMRT plans showed the highest and lowest value respectively. No statistically significant differences were observed in the dose of optic nerve and brainstem. For the monitor units, IMRT and VMAT plans showed the highest and lowest value respectively. Conclusion: For WBRT with simultaneous integrated boost in patients with multiple brain metastases, hybrid IMRT could reduce the doses to lens and eyes. It is feasible for patients with brain metastases.« less

Targeting brain cells with glutathione-modulated nanoliposomes: in vitro and in vivo study

PubMed Central

Salem, Heba F; Ahmed, Sayed M; Hassaballah, Ashraf E; Omar, Mahmoud M

2015-01-01

Background The blood–brain barrier prevents many drug moieties from reaching the central nervous system. Therefore, glutathione-modulated nanoliposomes have been engineered to enhance the targeting of flucytosine to the brain. Methods Glutathione-modulated nanoliposomes were prepared by thin-film hydration technique and evaluated in the primary brain cells of rats. Lecithin, cholesterol, and span 65 were mixed at 1:1:1 molar ratio. The molar percentage of PEGylated glutathione varied from 0 mol% to 0.75 mol%. The cellular binding and the uptake of the targeted liposomes were both monitored by epifluorescent microscope and flow cytometry techniques. A biodistribution and a pharmacokinetic study of flucytosine and flucytosine-loaded glutathione–modulated liposomes was carried out to evaluate the in vivo brain-targeting efficiency. Results The size of glutathione-modulated nanoliposomes was <100 nm and the zeta potential was more than −65 mV. The cumulative release reached 70% for certain formulations. The cellular uptake increased as molar percent of glutathione increased to reach the maximum at 0.75 mol%. The uptake of the targeted liposomes by brain cells of the rats was three times greater than that of the nontargeted liposomes. An in vivo study showed that the relative efficiency was 2.632±0.089 and the concentration efficiency was 1.590±0.049, and also, the drug-targeting index was 3.670±0.824. Conclusion Overall, these results revealed that glutathione-PEGylated nanoliposomes enhance the effective delivery of flucytosine to brain and could become a promising new therapeutic option for the treatment of the brain infections. PMID:26229435

Hearing and seeing meaning in speech and gesture: insights from brain and behaviour

PubMed Central

Özyürek, Aslı

2014-01-01

As we speak, we use not only the arbitrary form–meaning mappings of the speech channel but also motivated form–meaning correspondences, i.e. iconic gestures that accompany speech (e.g. inverted V-shaped hand wiggling across gesture space to demonstrate walking). This article reviews what we know about processing of semantic information from speech and iconic gestures in spoken languages during comprehension of such composite utterances. Several studies have shown that comprehension of iconic gestures involves brain activations known to be involved in semantic processing of speech: i.e. modulation of the electrophysiological recording component N400, which is sensitive to the ease of semantic integration of a word to previous context, and recruitment of the left-lateralized frontal–posterior temporal network (left inferior frontal gyrus (IFG), medial temporal gyrus (MTG) and superior temporal gyrus/sulcus (STG/S)). Furthermore, we integrate the information coming from both channels recruiting brain areas such as left IFG, posterior superior temporal sulcus (STS)/MTG and even motor cortex. Finally, this integration is flexible: the temporal synchrony between the iconic gesture and the speech segment, as well as the perceived communicative intent of the speaker, modulate the integration process. Whether these findings are special to gestures or are shared with actions or other visual accompaniments to speech (e.g. lips) or other visual symbols such as pictures are discussed, as well as the implications for a multimodal view of language. PMID:25092664

Hearing and seeing meaning in speech and gesture: insights from brain and behaviour.

PubMed

Özyürek, Aslı

2014-09-19

As we speak, we use not only the arbitrary form-meaning mappings of the speech channel but also motivated form-meaning correspondences, i.e. iconic gestures that accompany speech (e.g. inverted V-shaped hand wiggling across gesture space to demonstrate walking). This article reviews what we know about processing of semantic information from speech and iconic gestures in spoken languages during comprehension of such composite utterances. Several studies have shown that comprehension of iconic gestures involves brain activations known to be involved in semantic processing of speech: i.e. modulation of the electrophysiological recording component N400, which is sensitive to the ease of semantic integration of a word to previous context, and recruitment of the left-lateralized frontal-posterior temporal network (left inferior frontal gyrus (IFG), medial temporal gyrus (MTG) and superior temporal gyrus/sulcus (STG/S)). Furthermore, we integrate the information coming from both channels recruiting brain areas such as left IFG, posterior superior temporal sulcus (STS)/MTG and even motor cortex. Finally, this integration is flexible: the temporal synchrony between the iconic gesture and the speech segment, as well as the perceived communicative intent of the speaker, modulate the integration process. Whether these findings are special to gestures or are shared with actions or other visual accompaniments to speech (e.g. lips) or other visual symbols such as pictures are discussed, as well as the implications for a multimodal view of language. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Gray Matter Volume in Adolescent Anxiety: An Impact of the Brain-Derived Neurotrophic Factor Val[superscript 66]Met Polymorphism?

ERIC Educational Resources Information Center

Mueller, Sven C.; Aouidad, Aveline; Gorodetsky, Elena; Goldman, David; Pine, Daniel S.; Ernst, Monique

2013-01-01

Objective: Minimal research links anxiety disorders in adolescents to regional gray matter volume (GMV) abnormalities and their modulation by genetic factors. Prior research suggests that a brain-derived neurotrophic factor (BNDF) Val[superscript 66]Met polymorphism may modulate such brain morphometry profiles. Method: Using voxel-based…

Proteomic Profiling in the Brain of CLN1 Disease Model Reveals Affected Functional Modules.

PubMed

Tikka, Saara; Monogioudi, Evanthia; Gotsopoulos, Athanasios; Soliymani, Rabah; Pezzini, Francesco; Scifo, Enzo; Uusi-Rauva, Kristiina; Tyynelä, Jaana; Baumann, Marc; Jalanko, Anu; Simonati, Alessandro; Lalowski, Maciej

2016-03-01

Neuronal ceroid lipofuscinoses (NCL) are the most commonly inherited progressive encephalopathies of childhood. Pathologically, they are characterized by endolysosomal storage with different ultrastructural features and biochemical compositions. The molecular mechanisms causing progressive neurodegeneration and common molecular pathways linking expression of different NCL genes are largely unknown. We analyzed proteome alterations in the brains of a mouse model of human infantile CLN1 disease-palmitoyl-protein thioesterase 1 (Ppt1) gene knockout and its wild-type age-matched counterpart at different stages: pre-symptomatic, symptomatic and advanced. For this purpose, we utilized a combination of laser capture microdissection-based quantitative liquid chromatography tandem mass spectrometry (MS) and matrix-assisted laser desorption/ionization time-of-flight MS imaging to quantify/visualize the changes in protein expression in disease-affected brain thalamus and cerebral cortex tissue slices, respectively. Proteomic profiling of the pre-symptomatic stage thalamus revealed alterations mostly in metabolic processes and inhibition of various neuronal functions, i.e., neuritogenesis. Down-regulation in dynamics associated with growth of plasma projections and cellular protrusions was further corroborated by findings from RNA sequencing of CLN1 patients' fibroblasts. Changes detected at the symptomatic stage included: mitochondrial functions, synaptic vesicle transport, myelin proteome and signaling cascades, such as RhoA signaling. Considerable dysregulation of processes related to mitochondrial cell death, RhoA/Huntington's disease signaling and myelin sheath breakdown were observed at the advanced stage of the disease. The identified changes in protein levels were further substantiated by bioinformatics and network approaches, immunohistochemistry on brain tissues and literature knowledge, thus identifying various functional modules affected in the CLN1 childhood encephalopathy.

Teaching About "Brain and Learning" in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence.

PubMed

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about "Brain and Learning" using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in "Brain and Learning" and 1241 students in grades 8-9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of "Brain and Learning" had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into "Brain and Learning," and for changing students' beliefs about intelligence.

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.

Aging effects on DNA methylation modules in human brain and blood tissue

PubMed Central

2012-01-01

Background Several recent studies reported aging effects on DNA methylation levels of individual CpG dinucleotides. But it is not yet known whether aging-related consensus modules, in the form of clusters of correlated CpG markers, can be found that are present in multiple human tissues. Such a module could facilitate the understanding of aging effects on multiple tissues. Results We therefore employed weighted correlation network analysis of 2,442 Illumina DNA methylation arrays from brain and blood tissues, which enabled the identification of an age-related co-methylation module. Module preservation analysis confirmed that this module can also be found in diverse independent data sets. Biological evaluation showed that module membership is associated with Polycomb group target occupancy counts, CpG island status and autosomal chromosome location. Functional enrichment analysis revealed that the aging-related consensus module comprises genes that are involved in nervous system development, neuron differentiation and neurogenesis, and that it contains promoter CpGs of genes known to be down-regulated in early Alzheimer's disease. A comparison with a standard, non-module based meta-analysis revealed that selecting CpGs based on module membership leads to significantly increased gene ontology enrichment, thus demonstrating that studying aging effects via consensus network analysis enhances the biological insights gained. Conclusions Overall, our analysis revealed a robustly defined age-related co-methylation module that is present in multiple human tissues, including blood and brain. We conclude that blood is a promising surrogate for brain tissue when studying the effects of age on DNA methylation profiles. PMID:23034122

Novel Treatment Strategies Using TiO2-Nanowired Delivery of Histaminergic Drugs and Antibodies to Tau With Cerebrolysin for Superior Neuroprotection in the Pathophysiology of Alzheimer's Disease.

PubMed

Sharma, Aruna; Menon, Preeti K; Patnaik, Ranjana; Muresanu, Dafin F; Lafuente, José V; Tian, Z Ryan; Ozkizilcik, Asya; Castellani, Rudy J; Mössler, Herbert; Sharma, Hari S

2017-01-01

More than 5.5 million Americans of all ages are suffering from Alzheimer's disease (AD) till today for which no suitable therapy has been developed so far. Thus, there is an urgent need to explore novel therapeutic measures to contain brain pathology in AD. The hallmark of AD includes amyloid-beta peptide (AβP) deposition and phosphorylation of tau in AD brain. Recent evidences also suggest a marked decrease in neurotrophic factors in AD. Thus, exogenous supplement of neurotrophic factors could be one of the possible ways for AD therapy. Human postmortem brain in AD shows alterations in histamine receptors as well, indicating an involvement of the amine in AD-induced brain pathology. In this review, we focused on role of histamine 3 and 4 receptor-modulating drugs in the pathophysiology of AD. Moreover, antibodies to histamine and tau appear to be also beneficial in reducing brain pathology, blood-brain barrier breakdown, and edema formation in AD. Interestingly, TiO 2 -nanowired delivery of cerebrolysin-a balanced composition of several neurotrophic factors attenuated AβP deposition and reduced tau phosphorylation in AD brain leading to neuroprotection. Coadministration of cerebrolysin with histamine antibodies or tau antibodies has further enhanced neuroprotection in AD. These novel observations strongly suggest a role of nanomedicine in AD that requires further investigation. © 2017 Elsevier Inc. All rights reserved.

Orbitrap mass spectrometry characterization of hybrid chondroitin/dermatan sulfate hexasaccharide domains expressed in brain.

PubMed

Robu, Adrian C; Popescu, Laurentiu; Munteanu, Cristian V A; Seidler, Daniela G; Zamfir, Alina D

2015-09-15

In the central nervous system, chondroitin/dermatan sulfate (CS/DS) glycosaminoglycans (GAGs) modulate neurotrophic effects and glial cell maturation during brain development. Previous reports revealed that GAG composition could be responsible for CS/DS activities in brain. In this work, for the structural characterization of DS- and CS-rich domains in hybrid GAG chains extracted from neural tissue, we have developed an advanced approach based on high-resolution mass spectrometry (MS) using nanoelectrospray ionization Orbitrap in the negative ion mode. Our high-resolution MS and multistage MS approach was developed and applied to hexasaccharides obtained from 4- and 14-week-old mouse brains by GAG digestion with chondroitin B and in parallel with AC I lyase. The expression of DS- and CS-rich domains in the two tissues was assessed comparatively. The analyses indicated an age-related structural variability of the CS/DS motifs. The older brain was found to contain more structures and a higher sulfation of DS-rich regions, whereas the younger brain was found to be characterized by a higher sulfation of CS-rich regions. By multistage MS using collision-induced dissociation, we also demonstrated the incidence in mouse brain of an atypical [4,5-Δ-GlcAGalNAc(IdoAGalNAc)2], presenting a bisulfated CS disaccharide formed by 3-O-sulfate-4,5-Δ-GlcA and 6-O-sulfate-GalNAc moieties. Copyright © 2015 Elsevier Inc. All rights reserved.

Traumatic Brain Injury: A Guide for Caregivers of Service Members and Veterans. Welcome

DTIC Science & Technology

2010-04-01

Reed Army Medical Center, 33 percent had traumatic brain injury (as of March 2009). Due to medical and technological advances, we have seen a...Right to Appeal PEB Decision - Module 4, pages 139-141 PEG Tube (Per Cutaneous Gastronomy Tube) - Module 1, page 23 PRC (VA Polytrauma Rehabilitation...Per Cutaneous Gastronomy Tube (PEG tube) - Module 1, page 23 Peripheral Fatigue - Module 2, page 17 IN D EX 29 Permanent Disability Retired List (PDRL

Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus.

PubMed

Zhang, Jiyong; Sadowska, Grazyna B; Chen, Xiaodi; Park, Seon Yeong; Kim, Jeong-Eun; Bodge, Courtney A; Cummings, Erin; Lim, Yow-Pin; Makeyev, Oleksandr; Besio, Walter G; Gaitanis, John; Banks, William A; Stonestreet, Barbara S

2015-05-01

Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti-IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia. © FASEB.

Anxiety, Depression, and the Microbiome: A Role for Gut Peptides.

PubMed

Lach, Gilliard; Schellekens, Harriet; Dinan, Timothy G; Cryan, John F

2018-01-01

The complex bidirectional communication between the gut and the brain is finely orchestrated by different systems, including the endocrine, immune, autonomic, and enteric nervous systems. Moreover, increasing evidence supports the role of the microbiome and microbiota-derived molecules in regulating such interactions; however, the mechanisms underpinning such effects are only beginning to be resolved. Microbiota-gut peptide interactions are poised to be of great significance in the regulation of gut-brain signaling. Given the emerging role of the gut-brain axis in a variety of brain disorders, such as anxiety and depression, it is important to understand the contribution of bidirectional interactions between peptide hormones released from the gut and intestinal bacteria in the context of this axis. Indeed, the gastrointestinal tract is the largest endocrine organ in mammals, secreting dozens of different signaling molecules, including peptides. Gut peptides in the systemic circulation can bind cognate receptors on immune cells and vagus nerve terminals thereby enabling indirect gut-brain communication. Gut peptide concentrations are not only modulated by enteric microbiota signals, but also vary according to the composition of the intestinal microbiota. In this review, we will discuss the gut microbiota as a regulator of anxiety and depression, and explore the role of gut-derived peptides as signaling molecules in microbiome-gut-brain communication. Here, we summarize the potential interactions of the microbiota with gut hormones and endocrine peptides, including neuropeptide Y, peptide YY, pancreatic polypeptide, cholecystokinin, glucagon-like peptide, corticotropin-releasing factor, oxytocin, and ghrelin in microbiome-to-brain signaling. Together, gut peptides are important regulators of microbiota-gut-brain signaling in health and stress-related psychiatric illnesses.

Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

PubMed

Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

2015-03-01

The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P < 0.001. Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

Altered brain network modules induce helplessness in major depressive disorder.

PubMed

Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Fang, Yiru; Shen, Dinggang

2014-10-01

The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. Copyright © 2014 Elsevier B.V. All rights reserved.

Altered brain network modules induce helplessness in major depressive disorder

PubMed Central

Peng, Daihui; Shi, Feng; Shen, Ting; Peng, Ziwen; Zhang, Chen; Liu, Xiaohua; Qiu, Meihui; Liu, Jun; Jiang, Kaida; Shen, Dinggang

2017-01-01

Objective The abnormal brain functional connectivity (FC) has been assumed to be a pathophysiological aspect of major depressive disorder (MDD). However, it is poorly understood, regarding the underlying patterns of global FC network and their relationships with the clinical characteristics of MDD. Methods Resting-state functional magnetic resonance imaging data were acquired from 16 first episode, medication-naïve MDD patients and 16 healthy control subjects. The global FC network was constructed using 90 brain regions. The global topological patterns, e.g., small-worldness and modularity, and their relationships with depressive characteristics were investigated. Furthermore, the participant coefficient and module degree of MDD patients were measured to reflect the regional roles in module network, and the impairment of FC was examined by network based statistic. Results Small-world property was not altered in MDD. However, MDD patients exhibited 5 atypically reorganized modules compared to the controls. A positive relationship was also found among MDD patients between the intra-module I and helplessness factor evaluated via the Hamilton Depression Scale. Specifically, eight regions exhibited the abnormal participant coefficient or module degree, e.g., left superior orbital frontal cortex and right amygdala. The decreased FC was identified among the sub-network of 24 brain regions, e.g., frontal cortex, supplementary motor area, amygdala, thalamus, and hippocampus. Limitation The limited size of MDD samples precluded meaningful study of distinct clinical characteristics in relation to aberrant FC. Conclusions The results revealed altered patterns of brain module network at the global level in MDD patients, which might contribute to the feelings of helplessness. PMID:25033474

Teaching About “Brain and Learning” in High School Biology Classes: Effects on Teachers' Knowledge and Students' Theory of Intelligence

PubMed Central

Dekker, Sanne; Jolles, Jelle

2015-01-01

This study evaluated a new teaching module about “Brain and Learning” using a controlled design. The module was implemented in high school biology classes and comprised three lessons: (1) brain processes underlying learning; (2) neuropsychological development during adolescence; and (3) lifestyle factors that influence learning performance. Participants were 32 biology teachers who were interested in “Brain and Learning” and 1241 students in grades 8–9. Teachers' knowledge and students' beliefs about learning potential were examined using online questionnaires. Results indicated that before intervention, biology teachers were significantly less familiar with how the brain functions and develops than with its structure and with basic neuroscientific concepts (46 vs. 75% correct answers). After intervention, teachers' knowledge of “Brain and Learning” had significantly increased (64%), and more students believed that intelligence is malleable (incremental theory). This emphasizes the potential value of a short teaching module, both for improving biology teachers' insights into “Brain and Learning,” and for changing students' beliefs about intelligence. PMID:26648900

The BRAIN Initiative Provides a Unifying Context for Integrating Core STEM Competencies into a Neurobiology Course.

PubMed

Schaefer, Jennifer E

2016-01-01

The Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative introduced by the Obama Administration in 2013 presents a context for integrating many STEM competencies into undergraduate neuroscience coursework. The BRAIN Initiative core principles overlap with core STEM competencies identified by the AAAS Vision and Change report and other entities. This neurobiology course utilizes the BRAIN Initiative to serve as the unifying theme that facilitates a primary emphasis on student competencies such as scientific process, scientific communication, and societal relevance while teaching foundational neurobiological content such as brain anatomy, cellular neurophysiology, and activity modulation. Student feedback indicates that the BRAIN Initiative is an engaging and instructional context for this course. Course module organization, suitable BRAIN Initiative commentary literature, sample primary literature, and important assignments are presented.

Fluorescent Pressure Response of Protein-Nanocluster Polymer Composites

DTIC Science & Technology

2016-05-01

composites as pressure sensitive indicators of brain damage. The PNC composites are made up of protein coated gold nanoclusters and a styrene- ethylene ...styrene- ethylene /butylene-styrene (SEBS):mineral oil composites that were developed as a brain tissue surrogate at ARL. Finally, we would like to...allowing us to use solid samples and create a model for brain damage. To this end, we used styrene- ethylene /butylene-styrene (SEBS) as the matrix to

The bidirectional gut-brain-microbiota axis as a potential nexus between traumatic brain injury, inflammation, and disease.

PubMed

Sundman, Mark H; Chen, Nan-Kuei; Subbian, Vignesh; Chou, Ying-Hui

2017-11-01

As head injuries and their sequelae have become an increasingly salient matter of public health, experts in the field have made great progress elucidating the biological processes occurring within the brain at the moment of injury and throughout the recovery thereafter. Given the extraordinary rate at which our collective knowledge of neurotrauma has grown, new insights may be revealed by examining the existing literature across disciplines with a new perspective. This article will aim to expand the scope of this rapidly evolving field of research beyond the confines of the central nervous system (CNS). Specifically, we will examine the extent to which the bidirectional influence of the gut-brain axis modulates the complex biological processes occurring at the time of traumatic brain injury (TBI) and over the days, months, and years that follow. In addition to local enteric signals originating in the gut, it is well accepted that gastrointestinal (GI) physiology is highly regulated by innervation from the CNS. Conversely, emerging data suggests that the function and health of the CNS is modulated by the interaction between 1) neurotransmitters, immune signaling, hormones, and neuropeptides produced in the gut, 2) the composition of the gut microbiota, and 3) integrity of the intestinal wall serving as a barrier to the external environment. Specific to TBI, existing pre-clinical data indicates that head injuries can cause structural and functional damage to the GI tract, but research directly investigating the neuronal consequences of this intestinal damage is lacking. Despite this void, the proposed mechanisms emanating from a damaged gut are closely implicated in the inflammatory processes known to promote neuropathology in the brain following TBI, which suggests the gut-brain axis may be a therapeutic target to reduce the risk of Chronic Traumatic Encephalopathy and other neurodegenerative diseases following TBI. To better appreciate how various peripheral influences are implicated in the health of the CNS following TBI, this paper will also review the secondary biological injury mechanisms and the dynamic pathophysiological response to neurotrauma. Together, this review article will attempt to connect the dots to reveal novel insights into the bidirectional influence of the gut-brain axis and propose a conceptual model relevant to the recovery from TBI and subsequent risk for future neurological conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Liposomes Coloaded with Elacridar and Tariquidar To Modulate the P-Glycoprotein at the Blood-Brain Barrier.

PubMed

Nieto Montesinos, Rita; Béduneau, Arnaud; Lamprecht, Alf; Pellequer, Yann

2015-11-02

This study prepared three liposomal formulations coloaded with elacridar and tariquidar to overcome the P-glycoprotein-mediated efflux at the blood-brain barrier. Their pharmacokinetics, brain distribution, and impact on the model P-glycoprotein substrate, loperamide, were compared to those for the coadministration of free elacridar plus free tariquidar. After intravenous administration in rats, elacridar and tariquidar in conventional liposomes were rapidly cleared from the bloodstream. Their low levels in the brain did not improve the loperamide brain distribution. Although elacridar and tariquidar in PEGylated liposomes exhibited 2.6 and 1.9 longer half-lives than free elacridar and free tariquidar, respectively, neither their Kp for the brain nor the loperamide brain distribution was improved. However, the conjugation of OX26 F(ab')2 fragments to PEGylated liposomes increased the Kps for the brain of elacridar and tariquidar by 1.4- and 2.1-fold, respectively, in comparison to both free P-gp modulators. Consequently, the Kp for the brain of loperamide increased by 2.7-fold. Moreover, the plasma pharmacokinetic parameters and liver distribution of loperamide were not modified by the PEGylated OX26 F(ab')2 immunoliposomes. Thus, this formulation represents a promising tool for modulating the P-glycoprotein-mediated efflux at the blood-brain barrier and could improve the brain uptake of any P-glycoprotein substrate that is intended to treat central nervous system diseases.

Topological Alterations and Symptom-Relevant Modules in the Whole-Brain Structural Network in Semantic Dementia.

PubMed

Ding, Junhua; Chen, Keliang; Zhang, Weibin; Li, Ming; Chen, Yan; Yang, Qing; Lv, Yingru; Guo, Qihao; Han, Zaizhu

2017-01-01

Semantic dementia (SD) is characterized by a selective decline in semantic processing. Although the neuropsychological pattern of this disease has been identified, its topological global alterations and symptom-relevant modules in the whole-brain anatomical network have not been fully elucidated. This study aims to explore the topological alteration of anatomical network in SD and reveal the modules associated with semantic deficits in this disease. We first constructed the whole-brain white-matter networks of 20 healthy controls and 19 patients with SD. Then, the network metrics of graph theory were compared between these two groups. Finally, we separated the network of SD patients into different modules and correlated the structural integrity of each module with the severity of the semantic deficits across patients. The network of the SD patients presented a significantly reduced global efficiency, indicating that the long-distance connections were damaged. The network was divided into the following four distinctive modules: the left temporal/occipital/parietal, frontal, right temporal/occipital, and frontal/parietal modules. The first two modules were associated with the semantic deficits of SD. These findings illustrate the skeleton of the neuroanatomical network of SD patients and highlight the key role of the left temporal/occipital/parietal module and the left frontal module in semantic processing.

New Treatment Strategies of Depression: Based on Mechanisms Related to Neuroplasticity

PubMed Central

Lane, Hsien-Yuan

2017-01-01

Major depressive disorder is a severe and complex mental disorder. Impaired neurotransmission and disrupted signalling pathways may influence neuroplasticity, which is involved in the brain dysfunction in depression. Traditional neurobiological theories of depression, such as monoamine hypothesis, cannot fully explain the whole picture of depressive disorders. In this review, we discussed new treatment directions of depression, including modulation of glutamatergic system and noninvasive brain stimulation. Dysfunction of glutamatergic neurotransmission plays an important role in the pathophysiology of depression. Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, has rapid and lasting antidepressive effects in previous studies. In addition to ketamine, other glutamatergic modulators, such as sarcosine, also show potential antidepressant effect in animal models or clinical trials. Noninvasive brain stimulation is another new treatment strategy beyond pharmacotherapy. Growing evidence has demonstrated that superficial brain stimulations, such as transcranial magnetic stimulation, transcranial direct current stimulation, cranial electrotherapy stimulation, and magnetic seizure therapy, can improve depressive symptoms. The antidepressive effect of these brain stimulations may be through modulating neuroplasticity. In conclusion, drugs that modulate neurotransmission via NMDA receptor and noninvasive brain stimulation may provide new directions of treatment for depression. Furthermore, exploring the underlying mechanisms will help in developing novel therapies for depression in the future. PMID:28491480

FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network

PubMed Central

Qin, Wei; Tian, Jie; Bai, Lijun; Pan, Xiaohong; Yang, Lin; Chen, Peng; Dai, Jianping; Ai, Lin; Zhao, Baixiao; Gong, Qiyong; Wang, Wei; von Deneen, Karen M; Liu, Yijun

2008-01-01

Background Recently, increasing evidence has indicated that the primary acupuncture effects are mediated by the central nervous system. However, specific brain networks underpinning these effects remain unclear. Results In the present study using fMRI, we employed a within-condition interregional covariance analysis method to investigate functional connectivity of brain networks involved in acupuncture. The fMRI experiment was performed before, during and after acupuncture manipulations on healthy volunteers at an acupuncture point, which was previously implicated in a neural pathway for pain modulation. We first identified significant fMRI signal changes during acupuncture stimulation in the left amygdala, which was subsequently selected as a functional reference for connectivity analyses. Our results have demonstrated that there is a brain network associated with the amygdala during a resting condition. This network encompasses the brain structures that are implicated in both pain sensation and pain modulation. We also found that such a pain-related network could be modulated by both verum acupuncture and sham acupuncture. Furthermore, compared with a sham acupuncture, the verum acupuncture induced a higher level of correlations among the amygdala-associated network. Conclusion Our findings indicate that acupuncture may change this amygdala-specific brain network into a functional state that underlies pain perception and pain modulation. PMID:19014532

Spatiotemporal brain dynamics of emotional face processing modulations induced by the serotonin 1A/2A receptor agonist psilocybin.

PubMed

Bernasconi, Fosco; Schmidt, André; Pokorny, Thomas; Kometer, Michael; Seifritz, Erich; Vollenweider, Franz X

2014-12-01

Emotional face processing is critically modulated by the serotonergic system. For instance, emotional face processing is impaired by acute psilocybin administration, a serotonin (5-HT) 1A and 2A receptor agonist. However, the spatiotemporal brain mechanisms underlying these modulations are poorly understood. Here, we investigated the spatiotemporal brain dynamics underlying psilocybin-induced modulations during emotional face processing. Electrical neuroimaging analyses were applied to visual evoked potentials in response to emotional faces, following psilocybin and placebo administration. Our results indicate a first time period of strength (i.e., Global Field Power) modulation over the 168-189 ms poststimulus interval, induced by psilocybin. A second time period of strength modulation was identified over the 211-242 ms poststimulus interval. Source estimations over these 2 time periods further revealed decreased activity in response to both neutral and fearful faces within limbic areas, including amygdala and parahippocampal gyrus, and the right temporal cortex over the 168-189 ms interval, and reduced activity in response to happy faces within limbic and right temporo-occipital brain areas over the 211-242 ms interval. Our results indicate a selective and temporally dissociable effect of psilocybin on the neuronal correlates of emotional face processing, consistent with a modulation of the top-down control. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system

PubMed Central

Zamberletti, Erica; Piscitelli, Fabiana; De Castro, Valentina; Murru, Elisabetta; Gabaglio, Marina; Colucci, Paola; Fanali, Chiara; Prini, Pamela; Bisogno, Tiziana; Maccarrone, Mauro; Campolongo, Patrizia; Banni, Sebastiano; Rubino, Tiziana; Parolaro, Daniela

2017-01-01

Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition. PMID:27903595

Effect of the Mediterranean diet on cognition and brain morphology and function: a systematic review of randomized controlled trials.

PubMed

Radd-Vagenas, Sue; Duffy, Shantel L; Naismith, Sharon L; Brew, Bruce J; Flood, Victoria M; Fiatarone Singh, Maria A

2018-03-01

Observational studies of the Mediterranean diet suggest cognitive benefits, potentially reducing dementia risk. We performed the first published review to our knowledge of randomized controlled trials (RCTs) investigating Mediterranean diet effects on cognition or brain morphology and function, with an additional focus on intervention diet quality and its relation to "traditional" Mediterranean dietary patterns. We searched 9 databases from inception (final update December 2017) for RCTs testing a Mediterranean compared with alternate diet for cognitive or brain morphology and function outcomes. Analyses were based on 66 cognitive tests and 1 brain function outcome from 5 included studies (n = 1888 participants). The prescribed Mediterranean diets varied considerably between studies, particularly with regards to quantitative food advice. Only 8/66 (12.1%) of individual cognitive outcomes at trial level significantly favored a Mediterranean diet for cognitive performance, with effect sizes (ESs) ranging from small (0.32) to large (1.66), whereas 2 outcomes favored controls. Data limitations precluded a meta-analysis. Of 8 domain composite cognitive scores from 2 studies, the 3 (Memory, Frontal, and Global function) from PREDIMED (PREvención con DIeta MEDiterránea) were significant, with ESs ranging from 0.39 to 1.29. A posttest comparison at a second PREDIMED site found that the Mediterranean diet modulates the effect of several genotypes associated with dementia risk for some cognitive outcomes, with mixed results. Finally, the risk of low-plasma brain-derived neurotrophic factor was reduced by 78% (OR = 0.22; 95% CI: 0.05, 0.90) in those who consumed a Mediterranean diet compared to control diet at 3 y in this trial. There was no benefit of the Mediterranean diet for incident cognitive impairment or dementia. Five RCTs of the Mediterranean diet and cognition have been published to date. The data are mostly nonsignificant, with small ESs. However, the significant improvements in cognitive domain composites in the most robustly designed study warrant additional research.

A small world of weak ties provides optimal global integration of self-similar modules in functional brain networks.

PubMed

Gallos, Lazaros K; Makse, Hernán A; Sigman, Mariano

2012-02-21

The human brain is organized in functional modules. Such an organization presents a basic conundrum: Modules ought to be sufficiently independent to guarantee functional specialization and sufficiently connected to bind multiple processors for efficient information transfer. It is commonly accepted that small-world architecture of short paths and large local clustering may solve this problem. However, there is intrinsic tension between shortcuts generating small worlds and the persistence of modularity, a global property unrelated to local clustering. Here, we present a possible solution to this puzzle. We first show that a modified percolation theory can define a set of hierarchically organized modules made of strong links in functional brain networks. These modules are "large-world" self-similar structures and, therefore, are far from being small-world. However, incorporating weaker ties to the network converts it into a small world preserving an underlying backbone of well-defined modules. Remarkably, weak ties are precisely organized as predicted by theory maximizing information transfer with minimal wiring cost. This trade-off architecture is reminiscent of the "strength of weak ties" crucial concept of social networks. Such a design suggests a natural solution to the paradox of efficient information flow in the highly modular structure of the brain.

A small world of weak ties provides optimal global integration of self-similar modules in functional brain networks

PubMed Central

Gallos, Lazaros K.; Makse, Hernán A.; Sigman, Mariano

2012-01-01

The human brain is organized in functional modules. Such an organization presents a basic conundrum: Modules ought to be sufficiently independent to guarantee functional specialization and sufficiently connected to bind multiple processors for efficient information transfer. It is commonly accepted that small-world architecture of short paths and large local clustering may solve this problem. However, there is intrinsic tension between shortcuts generating small worlds and the persistence of modularity, a global property unrelated to local clustering. Here, we present a possible solution to this puzzle. We first show that a modified percolation theory can define a set of hierarchically organized modules made of strong links in functional brain networks. These modules are “large-world” self-similar structures and, therefore, are far from being small-world. However, incorporating weaker ties to the network converts it into a small world preserving an underlying backbone of well-defined modules. Remarkably, weak ties are precisely organized as predicted by theory maximizing information transfer with minimal wiring cost. This trade-off architecture is reminiscent of the “strength of weak ties” crucial concept of social networks. Such a design suggests a natural solution to the paradox of efficient information flow in the highly modular structure of the brain. PMID:22308319

Factor analysis of regional brain activation in bipolar and healthy individuals reveals a consistent modular structure.

PubMed

Fleck, David E; Welge, Jeffrey A; Eliassen, James C; Adler, Caleb M; DelBello, Melissa P; Strakowski, Stephen M

2018-07-01

The neurophysiological substrates of cognition and emotion, as seen with fMRI, are generally explained using modular structures. The present study was designed to probe the modular structure of cognitive-emotional processing in bipolar and healthy individuals using factor analysis and compare the results with current conceptions of the neurophysiology of bipolar disorder. Exploratory factor analysis was used to assess patterns of covariation among brain regions-of-interest activated during the Continuous Performance Task with Emotional and Neutral Distractors in healthy and bipolar individuals without a priori constraints on the number or composition of latent factors. Results indicated a common cognitive-emotional network consisting of prefrontal, medial temporal, limbic, parietal, anterior cingulate and posterior cingulate modules. However, reduced brain activation to emotional stimuli in the frontal, medial temporal and limbic modules was apparent in the bipolar relative to the healthy group, potentially accounting for emotional dysregulation in bipolar disorder. This study is limited by a relatively small sample size recruited at a single site. The results have yet to be validated on a larger independent sample. Although the modular structure of cognitive-emotional processing is similar in bipolar and healthy individuals, activation in response to emotional/neutral cues varies. These findings are not only consistent with recent conceptions of mood regulation in bipolar disorder, but also suggest that regional activation can be considered within tighter modular structures without compromising data interpretation. This demonstration may serve as a template for data reduction in future region-of-interest analyses to increase statistical power. Copyright © 2018 Elsevier B.V. All rights reserved.

A revision of brain composition in Onychophora (velvet worms) suggests that the tritocerebrum evolved in arthropods

PubMed Central

2010-01-01

Background The composition of the arthropod head is one of the most contentious issues in animal evolution. In particular, controversy surrounds the homology and innervation of segmental cephalic appendages by the brain. Onychophora (velvet worms) play a crucial role in understanding the evolution of the arthropod brain, because they are close relatives of arthropods and have apparently changed little since the Early Cambrian. However, the segmental origins of their brain neuropils and the number of cephalic appendages innervated by the brain - key issues in clarifying brain composition in the last common ancestor of Onychophora and Arthropoda - remain unclear. Results Using immunolabelling and neuronal tracing techniques in the developing and adult onychophoran brain, we found that the major brain neuropils arise from only the anterior-most body segment, and that two pairs of segmental appendages are innervated by the brain. The region of the central nervous system corresponding to the arthropod tritocerebrum is not differentiated as part of the onychophoran brain but instead belongs to the ventral nerve cords. Conclusions Our results contradict the assumptions of a tripartite (three-segmented) brain in Onychophora and instead confirm the hypothesis of bipartite (two-segmented) brain composition. They suggest that the last common ancestor of Onychophora and Arthropoda possessed a brain consisting of protocerebrum and deutocerebrum whereas the tritocerebrum evolved in arthropods. PMID:20727203

Toll-like receptor 4 enhancement of non-NMDA synaptic currents increases dentate excitability after brain injury.

PubMed

Li, Ying; Korgaonkar, Akshata A; Swietek, Bogumila; Wang, Jianfeng; Elgammal, Fatima S; Elkabes, Stella; Santhakumar, Vijayalakshmi

2015-02-01

Concussive brain injury results in neuronal degeneration, microglial activation and enhanced excitability in the hippocampal dentate gyrus, increasing the risk for epilepsy and memory dysfunction. Endogenous molecules released during injury can activate innate immune responses including toll-like receptor 4 (TLR4). Recent studies indicate that immune mediators can modulate neuronal excitability. Since non-specific agents that reduce TLR4 signaling can limit post-traumatic neuropathology, we examined whether TLR4 signaling contributes to early changes in dentate excitability after brain injury. Concussive brain injury caused a transient increase in hippocampal TLR4 expression within 4h, which peaked at 24h. Post-injury increase in TLR4 expression in the dentate gyrus was primarily neuronal and persisted for one week. Acute, in vitro treatment with TLR4 ligands caused bidirectional modulation of dentate excitability in control and brain-injured rats, with a reversal in the direction of modulation after brain injury. TLR4 antagonists decreased, and agonist increased, afferent-evoked dentate excitability one week after brain injury. NMDA receptor antagonist did not occlude the ability of LPS-RS, a TLR4 antagonist, to decrease post-traumatic dentate excitability. LPS-RS failed to modulate granule cell NMDA EPSCs but decreased perforant path-evoked non-NMDA EPSC peak amplitude and charge transfer in both granule cells and mossy cells. Our findings indicate an active role for TLR4 signaling in early post-traumatic dentate hyperexcitability. The novel TLR4 modulation of non-NMDA glutamatergic currents, identified herein, could represent a general mechanism by which immune activation influences neuronal excitability in neurological disorders that recruit sterile inflammatory responses. Copyright © 2014 Elsevier Inc. All rights reserved.

Cancer-specific health-related quality of life in children with brain tumors.

PubMed

Sato, Iori; Higuchi, Akiko; Yanagisawa, Takaaki; Mukasa, Akitake; Ida, Kohmei; Sawamura, Yutaka; Sugiyama, Kazuhiko; Saito, Nobuhito; Kumabe, Toshihiro; Terasaki, Mizuhiko; Nishikawa, Ryo; Ishida, Yasushi; Kamibeppu, Kiyoko

2014-05-01

To understand the influence of disease and treatment on the health-related quality of life (HRQOL) of children with brain tumors, compared to the HRQOL of children with other cancers, from the viewpoints of children and parents. A total of 133 children aged 5-18 years and 165 parents of children aged 2-18 completed questionnaires of the Pediatric Quality of Life Inventory Cancer Module (Pain and Hurt, Nausea, Procedural Anxiety, Treatment Anxiety, Worry, Cognitive Problems, Perceived Physical Appearance, and Communication scales); higher scores indicate a better HRQOL. The Cancer Module scores, weighted by age and treatment status, were compared to those obtained in a previous study of children with other cancers (mostly leukemia). The weighted mean scores for Pain and Hurt (effect size d = 0.26) and Nausea (d = 0.23) from child reports and the scores for Nausea (d = 0.28) from parent reports were higher for children with brain tumors than scores for children with other cancers. The scores for Procedural Anxiety (d = -0.22) and Treatment Anxiety (d = -0.32) from parent reports were lower for parents of children with brain tumors than the scores for parents of children with other cancers. The child-reported Pain and Hurt score of the Cancer Module was higher (d = 0.29) and in less agreement (intraclass correlation coefficient = 0.43) with scores from the Brain Tumor Module, indicating that assessments completed with the Cancer Module misesteem pain and hurt problems in children with brain tumors. The profiles of cancer-specific HRQOL in children with brain tumors differ from those of children with other cancers; we therefore suggest that these children receive specific psychological support.

The impact of microbiota on brain and behavior: mechanisms & therapeutic potential.

PubMed

Borre, Yuliya E; Moloney, Rachel D; Clarke, Gerard; Dinan, Timothy G; Cryan, John F

2014-01-01

There is increasing evidence that host-microbe interactions play a key role in maintaining homeostasis. Alterations in gut microbial composition is associated with marked changes in behaviors relevant to mood, pain and cognition, establishing the critical importance of the bi-directional pathway of communication between the microbiota and the brain in health and disease. Dysfunction of the microbiome-brain-gut axis has been implicated in stress-related disorders such as depression, anxiety and irritable bowel syndrome and neurodevelopmental disorders such as autism. Bacterial colonization of the gut is central to postnatal development and maturation of key systems that have the capacity to influence central nervous system (CNS) programming and signaling, including the immune and endocrine systems. Moreover, there is now expanding evidence for the view that enteric microbiota plays a role in early programming and later response to acute and chronic stress. This view is supported by studies in germ-free mice and in animals exposed to pathogenic bacterial infections, probiotic agents or antibiotics. Although communication between gut microbiota and the CNS are not fully elucidated, neural, hormonal, immune and metabolic pathways have been suggested. Thus, the concept of a microbiome-brain-gut axis is emerging, suggesting microbiota-modulating strategies may be a tractable therapeutic approach for developing novel treatments for CNS disorders.

Evaluation of Acoustic Emission NDE of Composite Crew Module Service Module/Alternate Launch Abort System (CCM SM/ALAS) Test Article Failure Tests

NASA Technical Reports Server (NTRS)

Horne, Michael R.; Madaras, Eric I.

2010-01-01

Failure tests of CCM SM/ALAS (Composite Crew Module Service Module / Alternate Launch Abort System) composite panels were conducted during July 10, 2008 and July 24, 2008 at Langley Research Center. This is a report of the analysis of the Acoustic Emission (AE) data collected during those tests.

The Microbiome-Gut-Behavior Axis: Crosstalk Between the Gut Microbiome and Oligodendrocytes Modulates Behavioral Responses.

PubMed

Ntranos, Achilles; Casaccia, Patrizia

2018-01-01

Environmental and dietary stimuli have always been implicated in brain development and behavioral responses. The gut, being the major portal of communication with the external environment, has recently been brought to the forefront of this interaction with the establishment of a gut-brain axis in health and disease. Moreover, recent breakthroughs in germ-free and antibiotic-treated mice have demonstrated the significant impact of the microbiome in modulating behavioral responses in mice and have established a more specific microbiome-gut-behavior axis. One of the mechanisms by which this axis affects social behavior is by regulating myelination at the prefrontal cortex, an important site for complex cognitive behavior planning and decision-making. The prefrontal cortex exhibits late myelination of its axonal projections that could extend into the third decade of life in humans, which make it susceptible to external influences, such as microbial metabolites. Changes in the gut microbiome were shown to alter the composition of the microbial metabolome affecting highly permeable bioactive compounds, such as p-cresol, which could impair oligodendrocyte differentiation. Dysregulated myelination in the prefrontal cortex is then able to affect behavioral responses in mice, shifting them towards social isolation. The reduced social interactions could then limit microbial exchange, which could otherwise pose a threat to the survival of the existing microbial community in the host and, thus, provide an evolutionary advantage to the specific microbial community. In this review, we will analyze the microbiome-gut-behavior axis, describe the interactions between the gut microbiome and oligodendrocytes and highlight their role in the modulation of social behavior.

Different impressions of other agents obtained through social interaction uniquely modulate dorsal and ventral pathway activities in the social human brain.

PubMed

Takahashi, Hideyuki; Terada, Kazunori; Morita, Tomoyo; Suzuki, Shinsuke; Haji, Tomoki; Kozima, Hideki; Yoshikawa, Masahiro; Matsumoto, Yoshio; Omori, Takashi; Asada, Minoru; Naito, Eiichi

2014-09-01

Internal (neuronal) representations in the brain are modified by our experiences, and this phenomenon is not unique to sensory and motor systems. Here, we show that different impressions obtained through social interaction with a variety of agents uniquely modulate activity of dorsal and ventral pathways of the brain network that mediates human social behavior. We scanned brain activity with functional magnetic resonance imaging (fMRI) in 16 healthy volunteers when they performed a simple matching-pennies game with a human, human-like android, mechanical robot, interactive robot, and a computer. Before playing this game in the scanner, participants experienced social interactions with each opponent separately and scored their initial impressions using two questionnaires. We found that the participants perceived opponents in two mental dimensions: one represented "mind-holderness" in which participants attributed anthropomorphic impressions to some of the opponents that had mental functions, while the other dimension represented "mind-readerness" in which participants characterized opponents as intelligent. Interestingly, this "mind-readerness" dimension correlated to participants frequently changing their game tactic to prevent opponents from envisioning their strategy, and this was corroborated by increased entropy during the game. We also found that the two factors separately modulated activity in distinct social brain regions. Specifically, mind-holderness modulated activity in the dorsal aspect of the temporoparietal junction (TPJ) and medial prefrontal and posterior paracingulate cortices, while mind-readerness modulated activity in the ventral aspect of TPJ and the temporal pole. These results clearly demonstrate that activity in social brain networks is modulated through pre-scanning experiences of social interaction with a variety of agents. Furthermore, our findings elucidated the existence of two distinct functional networks in the social human brain. Social interaction with anthropomorphic or intelligent-looking agents may distinctly shape the internal representation of our social brain, which may in turn determine how we behave for various agents that we encounter in our society. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Functional organization of the transcriptome in human brain

PubMed Central

Oldham, Michael C; Konopka, Genevieve; Iwamoto, Kazuya; Langfelder, Peter; Kato, Tadafumi; Horvath, Steve; Geschwind, Daniel H

2009-01-01

The enormous complexity of the human brain ultimately derives from a finite set of molecular instructions encoded in the human genome. These instructions can be directly studied by exploring the organization of the brain’s transcriptome through systematic analysis of gene coexpression relationships. We analyzed gene coexpression relationships in microarray data generated from specific human brain regions and identified modules of coexpressed genes that correspond to neurons, oligodendrocytes, astrocytes and microglia. These modules provide an initial description of the transcriptional programs that distinguish the major cell classes of the human brain and indicate that cell type–specific information can be obtained from whole brain tissue without isolating homogeneous populations of cells. Other modules corresponded to additional cell types, organelles, synaptic function, gender differences and the subventricular neurogenic niche. We found that subventricular zone astrocytes, which are thought to function as neural stem cells in adults, have a distinct gene expression pattern relative to protoplasmic astrocytes. Our findings provide a new foundation for neurogenetic inquiries by revealing a robust and previously unrecognized organization to the human brain transcriptome. PMID:18849986

Pharmacologic approaches to cerebral aging and neuroplasticity: insights from the stroke model.

PubMed

Chollet, François

2013-03-01

Brain plasticity is an intrinsic characteristic of the nervous system that allows continuous remodeling of brain functions in pathophysiological conditions. Although normal aging is associated with morphological modifications and decline of cerebral functions, brain plasticity is at least partially preserved in elderly individuals. A growing body of evidence supports the notion that cognitive enrichment and aerobic training induce a dynamic reorganization of higher cerebral functions, thereby helping to maintain operational skills in the elderly and reducing the incidence of dementia. The stroke model clearly shows that spontaneous brain plasticity exists after a lesion, even in old patients, and that it can be modulated through external factors like rehabilitation and drugs. Whether drugs can be used with the aim of modulating the effects of physical training or cognitive stimulation in healthy aged people has not been addressed until now. The risk:benefit ratio will be the key question with regard to the ethical aspect of this challenge. We review in this article the main aspects of human brain plasticity as shown in patients with stroke, the drug modulation of brain plasticity and its consequences on recovery, and finally we address the question of the influence of aging on brain plasticity.

Therapeutic brain modulation with targeted large neutral amino acid supplements in the Pah-enu2 phenylketonuria mouse model.

PubMed

van Vliet, Danique; Bruinenberg, Vibeke M; Mazzola, Priscila N; van Faassen, Martijn Hjr; de Blaauw, Pim; Pascucci, Tiziana; Puglisi-Allegra, Stefano; Kema, Ido P; Heiner-Fokkema, M Rebecca; van der Zee, Eddy A; van Spronsen, Francjan J

2016-11-01

Phenylketonuria treatment consists mainly of a Phe-restricted diet, which leads to suboptimal neurocognitive and psychosocial outcomes. Supplementation of large neutral amino acids (LNAAs) has been suggested as an alternative dietary treatment strategy to optimize neurocognitive outcome in phenylketonuria and has been shown to influence 3 brain pathobiochemical mechanisms in phenylketonuria, but its optimal composition has not been established. In order to provide additional pathobiochemical insight and develop optimal LNAA treatment, several targeted LNAA supplements were investigated with respect to all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria. Pah-enu2 (PKU) mice received 1 of 5 different LNAA-supplemented diets beginning at postnatal day 45. Control groups included phenylketonuria mice receiving an isonitrogenic and isocaloric high-protein diet or the AIN-93M diet, and wild-type mice receiving the AIN-93M diet. After 6 wk, brain and plasma amino acid profiles and brain monoaminergic neurotransmitter concentrations were measured. Brain Phe concentrations were most effectively reduced by supplementation of LNAAs, such as Leu and Ile, with a strong affinity for the LNAA transporter type 1. Brain non-Phe LNAAs could be restored on supplementation, but unbalanced LNAA supplementation further reduced brain concentrations of those LNAAs that were not (sufficiently) included in the LNAA supplement. To optimally ameliorate brain monoaminergic neurotransmitter concentrations, LNAA supplementation should include Tyr and Trp together with LNAAs that effectively reduce brain Phe concentrations. The requirement for Tyr supplementation is higher than it is for Trp, and the relative effect of brain Phe reduction is higher for serotonin than it is for dopamine and norepinephrine. The study shows that all 3 biochemical disturbances underlying brain dysfunction in phenylketonuria can be targeted by specific LNAA supplements. The study thus provides essential information for the development of optimal LNAA supplementation as an alternative dietary treatment strategy to optimize neurocognitive outcome in patients with phenylketonuria. © 2016 American Society for Nutrition.

Gut Microbiota Profiling and Gut-Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections.

PubMed

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4-8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides , Odoribacter , and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson's analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter . In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies.

Gut Microbiota Profiling and Gut–Brain Crosstalk in Children Affected by Pediatric Acute-Onset Neuropsychiatric Syndrome and Pediatric Autoimmune Neuropsychiatric Disorders Associated With Streptococcal Infections

PubMed Central

Quagliariello, Andrea; Del Chierico, Federica; Russo, Alessandra; Reddel, Sofia; Conte, Giulia; Lopetuso, Loris R.; Ianiro, Gianluca; Dallapiccola, Bruno; Cardona, Francesco; Gasbarrini, Antonio; Putignani, Lorenza

2018-01-01

Pediatric acute-onset neuropsychiatric syndrome (PANS) and pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections syndrome (PANDAS) are conditions that impair brain normal neurologic function, resulting in the sudden onset of tics, obsessive-compulsive disorder, and other behavioral symptoms. Recent studies have emphasized the crosstalk between gut and brain, highlighting how gut composition can influence behavior and brain functions. Thus, the present study investigates the relationship between PANS/PANDAS and gut microbiota ecology. The gut composition of a cohort of 30 patients with PANS/PANDAS was analyzed and compared to control subjects using 16S rRNA-based metagenomics. Data were analyzed for their α- and β-diversity; differences in bacterial distribution were detected by Wilcoxon and LEfSe tests, while metabolic profile was predicted via PICRUSt software. These analyses demonstrate the presence of an altered bacterial community structure in PANS/PANDAS patients with respect to controls. In particular, ecological analysis revealed the presence of two main clusters of subjects based on age range. Thus, to avoid age bias, data from patients and controls were split into two groups: 4–8 years old and >9 years old. The younger PANS/PANDAS group was characterized by a strong increase in Bacteroidetes; in particular, Bacteroides, Odoribacter, and Oscillospira were identified as potential microbial biomarkers of this composition type. Moreover, this group exhibited an increase of several pathways concerning the modulation of the antibody response to inflammation within the gut as well as a decrease in pathways involved in brain function (i.e., SCFA, D-alanine and tyrosine metabolism, and the dopamine pathway). The older group of patients displayed a less uniform bacterial profile, thus impairing the identification of distinct biomarkers. Finally, Pearson’s analysis between bacteria and anti-streptolysin O titer reveled a negative correlation between genera belonging to Firmicutes phylum and anti-streptolysin O while a positive correlation was observed with Odoribacter. In conclusion, this study suggests that streptococcal infections alter gut bacterial communities leading to a pro-inflammatory status through the selection of specific bacterial strains associated with gut inflammation and immune response activation. These findings highlight the possibility of studying bacterial biomarkers associated with this disorder and might led to novel potential therapeutic strategies. PMID:29686658

A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1

PubMed Central

Lattka, E.; Eggers, S.; Moeller, G.; Heim, K.; Weber, M.; Mehta, D.; Prokisch, H.; Illig, T.; Adamski, J.

2010-01-01

Fatty acid desaturases (FADS) play an important role in the formation of omega-6 and omega-3 highly unsaturated fatty acids (HUFAs). The composition of HUFAs in the human metabolome is important for membrane fluidity and for the modulation of essential physiological functions such as inflammation processes and brain development. Several recent studies reported significant associations of single nucleotide polymorphisms (SNPs) in the human FADS gene cluster with HUFA levels and composition. The presence of the minor allele correlated with a decrease of desaturase reaction products and an accumulation of substrates. We performed functional studies with two of the associated polymorphisms (rs3834458 and rs968567) and showed an influence of polymorphism rs968567 on FADS2 promoter activity by luciferase reporter gene assays. Electrophoretic mobility shift assays proved allele-dependent DNA-binding ability of at least two protein complexes to the region containing SNP rs968567. One of the proteins binding to this region in an allele-specific manner was shown to be the transcription factor ELK1 (a member of ETS domain transcription factor family). These results indicate that rs968567 influences FADS2 transcription and offer first insights into the modulation of complex regulation mechanisms of FADS2 gene transcription by SNPs. PMID:19546342

A common FADS2 promoter polymorphism increases promoter activity and facilitates binding of transcription factor ELK1.

PubMed

Lattka, E; Eggers, S; Moeller, G; Heim, K; Weber, M; Mehta, D; Prokisch, H; Illig, T; Adamski, J

2010-01-01

Fatty acid desaturases (FADS) play an important role in the formation of omega-6 and omega-3 highly unsaturated fatty acids (HUFAs). The composition of HUFAs in the human metabolome is important for membrane fluidity and for the modulation of essential physiological functions such as inflammation processes and brain development. Several recent studies reported significant associations of single nucleotide polymorphisms (SNPs) in the human FADS gene cluster with HUFA levels and composition. The presence of the minor allele correlated with a decrease of desaturase reaction products and an accumulation of substrates. We performed functional studies with two of the associated polymorphisms (rs3834458 and rs968567) and showed an influence of polymorphism rs968567 on FADS2 promoter activity by luciferase reporter gene assays. Electrophoretic mobility shift assays proved allele-dependent DNA-binding ability of at least two protein complexes to the region containing SNP rs968567. One of the proteins binding to this region in an allele-specific manner was shown to be the transcription factor ELK1 (a member of ETS domain transcription factor family). These results indicate that rs968567 influences FADS2 transcription and offer first insights into the modulation of complex regulation mechanisms of FADS2 gene transcription by SNPs.

Presence of claudins mRNA in the brain. Selective modulation of expression by kindling epilepsy.

PubMed

Lamas, Mónica; González-Mariscal, Lorenza; Gutiérrez, Rafael

2002-08-15

In the central nervous system, the junctional types that establish and maintain tissue architecture include gap junctions, for cytoplasmic connectivity, and tight junctions, for paracellular and/or cell polarity barriers. Connexins are the integral membrane proteins of gap junctions, whereas occludin and members of the multigene family of claudins form tight junctions. In the brain, there are no transendothelial pathways, as continuous tight junctions are present between the endothelial cells. Thus, they provide a continuous cellular barrier between the blood and the insterstitial fluid. However, several brain pathologies, including epilepsy, are known to alter the permeability of the blood-brain barrier and to cause edema. Therefore, since claudins, as constitutive proteins of tight junctions are likely candidates for modulation under pathological states, we explored their normal pattern of expression in the brain and its modulation by seizures. We found that several members of this family are normally expressed in the hippocampus and cortex. Interestingly, claudin-7 is expressed in the hippocampus but not in the cortex. On the other hand, the expression of claudin-8 is selectively down-regulated in the hippocampus as kindling evolves. These results link for the first time the modulation of expression of a tight junction protein to abnormal neuronal synchronization that could probably be reflected in permeability changes of the blood-brain barrier or edema.

Modulation of thermal pain-related brain activity with virtual reality: evidence from fMRI.

PubMed

Hoffman, Hunter G; Richards, Todd L; Coda, Barbara; Bills, Aric R; Blough, David; Richards, Anne L; Sharar, Sam R

2004-06-07

This study investigated the neural correlates of virtual reality analgesia. Virtual reality significantly reduced subjective pain ratings (i.e. analgesia). Using fMRI, pain-related brain activity was measured for each participant during conditions of no virtual reality and during virtual reality (order randomized). As predicted, virtual reality significantly reduced pain-related brain activity in all five regions of interest; the anterior cingulate cortex, primary and secondary somatosensory cortex, insula, and thalamus (p<0.002, corrected). Results showed direct modulation of human brain pain responses by virtual reality distraction. Copyright 2004 Lippincott Williams and Wilkins

The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress.

PubMed

Corcoran, Louise; Roche, Michelle; Finn, David P

2015-01-01

Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor. The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli. The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein. We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain's endocannabinoid system modulates pain. We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia. Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders. © 2015 Elsevier Inc. All rights reserved.

Long-Term Effect of Docosahexaenoic Acid Feeding on Lipid Composition and Brain Fatty Acid-Binding Protein Expression in Rats

PubMed Central

Elsherbiny, Marwa E.; Goruk, Susan; Monckton, Elizabeth A.; Richard, Caroline; Brun, Miranda; Emara, Marwan; Field, Catherine J.; Godbout, Roseline

2015-01-01

Arachidonic (AA) and docosahexaenoic acid (DHA) brain accretion is essential for brain development. The impact of DHA-rich maternal diets on offspring brain fatty acid composition has previously been studied up to the weanling stage; however, there has been no follow-up at later stages. Here, we examine the impact of DHA-rich maternal and weaning diets on brain fatty acid composition at weaning and three weeks post-weaning. We report that DHA supplementation during lactation maintains high DHA levels in the brains of pups even when they are fed a DHA-deficient diet for three weeks after weaning. We show that boosting dietary DHA levels for three weeks after weaning compensates for a maternal DHA-deficient diet during lactation. Finally, our data indicate that brain fatty acid binding protein (FABP7), a marker of neural stem cells, is down-regulated in the brains of six-week pups with a high DHA:AA ratio. We propose that elevated levels of DHA in developing brain accelerate brain maturation relative to DHA-deficient brains. PMID:26506385

Adenosine transiently modulates stimulated dopamine release in the caudate putamen via A1 receptors

PubMed Central

Ross, Ashley E.; Venton, B. Jill

2014-01-01

Adenosine modulates dopamine in the brain via A1 and A2A receptors, but that modulation has only been characterized on a slow time scale. Recent studies have characterized a rapid signaling mode of adenosine that suggests a possible rapid modulatory role. Here, fast-scan cyclic voltammetry was used to characterize the extent to which transient adenosine changes modulate stimulated dopamine release (5 pulses at 60 Hz) in rat caudate putamen brain slices. Exogenous adenosine was applied and dopamine concentration monitored. Adenosine only modulated dopamine when it was applied 2 or 5 s before stimulation. Longer time intervals and bath application of 5 µM adenosine did not decrease dopamine release. Mechanical stimulation of endogenous adenosine 2s before dopamine stimulation also decreased stimulated dopamine release by 41 ± 7 %, similar to the 54 ± 6 % decrease in dopamine after exogenous adenosine application. Dopamine inhibition by transient adenosine was recovered within 10 minutes. The A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) blocked the dopamine modulation, whereas dopamine modulation was unaffected by the A2A receptor antagonist SCH 442416. Thus, transient adenosine changes can transiently modulate phasic dopamine release via A1 receptors. These data demonstrate that adenosine has a rapid, but transient, modulatory role in the brain. PMID:25219576

New Therapeutic Drugs from Bioactive Natural Molecules: the Role of Gut Microbiota Metabolism in Neurodegenerative Diseases.

PubMed

Di Meo, Francesco; Donato, Stella; Di Pardo, Alba; Maglione, Vittorio; Filosa, Stefania; Crispi, Stefania

2018-04-03

The gut-brain axis is considered a neuroendocrine system, which connects brain and gastrointestinal tract and plays an important role in stress response. The homeostasis of gut-brain axis is important for healthy conditions and its alterations are associated to neurological disorders and neurodegenerative diseases. Gut microbiota is a dynamic ecosystem that can be altered by external factors such as diet composition, antibiotics or xenobiotics. Recent advances in gut microbiota analyses indicate that the gut bacterial community plays a key role in maintaining normal brain functions. Recent metagenomic analyses have elucidated that the relationship between gut and brain, either in normal or in pathological conditions, reflects the existence of a "microbiota-gut-brain" axis. Gut microbiota composition can be influenced by dietary ingestion of probiotics or natural bioactive molecules such as prebiotics and polyphenols. Their derivatives coming from microbiota metabolism can affect both gut bacterial composition and brain biochemistry. Modifications of microbiota composition by natural bioactive molecules could be used to restore the altered brain functions, which characterize neurodegenerative diseases, leading to consider these compounds as novel therapeutic strategies for the treatment of neuropathologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Synaptic Effects of Electric Fields

NASA Astrophysics Data System (ADS)

Rahman, Asif

Learning and sensory processing in the brain relies on the effective transmission of information across synapses. The strength and efficacy of synaptic transmission is modifiable through training and can be modulated with noninvasive electrical brain stimulation. Transcranial electrical stimulation (TES), specifically, induces weak intensity and spatially diffuse electric fields in the brain. Despite being weak, electric fields modulate spiking probability and the efficacy of synaptic transmission. These effects critically depend on the direction of the electric field relative to the orientation of the neuron and on the level of endogenous synaptic activity. TES has been used to modulate a wide range of neuropsychiatric indications, for various rehabilitation applications, and cognitive performance in diverse tasks. How can a weak and diffuse electric field, which simultaneously polarizes neurons across the brain, have precise changes in brain function? Designing therapies to maximize desired outcomes and minimize undesired effects presents a challenging problem. A series of experiments and computational models are used to define the anatomical and functional factors leading to specificity of TES. Anatomical specificity derives from guiding current to targeted brain structures and taking advantage of the direction-sensitivity of neurons with respect to the electric field. Functional specificity originates from preferential modulation of neuronal networks that are already active. Diffuse electric fields may recruit connected brain networks involved in a training task and promote plasticity along active synaptic pathways. In vitro, electric fields boost endogenous synaptic plasticity and raise the ceiling for synaptic learning with repeated stimulation sessions. Synapses undergoing strong plasticity are preferentially modulated over weak synapses. Therefore, active circuits that are involved in a task could be more susceptible to stimulation than inactive circuits. Moreover, stimulation polarity has asymmetric effects on synaptic strength making it easier to enhance ongoing plasticity. These results suggest that the susceptibility of brain networks to an electric field depends on the state of synaptic activity. Combining a training task, which activates specific circuits, with TES may lead to functionally-specific effects. Given the simplicity of TES and the complexity of brain function, understanding the mechanisms leading to specificity is fundamental to the rational advancement of TES.

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid

PubMed Central

Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D.; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R.

2013-01-01

In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of delta-9-tetrahydrocannabinol (THC), marijuana’s main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by re-exposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are currently no medications approved for treatment of marijuana dependence. Modulation of KYNA provides a novel pharmacological strategy for achieving abstinence from marijuana and preventing relapse. PMID:24121737

Reducing cannabinoid abuse and preventing relapse by enhancing endogenous brain levels of kynurenic acid.

PubMed

Justinova, Zuzana; Mascia, Paola; Wu, Hui-Qiu; Secci, Maria E; Redhi, Godfrey H; Panlilio, Leigh V; Scherma, Maria; Barnes, Chanel; Parashos, Alexandra; Zara, Tamara; Fratta, Walter; Solinas, Marcello; Pistis, Marco; Bergman, Jack; Kangas, Brian D; Ferré, Sergi; Tanda, Gianluigi; Schwarcz, Robert; Goldberg, Steven R

2013-11-01

In the reward circuitry of the brain, α-7-nicotinic acetylcholine receptors (α7nAChRs) modulate effects of Δ(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of α7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of α7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.

Credit Assignment in Multiple Goal Embodied Visuomotor Behavior

PubMed Central

Rothkopf, Constantin A.; Ballard, Dana H.

2010-01-01

The intrinsic complexity of the brain can lead one to set aside issues related to its relationships with the body, but the field of embodied cognition emphasizes that understanding brain function at the system level requires one to address the role of the brain-body interface. It has only recently been appreciated that this interface performs huge amounts of computation that does not have to be repeated by the brain, and thus affords the brain great simplifications in its representations. In effect the brain's abstract states can refer to coded representations of the world created by the body. But even if the brain can communicate with the world through abstractions, the severe speed limitations in its neural circuitry mean that vast amounts of indexing must be performed during development so that appropriate behavioral responses can be rapidly accessed. One way this could happen would be if the brain used a decomposition whereby behavioral primitives could be quickly accessed and combined. This realization motivates our study of independent sensorimotor task solvers, which we call modules, in directing behavior. The issue we focus on herein is how an embodied agent can learn to calibrate such individual visuomotor modules while pursuing multiple goals. The biologically plausible standard for module programming is that of reinforcement given during exploration of the environment. However this formulation contains a substantial issue when sensorimotor modules are used in combination: The credit for their overall performance must be divided amongst them. We show that this problem can be solved and that diverse task combinations are beneficial in learning and not a complication, as usually assumed. Our simulations show that fast algorithms are available that allot credit correctly and are insensitive to measurement noise. PMID:21833235

Low frequency steady-state brain responses modulate large scale functional networks in a frequency-specific means.

PubMed

Wang, Yi-Feng; Long, Zhiliang; Cui, Qian; Liu, Feng; Jing, Xiu-Juan; Chen, Heng; Guo, Xiao-Nan; Yan, Jin H; Chen, Hua-Fu

2016-01-01

Neural oscillations are essential for brain functions. Research has suggested that the frequency of neural oscillations is lower for more integrative and remote communications. In this vein, some resting-state studies have suggested that large scale networks function in the very low frequency range (<1 Hz). However, it is difficult to determine the frequency characteristics of brain networks because both resting-state studies and conventional frequency tagging approaches cannot simultaneously capture multiple large scale networks in controllable cognitive activities. In this preliminary study, we aimed to examine whether large scale networks can be modulated by task-induced low frequency steady-state brain responses (lfSSBRs) in a frequency-specific pattern. In a revised attention network test, the lfSSBRs were evoked in the triple network system and sensory-motor system, indicating that large scale networks can be modulated in a frequency tagging way. Furthermore, the inter- and intranetwork synchronizations as well as coherence were increased at the fundamental frequency and the first harmonic rather than at other frequency bands, indicating a frequency-specific modulation of information communication. However, there was no difference among attention conditions, indicating that lfSSBRs modulate the general attention state much stronger than distinguishing attention conditions. This study provides insights into the advantage and mechanism of lfSSBRs. More importantly, it paves a new way to investigate frequency-specific large scale brain activities. © 2015 Wiley Periodicals, Inc.

What happens when spins meet for ionizing radiation dosimetry?

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

Pavoni, Juliana F.; Baffa, Oswaldo, E-mail: baffa@usp.br; Neves-Junior, Wellington F. P.

2016-07-07

Electron spin resonance (ESR) and magnetic resonance imaging (MRI) can be used to measure radiation dose deposited in different milieu through its effects. Radiation can break chemical bonds and if they produce stable free radicals, ESR can measure their concentration through their spins and a dose can be inferred. Ionizing radiation can also promote polymerization and in this case proton relaxation times can be measured and an image weighed by T2 can be produced giving spatial information about dose. A review of the basics of these applications is presented concluding with an end-to-end test using a composite Gel-Alanine phantom tomore » validate 3-dimensionally dose distribution delivered in a simulation of Volume Modulated Arch Therapy on the simultaneous treatment of multiple brain metastases. The results obtained with the gel and alanine dosimeters are consistent with the expected by the treatment planning system, showing the potential of this multidosimetric approach and validating dosimetrically the multiple brain metastases treatment using VMAT.« less

What happens when spins meet for ionizing radiation dosimetry?

NASA Astrophysics Data System (ADS)

Pavoni, Juliana F.; Neves-Junior, Wellington F. P.; Baffa, Oswaldo

2016-07-01

Electron spin resonance (ESR) and magnetic resonance imaging (MRI) can be used to measure radiation dose deposited in different milieu through its effects. Radiation can break chemical bonds and if they produce stable free radicals, ESR can measure their concentration through their spins and a dose can be inferred. Ionizing radiation can also promote polymerization and in this case proton relaxation times can be measured and an image weighed by T2 can be produced giving spatial information about dose. A review of the basics of these applications is presented concluding with an end-to-end test using a composite Gel-Alanine phantom to validate 3-dimensionally dose distribution delivered in a simulation of Volume Modulated Arch Therapy on the simultaneous treatment of multiple brain metastases. The results obtained with the gel and alanine dosimeters are consistent with the expected by the treatment planning system, showing the potential of this multidosimetric approach and validating dosimetrically the multiple brain metastases treatment using VMAT.

Brain modularity controls the critical behavior of spontaneous activity.

PubMed

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

2014-03-13

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

Neural markers of social and monetary rewards in children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder.

PubMed

Gonzalez-Gadea, Maria Luz; Sigman, Mariano; Rattazzi, Alexia; Lavin, Claudio; Rivera-Rei, Alvaro; Marino, Julian; Manes, Facundo; Ibanez, Agustin

2016-07-28

Recent theories of decision making propose a shared value-related brain mechanism for encoding monetary and social rewards. We tested this model in children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Autism Spectrum Disorder (ASD) and control children. We monitored participants' brain dynamics using high density-electroencephalography while they played a monetary and social reward tasks. Control children exhibited a feedback Error-Related Negativity (fERN) modulation and Anterior Cingulate Cortex (ACC) source activation during both tasks. Remarkably, although cooperation resulted in greater losses for the participants, the betrayal options generated greater fERN responses. ADHD subjects exhibited an absence of fERN modulation and reduced ACC activation during both tasks. ASD subjects exhibited normal fERN modulation during monetary choices and inverted fERN/ACC responses in social options than did controls. These results suggest that in neurotypicals, monetary losses and observed disloyal social decisions induced similar activity in the brain value system. In ADHD children, difficulties in reward processing affected early brain signatures of monetary and social decisions. Conversely, ASD children showed intact neural markers of value-related monetary mechanisms, but no brain modulation by prosociality in the social task. These results offer insight into the typical and atypical developments of neural correlates of monetary and social reward processing.

Brain-wide Maps Reveal Stereotyped Cell-Type-Based Cortical Architecture and Subcortical Sexual Dimorphism.

PubMed

Kim, Yongsoo; Yang, Guangyu Robert; Pradhan, Kith; Venkataraju, Kannan Umadevi; Bota, Mihail; García Del Molino, Luis Carlos; Fitzgerald, Greg; Ram, Keerthi; He, Miao; Levine, Jesse Maurica; Mitra, Partha; Huang, Z Josh; Wang, Xiao-Jing; Osten, Pavel

2017-10-05

The stereotyped features of neuronal circuits are those most likely to explain the remarkable capacity of the brain to process information and govern behaviors, yet it has not been possible to comprehensively quantify neuronal distributions across animals or genders due to the size and complexity of the mammalian brain. Here we apply our quantitative brain-wide (qBrain) mapping platform to document the stereotyped distributions of mainly inhibitory cell types. We discover an unexpected cortical organizing principle: sensory-motor areas are dominated by output-modulating parvalbumin-positive interneurons, whereas association, including frontal, areas are dominated by input-modulating somatostatin-positive interneurons. Furthermore, we identify local cell type distributions with more cells in the female brain in 10 out of 11 sexually dimorphic subcortical areas, in contrast to the overall larger brains in males. The qBrain resource can be further mined to link stereotyped aspects of neuronal distributions to known and unknown functions of diverse brain regions. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between diet, the gut microbiota, and brain function.

PubMed

Tengeler, Anouk C; Kozicz, Tamas; Kiliaan, Amanda J

2018-04-28

The human intestinal microbiota, comprising trillions of microorganisms, exerts a substantial effect on the host. The microbiota plays essential roles in the function and development of several physiological processes, including those in the brain. A disruption in the microbial composition of the gut has been associated with many metabolic, inflammatory, neurodevelopmental, and neurodegenerative disorders. Nutrition is one of several key factors that shape the microbial composition during infancy and throughout life, thereby affecting brain structure and function. This review examines the effect of the gut microbiota on brain function. The ability of external factors, such as diet, to influence the microbial composition implies a certain vulnerability of the gut microbiota. However, it also offers a potential therapeutic strategy for ameliorating symptoms of mental and physical disorders. Therefore, this review examines the potential effect of nutritional components on gut microbial composition and brain function.

Brain Distribution and Modulation of Neuronal Excitability by Indicaxanthin From Opuntia Ficus Indica Administered at Nutritionally-Relevant Amounts

PubMed Central

Gambino, Giuditta; Allegra, Mario; Sardo, Pierangelo; Attanzio, Alessandro; Tesoriere, Luisa; Livrea, Maria A.; Ferraro, Giuseppe; Carletti, Fabio

2018-01-01

Several studies have recently investigated the role of nutraceuticals in complex pathophysiological processes such as oxidative damages, inflammatory conditions and excitotoxicity. In this regard, the effects of nutraceuticals on basic functions of neuronal cells, such as excitability, are still poorly investigated. For this reason, the possible modulation of neuronal excitability by phytochemicals (PhC) could represent an interesting field of research given that excitotoxicity phenomena are involved in neurodegenerative alterations leading, for example, to Alzheimer’s disease. The present study was focused on indicaxanthin from Opuntia ficus indica, a bioactive betalain pigment, with a proven antioxidant and anti-inflammatory potential, previously found to cross blood-brain barrier (BBB) and to modulate the bioelectric activity of hippocampal neurons. On this basis, we aimed at detecting the specific brain areas where indicaxanthin localizes after oral administration at dietary-achievable amounts and highlighting eventual local effects on the excitability of single neuronal units. HPLC analysis of brain tissue 1 h after ingestion of 2 μmol/kg indicaxanthin indicated that the phytochemical accumulates in cortex, hippocampus, diencephalon, brainstem and cerebellum, but not in the striato-pallidal complex. Then, electrophysiological recordings, applying the microiontophoretic technique, were carried out with different amounts of indicaxanthin (0.34, 0.17, 0.085 ng/neuron) to assess whether indicaxanthin influenced the neuronal firing rate. The data showed that the bioelectric activity of neurons belonging to different brain areas was modulated after local injection of indicaxanthin, mainly with dose-related responses. A predominating inhibitory effect was observed, suggesting a possible novel beneficial effect of indicaxanthin in reducing cell excitability. These findings can constitute a new rationale for exploring biological mechanisms through which PhC could modulate neuronal function with a relapse on complex cognitive brain process and related neurodegenerative conditions. PMID:29867444

The Pro-inflammatory Effects of Glucocorticoids in the Brain

PubMed Central

Duque, Erica de Almeida; Munhoz, Carolina Demarchi

2016-01-01

Glucocorticoids are a class of steroid hormones derived from cholesterol. Their actions are mediated by the glucocorticoid and mineralocorticoid receptors, members of the superfamily of nuclear receptors, which, once bound to their ligands, act as transcription factors that can directly modulate gene expression. Through protein–protein interactions with other transcription factors, they can also regulate the activity of many genes in a composite or tethering way. Rapid non-genomic signaling was also demonstrated since glucocorticoids can act through membrane receptors and activate signal transduction pathways, such as protein kinases cascades, to modulate other transcriptions factors and activate or repress various target genes. By all these different mechanisms, glucocorticoids regulate numerous important functions in a large variety of cells, not only in the peripheral organs but also in the central nervous system during development and adulthood. In general, glucocorticoids are considered anti-inflammatory and protective agents due to their ability to inhibit gene expression of pro-inflammatory mediators and other possible damaging molecules. Nonetheless, recent studies have uncovered situations in which these hormones can act as pro-inflammatory agents depending on the dose, chronicity of exposure, and the structure/organ analyzed. In this review, we will provide an overview of the conditions under which these phenomena occur, a discussion that will serve as a basis for exploring the mechanistic foundation of glucocorticoids pro-inflammatory gene regulation in the brain. PMID:27445981

Modulation of Synaptic Plasticity by Exercise Training as a Basis for Ischemic Stroke Rehabilitation.

PubMed

Nie, Jingjing; Yang, Xiaosu

2017-01-01

In recent years, rehabilitation of ischemic stroke draws more and more attention in the world, and has been linked to changes of synaptic plasticity. Exercise training improves motor function of ischemia as well as cognition which is associated with formation of learning and memory. The molecular basis of learning and memory might be synaptic plasticity. Research has therefore been conducted in an attempt to relate effects of exercise training to neuroprotection and neurogenesis adjacent to the ischemic injury brain. The present paper reviews the current literature addressing this question and discusses the possible mechanisms involved in modulation of synaptic plasticity by exercise training. This review shows the pathological process of synaptic dysfunction in ischemic roughly and then discusses the effects of exercise training on scaffold proteins and regulatory protein expression. The expression of scaffold proteins generally increased after training, but the effects on regulatory proteins were mixed. Moreover, the compositions of postsynaptic receptors were changed and the strength of synaptic transmission was enhanced after training. Finally, the recovery of cognition is critically associated with synaptic remodeling in an injured brain, and the remodeling occurs through a number of local regulations including mRNA translation, remodeling of cytoskeleton, and receptor trafficking into and out of the synapse. We do provide a comprehensive knowledge of synaptic plasticity enhancement obtained by exercise training in this review.

Composite Crew Module (CCM) Permeability Characterization

NASA Technical Reports Server (NTRS)

Kirsch, Michael T.

2013-01-01

In January 2007, the NASA Administrator chartered the NASA Engineering and Safety Center (NESC) to form an Agency team to design and build a composite crew module in 18 months in order to gain hands-on experience in anticipation that future exploration systems may be made of composite materials. One of the conclusions from this Composite Crew Module Primary Structure assessment was that there was a lack of understanding regarding the ability for composite pressure shells to contain consumable gases, which posed a technical risk relative to the use of a metallic design. After the completion of the Composite Crew Module test program, the test article was used in a new program to assess the overall leakage/permeability and identify specific features associated with high leak rates. This document contains the outcome of the leakage assessment.

Human connectome module pattern detection using a new multi-graph MinMax cut model.

PubMed

De, Wang; Wang, Yang; Nie, Feiping; Yan, Jingwen; Cai, Weidong; Saykin, Andrew J; Shen, Li; Huang, Heng

2014-01-01

Many recent scientific efforts have been devoted to constructing the human connectome using Diffusion Tensor Imaging (DTI) data for understanding the large-scale brain networks that underlie higher-level cognition in human. However, suitable computational network analysis tools are still lacking in human connectome research. To address this problem, we propose a novel multi-graph min-max cut model to detect the consistent network modules from the brain connectivity networks of all studied subjects. A new multi-graph MinMax cut model is introduced to solve this challenging computational neuroscience problem and the efficient optimization algorithm is derived. In the identified connectome module patterns, each network module shows similar connectivity patterns in all subjects, which potentially associate to specific brain functions shared by all subjects. We validate our method by analyzing the weighted fiber connectivity networks. The promising empirical results demonstrate the effectiveness of our method.

Effects of Parkinson's disease on brain-wave phase synchronisation and cross-modulation

NASA Astrophysics Data System (ADS)

Stumpf, K.; Schumann, A. Y.; Plotnik, M.; Gans, F.; Penzel, T.; Fietze, I.; Hausdorff, J. M.; Kantelhardt, J. W.

2010-02-01

We study the effects of Parkinson's disease (PD) on phase synchronisation and cross-modulation of instantaneous amplitudes and frequencies for brain waves during sleep. Analysing data from 40 full-night EEGs (electro-encephalograms) of ten patients with PD and ten age-matched healthy controls we find that phase synchronisation between the left and right hemisphere of the brain is characteristically reduced in patients with PD. Since there is no such difference in phase synchronisation for EEGs from the same hemisphere, our results suggest the possibility of a relation with problems in coordinated motion of left and right limbs in some patients with PD. Using the novel technique of amplitude and frequency cross-modulation analysis, relating oscillations in different EEG bands and distinguishing both positive and negative modulation, we observe an even more significant decrease in patients for several band combinations.

Temperature and metal exposure affect membrane fatty acid composition and transcription of desaturases and elongases in fathead minnow muscle and brain.

PubMed

Fadhlaoui, Mariem; Pierron, Fabien; Couture, Patrice

2018-02-01

In this study, we tested the hypothesis that metal exposure affected the normal thermal response of cell membrane FA composition and of elongase and desaturase gene transcription levels. To this end, muscle and brain membrane FA composition and FA desaturase (fads2, degs2 and scd2) and elongase (elovl2, elovl5 and elovl6) gene transcription levels were analyzed in fathead minnows (Pimephales promelas) acclimated for eight weeks to 15, 25 or 30°C exposed or not to cadmium (Cd, 6μg/l) or nickel (Ni, 450 6μg/l). The response of membrane FA composition to temperature variations or metal exposure differed between muscle and brain. In muscle, an increase of temperature induced a decrease of polyunsaturated FA (PUFA) and an increase of saturated FA (SFA) in agreement with the current paradigm. Although a similar response was observed in brain between 15 and 25°C, at 30°C, brain membrane unsaturation was higher than predicted. In both tissues, metal exposure affected the normal thermal response of membrane FA composition. The transcription of desaturases and elongases was higher in the brain and varied with acclimation temperature and metal exposure but these variations did not generally reflect changes in membrane FA composition. The mismatch between gene transcription and membrane composition highlights that several levels of control other than gene transcription are involved in adjusting membrane FA composition, including post-transcriptional regulation of elongases and desaturases and de novo phospholipid biosynthesis. Our study also reveals that metal exposure affects the mechanisms involved in adjusting cell membrane FA composition in ectotherms. Copyright © 2017 Elsevier Inc. All rights reserved.

Flavonoid nutraceuticals and ionotropic receptors for the inhibitory neurotransmitter GABA.

PubMed

Johnston, Graham A R

2015-10-01

Flavonoids that are found in nutraceuticals have many and varied effects on the activation of ionotropic receptors for GABA, the major inhibitory neurotransmitter in our brains. They can act as positive or negative modulators enhancing or reducing the effect of GABA. They can act as allosteric agonists. They can act to modulate the action of other modulators. There is considerable evidence that these flavonoids are able to enter the brain to influence brain function. They may have a range of effects including relief of anxiety, improvement in cognition, acting as neuroprotectants and as sedatives. All of these effects are sought after in nutraceuticals. A number of studies have likened flavonoids to the widely prescribed benzodiazepines as 'a new family of benzodiazepine receptor ligands'. They are much more than that with many flavonoid actions on ionotropic GABA receptors being insensitive to the classic benzodiazepine antagonist flumazenil and thus independent of the classic benzodiazepine actions. It is time to consider flavonoids in their own right as important modulators of these vital receptors in brain function. Flavonoids are rarely consumed as a single flavonoid except as dietary supplements. The effects of mixtures of flavonoids and other modulators on GABAA receptors need to be more thoroughly investigated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system.

PubMed

Zamberletti, Erica; Piscitelli, Fabiana; De Castro, Valentina; Murru, Elisabetta; Gabaglio, Marina; Colucci, Paola; Fanali, Chiara; Prini, Pamela; Bisogno, Tiziana; Maccarrone, Mauro; Campolongo, Patrizia; Banni, Sebastiano; Rubino, Tiziana; Parolaro, Daniela

2017-02-01

Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Longitudinal Dynamics of 3-Dimensional Components of Selfhood After Severe Traumatic Brain Injury: A qEEG Case Study.

PubMed

Fingelkurts, Andrew A; Fingelkurts, Alexander A

2017-09-01

In this report, we describe the case of a patient who sustained extremely severe traumatic brain damage with diffuse axonal injury in a traffic accident and whose recovery was monitored during 6 years. Specifically, we were interested in the recovery dynamics of 3-dimensional components of selfhood (a 3-dimensional construct model for the complex experiential selfhood has been recently proposed based on the empirical findings on the functional-topographical specialization of 3 operational modules of brain functional network responsible for the self-consciousness processing) derived from the electroencephalographic (EEG) signal. The analysis revealed progressive (though not monotonous) restoration of EEG functional connectivity of 3 modules of brain functional network responsible for the self-consciousness processing, which was also paralleled by the clinically significant functional recovery. We propose that restoration of normal integrity of the operational modules of the self-referential brain network may underlie the positive dynamics of 3 aspects of selfhood and provide a neurobiological mechanism for their recovery. The results are discussed in the context of recent experimental studies that support this inference. Studies of ongoing recovery after severe brain injury utilizing knowledge about each separate aspect of complex selfhood will likely help to develop more efficient and targeted rehabilitation programs for patients with brain trauma.

Auricular Neuromodulation: The Emerging Concept beyond the Stimulation of Vagus and Trigeminal Nerves

PubMed Central

Mercante, Beniamina; Rangon, Claire-Marie

2018-01-01

Neuromodulation, thanks to intrinsic and extrinsic brain feedback loops, seems to be the best way to exploit brain plasticity for therapeutic purposes. In the past years, there has been tremendous advances in the field of non-pharmacological modulation of brain activity. This review of different neurostimulation techniques will focus on sites and mechanisms of both transcutaneous vagus and trigeminal nerve stimulation. These methods are scientifically validated non-invasive bottom-up brain modulation techniques, easily implemented from the outer ear. In the light of this, auricles could transpire to be the most affordable target for non-invasive manipulation of central nervous system functions. PMID:29361732

Effects of GSM modulated radio-frequency electromagnetic radiation on permeability of blood-brain barrier in male & female rats.

PubMed

Sırav, Bahriye; Seyhan, Nesrin

2016-09-01

With the increased use of mobile phones, their biological and health effects have become more important. Usage of mobile phones near the head increases the possibility of effects on brain tissue. This study was designed to investigate the possible effects of pulse modulated 900MHz and 1800MHz radio-frequency radiation on the permeability of blood-brain barrier of rats. Study was performed with 6 groups of young adult male and female wistar albino rats. The permeability of blood-brain barrier to intravenously injected evans blue dye was quantitatively examined for both control and radio-frequency radiarion exposed groups. For male groups; Evans blue content in the whole brain was found to be 0.08±0.01mg% in the control, 0.13±0.03mg% in 900MHz exposed and 0.26±0.05mg% in 1800MHz exposed animals. In both male radio-frequency radiation exposed groups, the permeability of blood-brain barrier found to be increased with respect to the controls (p<0.01). 1800MHz pulse modulated radio-frequency radiation exposure was found more effective on the male animals (p<0.01). For female groups; dye contents in the whole brains were 0.14±0.01mg% in the control, 0.24±0.03mg% in 900MHz exposed and 0.14±0.02mg% in 1800MHz exposed animals. No statistical variance found between the control and 1800MHz exposed animals (p>0.01). However 900MHz pulse modulated radio-frequency exposure was found effective on the permeability of blood-brain barrier of female animals. Results have shown that 20min pulse modulated radio-frequency radiation exposure of 900MHz and 1800MHz induces an effect and increases the permeability of blood-brain barrier of male rats. For females, 900MHz was found effective and it could be concluded that this result may due to the physiological differences between female and male animals. The results of this study suggest that mobile phone radation could lead to increase the permeability of blood-brain barrier under non-thermal exposure levels. More studies are needed to demonstrate the mechanisms of that breakdown. Copyright © 2015 Elsevier B.V. All rights reserved.

MmTX1 and MmTX2 from coral snake venom potently modulate GABAA receptor activity.

PubMed

Rosso, Jean-Pierre; Schwarz, Jürgen R; Diaz-Bustamante, Marcelo; Céard, Brigitte; Gutiérrez, José M; Kneussel, Matthias; Pongs, Olaf; Bosmans, Frank; Bougis, Pierre E

2015-02-24

GABAA receptors shape synaptic transmission by modulating Cl(-) conductance across the cell membrane. Remarkably, animal toxins that specifically target GABAA receptors have not been identified. Here, we report the discovery of micrurotoxin1 (MmTX1) and MmTX2, two toxins present in Costa Rican coral snake venom that tightly bind to GABAA receptors at subnanomolar concentrations. Studies with recombinant and synthetic toxin variants on hippocampal neurons and cells expressing common receptor compositions suggest that MmTX1 and MmTX2 allosterically increase GABAA receptor susceptibility to agonist, thereby potentiating receptor opening as well as desensitization, possibly by interacting with the α(+)/β(-) interface. Moreover, hippocampal neuron excitability measurements reveal toxin-induced transitory network inhibition, followed by an increase in spontaneous activity. In concert, toxin injections into mouse brain result in reduced basal activity between intense seizures. Altogether, we characterized two animal toxins that enhance GABAA receptor sensitivity to agonist, thereby establishing a previously unidentified class of tools to study this receptor family.

Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders.

PubMed

Hsiao, Elaine Y; McBride, Sara W; Hsien, Sophia; Sharon, Gil; Hyde, Embriette R; McCue, Tyler; Codelli, Julian A; Chow, Janet; Reisman, Sarah E; Petrosino, Joseph F; Patterson, Paul H; Mazmanian, Sarkis K

2013-12-19

Neurodevelopmental disorders, including autism spectrum disorder (ASD), are defined by core behavioral impairments; however, subsets of individuals display a spectrum of gastrointestinal (GI) abnormalities. We demonstrate GI barrier defects and microbiota alterations in the maternal immune activation (MIA) mouse model that is known to display features of ASD. Oral treatment of MIA offspring with the human commensal Bacteroides fragilis corrects gut permeability, alters microbial composition, and ameliorates defects in communicative, stereotypic, anxiety-like and sensorimotor behaviors. MIA offspring display an altered serum metabolomic profile, and B. fragilis modulates levels of several metabolites. Treating naive mice with a metabolite that is increased by MIA and restored by B. fragilis causes certain behavioral abnormalities, suggesting that gut bacterial effects on the host metabolome impact behavior. Taken together, these findings support a gut-microbiome-brain connection in a mouse model of ASD and identify a potential probiotic therapy for GI and particular behavioral symptoms in human neurodevelopmental disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

Biological sources of inflexibility in brain and behavior with aging and neurodegenerative diseases

PubMed Central

Hong, S. Lee; Rebec, George V.

2012-01-01

Almost unequivocally, aging and neurodegeneration lead to deficits in neural information processing. These declines are marked by increased neural noise that is associated with increased variability or inconsistency in behavioral patterns. While it is often viewed that these problems arise from dysregulation of dopamine (DA), a monoamine modulator, glutamate (GLU), an excitatory amino acid that interacts with DA, also plays a role in determining the level of neural noise. We review literature demonstrating that neural noise is highest at both high and low levels of DA and GLU, allowing their interaction to form a many-to-one solution map for neural noise modulation. With aging and neurodegeneration, the range over which DA and GLU can be modulated is decreased leading to inflexibility in brain activity and behavior. As the capacity to modulate neural noise is restricted, the ability to shift noise from one brain region to another is reduced, leading to greater uniformity in signal-to-noise ratios across the entire brain. A negative consequence at the level of behavior is inflexibility that reduces the ability to: (1) switch from one behavior to another; and (2) stabilize a behavioral pattern against external perturbations. In this paper, we develop a theoretical framework where inflexibility across brain and behavior, rather than inconsistency and variability is the more important problem in aging and neurodegeneration. This theoretical framework of inflexibility in aging and neurodegeneration leads to the hypotheses that: (1) dysfunction in either or both of the DA and GLU systems restricts the ability to modulate neural noise; and (2) levels of neural noise and variability in brain activation will be dedifferentiated and more evenly distributed across the brain; and (3) changes in neural noise and behavioral variability in response to different task demands and changes in the environment will be reduced. PMID:23226117

Resting and Task-Modulated High-Frequency Brain Rhythms Measured by Scalp Encephalography in Infants with Tuberous Sclerosis Complex

ERIC Educational Resources Information Center

Stamoulis, Catherine; Vogel-Farley, Vanessa; Degregorio, Geneva; Jeste, Shafali S.; Nelson, Charles A.

2015-01-01

The electrophysiological correlates of cognitive deficits in tuberous sclerosis complex (TSC) are not well understood, and modulations of neural dynamics by neuroanatomical abnormalities that characterize the disorder remain elusive. Neural oscillations (rhythms) are a fundamental aspect of brain function, and have dominant frequencies in a wide…

Psychoneuroimmunology - psyche and autoimmunity.

PubMed

Ziemssen, Tjalf

2012-01-01

Psychoneuroimmunology is a relatively young field of research that investigates interactions between central nervous and immune system. The brain modulates the immune system by the endocrine and autonomic nervous system. Vice versa, the immune system modulates brain activity including sleep and body temperature. Based on a close functional and anatomical link, the immune and nervous systems act in a highly reciprocal manner. From fever to stress, the influence of one system on the other has evolved in an intricate manner to help sense danger and to mount an appropriate adaptive response. Over recent decades, reasonable evidence has emerged that these brain-to-immune interactions are highly modulated by psychological factors which influence immunity and autoimmune disease. For several diseases, the relevance of psychoneuroimmunological findings has already been demonstrated.

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.

Gut microbiota depletion from early adolescence in mice: Implications for brain and behaviour.

PubMed

Desbonnet, Lieve; Clarke, Gerard; Traplin, Alexander; O'Sullivan, Orla; Crispie, Fiona; Moloney, Rachel D; Cotter, Paul D; Dinan, Timothy G; Cryan, John F

2015-08-01

There is growing appreciation for the importance of bacteria in shaping brain development and behaviour. Adolescence and early adulthood are crucial developmental periods during which exposure to harmful environmental factors can have a permanent impact on brain function. Such environmental factors include perturbations of the gut bacteria that may affect gut-brain communication, altering the trajectory of brain development, and increasing vulnerability to psychiatric disorders. Here we assess the effects of gut bacterial depletion from weaning onwards on adult cognitive, social and emotional behaviours and markers of gut-brain axis dysfunction in mice. Mice were treated with a combination of antibiotics from weaning onwards and effects on behaviours and potential gut-brain axis neuromodulators (tryptophan, monoamines, and neuropeptides) and BDNF expression were assessed in adulthood. Antibiotic-treatment depleted and restructured gut microbiota composition of caecal contents and decreased spleen weights in adulthood. Depletion of the gut microbiota from weaning onwards reduced anxiety, induced cognitive deficits, altered dynamics of the tryptophan metabolic pathway, and significantly reduced BDNF, oxytocin and vasopressin expression in the adult brain. Microbiota depletion from weaning onwards by means of chronic treatment with antibiotics in mice impacts on anxiety and cognitive behaviours as well as key neuromodulators of gut-brain communication in a manner that is similar to that reported in germ-free mice. This model may represent a more amenable alternative for germ-free mice in the assessment of microbiota modulation of behaviour. Finally, these data suggest that despite the presence of a normal gut microbiome in early postnatal life, reduced abundance and diversity of the gut microbiota from weaning influences adult behaviours and key neuromodulators of the microbiota-gut-brain axis suggesting that dysregulation of this axis in the post-weaning period may contribute to the pathogenesis of disorders associated with altered anxiety and cognition. Copyright © 2015 Elsevier Inc. All rights reserved.

Analysis of the time-varying energy of brain responses to an oddball paradigm using short-term smoothed Wigner-Ville distribution.

PubMed

Tağluk, M E; Cakmak, E D; Karakaş, S

2005-04-30

Cognitive brain responses to external stimuli, as measured by event related potentials (ERPs), have been analyzed from a variety of perspectives to investigate brain dynamics. Here, the brain responses of healthy subjects to auditory oddball paradigms, standard and deviant stimuli, recorded on an Fz electrode site were studied using a short-term version of the smoothed Wigner-Ville distribution (STSW) method. A smoothing kernel was designed to preserve the auto energy of the signal with maximum time and frequency resolutions. Analysis was conducted mainly on the time-frequency distributions (TFDs) of sweeps recorded during successive trials including the TFD of averaged single sweeps as the evoked time-frequency (ETF) brain response and the average of TFDs of single sweeps as the time-frequency (TF) brain response. Also the power entropy and the phase angles of the signal at frequency f and time t locked to the stimulus onset were studied across single trials as the TF power-locked and the TF phase-locked brain responses, respectively. TFDs represented in this way demonstrated the ERP spectro-temporal characteristics from multiple perspectives. The time-varying energy of the individual components manifested interesting TF structures in the form of amplitude modulated (AM) and frequency modulated (FM) energy bursts. The TF power-locked and phase-locked brain responses provoked ERP energies in a manner modulated by cognitive functions, an observation requiring further investigation. These results may lead to a better understanding of integrative brain dynamics.

Brain mitochondrial bioenergetics change with rapid and prolonged shifts in aggression in the honey bee, Apis mellifera.

PubMed

Rittschof, Clare C; Vekaria, Hemendra J; Palmer, Joseph H; Sullivan, Patrick G

2018-04-25

Neuronal function demands high-level energy production, and as such, a decline in mitochondrial respiration characterizes brain injury and disease. A growing number of studies, however, link brain mitochondrial function to behavioral modulation in non-diseased contexts. In the honey bee, we show for the first time that an acute social interaction, which invokes an aggressive response, may also cause a rapid decline in brain mitochondrial bioenergetics. The degree and speed of this decline has only been previously observed in the context of brain injury. Furthermore, in the honey bee, age-related increases in aggressive tendency are associated with increased baseline brain mitochondrial respiration, as well as increased plasticity in response to metabolic fuel type in vitro Similarly, diet restriction and ketone body feeding, which commonly enhance mammalian brain mitochondrial function in vivo , cause increased aggression. Thus, even in normal behavioral contexts, brain mitochondria show a surprising degree of variation in function over both rapid and prolonged time scales, with age predicting both baseline function and plasticity in function. These results suggest that mitochondrial function is integral to modulating aggression-related neuronal signaling. We hypothesize that variation in function reflects mitochondrial calcium buffering activity, and that shifts in mitochondrial function signal to the neuronal soma to regulate gene expression and neural energetic state. Modulating brain energetic state is emerging as a critical component of the regulation of behavior in non-diseased contexts. © 2018. Published by The Company of Biologists Ltd.

Insights into TREM2 biology by network analysis of human brain gene expression data

PubMed Central

Forabosco, Paola; Ramasamy, Adaikalavan; Trabzuni, Daniah; Walker, Robert; Smith, Colin; Bras, Jose; Levine, Adam P.; Hardy, John; Pocock, Jennifer M.; Guerreiro, Rita; Weale, Michael E.; Ryten, Mina

2013-01-01

Rare variants in TREM2 cause susceptibility to late-onset Alzheimer's disease. Here we use microarray-based expression data generated from 101 neuropathologically normal individuals and covering 10 brain regions, including the hippocampus, to understand TREM2 biology in human brain. Using network analysis, we detect a highly preserved TREM2-containing module in human brain, show that it relates to microglia, and demonstrate that TREM2 is a hub gene in 5 brain regions, including the hippocampus, suggesting that it can drive module function. Using enrichment analysis we show significant overrepresentation of genes implicated in the adaptive and innate immune system. Inspection of genes with the highest connectivity to TREM2 suggests that it plays a key role in mediating changes in the microglial cytoskeleton necessary not only for phagocytosis, but also migration. Most importantly, we show that the TREM2-containing module is significantly enriched for genes genetically implicated in Alzheimer's disease, multiple sclerosis, and motor neuron disease, implying that these diseases share common pathways centered on microglia and that among the genes identified are possible new disease-relevant genes. PMID:23855984

Recording and Modulation of Epileptiform Activity in Rodent Brain Slices Coupled to Microelectrode Arrays.

PubMed

Panuccio, Gabriella; Colombi, Ilaria; Chiappalone, Michela

2018-05-15

Temporal lobe epilepsy (TLE) is the most common partial complex epileptic syndrome and the least responsive to medications. Deep brain stimulation (DBS) is a promising approach when pharmacological treatment fails or neurosurgery is not recommended. Acute brain slices coupled to microelectrode arrays (MEAs) represent a valuable tool to study neuronal network interactions and their modulation by electrical stimulation. As compared to conventional extracellular recording techniques, they provide the added advantages of a greater number of observation points and a known inter-electrode distance, which allow studying the propagation path and speed of electrophysiological signals. However, tissue oxygenation may be greatly impaired during MEA recording, requiring a high perfusion rate, which comes at the cost of decreased signal-to-noise ratio and higher oscillations in the experimental temperature. Electrical stimulation further stresses the brain tissue, making it difficult to pursue prolonged recording/stimulation epochs. Moreover, electrical modulation of brain slice activity needs to target specific structures/pathways within the brain slice, requiring that electrode mapping be easily and quickly performed live during the experiment. Here, we illustrate how to perform the recording and electrical modulation of 4-aminopyridine (4AP)-induced epileptiform activity in rodent brain slices using planar MEAs. We show that the brain tissue obtained from mice outperforms rat brain tissue and is thus better suited for MEA experiments. This protocol guarantees the generation and maintenance of a stable epileptiform pattern that faithfully reproduces the electrophysiological features observed with conventional field potential recording, persists for several hours, and outlasts sustained electrical stimulation for prolonged epochs. Tissue viability throughout the experiment is achieved thanks to the use of a small-volume custom recording chamber allowing for laminar flow and quick solution exchange even at low (1 mL/min) perfusion rates. Quick MEA mapping for real-time monitoring and selection of stimulating electrodes is performed by a custom graphic user interface (GUI).

Monetary reward magnitude effects on behavior and brain function during goal-directed behavior.

PubMed

Rosell-Negre, P; Bustamante, J C; Fuentes-Claramonte, P; Costumero, V; Benabarre, S; Barrós-Loscertales, A

2017-08-01

Reward may modulate the cognitive processes required for goal achievement, while individual differences in personality may affect reward modulation. Our aim was to test how different monetary reward magnitudes modulate brain activation and performance during goal-directed behavior, and whether individual differences in reward sensitivity affect this modulation. For this purpose, we scanned 37 subjects with a parametric design in which we varied the magnitude of monetary rewards (€0, €0.01, €0.5, €1 or €1.5) in a blocked fashion while participants performed an interference counting-Stroop condition. The results showed that the brain activity of left dorsolateral prefrontal cortex (DLPFC) and the striatum were modulated by increasing and decreasing reward magnitudes, respectively. Behavioral performance improved as the magnitude of monetary reward increased while comparing the non reward (€0) condition to any other reward condition, or the lower €0.01 to any other reward condition, and this improvement was related with individual differences in reward sensitivity. In conclusion, the locus of influence of monetary incentives overlaps the activity of the regions commonly involved in cognitive control.

Optimized Motor Imagery Paradigm Based on Imagining Chinese Characters Writing Movement.

PubMed

Qiu, Zhaoyang; Allison, Brendan Z; Jin, Jing; Zhang, Yu; Wang, Xingyu; Li, Wei; Cichocki, Andrzej

2017-07-01

motor imagery (MI) is a mental representation of motor behavior. The MI-based brain computer interfaces (BCIs) can provide communication for the physically impaired. The performance of MI-based BCI mainly depends on the subject's ability to self-modulate electroencephalogram signals. Proper training can help naive subjects learn to modulate brain activity proficiently. However, training subjects typically involve abstract motor tasks and are time-consuming. to improve the performance of naive subjects during motor imagery, a novel paradigm was presented that would guide naive subjects to modulate brain activity effectively. In this new paradigm, pictures of the left or right hand were used as cues for subjects to finish the motor imagery task. Fourteen healthy subjects (11 male, aged 22-25 years, and mean 23.6±1.16) participated in this study. The task was to imagine writing a Chinese character. Specifically, subjects could imagine hand movements corresponding to the sequence of writing strokes in the Chinese character. This paradigm was meant to find an effective and familiar action for most Chinese people, to provide them with a specific, extensively practiced task and help them modulate brain activity. results showed that the writing task paradigm yielded significantly better performance than the traditional arrow paradigm (p < 0.001). Questionnaire replies indicated that most subjects thought that the new paradigm was easier. the proposed new motor imagery paradigm could guide subjects to help them modulate brain activity effectively. Results showed that there were significant improvements using new paradigm, both in classification accuracy and usability.

Combining Functional Neuroimaging with Off-Line Brain Stimulation: Modulation of Task-Related Activity in Language Areas

ERIC Educational Resources Information Center

Andoh, Jamila; Paus, Tomas

2011-01-01

Repetitive TMS (rTMS) provides a noninvasive tool for modulating neural activity in the human brain. In healthy participants, rTMS applied over the language-related areas in the left hemisphere, including the left posterior temporal area of Wernicke (LTMP) and inferior frontal area of Broca, have been shown to affect performance on word…

miR-509 suppresses brain metastasis of breast cancer cells by modulating RhoC and TNF α

PubMed Central

Xing, Fei; Sharma, Sambad; Liu, Yin; Mo, Yin-Yuan; Wu, Kerui; Zhang, Ying-Yu; Pochampally, Radhika; Martinez, Luis A; Lo, Hui-wen; Watabe, Kounosuke

2014-01-01

The median survival time of breast cancer patients with brain metastasis is less than 6 months, and even a small metastatic lesion often causes severe neurological disabilities. Because of the location of metastatic lesions, a surgical approach is limited and most chemotherapeutic drugs are ineffective due to the blood brain barrier (BBB). Despite this clinical importance, the molecular basis of the brain metastasis is poorly understood. In this study, we have isolated RNA from samples obtained from primary breast tumors and also from brain metastatic lesions followed by microRNA profiling analysis. Our results revealed that the miR-509 is highly expressed in the primary tumors, while the expression of this microRNA is significantly decreased in the brain metastatic lesions. MicroRNA target prediction and the analysis of cytokine array for the cells ectopically expressed with miR-509 demonstrated that this microRNA was capable of modulating two genes essential for brain invasion, RhoC and TNFα that affect the invasion of cancer cells and permeability of BBB, respectively. Importantly, high levels of TNFα and RhoC-induced MMP9 were significantly correlated with brain metastasis-free survival of breast cancer patients. Furthermore, the results of our in vivo experiments indicate that miR-509 significantly suppressed the ability of cancer cells to metastasize to the brain. These findings suggest that miR-509 plays a critical role in brain metastasis of breast cancer by modulating the RhoC-TNFα network and that this miR-509 axis may represent a potential therapeutic target or serve as a prognostic tool for brain metastasis. PMID:25659578

Face-elicited ERPs and affective attitude: brain electric microstate and tomography analyses.

PubMed

Pizzagalli, D; Lehmann, D; Koenig, T; Regard, M; Pascual-Marqui, R D

2000-03-01

Although behavioral studies have demonstrated that normative affective traits modulate the processing of facial and emotionally charged stimuli, direct electrophysiological evidence for this modulation is still lacking. Event-related potential (ERP) data associated with personal, traitlike approach- or withdrawal-related attitude (assessed post-recording and 14 months later) were investigated in 18 subjects during task-free (i.e. unrequested, spontaneous) emotional evaluation of faces. Temporal and spatial aspects of 27 channel ERP were analyzed with microstate analysis and low resolution electromagnetic tomography (LORETA), a new method to compute 3 dimensional cortical current density implemented in the Talairach brain atlas. Microstate analysis showed group differences 132-196 and 196-272 ms poststimulus, with right-shifted electric gravity centers for subjects with negative affective attitude. During these (over subjects reliably identifiable) personality-modulated, face-elicited microstates, LORETA revealed activation of bilateral occipito-temporal regions, reportedly associated with facial configuration extraction processes. Negative compared to positive affective attitude showed higher activity right temporal; positive compared to negative attitude showed higher activity left temporo-parieto-occipital. These temporal and spatial aspects suggest that the subject groups differed in brain activity at early, automatic, stimulus-related face processing steps when structural face encoding (configuration extraction) occurs. In sum, the brain functional microstates associated with affect-related personality features modulate brain mechanisms during face processing already at early information processing stages.

Neural markers of social and monetary rewards in children with Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

PubMed Central

Gonzalez-Gadea, Maria Luz; Sigman, Mariano; Rattazzi, Alexia; Lavin, Claudio; Rivera-Rei, Alvaro; Marino, Julian; Manes, Facundo; Ibanez, Agustin

2016-01-01

Recent theories of decision making propose a shared value-related brain mechanism for encoding monetary and social rewards. We tested this model in children with Attention-Deficit/Hyperactivity Disorder (ADHD), children with Autism Spectrum Disorder (ASD) and control children. We monitored participants’ brain dynamics using high density-electroencephalography while they played a monetary and social reward tasks. Control children exhibited a feedback Error-Related Negativity (fERN) modulation and Anterior Cingulate Cortex (ACC) source activation during both tasks. Remarkably, although cooperation resulted in greater losses for the participants, the betrayal options generated greater fERN responses. ADHD subjects exhibited an absence of fERN modulation and reduced ACC activation during both tasks. ASD subjects exhibited normal fERN modulation during monetary choices and inverted fERN/ACC responses in social options than did controls. These results suggest that in neurotypicals, monetary losses and observed disloyal social decisions induced similar activity in the brain value system. In ADHD children, difficulties in reward processing affected early brain signatures of monetary and social decisions. Conversely, ASD children showed intact neural markers of value-related monetary mechanisms, but no brain modulation by prosociality in the social task. These results offer insight into the typical and atypical developments of neural correlates of monetary and social reward processing. PMID:27464551

Connecting the Brain to Itself through an Emulation

PubMed Central

Serruya, Mijail D.

2017-01-01

Pilot clinical trials of human patients implanted with devices that can chronically record and stimulate ensembles of hundreds to thousands of individual neurons offer the possibility of expanding the substrate of cognition. Parallel trains of firing rate activity can be delivered in real-time to an array of intermediate external modules that in turn can trigger parallel trains of stimulation back into the brain. These modules may be built in software, VLSI firmware, or biological tissue as in vitro culture preparations or in vivo ectopic construct organoids. Arrays of modules can be constructed as early stage whole brain emulators, following canonical intra- and inter-regional circuits. By using machine learning algorithms and classic tasks known to activate quasi-orthogonal functional connectivity patterns, bedside testing can rapidly identify ensemble tuning properties and in turn cycle through a sequence of external module architectures to explore which can causatively alter perception and behavior. Whole brain emulation both (1) serves to augment human neural function, compensating for disease and injury as an auxiliary parallel system, and (2) has its independent operation bootstrapped by a human-in-the-loop to identify optimal micro- and macro-architectures, update synaptic weights, and entrain behaviors. In this manner, closed-loop brain-computer interface pilot clinical trials can advance strong artificial intelligence development and forge new therapies to restore independence in children and adults with neurological conditions. PMID:28713235

Neural-endocrine-immune complex in the central modulation of tumorigenesis: facts, assumptions, and hypotheses.

PubMed

Mravec, Boris; Gidron, Yori; Kukanova, Barbara; Bizik, Jozef; Kiss, Alexander; Hulin, Ivan

2006-11-01

For the precise coordination of systemic functions, the nervous system uses a variety of peripherally and centrally localized receptors, which transmit information from internal and external environments to the central nervous system. Tight interconnections between the immune, nervous, and endocrine systems provide a base for monitoring and consequent modulation of immune system functions by the brain and vice versa. The immune system plays an important role in tumorigenesis. On the basis of rich interconnections between the immune, nervous and endocrine systems, the possibility that the brain may be informed about tumorigenesis is discussed in this review article. Moreover, the eventual modulation of tumorigenesis by central nervous system is also considered. Prospective consequences of the interactions between tumor and brain for diagnosis and therapy of cancer are emphasized.

A unifying model of concurrent spatial and temporal modularity in muscle activity.

PubMed

Delis, Ioannis; Panzeri, Stefano; Pozzo, Thierry; Berret, Bastien

2014-02-01

Modularity in the central nervous system (CNS), i.e., the brain capability to generate a wide repertoire of movements by combining a small number of building blocks ("modules"), is thought to underlie the control of movement. Numerous studies reported evidence for such a modular organization by identifying invariant muscle activation patterns across various tasks. However, previous studies relied on decompositions differing in both the nature and dimensionality of the identified modules. Here, we derive a single framework that encompasses all influential models of muscle activation modularity. We introduce a new model (named space-by-time decomposition) that factorizes muscle activations into concurrent spatial and temporal modules. To infer these modules, we develop an algorithm, referred to as sample-based nonnegative matrix trifactorization (sNM3F). We test the space-by-time decomposition on a comprehensive electromyographic dataset recorded during execution of arm pointing movements and show that it provides a low-dimensional yet accurate, highly flexible and task-relevant representation of muscle patterns. The extracted modules have a well characterized functional meaning and implement an efficient trade-off between replication of the original muscle patterns and task discriminability. Furthermore, they are compatible with the modules extracted from existing models, such as synchronous synergies and temporal primitives, and generalize time-varying synergies. Our results indicate the effectiveness of a simultaneous but separate condensation of spatial and temporal dimensions of muscle patterns. The space-by-time decomposition accommodates a unified view of the hierarchical mapping from task parameters to coordinated muscle activations, which could be employed as a reference framework for studying compositional motor control.

Measuring and Inducing Brain Plasticity in Chronic Aphasia

ERIC Educational Resources Information Center

Fridriksson, Julius

2011-01-01

Brain plasticity associated with anomia recovery in aphasia is poorly understood. Here, I review four recent studies from my lab that focused on brain modulation associated with long-term anomia outcome, its behavioral treatment, and the use of transcranial brain stimulation to enhance anomia treatment success in individuals with chronic aphasia…

Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system.

PubMed

Zeniya, Satoshi; Kuwahara, Hiroya; Daizo, Kaiichi; Watari, Akihiro; Kondoh, Masuo; Yoshida-Tanaka, Kie; Kaburagi, Hidetoshi; Asada, Ken; Nagata, Tetsuya; Nagahama, Masahiro; Yagi, Kiyohito; Yokota, Takanori

2018-05-17

Within the field of RNA therapeutics, antisense oligonucleotide-based therapeutics are a potentially powerful means of treating intractable diseases. However, if these therapeutics are used for the treatment of neurological disorders, safe yet efficient methods of delivering antisense oligonucleotides across the blood-brain barrier to the central nervous system must be developed. Here, we examined the use of angubindin-1, a binder to the tricellular tight junction, to modulate paracellular transport between brain microvascular endothelial cells in the blood-brain barrier for the delivery of antisense oligonucleotides to the central nervous system. This proof-of-concept study demonstrated that intravenously injected angubindin-1 increased the permeability of the blood-brain barrier and enabled transient delivery of subsequently administered antisense oligonucleotides into the mouse brain and spinal cord, leading to silencing of a target RNA without any overt adverse effects. We also found that two bicellular tight junction modulators did not produce such a silencing effect, suggesting that the tricellular tight junction is likely a better target for the delivery of antisense oligonucleotides than the bicellular tight junction. Our delivery strategy of modulating the tricellular tight junction in the blood-brain barrier via angubindin-1 provides a novel avenue of research for the development of antisense oligonucleotide-based therapeutics for the treatment of neurological disorders. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Synthesis and Characterization of a Hydrogel with Controllable Electroosmosis: A Potential Brain Tissue Surrogate for Electrokinetic Transport

PubMed Central

Faraji, Amir H.; Cui, Jonathan J.; Guy, Yifat; Li, Ling; Weber, Stephen G.

2011-01-01

Electroosmosis is the bulk fluid flow initiated by application of an electric field to an electrolyte solution in contact with immobile objects with a non-zero ζ-potential such as the surface of a porous medium. Electroosmosis may be used to assist analytical separations. Several gel-based systems with varying electroosmotic mobilities have been made in this context. A method was recently developed to determine the ζ-potential of organotypic hippocampal slice cultures (OHSC) as a representative model for normal brain tissue. The ζ-potential of the tissue is significant. However, determining the role of the ζ-potential in solute transport in tissue in an electric field is difficult because the tissue's ζ-potential cannot be altered. We hypothesized that mass transport properties, namely the ζ-potential and tortuosity, could be modulated by controlling the composition of a set of hydrogels. Thus, poly(acrylamide-co-acrylic acid) gels were prepared with three compositions (by monomer weight percent): acrylamide/acrylic acid 100/0, 90/10, and 75/25. The ζ-potentials of these gels at pH 7.4 are distinctly different, and in fact vary approximately linearly with the weight percent of acrylic acid. We discovered that the 25% acrylic acid gel is a respectable model for brain tissue, as its ζ-potential is comparable to the OHSC. This series of gels permits the experimental determination of the importance of electrokinetic properties in a particular experiment or protocol. Additionally, tortuosities were measured electrokinetically and by evaluating diffusion coefficients. Hydrogels with well-defined ζ-potential and tortuosity may find utility in biomaterials, analytical separations, and as a surrogate model for OHSC and living biological tissues. PMID:21905710

Interactions of sex and early life social experiences at two developmental stages shape nonapeptide receptor profiles.

PubMed

Hiura, Lisa C; Ophir, Alexander G

2018-05-31

Early life social experiences are critical to behavioral and cognitive development, and can have a tremendous influence on developing social phenotypes. Most work has focused on outcomes of experiences at a single stage of development (e.g., perinatal, or post-weaning). Few studies have assessed the impact of social experience at multiple developmental stages and across sex. Oxytocin and vasopressin are profoundly important for modulating social behavior and these nonapeptide systems are highly sensitive to developmental social experience, particularly in brain areas important for social behavior. We investigated whether oxytocin receptor (OTR) and vasopressin receptor (V1aR) distributions of prairie voles (Microtus ochrogaster) change as a function of parental composition within the natal nest or social composition after weaning. We raised pups either in the presence or absence of their fathers. At weaning, offspring were housed either individually or with a same-sex sibling. We also examined whether changes in receptor distributions are sexually dimorphic because the impact of the developmental environment on the nonapeptide system could be sex-dependent. We found that differences in nonapeptide receptor expression were region-, sex-, and rearing condition-specific, indicating a high level of complexity in the ways that early life experiences shape the social brain. We found many more differences in V1aR density compared to OTR density, indicating that nonapeptide receptors demonstrate differential levels of neural plasticity and sensitivity to environmental and biological variables. Our data highlight that critical factors including biological sex and multiple experiences across the developmental continuum interact in complex ways to shape the social brain. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Traumatic Brain Injury: A Guide for Caregivers of Service Members and Veterans

DTIC Science & Technology

2010-01-01

Fracture - Module 1, pages 2, 15, 22, 26...pages 6, 9, 13-16, 20, 22, 25, 27 Skull Fracture - Companion, page 9; Module 1, pages 14-15, 22, 26 Simple Fracture - Module 1, page 15 Compound... Fracture - Module 1, page 15 Depressed Skull Fracture - Module 1, page 15 Basal Skull Fracture - Module 1, page 15 Sleep Changes - Module 2, pages

Formation and remodeling of the brain extracellular matrix in neural plasticity: Roles of chondroitin sulfate and hyaluronan.

PubMed

Miyata, Shinji; Kitagawa, Hiroshi

2017-10-01

The extracellular matrix (ECM) of the brain is rich in glycosaminoglycans such as chondroitin sulfate (CS) and hyaluronan. These glycosaminoglycans are organized into either diffuse or condensed ECM. Diffuse ECM is distributed throughout the brain and fills perisynaptic spaces, whereas condensed ECM selectively surrounds parvalbumin-expressing inhibitory neurons (PV cells) in mesh-like structures called perineuronal nets (PNNs). The brain ECM acts as a non-specific physical barrier that modulates neural plasticity and axon regeneration. Here, we review recent progress in understanding of the molecular basis of organization and remodeling of the brain ECM, and the involvement of several types of experience-dependent neural plasticity, with a particular focus on the mechanism that regulates PV cell function through specific interactions between CS chains and their binding partners. We also discuss how the barrier function of the brain ECM restricts dendritic spine dynamics and limits axon regeneration after injury. The brain ECM not only forms physical barriers that modulate neural plasticity and axon regeneration, but also forms molecular brakes that actively controls maturation of PV cells and synapse plasticity in which sulfation patterns of CS chains play a key role. Structural remodeling of the brain ECM modulates neural function during development and pathogenesis. Genetic or enzymatic manipulation of the brain ECM may restore neural plasticity and enhance recovery from nerve injury. This article is part of a Special Issue entitled Neuro-glycoscience, edited by Kenji Kadomatsu and Hiroshi Kitagawa. Copyright © 2017 Elsevier B.V. All rights reserved.

Music modulation of pain perception and pain-related activity in the brain, brain stem, and spinal cord: a functional magnetic resonance imaging study.

PubMed

Dobek, Christine E; Beynon, Michaela E; Bosma, Rachael L; Stroman, Patrick W

2014-10-01

The oldest known method for relieving pain is music, and yet, to date, the underlying neural mechanisms have not been studied. Here, we investigate these neural mechanisms by applying a well-defined painful stimulus while participants listened to their favorite music or to no music. Neural responses in the brain, brain stem, and spinal cord were mapped with functional magnetic resonance imaging spanning the cortex, brain stem, and spinal cord. Subjective pain ratings were observed to be significantly lower when pain was administered with music than without music. The pain stimulus without music elicited neural activity in brain regions that are consistent with previous studies. Brain regions associated with pleasurable music listening included limbic, frontal, and auditory regions, when comparing music to non-music pain conditions. In addition, regions demonstrated activity indicative of descending pain modulation when contrasting the 2 conditions. These regions include the dorsolateral prefrontal cortex, periaqueductal gray matter, rostral ventromedial medulla, and dorsal gray matter of the spinal cord. This is the first imaging study to characterize the neural response of pain and how pain is mitigated by music, and it provides new insights into the neural mechanism of music-induced analgesia within the central nervous system. This article presents the first investigation of neural processes underlying music analgesia in human participants. Music modulates pain responses in the brain, brain stem, and spinal cord, and neural activity changes are consistent with engagement of the descending analgesia system. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

Catechol-O-methyltransferase (COMT) gene modulates private self-consciousness and self-flexibility.

PubMed

Wang, Bei; Ru, Wenzhao; Yang, Xing; Yang, Lu; Fang, Pengpeng; Zhu, Xu; Shen, Guomin; Gao, Xiaocai; Gong, Pingyuan

2016-08-01

Dopamine levels in the brain influence human consciousness. Inspired by the role of Catechol-O-methyltransferase (COMT) in inactivating dopamine in the brain, we investigated to what extent COMT could modulate individual's self-consciousness dispositions and self-consistency by genotyping the COMT Val158Met (rs4680) polymorphism and measuring self-consciousness and self-consistency and congruence in a college student population. The results indicated that COMT Val158Met polymorphism significantly modulated the private self-consciousness. The individuals with Val/Val genotype, corresponding to lower dopamine levels in the brain, were more likely to be aware of their feelings and beliefs. The results also indicated that this polymorphism modulated one's self-flexibility. The individuals with Val/Val genotype showed higher levels of stereotype in self-concept compared with those with Met/Met genotype. These findings suggest that COMT is a predictor of the individual differences in self-consciousness and self-flexibility. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrical Stimulation Modulates High γ Activity and Human Memory Performance

PubMed Central

Berry, Brent M.; Miller, Laura R.; Khadjevand, Fatemeh; Ezzyat, Youssef; Wanda, Paul; Sperling, Michael R.; Lega, Bradley; Stead, S. Matt

2018-01-01

Direct electrical stimulation of the brain has emerged as a powerful treatment for multiple neurological diseases, and as a potential technique to enhance human cognition. Despite its application in a range of brain disorders, it remains unclear how stimulation of discrete brain areas affects memory performance and the underlying electrophysiological activities. Here, we investigated the effect of direct electrical stimulation in four brain regions known to support declarative memory: hippocampus (HP), parahippocampal region (PH) neocortex, prefrontal cortex (PF), and lateral temporal cortex (TC). Intracranial EEG recordings with stimulation were collected from 22 patients during performance of verbal memory tasks. We found that high γ (62–118 Hz) activity induced by word presentation was modulated by electrical stimulation. This modulatory effect was greatest for trials with “poor” memory encoding. The high γ modulation correlated with the behavioral effect of stimulation in a given brain region: it was negative, i.e., the induced high γ activity was decreased, in the regions where stimulation decreased memory performance, and positive in the lateral TC where memory enhancement was observed. Our results suggest that the effect of electrical stimulation on high γ activity induced by word presentation may be a useful biomarker for mapping memory networks and guiding therapeutic brain stimulation. PMID:29404403

Analysis of tumor- and stroma-supplied proteolytic networks reveals a brain metastasis-promoting role for cathepsin S

PubMed Central

Sevenich, Lisa; Bowman, Robert L.; Mason, Steven D.; Quail, Daniela F.; Rapaport, Franck; Elie, Benelita T.; Brogi, Edi; Brastianos, Priscilla K.; Hahn, William C.; Holsinger, Leslie J.; Massagué, Joan; Leslie, Christina S.; Joyce, Johanna A.

2014-01-01

Metastasis remains the most common cause of death in most cancers, with limited therapies for combating disseminated disease. While the primary tumor microenvironment is an important regulator of cancer progression, it is less well understood how different tissue environments influence metastasis. We analyzed tumor-stroma interactions that modulate organ tropism of brain, bone and lung metastasis in xenograft models. We identified a number of potential modulators of site-specific metastasis, including cathepsin S as a regulator of breast-to-brain metastasis. High cathepsin S expression at the primary site correlated with decreased brain metastasis-free survival in breast cancer patients. Both macrophages and tumor cells produce cathepsin S, and only the combined depletion significantly reduced brain metastasis in vivo. Cathepsin S specifically mediates blood-brain barrier transmigration via proteolytic processing of the junctional adhesion molecule (JAM)-B. Pharmacological inhibition of cathepsin S significantly reduced experimental brain metastasis, supporting its consideration as a therapeutic target for this disease. PMID:25086747

The major brain cholesterol metabolite 24(S)-hydroxycholesterol is a potent allosteric modulator of N-methyl-D-aspartate receptors.

PubMed

Paul, Steven M; Doherty, James J; Robichaud, Albert J; Belfort, Gabriel M; Chow, Brian Y; Hammond, Rebecca S; Crawford, Devon C; Linsenbardt, Andrew J; Shu, Hong-Jin; Izumi, Yukitoshi; Mennerick, Steven J; Zorumski, Charles F

2013-10-30

N-methyl-D-aspartate receptors (NMDARs) are glutamate-gated ion channels that are critical to the regulation of excitatory synaptic function in the CNS. NMDARs govern experience-dependent synaptic plasticity and have been implicated in the pathophysiology of various neuropsychiatric disorders including the cognitive deficits of schizophrenia and certain forms of autism. Certain neurosteroids modulate NMDARs experimentally but their low potency, poor selectivity, and very low brain concentrations make them poor candidates as endogenous ligands or therapeutic agents. Here we show that the major brain-derived cholesterol metabolite 24(S)-hydroxycholesterol (24(S)-HC) is a very potent, direct, and selective positive allosteric modulator of NMDARs with a mechanism that does not overlap that of other allosteric modulators. At submicromolar concentrations 24(S)-HC potentiates NMDAR-mediated EPSCs in rat hippocampal neurons but fails to affect AMPAR or GABAA receptors (GABA(A)Rs)-mediated responses. Cholesterol itself and other naturally occurring oxysterols present in brain do not modulate NMDARs at concentrations ≤10 μM. In hippocampal slices, 24(S)-HC enhances the ability of subthreshold stimuli to induce long-term potentiation (LTP). 24(S)-HC also reverses hippocampal LTP deficits induced by the NMDAR channel blocker ketamine. Finally, we show that synthetic drug-like derivatives of 24(S)-HC, which potently enhance NMDAR-mediated EPSCs and LTP, restore behavioral and cognitive deficits in rodents treated with NMDAR channel blockers. Thus, 24(S)-HC may function as an endogenous modulator of NMDARs acting at a novel oxysterol modulatory site that also represents a target for therapeutic drug development.

Spatiotemporal reconstruction of auditory steady-state responses to acoustic amplitude modulations: Potential sources beyond the auditory pathway.

PubMed

Farahani, Ehsan Darestani; Goossens, Tine; Wouters, Jan; van Wieringen, Astrid

2017-03-01

Investigating the neural generators of auditory steady-state responses (ASSRs), i.e., auditory evoked brain responses, with a wide range of screening and diagnostic applications, has been the focus of various studies for many years. Most of these studies employed a priori assumptions regarding the number and location of neural generators. The aim of this study is to reconstruct ASSR sources with minimal assumptions in order to gain in-depth insight into the number and location of brain regions that are activated in response to low- as well as high-frequency acoustically amplitude modulated signals. In order to reconstruct ASSR sources, we applied independent component analysis with subsequent equivalent dipole modeling to single-subject EEG data (young adults, 20-30 years of age). These data were based on white noise stimuli, amplitude modulated at 4, 20, 40, or 80Hz. The independent components that exhibited a significant ASSR were clustered among all participants by means of a probabilistic clustering method based on a Gaussian mixture model. Results suggest that a widely distributed network of sources, located in cortical as well as subcortical regions, is active in response to 4, 20, 40, and 80Hz amplitude modulated noises. Some of these sources are located beyond the central auditory pathway. Comparison of brain sources in response to different modulation frequencies suggested that the identified brain sources in the brainstem, the left and the right auditory cortex show a higher responsiveness to 40Hz than to the other modulation frequencies. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulation of Rhamm (CD168) for selective adipose tissue development

DOEpatents

Turley, Eva A; Bissell, Mina J

2014-05-06

Herein is described the methods and compositions for modulation of Rhamm, also known as CD 186, and its effects on wound repair, muscle differentiation, bone density and adipogeneisis through its ability to regulate mesenchymal stem cell differentiation. Compositions and methods are provided for blocking Rhamm function for selectively increasing subcutaneous, but not, visceral fat. Compositions and methods for modulating Rhamm in wound repair are also described.

Modulatory Effect of Association of Brain Stimulation by Light and Binaural Beats in Specific Brain Waves

PubMed Central

Calomeni, Mauricio Rocha; Furtado da Silva, Vernon; Velasques, Bruna Brandão; Feijó, Olavo Guimarães; Bittencourt, Juliana Marques; Ribeiro de Souza e Silva, Alair Pedro

2017-01-01

Introduction: One of the positive effects of brain stimulation is interhemispheric modulation as shown in some scientific studies. This study examined if a type of noninvasive stimulation using binaural beats with led-lights and sound would show different modulatory effects upon Alfa and SMR brain waves of elderlies and children with some disease types. Subjects: The sample included 75 individuals of both genders, being, randomly, divided in 6 groups. Groups were named elderly without dementia diagnosis (EWD), n=15, 76±8 years, elderly diagnosed with Parkinson’s disease (EDP), n=15, 72±7 years, elderly diagnosed with Alzheimer’s disease (EDA), n=15, 81±6 years. The other groups were named children with Autism (CA), n=10, 11±4 years, children with Intellectual Impairment (CII), n=10, 12 ±5 years and children with normal cognitive development (CND), n=10, 11±4 years. Instruments and procedure: Instruments were the Mini Mental State Examination Test (MMSE), EEG-Neurocomputer instrument for brain waves registration, brain stimulator, Digit Span Test and a Protocol for working memory training. Data collection followed a pre and post-conjugated stimulation version. Results: The results of the inferential statistics showed that the stimulation protocol had different effects on Alpha and SMR brain waves of the patients. Also, indicated gains in memory functions, for both, children and elderlies as related to gains in brain waves modulation. Conclusion: The results may receive and provide support to a range of studies examining brain modulation and synaptic plasticity. Also, it was emphasized in the results discussion that there was the possibility of the technique serving as an accessory instrument to alternative brain therapies. PMID:29238390

Modulatory Effect of Association of Brain Stimulation by Light and Binaural Beats in Specific Brain Waves.

PubMed

Calomeni, Mauricio Rocha; Furtado da Silva, Vernon; Velasques, Bruna Brandão; Feijó, Olavo Guimarães; Bittencourt, Juliana Marques; Ribeiro de Souza E Silva, Alair Pedro

2017-01-01

One of the positive effects of brain stimulation is interhemispheric modulation as shown in some scientific studies. This study examined if a type of noninvasive stimulation using binaural beats with led-lights and sound would show different modulatory effects upon Alfa and SMR brain waves of elderlies and children with some disease types. The sample included 75 individuals of both genders, being, randomly, divided in 6 groups. Groups were named elderly without dementia diagnosis (EWD), n=15, 76±8 years, elderly diagnosed with Parkinson's disease (EDP), n=15, 72±7 years, elderly diagnosed with Alzheimer's disease (EDA), n=15, 81±6 years. The other groups were named children with Autism (CA), n=10, 11±4 years, children with Intellectual Impairment (CII), n=10, 12 ±5 years and children with normal cognitive development (CND), n=10, 11±4 years. Instruments were the Mini Mental State Examination Test (MMSE), EEG-Neurocomputer instrument for brain waves registration, brain stimulator, Digit Span Test and a Protocol for working memory training. Data collection followed a pre and post-conjugated stimulation version. The results of the inferential statistics showed that the stimulation protocol had different effects on Alpha and SMR brain waves of the patients. Also, indicated gains in memory functions, for both, children and elderlies as related to gains in brain waves modulation. The results may receive and provide support to a range of studies examining brain modulation and synaptic plasticity. Also, it was emphasized in the results discussion that there was the possibility of the technique serving as an accessory instrument to alternative brain therapies.

RM-SORN: a reward-modulated self-organizing recurrent neural network.

PubMed

Aswolinskiy, Witali; Pipa, Gordon

2015-01-01

Neural plasticity plays an important role in learning and memory. Reward-modulation of plasticity offers an explanation for the ability of the brain to adapt its neural activity to achieve a rewarded goal. Here, we define a neural network model that learns through the interaction of Intrinsic Plasticity (IP) and reward-modulated Spike-Timing-Dependent Plasticity (STDP). IP enables the network to explore possible output sequences and STDP, modulated by reward, reinforces the creation of the rewarded output sequences. The model is tested on tasks for prediction, recall, non-linear computation, pattern recognition, and sequence generation. It achieves performance comparable to networks trained with supervised learning, while using simple, biologically motivated plasticity rules, and rewarding strategies. The results confirm the importance of investigating the interaction of several plasticity rules in the context of reward-modulated learning and whether reward-modulated self-organization can explain the amazing capabilities of the brain.

Identification of common coexpression modules based on quantitative network comparison.

PubMed

Jo, Yousang; Kim, Sanghyeon; Lee, Doheon

2018-06-13

Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method. We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs. We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.

Probiotic modulation of the microbiota-gut-brain axis and behaviour in zebrafish.

PubMed

Borrelli, Luca; Aceto, Serena; Agnisola, Claudio; De Paolo, Sofia; Dipineto, Ludovico; Stilling, Roman M; Dinan, Timothy G; Cryan, John F; Menna, Lucia F; Fioretti, Alessandro

2016-07-15

The gut microbiota plays a crucial role in the bi-directional gut-brain axis, a communication that integrates the gut and central nervous system (CNS) activities. Animal studies reveal that gut bacteria influence behaviour, Brain-Derived Neurotrophic Factor (BDNF) levels and serotonin metabolism. In the present study, we report for the first time an analysis of the microbiota-gut-brain axis in zebrafish (Danio rerio). After 28 days of dietary administration with the probiotic Lactobacillus rhamnosus IMC 501, we found differences in shoaling behaviour, brain expression levels of bdnf and of genes involved in serotonin signalling/metabolism between control and treated zebrafish group. In addition, in microbiota we found a significant increase of Firmicutes and a trending reduction of Proteobacteria. This study demonstrates that selected microbes can be used to modulate endogenous neuroactive molecules in zebrafish.

SLC9A9 Co-expression modules in autism-associated brain regions.

PubMed

Patak, Jameson; Hess, Jonathan L; Zhang-James, Yanli; Glatt, Stephen J; Faraone, Stephen V

2017-03-01

SLC9A9 is a sodium hydrogen exchanger present in the recycling endosome and highly expressed in the brain. It is implicated in neuropsychiatric disorders, including autism spectrum disorders (ASDs). Little research concerning its gene expression patterns and biological pathways has been conducted. We sought to investigate its possible biological roles in autism-associated brain regions throughout development. We conducted a weighted gene co-expression network analysis on RNA-seq data downloaded from Brainspan. We compared prenatal and postnatal gene expression networks for three ASD-associated brain regions known to have high SLC9A9 gene expression. We also performed an ASD-associated single nucleotide polymorphism enrichment analysis and a cell signature enrichment analysis. The modules showed differences in gene constituents (membership), gene number, and connectivity throughout time. SLC9A9 was highly associated with immune system functions, metabolism, apoptosis, endocytosis, and signaling cascades. Gene list comparison with co-immunoprecipitation data was significant for multiple modules. We found a disproportionately high autism risk signal among genes constituting the prenatal hippocampal module. The modules were enriched with astrocyte and oligodendrocyte markers. SLC9A9 is potentially involved in the pathophysiology of ASDs. Our investigation confirmed proposed functions for SLC9A9, such as endocytosis and immune regulation, while also revealing potential roles in mTOR signaling and cell survival.. By providing a concise molecular map and interactions, evidence of cell type and implicated brain regions we hope this will guide future research on SLC9A9. Autism Res 2017, 10: 414-429. © 2016 International Society for Autism Research, Wiley Periodicals, Inc. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.

Intracranial spectral amplitude dynamics of perceptual suppression in fronto-insular, occipito-temporal, and primary visual cortex

PubMed Central

Vidal, Juan R.; Perrone-Bertolotti, Marcela; Kahane, Philippe; Lachaux, Jean-Philippe

2015-01-01

If conscious perception requires global information integration across active distant brain networks, how does the loss of conscious perception affect neural processing in these distant networks? Pioneering studies on perceptual suppression (PS) described specific local neural network responses in primary visual cortex, thalamus and lateral prefrontal cortex of the macaque brain. Yet the neural effects of PS have rarely been studied with intracerebral recordings outside these cortices and simultaneously across distant brain areas. Here, we combined (1) a novel experimental paradigm in which we produced a similar perceptual disappearance and also re-appearance by using visual adaptation with transient contrast changes, with (2) electrophysiological observations from human intracranial electrodes sampling wide brain areas. We focused on broadband high-frequency (50–150 Hz, i.e., gamma) and low-frequency (8–24 Hz) neural activity amplitude modulations related to target visibility and invisibility. We report that low-frequency amplitude modulations reflected stimulus visibility in a larger ensemble of recording sites as compared to broadband gamma responses, across distinct brain regions including occipital, temporal and frontal cortices. Moreover, the dynamics of the broadband gamma response distinguished stimulus visibility from stimulus invisibility earlier in anterior insula and inferior frontal gyrus than in temporal regions, suggesting a possible role of fronto-insular cortices in top–down processing for conscious perception. Finally, we report that in primary visual cortex only low-frequency amplitude modulations correlated directly with perceptual status. Interestingly, in this sensory area broadband gamma was not modulated during PS but became positively modulated after 300 ms when stimuli were rendered visible again, suggesting that local networks could be ignited by top–down influences during conscious perception. PMID:25642199

A conserved BDNF, glutamate- and GABA-enriched gene module related to human depression identified by coexpression meta-analysis and DNA variant genome-wide association studies.

PubMed

Chang, Lun-Ching; Jamain, Stephane; Lin, Chien-Wei; Rujescu, Dan; Tseng, George C; Sibille, Etienne

2014-01-01

Large scale gene expression (transcriptome) analysis and genome-wide association studies (GWAS) for single nucleotide polymorphisms have generated a considerable amount of gene- and disease-related information, but heterogeneity and various sources of noise have limited the discovery of disease mechanisms. As systematic dataset integration is becoming essential, we developed methods and performed meta-clustering of gene coexpression links in 11 transcriptome studies from postmortem brains of human subjects with major depressive disorder (MDD) and non-psychiatric control subjects. We next sought enrichment in the top 50 meta-analyzed coexpression modules for genes otherwise identified by GWAS for various sets of disorders. One coexpression module of 88 genes was consistently and significantly associated with GWAS for MDD, other neuropsychiatric disorders and brain functions, and for medical illnesses with elevated clinical risk of depression, but not for other diseases. In support of the superior discriminative power of this novel approach, we observed no significant enrichment for GWAS-related genes in coexpression modules extracted from single studies or in meta-modules using gene expression data from non-psychiatric control subjects. Genes in the identified module encode proteins implicated in neuronal signaling and structure, including glutamate metabotropic receptors (GRM1, GRM7), GABA receptors (GABRA2, GABRA4), and neurotrophic and development-related proteins [BDNF, reelin (RELN), Ephrin receptors (EPHA3, EPHA5)]. These results are consistent with the current understanding of molecular mechanisms of MDD and provide a set of putative interacting molecular partners, potentially reflecting components of a functional module across cells and biological pathways that are synchronously recruited in MDD, other brain disorders and MDD-related illnesses. Collectively, this study demonstrates the importance of integrating transcriptome data, gene coexpression modules and GWAS results for providing novel and complementary approaches to investigate the molecular pathology of MDD and other complex brain disorders.

Nutritional Cues Tie Living Organisms to Their Environment and Its Sustainability

PubMed Central

Adams, Melanie S.; Adams, Robert B.; Wessman, Carol A.; Demmig-Adams, Barbara

2016-01-01

We connect modern, intensive agriculture’s role in environmental degradation to its role in producing nutritionally unbalanced foods, and delineate specific approaches to reduce agriculture’s environmental impact, while producing healthful foods. We call attention to recently discovered genetic programs used by all living organisms to respond to their environment, and present a model of how these programs change body composition and function (of humans and their crop plants and livestock alike) in response to environmental cues. We propose that production of nutritionally balanced crops and livestock requires careful consideration of how these plants and animals are grown; the composition of plant food is modulated by growing conditions, body composition of livestock reflects their feed; composition and function of human body and brain are strongly affected by how food plants and animals are produced. We selected four nutritional features not only involved in (i) governing human health by modulating these genetic programs, but (ii) also affected by agricultural practices. These nutritional features are fat composition (especially saturated fat and the ratio of polyunsaturated omega-6 oils to omega-3 oils), carbohydrate composition (especially the proportion of carbohydrates with a high glycemic index, such as sugars and quick-burning starches) and the level of antioxidant micronutrients. We not only outline threats to human health presented by the current environment, but also potential gains in quality-of-life in a future environment designed to optimize human wellness using insights into the gene-programing effect of diet- and other lifestyle-related factors. These gains could extend beyond optimal human physical and mental health to gains in workforce productivity. The same changes in agricultural practices required to achieve these gains in human health are also needed to support environmental health and sustainable food production. The resulting vision of optimal human health and environmental health, supported by sustainable practices, is intended as an inspiring image of what sustainability has to offer to individuals and society. Our goal is to provide a transparent overview and illustrations intelligible not only to non-experts in each of the other respective areas involved but also to policy makers and the public. PMID:27570764

A role for the serotonin reuptake transporter in the brain and intestinal features of autism spectrum disorders and developmental antidepressant exposure.

PubMed

Margolis, Kara Gross

2017-10-01

Many disease conditions considered CNS-predominant harbor significant intestinal comorbidities. Serotonin (5-HT) and the serotonin reuptake transporter (SERT) have increasingly been shown to play important roles in both brain and intestinal development and long-term function. 5-HT and SERT may thus modulate critical functions in the development and perpetuation of brain-gut axis disease. We discuss the potential roles of 5-HT and SERT in the brain and intestinal manifestations of autism spectrum disorders and developmental antidepressant exposure. The potential therapeutic value of 5-HT 4 modulation in the subsequent treatment of these conditions is also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Motivation but not valence modulates neuroticism-dependent cingulate cortex and insula activity.

PubMed

Deng, Yaling; Li, Shijia; Zhou, Renlai; Walter, Martin

2018-04-01

Neuroticism has been found to specifically modulate amygdala activations during differential processing of valence and motivation while other brain networks yet are unexplored for associated effects. The main purpose of this study was to investigate whether neural mechanisms processing valence or motivation are prone to neuroticism in the salience network (SN), a network that is anchored in the anterior cingulate cortex (ACC) and the anterior insula. This study used functional magnetic resonance imaging (fMRI) and an approach/avoid emotional pictures task to investigate brain activations modulated by pictures' valence or motivational status between high and low neurotic individuals. We found that neuroticism-dependent SN and the parahippocampal-fusiform area activations were modulated by motivation but not valence. Valence in contrast interacted with neuroticism in the lateral orbitofrontal cortex. We suggested that neuroticism modulated valence and motivation processing, however, under the influence of the two distinct networks. Neuroticism modulated the motivation through the SN while it modulated the valence through the orbitofrontal networks. © 2018 Wiley Periodicals, Inc.

Dopamine Modulates the Functional Organization of the Orbitofrontal Cortex.

PubMed

Kahnt, Thorsten; Tobler, Philippe N

2017-02-08

Neuromodulators such as dopamine can alter the intrinsic firing properties of neurons and may thereby change the configuration of larger functional circuits. The primate orbitofrontal cortex (OFC) receives dopaminergic input from midbrain nuclei, but the role of dopamine in the OFC is still unclear. Here we tested the idea that dopaminergic activity changes the pattern of connectivity between the OFC and the rest of the brain and thereby reconfigures functional networks in the OFC. To this end, we combined double-blind, placebo-controlled pharmacology [D 2 receptor (D2R) antagonist amisulpride] in humans with resting-state functional magnetic resonance imaging and clustering methods. In the placebo group, we replicated previously observed parcellations of the OFC into two and six subregions based on connectivity patterns with the rest of the brain. Most importantly, while the twofold clustering did not differ significantly between groups, blocking D2Rs significantly changed the composition of the sixfold parcellation, suggesting a dopamine-dependent reconfiguration of functional OFC subregions. Moreover, multivariate decoding analyses revealed that amisulpride changed the whole-brain connectivity patterns of individual OFC subregions. In particular, D2R blockade shifted the balance of OFC connectivity from associative areas in the temporal and parietal lobe toward functional connectivity with the frontal cortex. In summary, our results suggest that dopamine alters the composition of functional OFC circuits, possibly indicating a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks. SIGNIFICANCE STATEMENT A key role of any neuromodulator may be the reconfiguration of functional brain circuits. Here we test this idea with regard to dopamine and the organization of functional networks in the orbitofrontal cortex (OFC). We show that blockade of dopamine D 2 receptors has profound effects on the functional connectivity patterns of the OFC, yielding altered connectivity-based subdivisions of this region. Our results suggest that dopamine changes the connectional configuration of the OFC, possibly leading to transitions between different operating modes that favor either sensory input or recurrent processing in the prefrontal cortex. More generally, our findings support a broader role for neuromodulators in the dynamic reconfiguration of functional brain networks and may have clinical implications for understanding the actions of antipsychotic agents. Copyright © 2017 the authors 0270-6474/17/371493-12$15.00/0.

High-Throughput Patch Clamp Screening in Human α6-Containing Nicotinic Acetylcholine Receptors

PubMed Central

Armstrong, Lucas C.; Kirsch, Glenn E.; Fedorov, Nikolai B.; Wu, Caiyun; Kuryshev, Yuri A.; Sewell, Abby L.; Liu, Zhiqi; Motter, Arianne L.; Leggett, Carmine S.; Orr, Michael S.

2017-01-01

Nicotine, the addictive component of tobacco products, is an agonist at nicotinic acetylcholine receptors (nAChRs) in the brain. The subtypes of nAChR are defined by their α- and β-subunit composition. The α6β2β3 nAChR subtype is expressed in terminals of dopaminergic neurons that project to the nucleus accumbens and striatum and modulate dopamine release in brain regions involved in nicotine addiction. Although subtype-dependent selectivity of nicotine is well documented, subtype-selective profiles of other tobacco product constituents are largely unknown and could be essential for understanding the addiction-related neurological effects of tobacco products. We describe the development and validation of a recombinant cell line expressing human α6/3β2β3V273S nAChR for screening and profiling assays in an automated patch clamp platform (IonWorks Barracuda). The cell line was pharmacologically characterized by subtype-selective and nonselective reference agonists, pore blockers, and competitive antagonists. Agonist and antagonist effects detected by the automated patch clamp approach were comparable to those obtained by conventional electrophysiological assays. A pilot screen of a library of Food and Drug Administration–approved drugs identified compounds, previously not known to modulate nAChRs, which selectively inhibited the α6/3β2β3V273S subtype. These assays provide new tools for screening and subtype-selective profiling of compounds that act at α6β2β3 nicotinic receptors. PMID:28298165

[Renin-angiotensin-aldosterone system (RAAS) and its pharmacologic modulation].

PubMed

Giestas, Anabela; Palma, Isabel; Ramos, Maria Helena

2010-01-01

The renin-angiotensin-aldosterone system (RAAS) is a neuroendocrine complex system that regulates the modulation of salt and water homeostasis, and regulation of blood pressure. Through its multiple interactions it protects the endothelium, heart, brain and kidney. In addition, the RAAS regulates the vascular response to injury and inflammation. Chronic activation/dysregulation of the RAAS leads to hypertension and perpetuates a cascade of proinflammatory, prothrombotic and atherogenic effects associated with endorgan damage (heart, brain, kidney, endothelium). Consequently, the RAAS is an important therapeutic target in these situations. This article presents an overview of physiology, pathophysiology and pharmacologic modulation of the RAAS.

Emphasis of spatial cues in the temporal fine structure during the rising segments of amplitude-modulated sounds

PubMed Central

Dietz, Mathias; Marquardt, Torsten; Salminen, Nelli H.; McAlpine, David

2013-01-01

The ability to locate the direction of a target sound in a background of competing sources is critical to the survival of many species and important for human communication. Nevertheless, brain mechanisms that provide for such accurate localization abilities remain poorly understood. In particular, it remains unclear how the auditory brain is able to extract reliable spatial information directly from the source when competing sounds and reflections dominate all but the earliest moments of the sound wave reaching each ear. We developed a stimulus mimicking the mutual relationship of sound amplitude and binaural cues, characteristic to reverberant speech. This stimulus, named amplitude modulated binaural beat, allows for a parametric and isolated change of modulation frequency and phase relations. Employing magnetoencephalography and psychoacoustics it is demonstrated that the auditory brain uses binaural information in the stimulus fine structure only during the rising portion of each modulation cycle, rendering spatial information recoverable in an otherwise unlocalizable sound. The data suggest that amplitude modulation provides a means of “glimpsing” low-frequency spatial cues in a manner that benefits listening in noisy or reverberant environments. PMID:23980161

Globally conditioned Granger causality in brain–brain and brain–heart interactions: a combined heart rate variability/ultra-high-field (7 T) functional magnetic resonance imaging study

PubMed Central

Passamonti, Luca; Wald, Lawrence L.; Barbieri, Riccardo

2016-01-01

The causal, directed interactions between brain regions at rest (brain–brain networks) and between resting-state brain activity and autonomic nervous system (ANS) outflow (brain–heart links) have not been completely elucidated. We collected 7 T resting-state functional magnetic resonance imaging (fMRI) data with simultaneous respiration and heartbeat recordings in nine healthy volunteers to investigate (i) the causal interactions between cortical and subcortical brain regions at rest and (ii) the causal interactions between resting-state brain activity and the ANS as quantified through a probabilistic, point-process-based heartbeat model which generates dynamical estimates for sympathetic and parasympathetic activity as well as sympathovagal balance. Given the high amount of information shared between brain-derived signals, we compared the results of traditional bivariate Granger causality (GC) with a globally conditioned approach which evaluated the additional influence of each brain region on the causal target while factoring out effects concomitantly mediated by other brain regions. The bivariate approach resulted in a large number of possibly spurious causal brain–brain links, while, using the globally conditioned approach, we demonstrated the existence of significant selective causal links between cortical/subcortical brain regions and sympathetic and parasympathetic modulation as well as sympathovagal balance. In particular, we demonstrated a causal role of the amygdala, hypothalamus, brainstem and, among others, medial, middle and superior frontal gyri, superior temporal pole, paracentral lobule and cerebellar regions in modulating the so-called central autonomic network (CAN). In summary, we show that, provided proper conditioning is employed to eliminate spurious causalities, ultra-high-field functional imaging coupled with physiological signal acquisition and GC analysis is able to quantify directed brain–brain and brain–heart interactions reflecting central modulation of ANS outflow. PMID:27044985

Individual differences in the dominance of interhemispheric connections predict cognitive ability beyond sex and brain size.

PubMed

Martínez, Kenia; Janssen, Joost; Pineda-Pardo, José Ángel; Carmona, Susanna; Román, Francisco Javier; Alemán-Gómez, Yasser; Garcia-Garcia, David; Escorial, Sergio; Quiroga, María Ángeles; Santarnecchi, Emiliano; Navas-Sánchez, Francisco Javier; Desco, Manuel; Arango, Celso; Colom, Roberto

2017-07-15

Global structural brain connectivity has been reported to be sex-dependent with women having increased interhemispheric connectivity (InterHc) and men having greater intrahemispheric connectivity (IntraHc). However, (a) smaller brains show greater InterHc, (b) larger brains show greater IntraHc, and (c) women have, on average, smaller brains than men. Therefore, sex differences in brain size may modulate sex differences in global brain connectivity. At the behavioural level, sex-dependent differences in connectivity are thought to contribute to men-women differences in spatial and verbal abilities. But this has never been tested at the individual level. The current study assessed whether individual differences in global structural connectome measures (InterHc, IntraHc and the ratio of InterHc relative to IntraHc) predict spatial and verbal ability while accounting for the effect of sex and brain size. The sample included forty men and forty women, who did neither differ in age nor in verbal and spatial latent components defined by a broad battery of tests and tasks. High-resolution T 1 -weighted and diffusion-weighted images were obtained for computing brain size and reconstructing the structural connectome. Results showed that men had higher IntraHc than women, while women had an increased ratio InterHc/IntraHc. However, these sex differences were modulated by brain size. Increased InterHc relative to IntraHc predicted higher spatial and verbal ability irrespective of sex and brain size. The positive correlations between the ratio InterHc/IntraHc and the spatial and verbal abilities were confirmed in 1000 random samples generated by bootstrapping. Therefore, sex differences in global structural connectome connectivity were modulated by brain size and did not underlie sex differences in verbal and spatial abilities. Rather, the level of dominance of InterHc over IntraHc may be associated with individual differences in verbal and spatial abilities in both men and women. Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical Composition and Antimigraine Activity of Essential Oil of Angelicae dahuricae Radix.

PubMed

Sun, Jingbo; Li, He; Sun, Jinghui; Liu, Huimin; Chen, Jianguang; Wang, Chunmei

2017-08-01

The aim of this study was to explore the chemical composition and the effect of essential oil of Angelicae dahuricae radix on a nitroglycerin (NTG)-induced rat model of migraine. The CO 2 supercritical fluid extraction method was optimized for the extraction of essential oil of A. dahuricae radix (EOAD) and its chemical composition was determined. The migraine model was established by subcutaneous injection of NTG (10 mg/kg) 1 h after the last administration of EOAD. The therapeutic effect of EOAD and its underlying mechanism were assessed by monitoring behavioral changes, levels of nitric oxide (NO) in serum and brain tissues, plasma levels of calcitonin gene-related peptide (CGRP) and endothelin (ET), and ET/NO ratio. The optimal conditions for CO 2 supercritical fluid extraction of EOAD, as determined by orthogonal test [L 9 (3 4 )], were as follows: 2 h extraction time, 20 MPa pressure, 40°C temperature, and 30 mesh. The yield of EOAD was 1.8%. On gas chromatography-mass spectrometry, 45 peaks were found in EOAD, and 22 compounds were identified and quantified. The main constituents of EOAD were 1-dodecanol (13.71%), elemene (7.54%), palmitic acid ethyl ester (7.32%), α-pinene (6.25%), and 1-pentadecanol (6.08%). Compared with rat migraine model controls, EOAD (35, 70, and 140 mg/kg) significantly reduced the number of head shaking, head scratching, and hind leg shooting events, decreased serum and brain NO levels, decreased plasma CGRP, and increased ET levels in rats. ET/NO ratio was elevated to 28.68 in the EOAD high-dose group. EOAD ameliorates NTG-induced migraine in rats likely by modulating the levels of vasoactive substances.

Neurokernel: An Open Source Platform for Emulating the Fruit Fly Brain

PubMed Central

2016-01-01

We have developed an open software platform called Neurokernel for collaborative development of comprehensive models of the brain of the fruit fly Drosophila melanogaster and their execution and testing on multiple Graphics Processing Units (GPUs). Neurokernel provides a programming model that capitalizes upon the structural organization of the fly brain into a fixed number of functional modules to distinguish between these modules’ local information processing capabilities and the connectivity patterns that link them. By defining mandatory communication interfaces that specify how data is transmitted between models of each of these modules regardless of their internal design, Neurokernel explicitly enables multiple researchers to collaboratively model the fruit fly’s entire brain by integration of their independently developed models of its constituent processing units. We demonstrate the power of Neurokernel’s model integration by combining independently developed models of the retina and lamina neuropils in the fly’s visual system and by demonstrating their neuroinformation processing capability. We also illustrate Neurokernel’s ability to take advantage of direct GPU-to-GPU data transfers with benchmarks that demonstrate scaling of Neurokernel’s communication performance both over the number of interface ports exposed by an emulation’s constituent modules and the total number of modules comprised by an emulation. PMID:26751378

Insights from neuroenergetics into the interpretation of functional neuroimaging: an alternative empirical model for studying the brain's support of behavior

PubMed Central

Shulman, Robert G; Hyder, Fahmeed; Rothman, Douglas L

2014-01-01

Functional neuroimaging measures quantitative changes in neurophysiological parameters coupled to neuronal activity during observable behavior. These results have usually been interpreted by assuming that mental causation of behavior arises from the simultaneous actions of distinct psychological mechanisms or modules. However, reproducible localization of these modules in the brain using functional magnetic resonance imaging (MRI) and positron emission tomography (PET) imaging has been elusive other than for sensory systems. In this paper, we show that neuroenergetic studies using PET, calibrated functional magnetic resonance imaging (fMRI), 13C magnetic resonance spectroscopy, and electrical recordings do not support the standard approach, which identifies the location of mental modules from changes in brain activity. Of importance in reaching this conclusion is that changes in neuronal activities underlying the fMRI signal are many times smaller than the high ubiquitous, baseline neuronal activity, or energy in resting, awake humans. Furthermore, the incremental signal depends on the baseline activity contradicting theoretical assumptions about linearity and insertion of mental modules. To avoid these problems, while making use of these valuable results, we propose that neuroimaging should be used to identify observable brain activities that are necessary for a person's observable behavior rather than being used to seek hypothesized mental processes. PMID:25160670

Brain Opioids and Autism: An Updated Analysis of Possible Linkages.

ERIC Educational Resources Information Center

Sahley, Tony L.; Panksepp, Jaak

1987-01-01

The paper summarizes experimental evidence supporting a neurological theory which posits that autism, at least partially, represents a disruptive overactivation of hypersensitization of neurohormone systems in the brain, such as brain opioids. These substances modulate social-emotional processes. (Author/DB)

Motor imagery learning modulates functional connectivity of multiple brain systems in resting state.

PubMed

Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

2014-01-01

Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning.

Oxytocin influences processing of socially relevant cues in the ventral tegmental area of the human brain.

PubMed

Groppe, Sarah E; Gossen, Anna; Rademacher, Lena; Hahn, Alexa; Westphal, Luzie; Gründer, Gerhard; Spreckelmeyer, Katja N

2013-08-01

Evidence accumulates that the neuropeptide oxytocin plays an important role in mediating social interaction among humans and that a dysfunction in oxytocin-modulated brain mechanisms might lie at the core of disturbed social behavior in neuropsychiatric disease. Explanatory models suggest that oxytocin guides social approach and avoidance by modulating the perceived salience of socially meaningful cues. Animal data point toward the ventral tegmental area (VTA) as the brain site where this modulation takes place. We used functional magnetic resonance imaging and a social incentive delay task to test the hypothesis that oxytocin modulates the neural processing of socially relevant cues in the VTA, hereby facilitating behavioral response. Twenty-eight nulliparous women (not taking any hormones) received intranasal oxytocin or placebo in a double-blind randomized clinical trial with a parallel-group design. Oxytocin significantly enhanced VTA activation in response to cues signaling social reward (friendly face) or social punishment (angry face). Oxytocin effects on behavioral performance were modulated by individual differences in sociability with enhanced performance in women scoring low but decreased performance in women scoring high on self-reported measures of agreeableness. Our data provide evidence that the VTA is the human brain site where oxytocin attaches salience to socially relevant cues. This mechanism might play an important role in triggering motivation to react at the prospect of social reward or punishment. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

Liang, Xiaodong, E-mail: lxdctopone@sina.com; Ni, Lingqin; Hu, Wei

The objective of this study was to evaluate the dose conformity and feasibility of whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in patients with 1 to 3 brain metastases. Forward intensity-modulated radiation therapy plans were generated for 10 patients with 1 to 3 brain metastases on Pinnacle 6.2 Treatment Planning System. The prescribed dose was 30 Gy to the whole brain (planning target volume [PTV]{sub wbrt}) and 40 Gy to individual brain metastases (PTV{sub boost}) simultaneously, and both doses were given in 10 fractions. The maximum diameters of individual brain metastases ranged from 1.6 tomore » 6 cm, and the summated PTVs per patient ranged from 1.62 to 69.81 cm{sup 3}. Conformity and feasibility were evaluated regarding conformation number and treatment delivery time. One hundred percent volume of the PTV{sub boost} received at least 95% of the prescribed dose in all cases. The maximum doses were less than 110% of the prescribed dose to the PTV{sub boost}, and all of the hot spots were within the PTV{sub boost}. The volume of the PTV{sub wbrt} that received at least 95% of the prescribed dose ranged from 99.2% to 100%. The mean values of conformation number were 0.682. The mean treatment delivery time was 2.79 minutes. Ten beams were used on an average in these plans. Whole-brain radiotherapy with a simultaneous integrated boost by forward intensity-modulated radiation therapy in 1 to 3 brain metastases is feasible, and treatment delivery time is short.« less

A gut feeling: Microbiome-brain-immune interactions modulate social and affective behaviors.

PubMed

Sylvia, Kristyn E; Demas, Gregory E

2018-03-01

The expression of a wide range of social and affective behaviors, including aggression and investigation, as well as anxiety- and depressive-like behaviors, involves interactions among many different physiological systems, including the neuroendocrine and immune systems. Recent work suggests that the gut microbiome may also play a critical role in modulating behavior and likely functions as an important integrator across physiological systems. Microbes within the gut may communicate with the brain via both neural and humoral pathways, providing numerous avenues of research in the area of the gut-brain axis. We are now just beginning to understand the intricate relationships among the brain, microbiome, and immune system and how they work in concert to influence behavior. The effects of different forms of experience (e.g., changes in diet, immune challenge, and psychological stress) on the brain, gut microbiome, and the immune system have often been studied independently. Though because these systems do not work in isolation, it is essential to shift our focus to the connections among them as we move forward in our investigations of the gut-brain axis, the shaping of behavioral phenotypes, and the possible clinical implications of these interactions. This review summarizes the recent progress the field has made in understanding the important role the gut microbiome plays in the modulation of social and affective behaviors, as well as some of the intricate mechanisms by which the microbiome may be communicating with the brain and immune system. Copyright © 2018 Elsevier Inc. All rights reserved.

Python Executable Script for Estimating Two Effective Parameters to Individualize Brain-Computer Interfaces: Individual Alpha Frequency and Neurophysiological Predictor.

PubMed

Alonso-Valerdi, Luz María

2016-01-01

A brain-computer interface (BCI) aims to establish communication between the human brain and a computing system so as to enable the interaction between an individual and his environment without using the brain output pathways. Individuals control a BCI system by modulating their brain signals through mental tasks (e.g., motor imagery or mental calculation) or sensory stimulation (e.g., auditory, visual, or tactile). As users modulate their brain signals at different frequencies and at different levels, the appropriate characterization of those signals is necessary. The modulation of brain signals through mental tasks is furthermore a skill that requires training. Unfortunately, not all the users acquire such skill. A practical solution to this problem is to assess the user probability of controlling a BCI system. Another possible solution is to set the bandwidth of the brain oscillations, which is highly sensitive to the users' age, sex and anatomy. With this in mind, NeuroIndex, a Python executable script, estimates a neurophysiological prediction index and the individual alpha frequency (IAF) of the user in question. These two parameters are useful to characterize the user EEG signals, and decide how to go through the complex process of adapting the human brain and the computing system on the basis of previously proposed methods. NeuroIndeX is not only the implementation of those methods, but it also complements the methods each other and provides an alternative way to obtain the prediction parameter. However, an important limitation of this application is its dependency on the IAF value, and some results should be interpreted with caution. The script along with some electroencephalographic datasets are available on a GitHub repository in order to corroborate the functionality and usability of this application.

Python Executable Script for Estimating Two Effective Parameters to Individualize Brain-Computer Interfaces: Individual Alpha Frequency and Neurophysiological Predictor

PubMed Central

Alonso-Valerdi, Luz María

2016-01-01

A brain-computer interface (BCI) aims to establish communication between the human brain and a computing system so as to enable the interaction between an individual and his environment without using the brain output pathways. Individuals control a BCI system by modulating their brain signals through mental tasks (e.g., motor imagery or mental calculation) or sensory stimulation (e.g., auditory, visual, or tactile). As users modulate their brain signals at different frequencies and at different levels, the appropriate characterization of those signals is necessary. The modulation of brain signals through mental tasks is furthermore a skill that requires training. Unfortunately, not all the users acquire such skill. A practical solution to this problem is to assess the user probability of controlling a BCI system. Another possible solution is to set the bandwidth of the brain oscillations, which is highly sensitive to the users' age, sex and anatomy. With this in mind, NeuroIndex, a Python executable script, estimates a neurophysiological prediction index and the individual alpha frequency (IAF) of the user in question. These two parameters are useful to characterize the user EEG signals, and decide how to go through the complex process of adapting the human brain and the computing system on the basis of previously proposed methods. NeuroIndeX is not only the implementation of those methods, but it also complements the methods each other and provides an alternative way to obtain the prediction parameter. However, an important limitation of this application is its dependency on the IAF value, and some results should be interpreted with caution. The script along with some electroencephalographic datasets are available on a GitHub repository in order to corroborate the functionality and usability of this application. PMID:27445783

Quantitative representations of an exaggerated anxiety response in the brain of female spider phobics-a parametric fMRI study.

PubMed

Zilverstand, Anna; Sorger, Bettina; Kaemingk, Anita; Goebel, Rainer

2017-06-01

We employed a novel parametric spider picture set in the context of a parametric fMRI anxiety provocation study, designed to tease apart brain regions involved in threat monitoring from regions representing an exaggerated anxiety response in spider phobics. For the stimulus set, we systematically manipulated perceived proximity of threat by varying a depicted spider's context, size, and posture. All stimuli were validated in a behavioral rating study (phobics n = 20; controls n = 20; all female). An independent group participated in a subsequent fMRI anxiety provocation study (phobics n = 7; controls n = 7; all female), in which we compared a whole-brain categorical to a whole-brain parametric analysis. Results demonstrated that the parametric analysis provided a richer characterization of the functional role of the involved brain networks. In three brain regions-the mid insula, the dorsal anterior cingulate, and the ventrolateral prefrontal cortex-activation was linearly modulated by perceived proximity specifically in the spider phobia group, indicating a quantitative representation of an exaggerated anxiety response. In other regions (e.g., the amygdala), activation was linearly modulated in both groups, suggesting a functional role in threat monitoring. Prefrontal regions, such as dorsolateral prefrontal cortex, were activated during anxiety provocation but did not show a stimulus-dependent linear modulation in either group. The results confirm that brain regions involved in anxiety processing hold a quantitative representation of a pathological anxiety response and more generally suggest that parametric fMRI designs may be a very powerful tool for clinical research in the future, particularly when developing novel brain-based interventions (e.g., neurofeedback training). Hum Brain Mapp 38:3025-3038, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

State-dependencies of learning across brain scales

PubMed Central

Ritter, Petra; Born, Jan; Brecht, Michael; Dinse, Hubert R.; Heinemann, Uwe; Pleger, Burkhard; Schmitz, Dietmar; Schreiber, Susanne; Villringer, Arno; Kempter, Richard

2015-01-01

Learning is a complex brain function operating on different time scales, from milliseconds to years, which induces enduring changes in brain dynamics. The brain also undergoes continuous “spontaneous” shifts in states, which, amongst others, are characterized by rhythmic activity of various frequencies. Besides the most obvious distinct modes of waking and sleep, wake-associated brain states comprise modulations of vigilance and attention. Recent findings show that certain brain states, particularly during sleep, are essential for learning and memory consolidation. Oscillatory activity plays a crucial role on several spatial scales, for example in plasticity at a synaptic level or in communication across brain areas. However, the underlying mechanisms and computational rules linking brain states and rhythms to learning, though relevant for our understanding of brain function and therapeutic approaches in brain disease, have not yet been elucidated. Here we review known mechanisms of how brain states mediate and modulate learning by their characteristic rhythmic signatures. To understand the critical interplay between brain states, brain rhythms, and learning processes, a wide range of experimental and theoretical work in animal models and human subjects from the single synapse to the large-scale cortical level needs to be integrated. By discussing results from experiments and theoretical approaches, we illuminate new avenues for utilizing neuronal learning mechanisms in developing tools and therapies, e.g., for stroke patients and to devise memory enhancement strategies for the elderly. PMID:25767445

Interpreter composition issues in the formal verification of a processor-memory module

NASA Technical Reports Server (NTRS)

Fura, David A.; Cohen, Gerald C.

1994-01-01

This report describes interpreter composition techniques suitable for the formal specification and verification of a processor-memory module using the HOL theorem proving system. The processor-memory module is a multichip subsystem within a fault-tolerant embedded system under development within the Boeing Defense and Space Group. Modeling and verification methods were developed that permit provably secure composition at the transaction-level of specification, significantly reducing the complexity of the hierarchical verification of the system.

A diet enriched with Mugil cephalus processed roes modulates the tissue lipid profile in healthy rats: a biochemical and chemometric assessment.

PubMed

Rosa, A; Atzeri, A; Putzu, D; Scano, P

2016-01-01

The effect of a diet enriched with mullet bottarga on the lipid profile (total lipids, total cholesterol, unsaturated fatty acids, α-tocopherol, and hydroperoxides) of plasma, liver, kidney, brain, and perirenal adipose tissues of healthy rats was investigated. Rats fed a 10% bottarga enriched-diet for 5 days showed body weights and tissue total lipid and cholesterol levels similar to those of animals fed control diet. Univariate and multivariate results showed that bottarga enriched-diet modified the fatty acid profile in all tissues, except brain. Significant increases of n-3 PUFA, particularly EPA, were observed together with a 20:4 n-6 decrease in plasma, liver, and kidney. Perirenal adipose tissue showed a fat accumulation that reflected the diet composition. The overall data suggest that mullet bottarga may be considered as a natural bioavailable source of n-3 PUFA and qualify it as a traditional food product with functional properties and a potential functional ingredient for preparation of n-3 PUFA enriched foods.

Variable Bandwidth Filtering for Improved Sensitivity of Cross-Frequency Coupling Metrics

PubMed Central

McDaniel, Jonathan; Liu, Song; Cornew, Lauren; Gaetz, William; Roberts, Timothy P.L.; Edgar, J. Christopher

2012-01-01

Abstract There is an increasing interest in examining cross-frequency coupling (CFC) between groups of oscillating neurons. Most CFC studies examine how the phase of lower-frequency brain activity modulates the amplitude of higher-frequency brain activity. This study focuses on the signal filtering that is required to isolate the higher-frequency neuronal activity which is hypothesized to be amplitude modulated. In particular, previous publications have used a filter bandwidth fixed to a constant for all assessed modulation frequencies. The present article demonstrates that fixed bandwidth filtering can destroy amplitude modulation and create false-negative CFC measures. To overcome this limitation, this study presents a variable bandwidth filter that ensures preservation of the amplitude modulation. Simulated time series data were created with theta-gamma, alpha-gamma, and beta-gamma phase-amplitude coupling. Comparisons between filtering methods indicate that the variable bandwidth approach presented in this article is preferred when examining amplitude modulations above the theta band. The variable bandwidth method of filtering an amplitude modulated signal is proposed to preserve amplitude modulation and enable accurate CFC measurements. PMID:22577870

Sex-specific effects of docosahexaenoic acid (DHA) on the microbiome and behavior of socially-isolated mice.

PubMed

Davis, Daniel J; Hecht, Patrick M; Jasarevic, Eldin; Beversdorf, David Q; Will, Matthew J; Fritsche, Kevin; Gillespie, Catherine H

2017-01-01

Dietary supplementation with the long-chain omega-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) has been shown to have a beneficial effect on reducing the symptoms associated with several neuropsychiatric conditions including anxiety and depression. However, the mechanisms underlying this effect remain largely unknown. Increasing evidence suggests that the vast repertoire of commensal bacteria within the gut plays a critical role in regulating various biological processes in the brain and may contribute to neuropsychiatric disease risk. The present study determined the contribution of DHA on anxiety and depressive-like behaviors through modulation of the gut microbiota in a paradigm of social isolation. Adult male and female mice were subjected to social isolation for 28days and then placed either on a control diet or a diet supplemented with 0.1% or 1.0% DHA. Fecal pellets were collected both 24h and 7days following the introduction of the new diets. Behavioral testing revealed that male mice fed a DHA diet, regardless of dose, exhibited reduced anxiety and depressive-like behaviors compared to control fed mice while no differences were observed in female mice. As the microbiota-brain-axis has been recently implicated in behavior, composition of microbial communities were analyzed to examine if these sex-specific effects of DHA may be associated with changes in the gut microbiota (GM). Clear sex differences were observed with males and females showing distinct microbial compositions prior to DHA supplementation. The introduction of DHA into the diet also induced sex-specific interactions on the GM with the fatty acid producing a significant effect on the microbial profiles in males but not in females. Interestingly, levels of Allobaculum and Ruminococcus were found to significantly correlate with the behavioral changes observed in the male mice. Predictive metagenome analysis using PICRUSt was performed on the fecal samples collected from males and identified enrichment in functional KEGG pathway terms relevant to processes such as the biosynthesis of unsaturated fatty acids and antioxidant metabolism. These results indicate that DHA alters commensal community composition and produces beneficial effects on anxiety and depressive-like behaviors in a sex-specific manner. The present study provides insight into the mechanistic role that gut microbes may play in the regulation of anxiety and depressive-like behaviors and how dietary intervention can modulate these effects. Copyright © 2016 Elsevier Inc. All rights reserved.

The Conundrum of Functional Brain Networks: Small-World Efficiency or Fractal Modularity

PubMed Central

Gallos, Lazaros K.; Sigman, Mariano; Makse, Hernán A.

2012-01-01

The human brain has been studied at multiple scales, from neurons, circuits, areas with well-defined anatomical and functional boundaries, to large-scale functional networks which mediate coherent cognition. In a recent work, we addressed the problem of the hierarchical organization in the brain through network analysis. Our analysis identified functional brain modules of fractal structure that were inter-connected in a small-world topology. Here, we provide more details on the use of network science tools to elaborate on this behavior. We indicate the importance of using percolation theory to highlight the modular character of the functional brain network. These modules present a fractal, self-similar topology, identified through fractal network methods. When we lower the threshold of correlations to include weaker ties, the network as a whole assumes a small-world character. These weak ties are organized precisely as predicted by theory maximizing information transfer with minimal wiring costs. PMID:22586406

Physics of the Brain. Prevention of the Epileptic Seizures by the Multi-photon Pulsed-operated Fiber Lasers in the Ultraviolet Range of Frequencies.

NASA Astrophysics Data System (ADS)

Stefan, V. Alexander; IAPS Team

The novel study of the epileptogenesis mechanisms is proposed. It is based on the pulsed-operated (amplitude modulation) multi-photon (frequency modulation) fiber-laser interaction with the brain epilepsy-topion (the epilepsy onset area), so as to prevent the excessive electrical discharge (epileptic seizure) in the brain. The repetition frequency, Ω, matches the low frequency (epileptic) phonon waves in the brain. The laser repetition frequency (5-100 pulses per second) enables the resonance-scanning of the wide range of the phonon (possible epileptic-to-be) activity in the brain. The tunable fiber laser frequencies, Δω (multi photon operation), are in the ultraviolet frequency range, thus enabling monitoring of the electrical charge imbalance (within the 10s of milliseconds), and the DNA-corruption in the epilepsy-topion, as the possible cause of the disease. Supported by Nikola Tesla Labs., Stefan University.

Dissociable effects of local inhibitory and excitatory theta-burst stimulation on large-scale brain dynamics

PubMed Central

Sale, Martin V.; Lord, Anton; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B.

2015-01-01

Normal brain function depends on a dynamic balance between local specialization and large-scale integration. It remains unclear, however, how local changes in functionally specialized areas can influence integrated activity across larger brain networks. By combining transcranial magnetic stimulation with resting-state functional magnetic resonance imaging, we tested for changes in large-scale integration following the application of excitatory or inhibitory stimulation on the human motor cortex. After local inhibitory stimulation, regions encompassing the sensorimotor module concurrently increased their internal integration and decreased their communication with other modules of the brain. There were no such changes in modular dynamics following excitatory stimulation of the same area of motor cortex nor were there changes in the configuration and interactions between core brain hubs after excitatory or inhibitory stimulation of the same area. These results suggest the existence of selective mechanisms that integrate local changes in neural activity, while preserving ongoing communication between brain hubs. PMID:25717162

Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

PubMed

Persinger, Michael A

2009-01-01

To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

Gut microbiota alterations and dietary modulation in childhood malnutrition - The role of short chain fatty acids.

PubMed

Pekmez, Ceyda Tugba; Dragsted, Lars Ove; Brahe, Lena Kirchner

2018-02-17

The gut microbiome affects the health status of the host through different mechanisms and is associated with a wide variety of diseases. Both childhood undernutrition and obesity are linked to alterations in composition and functionality of the gut microbiome. One of the possible mechanisms underlying the interplay between microbiota and host metabolism is through appetite-regulating hormones (including leptin, ghrelin, glucagon-like peptide-1). Short chain fatty acids, the end product of bacterial fermentation of non-digestible carbohydrates, might be able to alter energy harvest and metabolism through enteroendocrine cell signaling, adipogenesis and insulin-like growth factor-1 production. Elucidating these mechanisms may lead to development of new modulation practices of the gut microbiota as a potential prevention and treatment strategy for childhood malnutrition. The present overview will briefly outline the gut microbiota development in the early life, gut microbiota alterations in childhood undernutrition and obesity, and whether this relationship is causal. Further we will discuss possible underlying mechanisms in relation to the gut-brain axis and short chain fatty acids, and the potential of probiotics, prebiotics and synbiotics for modulating the gut microbiota during childhood as a prevention and treatment strategy against undernutrition and obesity. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Fast and precise thermoregulation system in physiological brain slice experiment

NASA Astrophysics Data System (ADS)

Sheu, Y. H.; Young, M. S.

1995-12-01

We have developed a fast and precise thermoregulation system incorporated within a physiological experiment on a brain slice. The thermoregulation system is used to control the temperature of a recording chamber in which the brain slice is placed. It consists of a single-chip microcomputer, a set command module, a display module, and an FLC module. A fuzzy control algorithm was developed and a fuzzy logic controller then designed for achieving fast, smooth thermostatic performance and providing precise temperature control with accuracy to 0.1 °C, from room temperature through 42 °C (experimental temperature range). The fuzzy logic controller is implemented by microcomputer software and related peripheral hardware circuits. Six operating modes of thermoregulation are offered with the system and this can be further extended according to experimental needs. The test results of this study demonstrate that the fuzzy control method is easily implemented by a microcomputer and also verifies that this method provides a simple way to achieve fast and precise high-performance control of a nonlinear thermoregulation system in a physiological brain slice experiment.

Modulation of brain glutamate dehydrogenase as a tool for controlling seizures.

PubMed

Rasgado, Lourdes A Vega; Reyes, Guillermo Ceballos; Díaz, Fernando Vega

2015-12-01

Glutamate (Glu) is a major excitatory neurotransmitter involved in epilepsy. Glu is synthesized by glutamate dehydrogenase (GDH, E.C. 1.4.1.3) and dysfunction of the enzymatic activity of GDH is associated with brain pathologies. The main goal of this work is to establish the role of GDH in the effects of antiepileptic drugs (AEDs) such as valproate (VALP), diazepam (DIAZ) and diphenylhydantoin (DPH) and its repercussions on oxygen consumption. Oxidative deamination of Glu and reductive amination of αketoglutarate (αK) in mice brain were investigated. Our results show that AEDs decrease GDH activity and oxygen consumption in vitro. In ex vivo experiments, AEDs increased GDH activity but decreased oxygen consumption during Glu oxidative deamination. VALP and DPH reversed the increase in reductive amination of αK caused by the chemoconvulsant pentylenetetrazol. These results suggest that AEDs act by modulating brain GDH activity, which in turn decreased oxygen consumption. GDH represents an important regulation point of neuronal excitability, and modulation of its activity represents a potential target for metabolic treatment of epilepsy and for the development of new AEDs.

Effective connectivity of ascending and descending frontalthalamic pathways during sustained attention: Complex brain network interactions in adolescence.

PubMed

Jagtap, Pranav; Diwadkar, Vaibhav A

2016-07-01

Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals [dynamic causal modeling (DCM)] to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian model selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: while positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. Hum Brain Mapp 37:2557-2570, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Influence of White and Gray Matter Connections on Endogenous Human Cortical Oscillations

PubMed Central

Hawasli, Ammar H.; Kim, DoHyun; Ledbetter, Noah M.; Dahiya, Sonika; Barbour, Dennis L.; Leuthardt, Eric C.

2016-01-01

Brain oscillations reflect changes in electrical potentials summated across neuronal populations. Low- and high-frequency rhythms have different modulation patterns. Slower rhythms are spatially broad, while faster rhythms are more local. From this observation, we hypothesized that low- and high-frequency oscillations reflect white- and gray-matter communications, respectively, and synchronization between low-frequency phase with high-frequency amplitude represents a mechanism enabling distributed brain-networks to coordinate local processing. Testing this common understanding, we selectively disrupted white or gray matter connections to human cortex while recording surface field potentials. Counter to our original hypotheses, we found that cortex consists of independent oscillatory-units (IOUs) that maintain their own complex endogenous rhythm structure. IOUs are differentially modulated by white and gray matter connections. White-matter connections maintain topographical anatomic heterogeneity (i.e., separable processing in cortical space) and gray-matter connections segregate cortical synchronization patterns (i.e., separable temporal processing through phase-power coupling). Modulation of distinct oscillatory modules enables the functional diversity necessary for complex processing in the human brain. PMID:27445767

To cut or not to cut? Assessing the modular structure of brain networks.

PubMed

Chang, Yu-Teng; Pantazis, Dimitrios; Leahy, Richard M

2014-05-01

A wealth of methods has been developed to identify natural divisions of brain networks into groups or modules, with one of the most prominent being modularity. Compared with the popularity of methods to detect community structure, only a few methods exist to statistically control for spurious modules, relying almost exclusively on resampling techniques. It is well known that even random networks can exhibit high modularity because of incidental concentration of edges, even though they have no underlying organizational structure. Consequently, interpretation of community structure is confounded by the lack of principled and computationally tractable approaches to statistically control for spurious modules. In this paper we show that the modularity of random networks follows a transformed version of the Tracy-Widom distribution, providing for the first time a link between module detection and random matrix theory. We compute parametric formulas for the distribution of modularity for random networks as a function of network size and edge variance, and show that we can efficiently control for false positives in brain and other real-world networks. Copyright © 2014 Elsevier Inc. All rights reserved.

Intra- and interbrain synchronization and network properties when playing guitar in duets

PubMed Central

Sänger, Johanna; Müller, Viktor; Lindenberger, Ulman

2012-01-01

To further test and explore the hypothesis that synchronous oscillatory brain activity supports interpersonally coordinated behavior during dyadic music performance, we simultaneously recorded the electroencephalogram (EEG) from the brains of each of 12 guitar duets repeatedly playing a modified Rondo in two voices by C.G. Scheidler. Indicators of phase locking and of within-brain and between-brain phase coherence were obtained from complex time-frequency signals based on the Gabor transform. Analyses were restricted to the delta (1–4 Hz) and theta (4–8 Hz) frequency bands. We found that phase locking as well as within-brain and between-brain phase-coherence connection strengths were enhanced at frontal and central electrodes during periods that put particularly high demands on musical coordination. Phase locking was modulated in relation to the experimentally assigned musical roles of leader and follower, corroborating the functional significance of synchronous oscillations in dyadic music performance. Graph theory analyses revealed within-brain and hyperbrain networks with small-worldness properties that were enhanced during musical coordination periods, and community structures encompassing electrodes from both brains (hyperbrain modules). We conclude that brain mechanisms indexed by phase locking, phase coherence, and structural properties of within-brain and hyperbrain networks support interpersonal action coordination (IAC). PMID:23226120

Peripheral DNA methylation, cognitive decline and brain aging: pilot findings from the Whitehall II imaging study.

PubMed

Chouliaras, Leonidas; Pishva, Ehsan; Haapakoski, Rita; Zsoldos, Eniko; Mahmood, Abda; Filippini, Nicola; Burrage, Joe; Mill, Jonathan; Kivimäki, Mika; Lunnon, Katie; Ebmeier, Klaus P

2018-05-01

The present study investigated the link between peripheral DNA methylation (DNAm), cognitive impairment and brain aging. We tested the association between blood genome-wide DNAm profiles using the Illumina 450K arrays, cognitive dysfunction and brain MRI measures in selected participants of the Whitehall II imaging sub-study. Eight differentially methylated regions were associated with cognitive impairment. Accelerated aging based on the Hannum epigenetic clock was associated with mean diffusivity and global fractional anisotropy. We also identified modules of co-methylated loci associated with white matter hyperintensities. These co-methylation modules were enriched among pathways relevant to β-amyloid processing and glutamatergic signaling. Our data support the notion that blood DNAm changes may have utility as a biomarker for cognitive dysfunction and brain aging.

Cognitive reserve and TMEM106B genotype modulate brain damage in presymptomatic frontotemporal dementia: a GENFI study

PubMed Central

Premi, Enrico; Grassi, Mario; van Swieten, John; Galimberti, Daniela; Graff, Caroline; Masellis, Mario; Tartaglia, Carmela; Tagliavini, Fabrizio; Rowe, James B.; Laforce Jr, Robert; Finger, Elizabeth; Frisoni, Giovanni B.; de Mendonça, Alexandre; Sorbi, Sandro; Gazzina, Stefano; Cosseddu, Maura; Archetti, Silvana; Gasparotti, Roberto; Manes, Marta; Alberici, Antonella; Cardoso, Manuel J.; Bocchetta, Martina; Cash, David M.; Ourselin, Sebastian; Padovani, Alessandro; Rohrer, Jonathan D.

2017-01-01

Abstract Frontotemporal dementia is a heterogeneous neurodegenerative disorder with around a third of cases having autosomal dominant inheritance. There is wide variability in phenotype even within affected families, raising questions about the determinants of the progression of disease and age at onset. It has been recently demonstrated that cognitive reserve, as measured by years of formal schooling, can counteract the ongoing pathological process. The TMEM106B genotype has also been found to be a modifier of the age at disease onset in frontotemporal dementia patients with TDP-43 pathology. This study therefore aimed to elucidate the modulating effect of environment (i.e. cognitive reserve as measured by educational attainment) and genetic background (i.e. TMEM106B polymorphism, rs1990622 T/C) on grey matter volume in a large cohort of presymptomatic subjects bearing frontotemporal dementia-related pathogenic mutations. Two hundred and thirty-one participants from the GENFI study were included: 108 presymptomatic MAPT, GRN, and C9orf72 mutation carriers and 123 non-carriers. For each subject, cortical and subcortical grey matter volumes were generated using a parcellation of the volumetric T1-weighted magnetic resonance imaging brain scan. TMEM106B genotyping was carried out, and years of education recorded. First, we obtained a composite measure of grey matter volume by graph-Laplacian principal component analysis, and then fitted a linear mixed-effect interaction model, considering the role of (i) genetic status; (ii) educational attainment; and (iii) TMEM106B genotype on grey matter volume. The presence of a mutation was associated with a lower grey matter volume (P = 0.002), even in presymptomatic subjects. Education directly affected grey matter volume in all the samples (P = 0.02) with lower education attainment being associated with lower volumes. TMEM106B genotype did not influence grey matter volume directly on its own but in mutation carriers it modulated the slope of the correlation between education and grey matter volume (P = 0.007). Together, these results indicate that brain atrophy in presymptomatic carriers of common frontotemporal dementia mutations is affected by both genetic and environmental factors such that TMEM106B enhances the benefit of cognitive reserve on brain structure. These findings should be considered in evaluating outcomes in future disease-modifying trials, and support the search for protective mechanisms in people at risk of dementia that might facilitate new therapeutic strategies. PMID:28460069

Peripheral Tumor Necrosis Factor-Alpha (TNF-α) Modulates Amyloid Pathology by Regulating Blood-Derived Immune Cells and Glial Response in the Brain of AD/TNF Transgenic Mice.

PubMed

Paouri, Evi; Tzara, Ourania; Kartalou, Georgia-Ioanna; Zenelak, Sofia; Georgopoulos, Spiros

2017-05-17

Increasing evidence has suggested that systemic inflammation along with local brain inflammation can play a significant role in Alzheimer's disease (AD) pathogenesis. Identifying key molecules that regulate the crosstalk between the immune and the CNS can provide potential therapeutic targets. TNF-α is a proinflammatory cytokine implicated in the pathogenesis of systemic inflammatory and neurodegenerative diseases, such as rheumatoid arthritis (RA) and AD. Recent studies have reported that anti-TNF-α therapy or RA itself can modulate AD pathology, although the underlying mechanism is unclear. To investigate the role of peripheral TNF-α as a mediator of RA in the pathogenesis of AD, we generated double-transgenic 5XFAD/Tg197 AD/TNF mice that develop amyloid deposits and inflammatory arthritis induced by human TNF-α (huTNF-α) expression. We found that 5XFAD/Tg197 mice display decreased amyloid deposition, compromised neuronal integrity, and robust brain inflammation characterized by extensive gliosis and elevated blood-derived immune cell populations, including phagocytic macrophages and microglia. To evaluate the contribution of peripheral huTNF-α in the observed brain phenotype, we treated 5XFAD/Tg197 mice systemically with infliximab, an anti-huTNF-α antibody that does not penetrate the blood-brain barrier and prevents arthritis. Peripheral inhibition of huTNF-α increases amyloid deposition, rescues neuronal impairment, and suppresses gliosis and recruitment of blood-derived immune cells, without affecting brain huTNF-α levels. Our data report, for the first time, a distinctive role for peripheral TNF-α in the modulation of the amyloid phenotype in mice by regulating blood-derived and local brain inflammatory cell populations involved in β-amyloid clearance. SIGNIFICANCE STATEMENT Mounting evidence supports the active involvement of systemic inflammation, in addition to local brain inflammation, in Alzheimer's disease (AD) progression. TNF-α is a pluripotent cytokine that has been independently involved in the pathogenesis of systemic inflammatory rheumatoid arthritis (RA) and AD. Here we first demonstrate that manipulation of peripheral TNF-α in the context of arthritis modulates the amyloid phenotype by regulating immune cell trafficking in the mouse brain. Our study suggests that additionally to its local actions in the AD brain, TNF-α can also indirectly modulate amyloid pathology as a regulator of peripheral inflammation. Our findings may have significant implications in the treatment of RA patients with anti-TNF-α drugs and in the potential use of TNF-targeted therapies for AD. Copyright © 2017 the authors 0270-6474/17/375155-17$15.00/0.

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.

A Nested Phosphorus and Proton Coil Array for Brain Magnetic Resonance Imaging and Spectroscopy

PubMed Central

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2015-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7 Tesla. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4 cm nominal isotropic resolution in 15 min (2.3 cm actual resolution), while additionally enabling 1 mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer’s and Parkinson’s diseases, as well as mental disorders such as schizophrenia. PMID:26375209

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

A nested phosphorus and proton coil array for brain magnetic resonance imaging and spectroscopy.

PubMed

Brown, Ryan; Lakshmanan, Karthik; Madelin, Guillaume; Parasoglou, Prodromos

2016-01-01

A dual-nuclei radiofrequency coil array was constructed for phosphorus and proton magnetic resonance imaging and spectroscopy of the human brain at 7T. An eight-channel transceive degenerate birdcage phosphorus module was implemented to provide whole-brain coverage and significant sensitivity improvement over a standard dual-tuned loop coil. A nested eight-channel proton module provided adequate sensitivity for anatomical localization without substantially sacrificing performance on the phosphorus module. The developed array enabled phosphorus spectroscopy, a saturation transfer technique to calculate the global creatine kinase forward reaction rate, and single-metabolite whole-brain imaging with 1.4cm nominal isotropic resolution in 15min (2.3cm actual resolution), while additionally enabling 1mm isotropic proton imaging. This study demonstrates that a multi-channel array can be utilized for phosphorus and proton applications with improved coverage and/or sensitivity over traditional single-channel coils. The efficient multi-channel coil array, time-efficient pulse sequences, and the enhanced signal strength available at ultra-high fields can be combined to allow volumetric assessment of the brain and could provide new insights into the underlying energy metabolism impairment in several neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, as well as mental disorders such as schizophrenia. Copyright © 2015 Elsevier Inc. All rights reserved.

Identification of genetic loci that modulate cell proliferation in the adult rostral migratory stream using the expanded panel of BXD mice.

PubMed

Poon, Anna; Goldowitz, Daniel

2014-03-19

Adult neurogenesis, which is the continual production of new neurons in the mature brain, demonstrates the strikingly plastic nature of the nervous system. Adult neural stem cells and their neural precursors, collectively referred to as neural progenitor cells (NPCs), are present in the subgranular zone (SGZ) of the dentate gyrus, the subventricular zone (SVZ), and rostral migratory stream (RMS). In order to harness the potential of NPCs to treat neurodegenerative diseases and brain injuries, it will be important to understand the molecules that regulate NPCs in the adult brain. The genetic basis underlying NPC proliferation is still not fully understood. From our previous quantitative trait locus (QTL) analysis, we had success in using a relatively small reference population of recombinant inbred strains of mice (AXBXA) to identify a genetic region that is significantly correlated with NPC proliferation in the RMS. In this study, we expanded our initial QTL mapping of RMS proliferation to a far richer genetic resource, the BXD RI mouse strains. A 3-fold difference in the number of proliferative, bromodeoxyuridine (BrdU)-labeled cells was quantified in the adult RMS of 61 BXD RI strains. RMS cell proliferation is highly dependent on the genetic background of the mice with an estimated heritability of 0.58. Genome-wide mapping revealed a significant QTL on chromosome (Chr) 6 and a suggestive QTL on Chr 11 regulating the number of NPCs in the RMS. Composite interval analysis further revealed secondary QTLs on Chr 14 and Chr 18. The loci regulating RMS cell proliferation did not overlap with the suggestive loci modulating cell proliferation in the SGZ. These mapped loci serve as starting points to identify genes important for this process. A subset of candidate genes in this region is associated with cell proliferation and neurogenesis. Interconnectivity of these candidate genes was demonstrated using pathway and transcriptional covariance analyses. Differences in RMS cell proliferation across the BXD RI strains identifies genetic loci that serve to provide insights into the interplay of underlying genes that may be important for regulating NPC proliferation in the adult mouse brain.

Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury

DTIC Science & Technology

2012-11-01

DATES COVERED 4 October 2011- 3 October 2012 4. TITLE AND SUBTITLE Endocannabinoids as a Target for the Treatment of Traumatic Brain Injury 5a...interventions aimed at modulation of the endocannabinoid (EC) system targeting degradation of 20arachidonoyl glycerlol (2- AG) and N-arachidonoyl...percussion, traumatic brain injury, blood brain barrier, neuroinflammination, neurological dysfunction, endocannabinoids . 16. SECURITY CLASSIFICATION

Aquaporins: important but elusive drug targets

PubMed Central

Verkman, Alan S.; Anderson, Marc O.; Papadopoulos, Marios C.

2014-01-01

The aquaporins (AQPs) are a family of small, integral membrane proteins that facilitate water transport across the plasma membranes of cells in response to osmotic gradients. Data from knockout mice support the involvement of AQPs in epithelial fluid secretion, cell migration, brain oedema and adipocyte metabolism, which suggests that modulation of AQP function or expression could have therapeutic potential in oedema, cancer, obesity, brain injury, glaucoma and several other conditions. Moreover, loss-of-function mutations in human AQPs cause congenital cataracts (AQP0) and nephrogenic diabetes insipidus (AQP2), and autoantibodies against AQP4 cause the autoimmune demyelinating disease neuromyelitis optica. Although some potential AQP modulators have been identified, challenges associated with the development of better modulators include the druggability of the target and the suitability of the assay methods used to identify modulators. PMID:24625825

Experience modulates motor imagery-based brain activity.

PubMed

Kraeutner, Sarah N; McWhinney, Sean R; Solomon, Jack P; Dithurbide, Lori; Boe, Shaun G

2018-05-01

Whether or not brain activation during motor imagery (MI), the mental rehearsal of movement, is modulated by experience (i.e. skilled performance, achieved through long-term practice) remains unclear. Specifically, MI is generally associated with diffuse activation patterns that closely resemble novice physical performance, which may be attributable to a lack of experience with the task being imagined vs. being a distinguishing feature of MI. We sought to examine how experience modulates brain activity driven via MI, implementing a within- and between-group design to manipulate experience across tasks as well as expertise of the participants. Two groups of 'experts' (basketball/volleyball athletes) and 'novices' (recreational controls) underwent magnetoencephalography (MEG) while performing MI of four multi-articular tasks, selected to ensure that the degree of experience that participants had with each task varied. Source-level analysis was applied to MEG data and linear mixed effects modelling was conducted to examine task-related changes in activity. Within- and between-group comparisons were completed post hoc and difference maps were plotted. Brain activation patterns observed during MI of tasks for which participants had a low degree of experience were more widespread and bilateral (i.e. within-groups), with limited differences observed during MI of tasks for which participants had similar experience (i.e. between-groups). Thus, we show that brain activity during MI is modulated by experience; specifically, that novice performance is associated with the additional recruitment of regions across both hemispheres. Future investigations of the neural correlates of MI should consider prior experience when selecting the task to be performed. © 2018 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Modulation of critical brain dynamics using closed-loop neurofeedback stimulation.

PubMed

Zhigalov, Alexander; Kaplan, Alexander; Palva, J Matias

2016-08-01

EEG long-range temporal correlations (LRTCs) are a significant for both human cognition and brain disorders, but beyond suppression by sensory disruption, there are little means for influencing them non-invasively. We hypothesized that LRTCs could be controlled by engaging intrinsic neuroregulation through closed-loop neurofeedback stimulation. We used a closed-loop-stimulation paradigm where supra-threshold α-waves trigger visual flash stimuli while the subject performs the standard eyes-closed resting-state task. As a "sham" control condition, we applied similar stimulus sequences without the neurofeedback. Over three sessions, a significant difference in the LRTCs of α-band oscillations (U=89, p<0.028, Wilcoxon rank sum test) and their scalp topography (T=-2.92, p<0.010, T-test) emerged between the neurofeedback and sham conditions so that the LRTCs were stronger during neurofeedback than sham. No changes (F=0.16, p>0.69, ANOVA test) in the scalp topography of α-band power were observed in either condition. This study provides proof-of-concept for that EEG LRTCs, and hence critical brain dynamics, can be modulated with closed-loop stimulation in an automatic, involuntary fashion. We suggest that this modulation is mediated by an excitation-inhibition balance change achieved by the closed-loop neuroregulation. Automatic LRTC modulation opens novel avenues for both examining the functional roles of brain criticality in healthy subjects and for developing novel therapeutic approaches for brain disorders associated with abnormal LRTCs. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Modulation of taurine release by glutamate receptors and nitric oxide.

PubMed

Oja, S S; Saransaari, P

2000-11-01

Taurine is held to function as a modulator and osmoregulator in the central nervous system, being of particular importance in the immature brain. In view of the possible involvement of excitatory pathways in the regulation of taurine function in the brain, the interference of glutamate receptors with taurine release from different tissue preparations in vitro and from the brain in vivo is of special interest. The release of taurine from the brain is enhanced by glutamate receptor agonists. This enhancement is inhibited by the respective receptor antagonists both in vitro and in vivo. The ionotropic N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor agonists appear to be the most effective in enhancing taurine release, their effects being receptor-mediated. Kainate is less effective, particularly in adults. Of the glutamate receptors, the NMDA class seems to be the most susceptible to modulation by nitric oxide. Nitric oxide also modulates taurine release, enhancing the basal release in both immature and mature hippocampus, whereas the K(+)-stimulated release is generally inhibited. Metabotropic glutamate receptors also participate in the regulation of taurine release, group I metabotropic glutamate receptors potentiating the release in the developing hippocampus, while group III receptors may be involved in the adult. Under various cell-damaging conditions, including ischemia, hypoxia and hypoglycemia, taurine release is enhanced, together with an enhanced release of excitatory amino acids. The increase in extracellular taurine upon excessive stimulation of glutamate receptors and under cell-damaging conditions may serve as an important protective mechanism against excitotoxicity, being particularly effective in the immature brain.

The hypnotic zolpidem increases the synchrony of BOLD signal fluctuations in widespread brain networks during a resting paradigm

PubMed Central

Licata, Stephanie C.; Nickerson, Lisa D.; Lowen, Steven B.; Trksak, George H.; MacLean, Robert R.; Lukas, Scott E.

2013-01-01

Networks of brain regions having synchronized fluctuations of the blood oxygen level-dependent functional magnetic resonance imaging (BOLD fMRI) time-series at rest, or “resting state networks” (RSNs), are emerging as a basis for understanding intrinsic brain activity. RSNs are topographically consistent with activity-related networks subserving sensory, motor, and cognitive processes, and studying their spontaneous fluctuations following acute drug challenge may provide a way to understand better the neuroanatomical substrates of drug action. The present within-subject double-blind study used BOLD fMRI at 3T to investigate the functional networks influenced by the non-benzodiazepine hypnotic zolpidem (Ambien®). Zolpidem is a positive modulator of γ-aminobutyric acidA (GABAA) receptors, and engenders sedative effects that may be explained in part by how it modulates intrinsic brain activity. Healthy participants (n= 12) underwent fMRI scanning 45 min after acute oral administration of zolpidem (0, 5, 10, or 20 mg), and changes in BOLD signal were measured while participants gazed at a static fixation point (i.e., at rest). Data were analyzed using group independent component analysis (ICA) with dual regression and results indicated that compared to placebo, the highest dose of zolpidem increased functional connectivity within a number of sensory, motor, and limbic networks. These results are consistent with previous studies showing an increase in functional connectivity at rest following administration of the positive GABAA receptor modulators midazolam and alcohol, and suggest that investigating how zolpidem modulates intrinsic brain activity may have implications for understanding the etiology of its powerful sedative effects. PMID:23296183

Circuit design tool. User's manual, revision 2

NASA Technical Reports Server (NTRS)

Miyake, Keith M.; Smith, Donald E.

1992-01-01

The CAM chip design was produced in a UNIX software environment using a design tool that supports definition of digital electronic modules, composition of these modules into higher level circuits, and event-driven simulation of these circuits. Our design tool provides an interface whose goals include straightforward but flexible primitive module definition and circuit composition, efficient simulation, and a debugging environment that facilitates design verification and alteration. The tool provides a set of primitive modules which can be composed into higher level circuits. Each module is a C-language subroutine that uses a set of interface protocols understood by the design tool. Primitives can be altered simply by recoding their C-code image; in addition new primitives can be added allowing higher level circuits to be described in C-code rather than as a composition of primitive modules--this feature can greatly enhance the speed of simulation.

76 FR 68460 - Findings of Research Misconduct

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-04

... Plasticity after Head Injury,'' D.A. Hovda, P.I. R01 NS052406, ``Age-dependent Ketone Metabolism after Brain Injury,'' M.L. Prims, P.I. K08 NS002197, ``NMDA Receptor Dysfunction after Traumatic Brain Injury,'' C.C... of calcium influx and modulation of local neurotransmitters as hallmarks of pediatric traumatic brain...

Differential Responses of Brain, Gonad and Muscle Steroid Levels to Changes in Social Status and Sex in a Sequential and Bidirectional Hermaphroditic Fish

PubMed Central

Lorenzi, Varenka; Earley, Ryan L.; Grober, Matthew S.

2012-01-01

Sex steroids can both modulate and be modulated by behavior, and their actions are mediated by complex interactions among multiple hormone sources and targets. While gonadal steroids delivered via circulation can affect behavior, changes in local brain steroid synthesis also can modulate behavior. The relative steroid load across different tissues and the association of these levels with rates of behavior have not been well studied. The bluebanded goby (Lythrypnus dalli) is a sex changing fish in which social status determines sexual phenotype. We examined changes in steroid levels in brain, gonad and body muscle at either 24 hours or 6 days after social induction of protogynous sex change, and from individuals in stable social groups not undergoing sex change. For each tissue, we measured levels of estradiol (E2), testosterone (T) and 11-ketotestosterone (KT). Females had more T than males in the gonads, and more E2 in all tissues but there was no sex difference in KT. For both sexes, E2 was higher in the gonad than in other tissues while androgens were higher in the brain. During sex change, brain T levels dropped while brain KT increased, and brain E2 levels did not change. We found a positive relationship between androgens and aggression in the most dominant females but only when the male was removed from the social group. The results demonstrate that steroid levels are responsive to changes in the social environment, and that their concentrations vary in different tissues. Also, we suggest that rapid changes in brain androgen levels might be important in inducing behavioral and/or morphological changes associated with protogynous sex change. PMID:23251444

The first taste is always with the eyes: a meta-analysis on the neural correlates of processing visual food cues.

PubMed

van der Laan, L N; de Ridder, D T D; Viergever, M A; Smeets, P A M

2011-03-01

Food selection is primarily guided by the visual system. Multiple functional neuro-imaging studies have examined the brain responses to visual food stimuli. However, the results of these studies are heterogeneous and there still is uncertainty about the core brain regions involved in the neural processing of viewing food pictures. The aims of the present study were to determine the concurrence in the brain regions activated in response to viewing pictures of food and to assess the modulating effects of hunger state and the food's energy content. We performed three Activation Likelihood Estimation (ALE) meta-analyses on data from healthy normal weight subjects in which we examined: 1) the contrast between viewing food and nonfood pictures (17 studies, 189 foci), 2) the modulation by hunger state (five studies, 48 foci) and 3) the modulation by energy content (seven studies, 86 foci). The most concurrent brain regions activated in response to viewing food pictures, both in terms of ALE values and the number of contributing experiments, were the bilateral posterior fusiform gyrus, the left lateral orbitofrontal cortex (OFC) and the left middle insula. Hunger modulated the response to food pictures in the right amygdala and left lateral OFC, and energy content modulated the response in the hypothalamus/ventral striatum. Overall, the concurrence between studies was moderate: at best 41% of the experiments contributed to the clusters for the contrast between food and nonfood. Therefore, future research should further elucidate the separate effects of methodological and physiological factors on between-study variations. Copyright © 2010 Elsevier Inc. All rights reserved.

Auditory neural networks involved in attention modulation prefer biologically significant sounds and exhibit sexual dimorphism in anurans.

PubMed

Xue, Fei; Yue, Xizi; Fan, Yanzhu; Cui, Jianguo; Brauth, Steven E; Tang, Yezhong; Fang, Guangzhan

2018-03-09

Allocating attention to biologically relevant stimuli in a complex environment is critically important for survival and reproductive success. In humans, attention modulation is regulated by the frontal cortex, and is often reflected by changes in specific components of the event-related potential (ERP). Although brain networks for attention modulation have been widely studied in primates and avian species, little is known about attention modulation in amphibians. The present study aimed to investigate the attention modulation networks in an anuran species, the Emei music frog ( Babina daunchina ). Male music frogs produce advertisement calls from within underground nest burrows that modify the acoustic features of the calls, and both males and females prefer calls produced from inside burrows. We broadcast call stimuli to male and female music frogs while simultaneously recording electroencephalographic (EEG) signals from the telencephalon and mesencephalon. Granger causal connectivity analysis was used to elucidate functional brain networks within the time window of ERP components. The results show that calls produced from inside nests which are highly sexually attractive result in the strongest brain connections; both ascending and descending connections involving the left telencephalon were stronger in males while those in females were stronger with the right telencephalon. Our findings indicate that the frog brain allocates neural attention resources to highly attractive sounds within the window of early components of ERP, and that such processing is sexually dimorphic, presumably reflecting the different reproductive strategies of males and females. © 2018. Published by The Company of Biologists Ltd.

Nonlinear modulation of interacting between COMT and depression on brain function.

PubMed

Gong, L; He, C; Yin, Y; Ye, Q; Bai, F; Yuan, Y; Zhang, H; Lv, L; Zhang, H; Zhang, Z; Xie, C

2017-09-01

The catechol-O-methyltransferase (COMT) gene is related to dopamine degradation and has been suggested to be involved in the pathogenesis of major depressive disorder (MDD). However, how this gene affects brain function properties in MDD is still unclear. Fifty patients with MDD and 35 cognitively normal participants underwent a resting-state functional magnetic resonance imaging scan. A voxelwise and data-drive global functional connectivity density (gFCD) analysis was used to investigate the main effects and the interactions of disease states and COMT rs4680 gene polymorphism on brain function. We found significant group differences of the gFCD in bilateral fusiform area (FFA), post-central and pre-central cortex, left superior temporal gyrus (STG), rectal and superior temporal gyrus and right ventrolateral prefrontal cortex (vlPFC); abnormal gFCDs in left STG were positively correlated with severity of depression in MDD group. Significant disease×COMT interaction effects were found in the bilateral calcarine gyrus, right vlPFC, hippocampus and thalamus, and left SFG and FFA. Further post-hoc tests showed a nonlinear modulation effect of COMT on gFCD in the development of MDD. Interestingly, an inverted U-shaped modulation was found in the prefrontal cortex (control system) but U-shaped modulations were found in the hippocampus, thalamus and occipital cortex (processing system). Our study demonstrated nonlinear modulation of the interaction between COMT and depression on brain function. These findings expand our understanding of the COMT effect underlying the pathophysiology of MDD. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Effects of chronic morphine and morphine withdrawal on gene expression in rat peripheral blood mononuclear cells.

PubMed

Desjardins, Stephane; Belkai, Emilie; Crete, Dominique; Cordonnier, Laurie; Scherrmann, Jean-Michel; Noble, Florence; Marie-Claire, Cynthia

2008-12-01

Chronic morphine treatment alters gene expression in brain structures. There are increasing evidences showing a correlation, in gene expression modulation, between blood cells and brain in psychological troubles. To test whether gene expression regulation in blood cells could be found in drug addiction, we investigated gene expression profiles in peripheral blood mononuclear (PBMC) cells of saline and morphine-treated rats. In rats chronically treated with morphine, the behavioral signs of spontaneous withdrawal were observed and a withdrawal score was determined. This score enabled to select the time points at which the animals displayed the mildest and strongest withdrawal signs (12 h and 36 h after the last injection). Oligonucleotide arrays were used to assess differential gene expression in the PBMCs and quantitative real-time RT-PCR to validate the modulation of several candidate genes 12 h and 36 h after the last injection. Among the 812 differentially expressed candidates, several genes (Adcy5, Htr2a) and pathways (Map kinases, G-proteins, integrins) have already been described as modulated in the brain of morphine-treated rats. Sixteen out of the twenty-four tested candidates were validated at 12 h, some of them showed a sustained modulation at 36 h while for most of them the modulation evolved as the withdrawal score increased. This study suggests similarities between the gene expression profile in PBMCs and brain of morphine-treated rats. Thus, the searching of correlations between the severity of the withdrawal and the PBMCs gene expression pattern by transcriptional analysis of blood cells could be promising for the study of the mechanisms of addiction.

Motor Imagery Learning Modulates Functional Connectivity of Multiple Brain Systems in Resting State

PubMed Central

Zhang, Hang; Long, Zhiying; Ge, Ruiyang; Xu, Lele; Jin, Zhen; Yao, Li; Liu, Yijun

2014-01-01

Background Learning motor skills involves subsequent modulation of resting-state functional connectivity in the sensory-motor system. This idea was mostly derived from the investigations on motor execution learning which mainly recruits the processing of sensory-motor information. Behavioral evidences demonstrated that motor skills in our daily lives could be learned through imagery procedures. However, it remains unclear whether the modulation of resting-state functional connectivity also exists in the sensory-motor system after motor imagery learning. Methodology/Principal Findings We performed a fMRI investigation on motor imagery learning from resting state. Based on previous studies, we identified eight sensory and cognitive resting-state networks (RSNs) corresponding to the brain systems and further explored the functional connectivity of these RSNs through the assessments, connectivity and network strengths before and after the two-week consecutive learning. Two intriguing results were revealed: (1) The sensory RSNs, specifically sensory-motor and lateral visual networks exhibited greater connectivity strengths in precuneus and fusiform gyrus after learning; (2) Decreased network strength induced by learning was proved in the default mode network, a cognitive RSN. Conclusions/Significance These results indicated that resting-state functional connectivity could be modulated by motor imagery learning in multiple brain systems, and such modulation displayed in the sensory-motor, visual and default brain systems may be associated with the establishment of motor schema and the regulation of introspective thought. These findings further revealed the neural substrates underlying motor skill learning and potentially provided new insights into the therapeutic benefits of motor imagery learning. PMID:24465577

Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

NASA Astrophysics Data System (ADS)

Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.

2016-09-01

Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought.

Deep brain stimulation of the subthalamic nucleus modulates sensitivity to decision outcome value in Parkinson’s disease

PubMed Central

Seymour, Ben; Barbe, Michael; Dayan, Peter; Shiner, Tamara; Dolan, Ray; Fink, Gereon R.

2016-01-01

Deep brain stimulation (DBS) of the subthalamic nucleus in Parkinson’s disease is known to cause a subtle but important adverse impact on behaviour, with impulsivity its most widely reported manifestation. However, precisely which computational components of the decision process are modulated is not fully understood. Here we probe a number of distinct subprocesses, including temporal discount, outcome utility, instrumental learning rate, instrumental outcome sensitivity, reward-loss trade-offs, and perseveration. We tested 22 Parkinson’s Disease patients both on and off subthalamic nucleus deep brain stimulation (STN-DBS), while they performed an instrumental learning task involving financial rewards and losses, and an inter-temporal choice task for financial rewards. We found that instrumental learning performance was significantly worse following stimulation, due to modulation of instrumental outcome sensitivity. Specifically, patients became less sensitive to decision values for both rewards and losses, but without any change to the learning rate or reward-loss trade-offs. However, we found no evidence that DBS modulated different components of temporal impulsivity. In conclusion, our results implicate the subthalamic nucleus in a modulation of outcome value in experience-based learning and decision-making in Parkinson’s disease, suggesting a more pervasive role of the subthalamic nucleus in the control of human decision-making than previously thought. PMID:27624437

Memory modulation across neural systems: intra-amygdala glucose reverses deficits caused by intraseptal morphine on a spatial task but not on an aversive task.

PubMed

McNay, E C; Gold, P E

1998-05-15

Based largely on dissociations of the effects of different lesions on learning and memory, memories for different attributes appear to be organized in independent neural systems. Results obtained with direct injections of drugs into one brain region at a time support a similar conclusion. The present experiments investigated the effects of simultaneous pharmacological manipulation of two neural systems, the amygdala and the septohippocampal system, to examine possible interactions of memory modulation across systems. Morphine injected into the medial septum impaired memory both for avoidance training and during spontaneous alternation. When glucose was concomitantly administered to the amygdala, glucose reversed the morphine-induced deficits in memory during alternation but not for avoidance training. These results suggest that the amygdala is involved in modulation of spatial memory processes and that direct injections of memory-modulating drugs into the amygdala do not always modulate memory for aversive events. These findings are contrary to predictions from the findings of lesion studies and of studies using direct injections of drugs into single brain areas. Thus, the independence of neural systems responsible for processing different classes of memory is less clear than implied by studies using lesions or injections of drugs into single brain areas.

Stress modulation of cognitive and affective processes

PubMed Central

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Electromagnetic interference in the permeability of saquinavir across the blood-brain barrier using nanoparticulate carriers.

PubMed

Kuo, Yung-Chih; Kuo, Chan-Ying

2008-03-03

Transport of antiretroviral agents across the blood-brain barrier (BBB) is of key importance to the treatment for the acquired immunodeficiency syndrome (AIDS). In this study, impact of exposure to electromagnetic field (EMF) on the permeability of saquinavir (SQV) across BBB was investigated. The in vitro BBB model was based on human brain-microvascular endothelial cells (HBMEC), and the concentration of SQV in receiver chamber of the transport system was evaluated. Polybutylcyanoacrylate (PBCA), methylmethacrylate-sulfopropylmethacrylate (MMA-SPM), and solid lipid nanoparticle (SLN) were employed as carriers for the delivery systems. Cytotoxicity of SLN decreased as content of cacao butter increased. Power of 5mV was apposite for the study on HBMEC without obvious apoptosis. Square wave produced greater permeability than sine and triangle waves. The carrier order on permeability of SQV across HBMEC monolayer under exposure to EMF was SLN>PBCA>MMA-SPM. Also, a larger frequency, modulation or depth of amplitude modulation (AM), or modulation or deviation of frequency modulation (FM) yielded a greater permeability. Besides, enhancement of permeability by AM wave was more significant than that by FM wave. Transport behavior of SQV across BBB was strongly influenced by the combination of nanoparticulate PBCA, MMA-SPM, and SLN with EMF exposure. This combination would be beneficial to the clinical application to the therapy of AIDS and other brain-related diseases.

Intelligence is associated with the modular structure of intrinsic brain networks.

PubMed

Hilger, Kirsten; Ekman, Matthias; Fiebach, Christian J; Basten, Ulrike

2017-11-22

General intelligence is a psychological construct that captures in a single metric the overall level of behavioural and cognitive performance in an individual. While previous research has attempted to localise intelligence in circumscribed brain regions, more recent work focuses on functional interactions between regions. However, even though brain networks are characterised by substantial modularity, it is unclear whether and how the brain's modular organisation is associated with general intelligence. Modelling subject-specific brain network graphs from functional MRI resting-state data (N = 309), we found that intelligence was not associated with global modularity features (e.g., number or size of modules) or the whole-brain proportions of different node types (e.g., connector hubs or provincial hubs). In contrast, we observed characteristic associations between intelligence and node-specific measures of within- and between-module connectivity, particularly in frontal and parietal brain regions that have previously been linked to intelligence. We propose that the connectivity profile of these regions may shape intelligence-relevant aspects of information processing. Our data demonstrate that not only region-specific differences in brain structure and function, but also the network-topological embedding of fronto-parietal as well as other cortical and subcortical brain regions is related to individual differences in higher cognitive abilities, i.e., intelligence.

Repeated Gestational Exposure of Mice to Chlorpyrifos Oxon Is Associated with Paraoxonase 1 (PON1) Modulated Effects in Maternal and Fetal Tissues

PubMed Central

Co, Aila L.; Hay, Ariel M.; MacDonald, James W.; Bammler, Theo K.; Farin, Federico M.; Costa, Lucio G.; Furlong, Clement E.

2014-01-01

Chlorpyrifos oxon (CPO), the toxic metabolite of the organophosphorus (OP) insecticide chlorpyrifos, causes developmental neurotoxicity in humans and rodents. CPO is hydrolyzed by paraoxonase-1 (PON1), with protection determined by PON1 levels and the human Q192R polymorphism. To examine how the Q192R polymorphism influences fetal toxicity associated with gestational CPO exposure, we measured enzyme inhibition and fetal-brain gene expression in wild-type (PON1+/+), PON1-knockout (PON1−/−), and tgHuPON1R192 and tgHuPON1Q192 transgenic mice. Pregnant mice exposed dermally to 0, 0.50, 0.75, or 0.85 mg/kg/d CPO from gestational day (GD) 6 through 17 were sacrificed on GD18. Biomarkers of CPO exposure inhibited in maternal tissues included brain acetylcholinesterase (AChE), red blood cell acylpeptide hydrolase (APH), and plasma butyrylcholinesterase (BChE) and carboxylesterase (CES). Fetal plasma BChE was inhibited in PON1−/− and tgHuPON1Q192, but not PON1+/+ or tgHuPON1R192 mice. Fetal brain AChE and plasma CES were inhibited in PON1−/− mice, but not in other genotypes. Weighted gene co-expression network analysis identified five gene modules based on clustering of the correlations among their fetal-brain expression values, allowing for correlation of module membership with the phenotypic data on enzyme inhibition. One module that correlated highly with maternal brain AChE activity had a large representation of homeobox genes. Gene set enrichment analysis revealed multiple gene sets affected by gestational CPO exposure in tgHuPON1Q192 but not tgHuPON1R192 mice, including gene sets involved in protein export, lipid metabolism, and neurotransmission. These data indicate that maternal PON1 status modulates the effects of repeated gestational CPO exposure on fetal-brain gene expression and on inhibition of both maternal and fetal biomarker enzymes. PMID:25070982

S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of γ-Rays: The Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose

PubMed Central

Nicolas, Fadia; Wu, Changgong; Bukhari, Salwa; de Toledo, Sonia M.; Li, Hong; Shibata, Masayuki; Azzam, Edouard I.

2015-01-01

The covalent addition of nitric oxide (NO•) onto cysteine thiols, or S-nitrosylation, modulates the activity of key signaling proteins. The dysregulation of normal S-nitrosylation contributes to degenerative conditions and to cancer. To gain insight into the biochemical changes induced by low-dose ionizing radiation, we determined global S-nitrosylation by the “biotin switch” assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed to acute 0.1 Gy of 137Cs γ-rays. The dose of radiation was delivered to the whole body in the presence or absence of iopamidol, an iodinated contrast agent used during radiological examinations. To investigate whether similar or distinct nitrosylation patterns are induced following high-dose irradiation, mice were exposed in parallel to acute 4 Gy of 137Cs γ rays. Analysis of modulated S-nitrosothiols (SNO-proteins) in freshly-harvested organs of animals sacrificed 13 days after irradiation revealed radiation dose- and contrast agent-dependent changes. The major results were as follows: (i) iopamidol alone had significant effects on S-nitrosylation in brain, lung and liver; (ii) relative to the control, exposure to 0.1 Gy without iopamidol resulted in statistically-significant SNO changes in proteins that differ in molecular weight in liver, lung, brain and blood plasma; (iii) iopamidol enhanced the decrease in S-nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease in S-nitrosylation occurred at 0.1 Gy for proteins of ~50 kDa in brain and for proteins of ~37 kDa in liver, an increase was detected at 4 Gy in both organs; (v) mass spectrometry analyses of nitrosylated proteins in brain revealed differential modulation of SNO proteins (e.g., sodium/potassium-transporting ATPase subunit beta-1; beta tubulins; ADP-ribosylation factor 5) by low- and high-dose irradiation; and (vi) ingenuity pathway analysis identified major signaling networks to be modulated, in particular the neuronal nitric oxide synthase signaling pathway was differentially modulated by low- and high-dose γ-irradiation. PMID:26317069

S-Nitrosylation in Organs of Mice Exposed to Low or High Doses of γ-Rays: The Modulating Effect of Iodine Contrast Agent at a Low Radiation Dose.

PubMed

Nicolas, Fadia; Wu, Changgong; Bukhari, Salwa; de Toledo, Sonia M; Li, Hong; Shibata, Masayuki; Azzam, Edouard I

2015-04-28

The covalent addition of nitric oxide (NO • ) onto cysteine thiols, or S -nitrosylation, modulates the activity of key signaling proteins. The dysregulation of normal S -nitrosylation contributes to degenerative conditions and to cancer. To gain insight into the biochemical changes induced by low-dose ionizing radiation, we determined global S -nitrosylation by the "biotin switch" assay coupled with mass spectrometry analyses in organs of C57BL/6J mice exposed to acute 0.1 Gy of 137 Cs γ-rays. The dose of radiation was delivered to the whole body in the presence or absence of iopamidol, an iodinated contrast agent used during radiological examinations. To investigate whether similar or distinct nitrosylation patterns are induced following high-dose irradiation, mice were exposed in parallel to acute 4 Gy of 137 Cs γ rays. Analysis of modulated S -nitrosothiols (SNO-proteins) in freshly-harvested organs of animals sacrificed 13 days after irradiation revealed radiation dose- and contrast agent-dependent changes. The major results were as follows: (i) iopamidol alone had significant effects on S -nitrosylation in brain, lung and liver; (ii) relative to the control, exposure to 0.1 Gy without iopamidol resulted in statistically-significant SNO changes in proteins that differ in molecular weight in liver, lung, brain and blood plasma; (iii) iopamidol enhanced the decrease in S -nitrosylation induced by 0.1 Gy in brain; (iv) whereas a decrease in S -nitrosylation occurred at 0.1 Gy for proteins of ~50 kDa in brain and for proteins of ~37 kDa in liver, an increase was detected at 4 Gy in both organs; (v) mass spectrometry analyses of nitrosylated proteins in brain revealed differential modulation of SNO proteins (e.g., sodium/potassium-transporting ATPase subunit beta-1; beta tubulins; ADP-ribosylation factor 5) by low- and high-dose irradiation; and (vi) ingenuity pathway analysis identified major signaling networks to be modulated, in particular the neuronal nitric oxide synthase signaling pathway was differentially modulated by low- and high-dose γ-irradiation.

Some Lower Valence Vanadium Fluorides: Their Crystal Distortions, Domain Structures, Modulated Structures, Ferrimagnetism, and Composition Dependence.

ERIC Educational Resources Information Center

Hong, Y. S.; And Others

1980-01-01

Describes some contemporary concepts unique to the structure of advanced solids, i.e., their crystal distortions, domain structures, modulated structures, ferrimagnetism, and composition dependence. (Author/CS)

Radiological Society of North America

MedlinePlus

... Courses Electronic Education Exhibits RSNA Journals RSNA/AAPM Physics Modules RadioGraphics ABR Diagnostic Radiology Core Exam Study ... Brain Tumor Classification System In 2016, the World Health Organization (WHO) released an update to its brain ...

Bidirectional phase-modulated hybrid cable television/radio-over-fiber lightwave transport systems.

PubMed

Chen, Chia-Yi; Wu, Po-Yi; Lu, Hai-Han; Lin, Ying-Pyng; Gao, Ming-Cian; Wen, Jian-Ying; Chen, Hwan-Wen

2013-02-15

A bidirectional phase-modulated hybrid cable television/radio-over-fiber lightwave transport system employing fiber Bragg grating tilt filter as a phase modulation-to-intensity modulation conversion scheme is proposed and demonstrated. Impressive performances of carrier-to-noise ratio, composite second-order, composite triple-beat, and bit-error rate are obtained in our proposed systems over a combination of 40 km single-mode fiber-and 1.43 km photonic crystal fiber transmission.

Acupuncture Modulates Resting State Connectivity in Default and Sensorimotor Brain Networks

PubMed Central

Dhond, Rupali P.; Yeh, Calvin; Park, Kyungmo; Kettner, Norman; Napadow, Vitaly

2008-01-01

Previous studies have defined low-frequency, spatially consistent networks in resting fMRI data which may reflect functional connectivity. We sought to explore how a complex somatosensory stimulation, acupuncture, influences intrinsic connectivity in two of these networks: the default mode network (DMN) and sensorimotor network (SMN). We analyzed resting fMRI data taken before and after verum and sham acupuncture. Electrocardiography data was used to infer autonomic modulation through measures of heart rate variability (HRV). Probabilistic independent component analysis was used to separate resting fMRI data into DMN and SMN components. Following verum, but not sham, acupuncture there was increased DMN connectivity with pain (anterior cingulate cortex (ACC), periaqueductal gray), affective (amygdala, ACC), and memory (hippocampal formation, middle temporal gyrus) related brain regions. Furthermore, increased DMN connectivity with the hippocampal formation, a region known to support memory and interconnected with autonomic brain regions, was negatively correlated with acupuncture-induced increase in a sympathetic related HRV metric (LFu), and positively correlated with a parasympathetic related metric (HFu). Following verum, but not sham, acupuncture there was also increased SMN connectivity with pain related brain regions (ACC, cerebellum). We attribute differences between verum and sham acupuncture to more varied and stronger sensations evoked by verum acupuncture. Our results demonstrate for the first time that acupuncture can enhance the post-stimulation spatial extent of resting brain networks to include anti-nociceptive, memory, and affective brain regions. This modulation and sympathovagal response may relate to acupuncture analgesia and other potential therapeutic effects. PMID:18337009

Disrupted topological organization of resting-state functional brain network in subcortical vascular mild cognitive impairment.

PubMed

Yi, Li-Ye; Liang, Xia; Liu, Da-Ming; Sun, Bo; Ying, Sun; Yang, Dong-Bo; Li, Qing-Bin; Jiang, Chuan-Lu; Han, Ying

2015-10-01

Neuroimaging studies have demonstrated both structural and functional abnormalities in widespread brain regions in patients with subcortical vascular mild cognitive impairment (svMCI). However, whether and how these changes alter functional brain network organization remains largely unknown. We recruited 21 patients with svMCI and 26 healthy control (HC) subjects who underwent resting-state functional magnetic resonance imaging scans. Graph theory-based network analyses were used to investigate alterations in the topological organization of functional brain networks. Compared with the HC individuals, the patients with svMCI showed disrupted global network topology with significantly increased path length and modularity. Modular structure was also impaired in the svMCI patients with a notable rearrangement of the executive control module, where the parietal regions were split out and grouped as a separate module. The svMCI patients also revealed deficits in the intra- and/or intermodule connectivity of several brain regions. Specifically, the within-module degree was decreased in the middle cingulate gyrus while it was increased in the left anterior insula, medial prefrontal cortex and cuneus. Additionally, increased intermodule connectivity was observed in the inferior and superior parietal gyrus, which was associated with worse cognitive performance in the svMCI patients. Together, our results indicate that svMCI patients exhibit dysregulation of the topological organization of functional brain networks, which has important implications for understanding the pathophysiological mechanism of svMCI. © 2015 John Wiley & Sons Ltd.

Influence of gut microbiota on neuropsychiatric disorders.

PubMed

Cenit, María Carmen; Sanz, Yolanda; Codoñer-Franch, Pilar

2017-08-14

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson's disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and the possible microbiota-targeted intervention strategies that could improve health status and prevent psychiatric disorders in the near future.

Influence of gut microbiota on neuropsychiatric disorders

PubMed Central

Cenit, María Carmen; Sanz, Yolanda; Codoñer-Franch, Pilar

2017-01-01

The last decade has witnessed a growing appreciation of the fundamental role played by an early assembly of a diverse and balanced gut microbiota and its subsequent maintenance for future health of the host. Gut microbiota is currently viewed as a key regulator of a fluent bidirectional dialogue between the gut and the brain (gut-brain axis). A number of preclinical studies have suggested that the microbiota and its genome (microbiome) may play a key role in neurodevelopmental and neurodegenerative disorders. Furthermore, alterations in the gut microbiota composition in humans have also been linked to a variety of neuropsychiatric conditions, including depression, autism and Parkinson’s disease. However, it is not yet clear whether these changes in the microbiome are causally related to such diseases or are secondary effects thereof. In this respect, recent studies in animals have indicated that gut microbiota transplantation can transfer a behavioral phenotype, suggesting that the gut microbiota may be a modifiable factor modulating the development or pathogenesis of neuropsychiatric conditions. Further studies are warranted to establish whether or not the findings of preclinical animal experiments can be generalized to humans. Moreover, although different communication routes between the microbiota and brain have been identified, further studies must elucidate all the underlying mechanisms involved. Such research is expected to contribute to the design of strategies to modulate the gut microbiota and its functions with a view to improving mental health, and thus provide opportunities to improve the management of psychiatric diseases. Here, we review the evidence supporting a role of the gut microbiota in neuropsychiatric disorders and the state of the art regarding the mechanisms underlying its contribution to mental illness and health. We also consider the stages of life where the gut microbiota is more susceptible to the effects of environmental stressors, and the possible microbiota-targeted intervention strategies that could improve health status and prevent psychiatric disorders in the near future. PMID:28852308

Clinical applications of image guided-intensity modulated radiation therapy (IG-IMRT) for conformal avoidance of normal tissue

NASA Astrophysics Data System (ADS)

Gutierrez, Alonso Navar

2007-12-01

Recent improvements in imaging technology and radiation delivery have led to the development of advanced treatment techniques in radiotherapy which have opened the door for novel therapeutic approaches to improve the efficacy of radiation cancer treatments. Among these advances is image-guided, intensity modulated radiation therapy (IG-IMRT), in which imaging is incorporated to aid in inter-/intra-fractional target localization and to ensure accurate delivery of precise and highly conformal dose distributions. In principle, clinical implementation of IG-IMRT should improve normal tissue sparing and permit effective biological dose escalation thus widening the radiation therapeutic window and lead to increases in survival through improved local control of primary neoplastic diseases. Details of the development of three clinical applications made possible solely with IG-IMRT radiation delivery techniques are presented: (1) Laparoscopically implanted tissue expander radiotherapy (LITE-RT) has been developed to enhance conformal avoidance of normal tissue during the treatment of intra-abdominopelvic cancers. LITE-RT functions by geometrically displacing surrounding normal tissue and isolating the target volume through the interfractional inflation of a custom-shaped tissue expander throughout the course of treatment. (2) The unique delivery geometry of helical tomotherapy, a novel form of IG-IMRT, enables the delivery of composite treatment plan m which whole brain radiotherapy (WBRT) with hippocampal avoidance, hypothesized to reduce the risk of memory function decline and improve the patient's quality of life, and simultaneously integrated boost to multiple brain metastases to improve intracranial tumor control is achieved. (3) Escalation of biological dose to targets through integrated, selective subvolume boosts have been shown to efficiently increase tumor dose without significantly increasing normal tissue dose. Helical tomotherapy was used to investigate the feasibility of delivering a simultaneously integrated subvolume boost to canine nasal tumors and was found to dramatically increase estimated 1-year tumor control probability (TCP) without increasing the dose to the eyes, so as to preserve vision, and to the brain, so as to prevent neuropathy.

Using Brain Imaging to Extract the Structure of Complex Events at the Rational Time Band

PubMed Central

Anderson, John R.; Qin, Yulin

2017-01-01

A functional magnetic resonance imaging (fMRI) study was performed in which participants performed a complex series of mental calculations that spanned about 2 min. An Adaptive Control of Thought—Rational (ACT-R) model [Anderson, J. R. How can the human mind occur in the physical universe? New York: Oxford University Press, 2007] was developed that successfully fit the distribution of latencies. This model generated predictions for the fMRI signal in six brain regions that have been associated with modules in the ACT-R theory. The model’s predictions were confirmed for a fusiform region that reflects the visual module, for a prefrontal region that reflects the retrieval module, and for an anterior cingulate region that reflects the goal module. In addition, the only significant deviations to the motor region that reflects the manual module were anticipatory hand movements. In contrast, the predictions were relatively poor for a parietal region that reflects an imaginal module and for a caudate region that reflects the procedural module. Possible explanations of these poor fits are discussed. In addition, exploratory analyses were performed to find regions that might correspond to the predictions of the modules. PMID:18345979

Using brain imaging to extract the structure of complex events at the rational time band.

PubMed

Anderson, John R; Qin, Yulin

2008-09-01

A functional magnetic resonance imaging (fMRI) study was performed in which participants performed a complex series of mental calculations that spanned about 2 min. An Adaptive Control of Thought--Rational (ACT-R) model [Anderson, J. R. How can the human mind occur in the physical universe? New York: Oxford University Press, 2007] was developed that successfully fit the distribution of latencies. This model generated predictions for the fMRI signal in six brain regions that have been associated with modules in the ACT-R theory. The model's predictions were confirmed for a fusiform region that reflects the visual module, for a prefrontal region that reflects the retrieval module, and for an anterior cingulate region that reflects the goal module. In addition, the only significant deviations to the motor region that reflects the manual module were anticipatory hand movements. In contrast, the predictions were relatively poor for a parietal region that reflects an imaginal module and for a caudate region that reflects the procedural module. Possible explanations of these poor fits are discussed. In addition, exploratory analyses were performed to find regions that might correspond to the predictions of the modules.

Analogy-Integrated e-Learning Module: Facilitating Students' Conceptual Understanding

ERIC Educational Resources Information Center

Florida, Jennifer

2012-01-01

The study deals with the development of an analogy-integrated e-learning module on Cellular Respiration, which is intended to facilitate conceptual understanding of students with different brain hemisphere dominance and learning styles. The module includes eight analogies originally conceptualized following the specific steps used to prepare…

Understanding the evolution of Mammalian brain structures; the need for a (new) cerebrotype approach.

PubMed

Willemet, Romain

2012-05-18

The mammalian brain varies in size by a factor of 100,000 and is composed of anatomically and functionally distinct structures. Theoretically, the manner in which brain composition can evolve is limited, ranging from highly modular ("mosaic evolution") to coordinated changes in brain structure size ("concerted evolution") or anything between these two extremes. There is a debate about the relative importance of these distinct evolutionary trends. It is shown here that the presence of taxa-specific allometric relationships between brain structures makes a taxa-specific approach obligatory. In some taxa, the evolution of the size of brain structures follows a unique, coordinated pattern, which, in addition to other characteristics at different anatomical levels, defines what has been called here a "taxon cerebrotype". In other taxa, no clear pattern is found, reflecting heterogeneity of the species' lifestyles. These results suggest that the evolution of brain size and composition depends on the complex interplay between selection pressures and constraints that have changed constantly during mammalian evolution. Therefore the variability in brain composition between species should not be considered as deviations from the normal, concerted mammalian trend, but in taxa and species-specific versions of the mammalian brain. Because it forms homogenous groups of species within this complex "space" of constraints and selection pressures, the cerebrotype approach developed here could constitute an adequate level of analysis for evo-devo studies, and by extension, for a wide range of disciplines related to brain evolution.

Understanding the Evolution of Mammalian Brain Structures; the Need for a (New) Cerebrotype Approach

PubMed Central

Willemet, Romain

2012-01-01

The mammalian brain varies in size by a factor of 100,000 and is composed of anatomically and functionally distinct structures. Theoretically, the manner in which brain composition can evolve is limited, ranging from highly modular (“mosaic evolution”) to coordinated changes in brain structure size (“concerted evolution”) or anything between these two extremes. There is a debate about the relative importance of these distinct evolutionary trends. It is shown here that the presence of taxa-specific allometric relationships between brain structures makes a taxa-specific approach obligatory. In some taxa, the evolution of the size of brain structures follows a unique, coordinated pattern, which, in addition to other characteristics at different anatomical levels, defines what has been called here a “taxon cerebrotype”. In other taxa, no clear pattern is found, reflecting heterogeneity of the species’ lifestyles. These results suggest that the evolution of brain size and composition depends on the complex interplay between selection pressures and constraints that have changed constantly during mammalian evolution. Therefore the variability in brain composition between species should not be considered as deviations from the normal, concerted mammalian trend, but in taxa and species-specific versions of the mammalian brain. Because it forms homogenous groups of species within this complex “space” of constraints and selection pressures, the cerebrotype approach developed here could constitute an adequate level of analysis for evo-devo studies, and by extension, for a wide range of disciplines related to brain evolution. PMID:24962772

Reconsidering the evolution of brain, cognition, and behavior in birds and mammals

PubMed Central

Willemet, Romain

2013-01-01

Despite decades of research, some of the most basic issues concerning the extraordinarily complex brains and behavior of birds and mammals, such as the factors responsible for the diversity of brain size and composition, are still unclear. This is partly due to a number of conceptual and methodological issues. Determining species and group differences in brain composition requires accounting for the presence of taxon-cerebrotypes and the use of precise statistical methods. The role of allometry in determining brain variables should be revised. In particular, bird and mammalian brains appear to have evolved in response to a variety of selective pressures influencing both brain size and composition. “Brain” and “cognition” are indeed meta-variables, made up of the variables that are ecologically relevant and evolutionarily selected. External indicators of species differences in cognition and behavior are limited by the complexity of these differences. Indeed, behavioral differences between species and individuals are caused by cognitive and affective components. Although intra-species variability forms the basis of species evolution, some of the mechanisms underlying individual differences in brain and behavior appear to differ from those between species. While many issues have persisted over the years because of a lack of appropriate data or methods to test them; several fallacies, particularly those related to the human brain, reflect scientists' preconceptions. The theoretical framework on the evolution of brain, cognition, and behavior in birds and mammals should be reconsidered with these biases in mind. PMID:23847570

Intrinsic electrical properties of mammalian neurons and CNS function: a historical perspective

PubMed Central

Llinás, Rodolfo R.

2014-01-01

This brief review summarizes work done in mammalian neuroscience concerning the intrinsic electrophysiological properties of four neuronal types; Cerebellar Purkinje cells, inferior olivary cells, thalamic cells, and some cortical interneurons. It is a personal perspective addressing an interesting time in neuroscience when the reflex view of brain function, as the paradigm to understand global neuroscience, began to be modified toward one in which sensory input modulates rather than dictates brain function. The perspective of the paper is not a comprehensive description of the intrinsic electrical properties of all nerve cells but rather addresses a set of cell types that provide indicative examples of mechanisms that modulate brain function. PMID:25408634

The Brain.

ERIC Educational Resources Information Center

Hubel, David H.

1979-01-01

This article on the brain is part of an entire issue about neurobiology and the question of how the human brain works. The brain as an intricate tissue composed of cells is discussed based on the current knowledge and understanding of its composition and structure. (SA)

Perivascular Spaces--MRI Marker of Inflammatory Activity in the Brain?

ERIC Educational Resources Information Center

Wuerfel, Jens; Haertle, Mareile; Waiczies, Helmar; Tysiak, Eva; Bechmann, Ingo; Wernecke, Klaus D.; Zipp, Frauke; Paul, Friedemann

2008-01-01

The Virchow-Robin spaces (VRS), perivascular compartments surrounding small blood vessels as they penetrate the brain parenchyma, are increasingly recognized for their role in leucocyte trafficking as well as for their potential to modulate immune responses. In the present study, we investigated VRS numbers and volumes in different brain regions…

Inside the Adolescent Brain

ERIC Educational Resources Information Center

Drury, Stacy S.

2009-01-01

Dr. Jay Giedd says that the main alterations in the adolescent brain are the inverted U-shaped developmental trajectories with late childhood/early teen peaks for gray matter volume among others. Giedd adds that the adolescent brain is vulnerable to substances that artificially modulate dopamine levels since its reward system is in a state of flux.

Alterations in Normal Aging Revealed by Cortical Brain Network Constructed Using IBASPM.

PubMed

Li, Wan; Yang, Chunlan; Shi, Feng; Wang, Qun; Wu, Shuicai; Lu, Wangsheng; Li, Shaowu; Nie, Yingnan; Zhang, Xin

2018-04-16

Normal aging has been linked with the decline of cognitive functions, such as memory and executive skills. One of the prominent approaches to investigate the age-related alterations in the brain is by examining the cortical brain connectome. IBASPM is a toolkit to realize individual atlas-based volume measurement. Hence, this study seeks to determine what further alterations can be revealed by cortical brain networks formed by IBASPM-extracted regional gray matter volumes. We found the reduced strength of connections between the superior temporal pole and middle temporal pole in the right hemisphere, global hubs as the left fusiform gyrus and right Rolandic operculum in the young and aging groups, respectively, and significantly reduced inter-module connection of one module in the aging group. These new findings are consistent with the phenomenon of normal aging mentioned in previous studies and suggest that brain network built with the IBASPM could provide supplementary information to some extent. The individualization of morphometric features extraction deserved to be given more attention in future cortical brain network research.

Interventional programmes to improve cognition during healthy and pathological ageing: Cortical modulations and evidence for brain plasticity.

PubMed

Cespón, Jesús; Miniussi, Carlo; Pellicciari, Maria Concetta

2018-05-01

A growing body of evidence suggests that healthy elderly individuals and patients with Alzheimer's disease retain an important potential for neuroplasticity. This review summarizes studies investigating the modulation of neural activity and structural brain integrity in response to interventions involving cognitive training, physical exercise and non-invasive brain stimulation in healthy elderly and cognitively impaired subjects (including patients with mild cognitive impairment (MCI) and Alzheimer's disease). Moreover, given the clinical relevance of neuroplasticity, we discuss how evidence for neuroplasticity can be inferred from the functional and structural brain changes observed after implementing these interventions. We emphasize that multimodal programmes, which combine several types of interventions, improve cognitive function to a greater extent than programmes that use a single interventional approach. We suggest specific methods for weighting the relative importance of cognitive training, physical exercise and non-invasive brain stimulation according to the functional and structural state of the brain of the targeted subject to maximize the cognitive improvements induced by multimodal programmes. Copyright © 2018 Elsevier B.V. All rights reserved.

Visual attention: Linking prefrontal sources to neuronal and behavioral correlates.

PubMed

Clark, Kelsey; Squire, Ryan Fox; Merrikhi, Yaser; Noudoost, Behrad

2015-09-01

Attention is a means of flexibly selecting and enhancing a subset of sensory input based on the current behavioral goals. Numerous signatures of attention have been identified throughout the brain, and now experimenters are seeking to determine which of these signatures are causally related to the behavioral benefits of attention, and the source of these modulations within the brain. Here, we review the neural signatures of attention throughout the brain, their theoretical benefits for visual processing, and their experimental correlations with behavioral performance. We discuss the importance of measuring cue benefits as a way to distinguish between impairments on an attention task, which may instead be visual or motor impairments, and true attentional deficits. We examine evidence for various areas proposed as sources of attentional modulation within the brain, with a focus on the prefrontal cortex. Lastly, we look at studies that aim to link sources of attention to its neuronal signatures elsewhere in the brain. Copyright © 2015. Published by Elsevier Ltd.

The impact of verbal framing on brain activity evoked by emotional images.

PubMed

Kisley, Michael A; Campbell, Alana M; Larson, Jenna M; Naftz, Andrea E; Regnier, Jesse T; Davalos, Deana B

2011-12-01

Emotional stimuli generally command more brain processing resources than non-emotional stimuli, but the magnitude of this effect is subject to voluntary control. Cognitive reappraisal represents one type of emotion regulation that can be voluntarily employed to modulate responses to emotional stimuli. Here, the late positive potential (LPP), a specific event-related brain potential (ERP) component, was measured in response to neutral, positive and negative images while participants performed an evaluative categorization task. One experimental group adopted a "negative frame" in which images were categorized as negative or not. The other adopted a "positive frame" in which the exact same images were categorized as positive or not. Behavioral performance confirmed compliance with random group assignment, and peak LPP amplitude to negative images was affected by group membership: brain responses to negative images were significantly reduced in the "positive frame" group. This suggests that adopting a more positive appraisal frame can modulate brain activity elicited by negative stimuli in the environment.

Inflammatory Responses in Brain Ischemia

PubMed Central

Kawabori, Masahito; Yenari, Midori A.

2017-01-01

Brain infarction causes tissue death by ischemia due to occlusion of the cerebral vessels and recent work has shown that post stroke inflammation contributes significantly to the development of ischemic pathology. Because secondary damage by brain inflammation may have a longer therapeutic time window compared to the rescue of primary damage following arterial occlusion, controlling inflammation would be an obvious therapeutic target. A substantial amount of experimentall progress in this area has been made in recent years. However, it is difficult to elucidate the precise mechanisms of the inflammatory responses following ischemic stroke because inflammation is a complex series of interactions between inflammatory cells and molecules, all of which could be either detrimental or beneficial. We review recent advances in neuroinflammation and the modulation of inflammatory signaling pathways in brain ischemia. Potential targets for treatment of ischemic stroke will also be covered. The roles of the immune system and brain damage versus repair will help to clarify how immune modulation may treat stroke. PMID:25666795

NeuroGrid: recording action potentials from the surface of the brain.

PubMed

Khodagholy, Dion; Gelinas, Jennifer N; Thesen, Thomas; Doyle, Werner; Devinsky, Orrin; Malliaras, George G; Buzsáki, György

2015-02-01

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

Role of voltage-gated L-type Ca2+ channel isoforms for brain function.

PubMed

Striessnig, J; Koschak, A; Sinnegger-Brauns, M J; Hetzenauer, A; Nguyen, N K; Busquet, P; Pelster, G; Singewald, N

2006-11-01

Voltage-gated LTCCs (L-type Ca2+ channels) are established drug targets for the treatment of cardiovascular diseases. LTCCs are also expressed outside the cardiovascular system. In the brain, LTCCs control synaptic plasticity in neurons, and DHP (dihydropyridine) LTCC blockers such as nifedipine modulate brain function (such as fear memory extinction and depression-like behaviour). Voltage-sensitive Ca2+ channels Cav1 .2 and Cav1.3 are the predominant brain LTCCs. As DHPs and other classes of organic LTCC blockers inhibit both isoforms, their pharmacological distinction is impossible and their individual contributions to defined brain functions remain largely unknown. Here, we summarize our recent experiments with two genetically modified mouse strains, which we generated to explore the individual biophysical features of Cav1.2 and Cav1.3 LTCCs and to determine their relative contributions to various physiological peripheral and neuronal functions. The results described here also allow predictions about the pharmacotherapeutic potential of isoform-selective LTCC modulators.

The temporal structures and functional significance of scale-free brain activity

PubMed Central

He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

2010-01-01

SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

Structure and function of complex brain networks

PubMed Central

Sporns, Olaf

2013-01-01

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

Functional complexity emerging from anatomical constraints in the brain: the significance of network modularity and rich-clubs

NASA Astrophysics Data System (ADS)

Zamora-López, Gorka; Chen, Yuhan; Deco, Gustavo; Kringelbach, Morten L.; Zhou, Changsong

2016-12-01

The large-scale structural ingredients of the brain and neural connectomes have been identified in recent years. These are, similar to the features found in many other real networks: the arrangement of brain regions into modules and the presence of highly connected regions (hubs) forming rich-clubs. Here, we examine how modules and hubs shape the collective dynamics on networks and we find that both ingredients lead to the emergence of complex dynamics. Comparing the connectomes of C. elegans, cats, macaques and humans to surrogate networks in which either modules or hubs are destroyed, we find that functional complexity always decreases in the perturbed networks. A comparison between simulated and empirically obtained resting-state functional connectivity indicates that the human brain, at rest, lies in a dynamical state that reflects the largest complexity its anatomical connectome can host. Last, we generalise the topology of neural connectomes into a new hierarchical network model that successfully combines modular organisation with rich-club forming hubs. This is achieved by centralising the cross-modular connections through a preferential attachment rule. Our network model hosts more complex dynamics than other hierarchical models widely used as benchmarks.

Functional complexity emerging from anatomical constraints in the brain: the significance of network modularity and rich-clubs

PubMed Central

Zamora-López, Gorka; Chen, Yuhan; Deco, Gustavo; Kringelbach, Morten L.; Zhou, Changsong

2016-01-01

The large-scale structural ingredients of the brain and neural connectomes have been identified in recent years. These are, similar to the features found in many other real networks: the arrangement of brain regions into modules and the presence of highly connected regions (hubs) forming rich-clubs. Here, we examine how modules and hubs shape the collective dynamics on networks and we find that both ingredients lead to the emergence of complex dynamics. Comparing the connectomes of C. elegans, cats, macaques and humans to surrogate networks in which either modules or hubs are destroyed, we find that functional complexity always decreases in the perturbed networks. A comparison between simulated and empirically obtained resting-state functional connectivity indicates that the human brain, at rest, lies in a dynamical state that reflects the largest complexity its anatomical connectome can host. Last, we generalise the topology of neural connectomes into a new hierarchical network model that successfully combines modular organisation with rich-club forming hubs. This is achieved by centralising the cross-modular connections through a preferential attachment rule. Our network model hosts more complex dynamics than other hierarchical models widely used as benchmarks. PMID:27917958

Modulation of [3H]DAGO binding by substance P (SP) and SP fragments in the mouse brain and spinal cord via MU1 interactions.

PubMed

Krumins, S A; Kim, D C; Seybold, V S; Larson, A A

1989-01-01

Binding of [3H]DAGO to fresh, frozen or beta-funaltrexamine (beta-FNA) pretreated membranes of mouse brain and spinal cord was extensively studied using substance P (SP) or SP fragments as potential competitors and/or modulators. The objective was to determine whether SP exerts its analgesic effect by interacting with mu opioid receptors. The affinity of DAGO was reduced and binding capacity was increased in the presence of SP or the N-terminal SP fragments SP(1-9) and SP(1-4) but not the C-terminal SP fragment SP(5-11). Because sub-nanomolar concentrations of SP or N-terminal SP fragments displaced [3H] DAGO binding to a minor but detectable degree, it is suggested that SP interacts with mu 1 sites through its N-terminus portion. The effect of SP on DAGO binding was less in the spinal cord compared to the rest of the brain. Modulation of DAGO binding by SP was enhanced in the brain after pretreatment of membranes with the narcotic antagonist beta-FNA. These results suggest a novel mechanism for the analgesic action of SP.

Modulation of Posterior Alpha Activity by Spatial Attention Allows for Controlling A Continuous Brain-Computer Interface.

PubMed

Horschig, Jörn M; Oosterheert, Wouter; Oostenveld, Robert; Jensen, Ole

2015-11-01

Here we report that the modulation of alpha activity by covert attention can be used as a control signal in an online brain-computer interface, that it is reliable, and that it is robust. Subjects were instructed to orient covert visual attention to the left or right hemifield. We decoded the direction of attention from the magnetoencephalogram by a template matching classifier and provided the classification outcome to the subject in real-time using a novel graphical user interface. Training data for the templates were obtained from a Posner-cueing task conducted just before the BCI task. Eleven subjects participated in four sessions each. Eight of the subjects achieved classification rates significantly above chance level. Subjects were able to significantly increase their performance from the first to the second session. Individual patterns of posterior alpha power remained stable throughout the four sessions and did not change with increased performance. We conclude that posterior alpha power can successfully be used as a control signal in brain-computer interfaces. We also discuss several ideas for further improving the setup and propose future research based on solid hypotheses about behavioral consequences of modulating neuronal oscillations by brain computer interfacing.

Driving working memory with frequency-tuned noninvasive brain stimulation.

PubMed

Albouy, Philippe; Baillet, Sylvain; Zatorre, Robert J

2018-04-29

Frequency-tuned noninvasive brain stimulation is a recent approach in cognitive neuroscience that involves matching the frequency of transcranially applied electromagnetic fields to that of specific oscillatory components of the underlying neurophysiology. The objective of this method is to modulate ongoing/intrinsic brain oscillations, which correspond to rhythmic fluctuations of neural excitability, to causally change behavior. We review the impact of frequency-tuned noninvasive brain stimulation on the research field of human working memory. We argue that this is a powerful method to probe and understand the mechanisms of memory functions, targeting specifically task-related oscillatory dynamics, neuronal representations, and brain networks. We report the main behavioral and neurophysiological outcomes published to date, in particular, how functionally relevant oscillatory signatures in signal power and interregional connectivity yield causal changes of working memory abilities. We also present recent developments of the technique that aim to modulate cross-frequency coupling in polyrhythmic neural activity. Overall, the method has led to significant advances in our understanding of the mechanisms of systems neuroscience, and the role of brain oscillations in cognition and behavior. We also emphasize the translational impact of noninvasive brain stimulation techniques in the development of therapeutic approaches. © 2018 New York Academy of Sciences.

Morphofunctional aspects of the blood-brain barrier.

PubMed

Nico, Beatrice; Ribatti, Domenico

2012-01-01

The blood-brain barrier (BBB) selectively controls the homeostasis of the Central Nervous System (CNS) environment by the specific structural and biochemical features of the endothelial cells, pericytes and glial endfeet, which represent the cellular components of the mature BBB. Endothelial tight junctions (TJs) are the most important structural component of the BBB, and molecular alteration in the phosphorylation state of some TJs proteins, like ZO-1 or occludin, are crucial in determining alterations in the control of BBB vascular permeability. Astrocytes endfeet enveloping the vessels wall, are considered important in the induction and maintenance of the BBB, through secretion of soluble factors, which modulate the expression of enzymatic complexes and antigens by endothelial cells and TJs - associated proteins. Moreover, astrocytes control water flux at BBB site by expressing a specific water channel, namely aquaporin-4 (AQP4), involved in the molecular composition of the orthogonal particles arrays (OAPs) on the perivascular glial endfeet and tightly coupled with the maintenance of the BBB integrity. Disruption of the BBB is a consistent event occurring in the development of several CNS diseases, including demyelinating lesions in the course of relapsing multiple sclerosis, stroke, Duchenne muscular dystrophy (DMD), but also mechanical injures, neurological insults, septic encephalopathy, brain tumors, permanent ischemia or transient ischemia followed by reperfusion. In most cases, these pathological conditions are associated with an increase in microvascular permeability, vasogenic edema, swollen atrocyte endfeet, and BBB disruption.

Modality-specific spectral dynamics in response to visual and tactile sequential shape information processing tasks: An MEG study using multivariate pattern classification analysis.

PubMed

Gohel, Bakul; Lee, Peter; Jeong, Yong

2016-08-01

Brain regions that respond to more than one sensory modality are characterized as multisensory regions. Studies on the processing of shape or object information have revealed recruitment of the lateral occipital cortex, posterior parietal cortex, and other regions regardless of input sensory modalities. However, it remains unknown whether such regions show similar (modality-invariant) or different (modality-specific) neural oscillatory dynamics, as recorded using magnetoencephalography (MEG), in response to identical shape information processing tasks delivered to different sensory modalities. Modality-invariant or modality-specific neural oscillatory dynamics indirectly suggest modality-independent or modality-dependent participation of particular brain regions, respectively. Therefore, this study investigated the modality-specificity of neural oscillatory dynamics in the form of spectral power modulation patterns in response to visual and tactile sequential shape-processing tasks that are well-matched in terms of speed and content between the sensory modalities. Task-related changes in spectral power modulation and differences in spectral power modulation between sensory modalities were investigated at source-space (voxel) level, using a multivariate pattern classification (MVPC) approach. Additionally, whole analyses were extended from the voxel level to the independent-component level to take account of signal leakage effects caused by inverse solution. The modality-specific spectral dynamics in multisensory and higher-order brain regions, such as the lateral occipital cortex, posterior parietal cortex, inferior temporal cortex, and other brain regions, showed task-related modulation in response to both sensory modalities. This suggests modality-dependency of such brain regions on the input sensory modality for sequential shape-information processing. Copyright © 2016 Elsevier B.V. All rights reserved.

Brain correlates of autonomic modulation: combining heart rate variability with fMRI.

PubMed

Napadow, Vitaly; Dhond, Rupali; Conti, Giulia; Makris, Nikos; Brown, Emery N; Barbieri, Riccardo

2008-08-01

The central autonomic network (CAN) has been described in animal models but has been difficult to elucidate in humans. Potential confounds include physiological noise artifacts affecting brainstem neuroimaging data, and difficulty in deriving non-invasive continuous assessments of autonomic modulation. We have developed and implemented a new method which relates cardiac-gated fMRI timeseries with continuous-time heart rate variability (HRV) to estimate central autonomic processing. As many autonomic structures of interest are in brain regions strongly affected by cardiogenic pulsatility, we chose to cardiac-gate our fMRI acquisition to increase sensitivity. Cardiac-gating introduces T1-variability, which was corrected by transforming fMRI data to a fixed TR using a previously published method [Guimaraes, A.R., Melcher, J.R., et al., 1998. Imaging subcortical auditory activity in humans. Hum. Brain Mapp. 6(1), 33-41]. The electrocardiogram was analyzed with a novel point process adaptive-filter algorithm for computation of the high-frequency (HF) index, reflecting the time-varying dynamics of efferent cardiovagal modulation. Central command of cardiovagal outflow was inferred by using the resample HF timeseries as a regressor to the fMRI data. A grip task was used to perturb the autonomic nervous system. Our combined HRV-fMRI approach demonstrated HF correlation with fMRI activity in the hypothalamus, cerebellum, parabrachial nucleus/locus ceruleus, periaqueductal gray, amygdala, hippocampus, thalamus, and dorsomedial/dorsolateral prefrontal, posterior insular, and middle temporal cortices. While some regions consistent with central cardiovagal control in animal models gave corroborative evidence for our methodology, other mostly higher cortical or limbic-related brain regions may be unique to humans. Our approach should be optimized and applied to study the human brain correlates of autonomic modulation for various stimuli in both physiological and pathological states.

High-density EEG characterization of brain responses to auditory rhythmic stimuli during wakefulness and NREM sleep.

PubMed

Lustenberger, Caroline; Patel, Yogi A; Alagapan, Sankaraleengam; Page, Jessica M; Price, Betsy; Boyle, Michael R; Fröhlich, Flavio

2018-04-01

Auditory rhythmic sensory stimulation modulates brain oscillations by increasing phase-locking to the temporal structure of the stimuli and by increasing the power of specific frequency bands, resulting in Auditory Steady State Responses (ASSR). The ASSR is altered in different diseases of the central nervous system such as schizophrenia. However, in order to use the ASSR as biological markers for disease states, it needs to be understood how different vigilance states and underlying brain activity affect the ASSR. Here, we compared the effects of auditory rhythmic stimuli on EEG brain activity during wake and NREM sleep, investigated the influence of the presence of dominant sleep rhythms on the ASSR, and delineated the topographical distribution of these modulations. Participants (14 healthy males, 20-33 years) completed on the same day a 60 min nap session and two 30 min wakefulness sessions (before and after the nap). During these sessions, amplitude modulated (AM) white noise auditory stimuli at different frequencies were applied. High-density EEG was continuously recorded and time-frequency analyses were performed to assess ASSR during wakefulness and NREM periods. Our analysis revealed that depending on the electrode location, stimulation frequency applied and window/frequencies analysed the ASSR was significantly modulated by sleep pressure (before and after sleep), vigilance state (wake vs. NREM sleep), and the presence of slow wave activity and sleep spindles. Furthermore, AM stimuli increased spindle activity during NREM sleep but not during wakefulness. Thus, (1) electrode location, sleep history, vigilance state and ongoing brain activity needs to be carefully considered when investigating ASSR and (2) auditory rhythmic stimuli during sleep might represent a powerful tool to boost sleep spindles. Copyright © 2017 Elsevier Inc. All rights reserved.

Modulation of Acid-sensing Ion Channel 1a by Intracellular pH and Its Role in Ischemic Stroke.

PubMed

Li, Ming-Hua; Leng, Tian-Dong; Feng, Xue-Chao; Yang, Tao; Simon, Roger P; Xiong, Zhi-Gang

2016-08-26

An important contributor to brain ischemia is known to be extracellular acidosis, which activates acid-sensing ion channels (ASICs), a family of proton-gated sodium channels. Lines of evidence suggest that targeting ASICs may lead to novel therapeutic strategies for stroke. Investigations of the role of ASICs in ischemic brain injury have naturally focused on the role of extracellular pH in ASIC activation. By contrast, intracellular pH (pHi) has received little attention. This is a significant gap in our understanding because the ASIC response to extracellular pH is modulated by pHi, and activation of ASICs by extracellular protons is paradoxically enhanced by intracellular alkalosis. Our previous studies show that acidosis-induced cell injury in in vitro models is attenuated by intracellular acidification. However, whether pHi affects ischemic brain injury in vivo is completely unknown. Furthermore, whereas ASICs in native neurons are composed of different subunits characterized by distinct electrophysiological/pharmacological properties, the subunit-dependent modulation of ASIC activity by pHi has not been investigated. Using a combination of in vitro and in vivo ischemic brain injury models, electrophysiological, biochemical, and molecular biological approaches, we show that the intracellular alkalizing agent quinine potentiates, whereas the intracellular acidifying agent propionate inhibits, oxygen-glucose deprivation-induced cell injury in vitro and brain ischemia-induced infarct volume in vivo Moreover, we find that the potentiation of ASICs by quinine depends on the presence of the ASIC1a, ASIC2a subunits, but not ASIC1b, ASIC3 subunits. Furthermore, we have determined the amino acids in ASIC1a that are involved in the modulation of ASICs by pHi. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Effects of Adenosinergic Modulation on Cytokine Levels in a Pentylenetetrazole-Induced Generalized Tonic-Clonic Seizure Model.

PubMed

Dede, Fazilet; Karadenizli, Sabriye; Özsoy, Özgür Doğa; Eraldemir, Fatma Ceyla; Şahin, Deniz; Ateş, Nurbay

2017-01-01

It has been suggested that the adenosinergic system and cytokines play a role in the pathogenesis of epilepsy. Although the role of the adenosinergic system in the modulation of seizure activity is well known, the mechanism of this modulation needs to be described in detail. We performed this study to determine the contribution of the proinflammatory cytokines to the generalized seizure activity during adenosine and caffeine treatment. We induced generalized tonic-clonic seizures with the administration of 60 mg/kg pentylenetetrazole (PTZ) in male Wistar Albino rats. Adenosine (500 mg/kg) or caffeine (5 mg/kg) was administered before PTZ injection. We monitored seizure activity and then determined the TNF-α, IL-1β, and IL-6 levels in the cortical and thalamic brain regions of rats by ELISA. Adenosine pretreatment significantly extended seizure latency (p < 0.05), but did not affect seizure duration and entry time to stage 4 seizure. Caffeine pretreatment did not change seizure latency and seizure duration. PTZ treatment did not change brain cytokine levels significantly (p > 0.05) compared to the control group. Whereas adenosine pretreatment decreased brain TNF-α, IL-1β, and IL-6 levels significantly (p < 0.05), caffeine pretreatment reduced brain cytokine levels slightly but nonsignificantly (p > 0.05). Our results show that there is a clear relation between adenosinergic system and brain tissue cytokine levels. Our findings indicated that TNF-α, IL-1β, and IL-6 participate in the pathogenesis of generalized seizures, and the inhibition of TNF-α, IL-1β, and IL-6 with adenosinergic modulation may decrease seizure severity. © 2017 S. Karger AG, Basel.

SU-E-T-449: Hippocampal Sparing Radiotherapy Using Intensity Modulated Radiotherapy and Volumetric Modulated Arc Therapy

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

Moon, S; Kyung Hee University Hospital at Gangdong, Gangdong-gu; Kim, D

2015-06-15

Purpose: The hippocampus sparing during the cranial irradiation has become interesting because it may mitigate radiation-induced neurocognitive toxicity. Herein we report our preliminary study for sparing the hippocampus with and without tilling condition for patient with brain metastases. Methods: Ten patients previously treated with whole brain were reviewed. Five patients tilted the head to around 30 degrees and others were treated without tilting. Treatment plans of linear accelerator (Linac)-based volumetric modulated arc therapy (VMAT) and intensity modulated radiotherapy (IMRT) were generated for prescription dose of 30 Gy in 15 fractions. Hippocampal avoidance regions were created with 5-mm volumetric expansion aroundmore » the hippocampus. Whole brain, hippocampus and hippocampal avoidance volume were 1372cm3, 6cm3 and 30cm3 and hippocampal avoidance volume was 2.2% of the whole brain planned target volume in average. Organs at risk (OARs) are hippocampus, eyes, lens, and cochleae. Coverage index (CVI), conformity index (CI), homogeneity index (HI) and mean dose to OARs were used to compare dose characteristic of tilted and non-tilted cases. Results: In IMRT, when CI, CVI and HI of whole brain were 0.88, 0.09 and 0.98 in both tilted and non-tilted cases, absorbed dose of hippocampal avoidance volume in tilted cases were 10% lower than non-tilted cases. Doses in other OARs such as eyes, lens, and cochleae were also decreased about 20% when tilting the head. When CI, HI and CVI in VMAT were 0.9, 0.08 and 0.99, the dose-decreased ratio of OARs in both with and without tilting cases were almost the same with IMRT. But absolute dose of hippocampal avoidance volume in VMAT was 30% lower than IMRT. Conclusion: This study confirms that dose to hippocampus decreases if patients tilt the head. When treating the whole brain with head tilted, patients can acquire the same successful treatment Result and also preserve their valuable memory.« less

Tired and misconnected: A breakdown of brain modularity following sleep deprivation.

PubMed

Ben Simon, Eti; Maron-Katz, Adi; Lahav, Nir; Shamir, Ron; Hendler, Talma

2017-06-01

Sleep deprivation (SD) critically affects a range of cognitive and affective functions, typically assessed during task performance. Whether such impairments stem from changes to the brain's intrinsic functional connectivity remain largely unknown. To examine this hypothesis, we applied graph theoretical analysis on resting-state fMRI data derived from 18 healthy participants, acquired during both sleep-rested and sleep-deprived states. We hypothesized that parameters indicative of graph connectivity, such as modularity, will be impaired by sleep deprivation and that these changes will correlate with behavioral outcomes elicited by sleep loss. As expected, our findings point to a profound reduction in network modularity without sleep, evident in the limbic, default-mode, salience and executive modules. These changes were further associated with behavioral impairments elicited by SD: a decrease in salience module density was associated with worse task performance, an increase in limbic module density was predictive of stronger amygdala activation in a subsequent emotional-distraction task and a shift in frontal hub lateralization (from left to right) was associated with increased negative mood. Altogether, these results portray a loss of functional segregation within the brain and a shift towards a more random-like network without sleep, already detected in the spontaneous activity of the sleep-deprived brain. Hum Brain Mapp 38:3300-3314, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Impact of personality on the cerebral processing of emotional prosody.

PubMed

Brück, Carolin; Kreifelts, Benjamin; Kaza, Evangelia; Lotze, Martin; Wildgruber, Dirk

2011-09-01

While several studies have focused on identifying common brain mechanisms governing the decoding of emotional speech melody, interindividual variations in the cerebral processing of prosodic information, in comparison, have received only little attention to date: Albeit, for instance, differences in personality among individuals have been shown to modulate emotional brain responses, personality influences on the neural basis of prosody decoding have not been investigated systematically yet. Thus, the present study aimed at delineating relationships between interindividual differences in personality and hemodynamic responses evoked by emotional speech melody. To determine personality-dependent modulations of brain reactivity, fMRI activation patterns during the processing of emotional speech cues were acquired from 24 healthy volunteers and subsequently correlated with individual trait measures of extraversion and neuroticism obtained for each participant. Whereas correlation analysis did not indicate any link between brain activation and extraversion, strong positive correlations between measures of neuroticism and hemodynamic responses of the right amygdala, the left postcentral gyrus as well as medial frontal structures including the right anterior cingulate cortex emerged, suggesting that brain mechanisms mediating the decoding of emotional speech melody may vary depending on differences in neuroticism among individuals. Observed trait-specific modulations are discussed in the light of processing biases as well as differences in emotion control or task strategies which may be associated with the personality trait of neuroticism. Copyright © 2011 Elsevier Inc. All rights reserved.

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.

Film/Adhesive Processing Module for Fiber-Placement Processing of Composites

NASA Technical Reports Server (NTRS)

Hulcher, A. Bruce

2007-01-01

An automated apparatus has been designed and constructed that enables the automated lay-up of composite structures incorporating films, foils, and adhesives during the automated fiber-placement process. This apparatus, denoted a film module, could be used to deposit materials in film or thin sheet form either simultaneously when laying down the fiber composite article or in an independent step.

Task relevance modulates the behavioural and neural effects of sensory predictions

PubMed Central

Friston, Karl J.; Nobre, Anna C.

2017-01-01

The brain is thought to generate internal predictions to optimize behaviour. However, it is unclear whether predictions signalling is an automatic brain function or depends on task demands. Here, we manipulated the spatial/temporal predictability of visual targets, and the relevance of spatial/temporal information provided by auditory cues. We used magnetoencephalography (MEG) to measure participants’ brain activity during task performance. Task relevance modulated the influence of predictions on behaviour: spatial/temporal predictability improved spatial/temporal discrimination accuracy, but not vice versa. To explain these effects, we used behavioural responses to estimate subjective predictions under an ideal-observer model. Model-based time-series of predictions and prediction errors (PEs) were associated with dissociable neural responses: predictions correlated with cue-induced beta-band activity in auditory regions and alpha-band activity in visual regions, while stimulus-bound PEs correlated with gamma-band activity in posterior regions. Crucially, task relevance modulated these spectral correlates, suggesting that current goals influence PE and prediction signalling. PMID:29206225

Love as a Modulator of Pain

PubMed Central

Tamam, Sofina; Ahmad, Asma Hayati

2017-01-01

Pain is modulated by various factors, the most notable of which is emotions. Since love is an emotion, it can also modulate pain. The answer to the question of whether it enhances or reduces pain needs to be determined. A review was conducted of animal and human studies in which this enigmatic emotion and its interaction with pain was explored. Recent advances in neuroimaging have revealed similarities in brain activation relating to love and pain. At the simplest level, this interaction can be explained by the overlapping network structure in brain functional connectivity, although the explanation is considerably more complex. The effect of love can either result in increased or decreased pain perception. An explanation of the interaction between pain and love relates to the functional connectivity of the brain and to the psychological construct of the individual, as well as to his or her ability to engage resources relating to emotion regulation. In turn, this determines how a person relates to love and reacts to pain. PMID:28814928

A proteomic network approach across the ALS-FTD disease spectrum resolves clinical phenotypes and genetic vulnerability in human brain.

PubMed

Umoh, Mfon E; Dammer, Eric B; Dai, Jingting; Duong, Duc M; Lah, James J; Levey, Allan I; Gearing, Marla; Glass, Jonathan D; Seyfried, Nicholas T

2018-01-01

Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are neurodegenerative diseases with overlap in clinical presentation, neuropathology, and genetic underpinnings. The molecular basis for the overlap of these disorders is not well established. We performed a comparative unbiased mass spectrometry-based proteomic analysis of frontal cortical tissues from postmortem cases clinically defined as ALS, FTD, ALS and FTD (ALS/FTD), and controls. We also included a subset of patients with the C9orf72 expansion mutation, the most common genetic cause of both ALS and FTD Our systems-level analysis of the brain proteome integrated both differential expression and co-expression approaches to assess the relationship of these differences to clinical and pathological phenotypes. Weighted co-expression network analysis revealed 15 modules of co-expressed proteins, eight of which were significantly different across the ALS-FTD disease spectrum. These included modules associated with RNA binding proteins, synaptic transmission, and inflammation with cell-type specificity that showed correlation with TDP-43 pathology and cognitive dysfunction. Modules were also examined for their overlap with TDP-43 protein-protein interactions, revealing one module enriched with RNA-binding proteins and other causal ALS genes that increased in FTD/ALS and FTD cases. A module enriched with astrocyte and microglia proteins was significantly increased in ALS cases carrying the C9orf72 mutation compared to sporadic ALS cases, suggesting that the genetic expansion is associated with inflammation in the brain even without clinical evidence of dementia. Together, these findings highlight the utility of integrative systems-level proteomic approaches to resolve clinical phenotypes and genetic mechanisms underlying the ALS-FTD disease spectrum in human brain. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

Web service module for access to g-Lite

NASA Astrophysics Data System (ADS)

Goranova, R.; Goranov, G.

2012-10-01

G-Lite is a lightweight grid middleware for grid computing installed on all clusters of the European Grid Infrastructure (EGI). The middleware is partially service-oriented and does not provide well-defined Web services for job management. The existing Web services in the environment cannot be directly used by grid users for building service compositions in the EGI. In this article we present a module of well-defined Web services for job management in the EGI. We describe the architecture of the module and the design of the developed Web services. The presented Web services are composable and can participate in service compositions (workflows). An example of usage of the module with tools for service compositions in g-Lite is shown.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4

PubMed Central

Okuda, Hiroshi; Xing, Fei; Pandey, Puspa R; Sharma, Sambad; Watabe, Misako; Pai, Sudha K.; Mo, Yin-Yuan; Iiizumi-Gairani, Megumi; Hirota, Shigeru; Liu, Yin; Wu, Kerui; Pochampally, Radhika; Watabe, Kounosuke

2012-01-01

Despite significant improvement in survival rates of breast cancer patients, prognosis of metastatic disease is still dismal. Cancer stem-like cells (CSCs) are considered to play a role in metastatic progression of breast cancer; however, the exact pathological role of CSCs is yet to be elucidated. In this report, we found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ specific manner. The results of our microRNA profile analysis for these cells revealed that CSCs that are highly metastatic to bone and brain expressed significantly lower level of miR-7 and that this microRNA was capable of modulating one of the essential genes for induced pluripotent stem cell, KLF4. Interestingly, high expression of KLF4 was significantly and inversely correlated to brain- but not bone-metastasis free survival of breast cancer patients, and we indeed found that the expression of miR-7 significantly suppressed the ability of CSCs to metastasize to brain but not to bone in our animal model. We also examined the expression of miR-7 and KLF4 in brain-metastatic lesions and found that these genes were significantly down- or up-regulated, respectively, in the tumor cells in brain. Furthermore, the results of our in vitro experiments indicate that miR-7 attenuates the abilities of invasion and self-renewal of CSCs by modulating KLF4 expression. These results suggest that miR-7 and KLF4 may serve as biomarkers or therapeutic targets for brain metastasis of breast cancer. PMID:23384942

Tunneling studies of compositionally modulated PB/Fe films

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

Wawro, A.; Witek, A.; Majewski, J.

1988-01-01

Preliminary results of preparation and investigation of compositionally modulated Pb/Fe films are reported. These films have been used as electrodes in Al/Al/sub 2/O/sub 3//{kappa}(Pb/Fe) tunnel junctions and the tunnelling characteristics I-V, dV/dI and d/sup 2/V/d/I/sup 2/ vs V have been studied in dependence on the modulation period.

Composite Crew Module: Primary Structure

NASA Technical Reports Server (NTRS)

Kirsch, Michael T.

2011-01-01

In January 2007, the NASA Administrator and Associate Administrator for the Exploration Systems Mission Directorate chartered the NASA Engineering and Safety Center to design, build, and test a full-scale crew module primary structure, using carbon fiber reinforced epoxy based composite materials. The overall goal of the Composite Crew Module project was to develop a team from the NASA family with hands-on experience in composite design, manufacturing, and testing in anticipation of future space exploration systems being made of composite materials. The CCM project was planned to run concurrently with the Orion project's baseline metallic design within the Constellation Program so that features could be compared and discussed without inducing risk to the overall Program. This report discusses the project management aspects of the project including team organization, decision making, independent technical reviews, and cost and schedule management approach.

Functional Imaging of Audio-Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

PubMed

Rinne, Teemu; Muers, Ross S; Salo, Emma; Slater, Heather; Petkov, Christopher I

2017-06-01

The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio-visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio-visual selective attention modulates the primate brain, identify sources for "lost" attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. © The Author 2017. Published by Oxford University Press.

Functional Imaging of Audio–Visual Selective Attention in Monkeys and Humans: How do Lapses in Monkey Performance Affect Cross-Species Correspondences?

PubMed Central

Muers, Ross S.; Salo, Emma; Slater, Heather; Petkov, Christopher I.

2017-01-01

Abstract The cross-species correspondences and differences in how attention modulates brain responses in humans and animal models are poorly understood. We trained 2 monkeys to perform an audio–visual selective attention task during functional magnetic resonance imaging (fMRI), rewarding them to attend to stimuli in one modality while ignoring those in the other. Monkey fMRI identified regions strongly modulated by auditory or visual attention. Surprisingly, auditory attention-related modulations were much more restricted in monkeys than humans performing the same tasks during fMRI. Further analyses ruled out trivial explanations, suggesting that labile selective-attention performance was associated with inhomogeneous modulations in wide cortical regions in the monkeys. The findings provide initial insights into how audio–visual selective attention modulates the primate brain, identify sources for “lost” attention effects in monkeys, and carry implications for modeling the neurobiology of human cognition with nonhuman animals. PMID:28419201

Stable long-term chronic brain mapping at the single-neuron level.

PubMed

Fu, Tian-Ming; Hong, Guosong; Zhou, Tao; Schuhmann, Thomas G; Viveros, Robert D; Lieber, Charles M

2016-10-01

Stable in vivo mapping and modulation of the same neurons and brain circuits over extended periods is critical to both neuroscience and medicine. Current electrical implants offer single-neuron spatiotemporal resolution but are limited by such factors as relative shear motion and chronic immune responses during long-term recording. To overcome these limitations, we developed a chronic in vivo recording and stimulation platform based on flexible mesh electronics, and we demonstrated stable multiplexed local field potentials and single-unit recordings in mouse brains for at least 8 months without probe repositioning. Properties of acquired signals suggest robust tracking of the same neurons over this period. This recording and stimulation platform allowed us to evoke stable single-neuron responses to chronic electrical stimulation and to carry out longitudinal studies of brain aging in freely behaving mice. Such advantages could open up future studies in mapping and modulating changes associated with learning, aging and neurodegenerative diseases.

Attentional Modulation of Brain Responses to Primary Appetitive and Aversive Stimuli

PubMed Central

Field, Brent A.; Buck, Cara L.; McClure, Samuel M.; Nystrom, Leigh E.; Kahneman, Daniel; Cohen, Jonathan D.

2015-01-01

Studies of subjective well-being have conventionally relied upon self-report, which directs subjects’ attention to their emotional experiences. This method presumes that attention itself does not influence emotional processes, which could bias sampling. We tested whether attention influences experienced utility (the moment-by-moment experience of pleasure) by using functional magnetic resonance imaging (fMRI) to measure the activity of brain systems thought to represent hedonic value while manipulating attentional load. Subjects received appetitive or aversive solutions orally while alternatively executing a low or high attentional load task. Brain regions associated with hedonic processing, including the ventral striatum, showed a response to both juice and quinine. This response decreased during the high-load task relative to the low-load task. Thus, attentional allocation may influence experienced utility by modulating (either directly or indirectly) the activity of brain mechanisms thought to represent hedonic value. PMID:26158468

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I.

PubMed

Fernandez, Ana M; Hernandez-Garzón, Edwin; Perez-Domper, Paloma; Perez-Alvarez, Alberto; Mederos, Sara; Matsui, Takashi; Santi, Andrea; Trueba-Saiz, Angel; García-Guerra, Lucía; Pose-Utrilla, Julia; Fielitz, Jens; Olson, Eric N; Fernandez de la Rosa, Ruben; Garcia Garcia, Luis; Pozo, Miguel Angel; Iglesias, Teresa; Araque, Alfonso; Soya, Hideaki; Perea, Gertrudis; Martin, Eduardo D; Torres Aleman, Ignacio

2017-01-01

Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes. © 2017 by the American Diabetes Association.

Assessment and modulation of neuroplasticity in rehabilitation with transcranial magnetic stimulation

PubMed Central

Bashir, Shahid; Mizrahi, Ilan; Weaver, Kayleen; Fregni, Felipe; Pascual-Leone, Alvaro

2013-01-01

Despite intensive efforts towards the improvement of outcomes after acquired brain injury functional recovery is often limited. One reasons is the challenge in assessing and guiding plasticity after brain injury. In this context, Transcranial Magnetic Stimulation (TMS) - a noninvasive tool of brain stimulation - could play a major role. TMS has shown to be a reliable tool to measure plastic changes in the motor cortex associated with interventions in the motor system; such as motor training and motor cortex stimulation. In addition, as illustrated by the experience in promoting recovery from stroke, TMS a promising therapeutic tool to minimize motor, speech, cognitive, and mood deficits. In this review, we will focus on stroke to discuss how TMS can provide insights into the mechanisms of neurological recovery, and can be used for measurement and modulation of plasticity after an acquired brain insult. PMID:21172687

Application of Pi Preform Composite Joints in Fabrication of NASA Composite Crew Module Demonstration Structure

NASA Technical Reports Server (NTRS)

Higgins, John E.; Pelham, Larry

2008-01-01

This paper will describe unique and extensive use of pre-woven and impregnated pi cross-sections in fabrication of a carbon composite demonstration structure for the Composite Crew Module (CCM) Program. The program is managed by the NASA Safety and Engineering Center with participants from ten NASA Centers and AFRL. Multiple aerospace contractors are participating in the design development, tooling and fabrication effort as well. The goal of the program is to develop an agency wide design team for composite habitable spacecraft. The specific goals for this development project are: a) To gain hands on experience in design, building and testing a composite crew module. b) To validate key assumptions by resolving composite spacecraft design details through fabrication and testing of hardware. This paper will focus on the design and fabrication issues supporting selection of the Lockheed Martin patented Pi pre-form to provide sound composite joints a numerous locations in the structure. This abstract is based on Preliminary Design data. The final design will continue to evolve through the fall of 2007 with fabrication mostly completed by conference date.

Functional cortical network in alpha band correlates with social bargaining.

PubMed

Billeke, Pablo; Zamorano, Francisco; Chavez, Mario; Cosmelli, Diego; Aboitiz, Francisco

2014-01-01

Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals' alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts.

Functional Cortical Network in Alpha Band Correlates with Social Bargaining

PubMed Central

Billeke, Pablo; Zamorano, Francisco; Chavez, Mario; Cosmelli, Diego; Aboitiz, Francisco

2014-01-01

Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals’ alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts. PMID:25286240

Toward an autonomous brain machine interface: integrating sensorimotor reward modulation and reinforcement learning.

PubMed

Marsh, Brandi T; Tarigoppula, Venkata S Aditya; Chen, Chen; Francis, Joseph T

2015-05-13

For decades, neurophysiologists have worked on elucidating the function of the cortical sensorimotor control system from the standpoint of kinematics or dynamics. Recently, computational neuroscientists have developed models that can emulate changes seen in the primary motor cortex during learning. However, these simulations rely on the existence of a reward-like signal in the primary sensorimotor cortex. Reward modulation of the primary sensorimotor cortex has yet to be characterized at the level of neural units. Here we demonstrate that single units/multiunits and local field potentials in the primary motor (M1) cortex of nonhuman primates (Macaca radiata) are modulated by reward expectation during reaching movements and that this modulation is present even while subjects passively view cursor motions that are predictive of either reward or nonreward. After establishing this reward modulation, we set out to determine whether we could correctly classify rewarding versus nonrewarding trials, on a moment-to-moment basis. This reward information could then be used in collaboration with reinforcement learning principles toward an autonomous brain-machine interface. The autonomous brain-machine interface would use M1 for both decoding movement intention and extraction of reward expectation information as evaluative feedback, which would then update the decoding algorithm as necessary. In the work presented here, we show that this, in theory, is possible. Copyright © 2015 the authors 0270-6474/15/357374-14$15.00/0.

An fMRI investigation into the effect of preceding stimuli during visual oddball tasks.

PubMed

Fajkus, Jiří; Mikl, Michal; Shaw, Daniel Joel; Brázdil, Milan

2015-08-15

This study investigates the modulatory effect of stimulus sequence on neural responses to novel stimuli. A group of 34 healthy volunteers underwent event-related functional magnetic resonance imaging while performing a three-stimulus visual oddball task, involving randomly presented frequent stimuli and two types of infrequent stimuli - targets and distractors. We developed a modified categorization of rare stimuli that incorporated the type of preceding rare stimulus, and analyzed the event-related functional data according to this sequence categorization; specifically, we explored hemodynamic response modulation associated with increasing rare-to-rare stimulus interval. For two consecutive targets, a modulation of brain function was evident throughout posterior midline and lateral temporal cortex, while responses to targets preceded by distractors were modulated in a widely distributed fronto-parietal system. As for distractors that follow targets, brain function was modulated throughout a set of posterior brain structures. For two successive distractors, however, no significant modulation was observed, which is consistent with previous studies and our primary hypothesis. The addition of the aforementioned technique extends the possibilities of conventional oddball task analysis, enabling researchers to explore the effects of the whole range of rare stimuli intervals. This methodology can be applied to study a wide range of associated cognitive mechanisms, such as decision making, expectancy and attention. Copyright © 2015 Elsevier B.V. All rights reserved.

Traumatic Brain Injury: A Guide for Caregivers of Service Members and Veterans. Module 1: Introduction to Traumatic Brain Injury

DTIC Science & Technology

2010-04-01

bruising. An MRI scan provides detailed images of the brain using magnetic energy rather than x-ray technology . Intracranial means within the...member/veteran is unable to swallow for many days to weeks, a per cutaneous gastronomy tube (PEG tube) will be placed directly into his or her

Identification of Unstable Network Modules Reveals Disease Modules Associated with the Progression of Alzheimer’s Disease

PubMed Central

Kikuchi, Masataka; Ogishima, Soichi; Miyamoto, Tadashi; Miyashita, Akinori; Kuwano, Ryozo; Nakaya, Jun; Tanaka, Hiroshi

2013-01-01

Alzheimer’s disease (AD), the most common cause of dementia, is associated with aging, and it leads to neuron death. Deposits of amyloid β and aberrantly phosphorylated tau protein are known as pathological hallmarks of AD, but the underlying mechanisms have not yet been revealed. A high-throughput gene expression analysis previously showed that differentially expressed genes accompanying the progression of AD were more down-regulated than up-regulated in the later stages of AD. This suggested that the molecular networks and their constituent modules collapsed along with AD progression. In this study, by using gene expression profiles and protein interaction networks (PINs), we identified the PINs expressed in three brain regions: the entorhinal cortex (EC), hippocampus (HIP) and superior frontal gyrus (SFG). Dividing the expressed PINs into modules, we examined the stability of the modules with AD progression and with normal aging. We found that in the AD modules, the constituent proteins, interactions and cellular functions were not maintained between consecutive stages through all brain regions. Interestingly, the modules were collapsed with AD progression, specifically in the EC region. By identifying the modules that were affected by AD pathology, we found the transcriptional regulation-associated modules that interact with the proteasome-associated module via UCHL5 hub protein, which is a deubiquitinating enzyme. Considering PINs as a system made of network modules, we found that the modules relevant to the transcriptional regulation are disrupted in the EC region, which affects the ubiquitin-proteasome system. PMID:24348898

KV1 and KV3 Potassium Channels Identified at Presynaptic Terminals of the Corticostriatal Synapses in Rat

PubMed Central

Meneses, David; Vega, Ana V.; Torres-Cruz, Francisco Miguel; Barral, Jaime

2016-01-01

In the last years it has been increasingly clear that KV-channel activity modulates neurotransmitter release. The subcellular localization and composition of potassium channels are crucial to understanding its influence on neurotransmitter release. To investigate the role of KV in corticostriatal synapses modulation, we combined extracellular recording of population-spike and pharmacological blockage with specific and nonspecific blockers to identify several families of KV channels. We induced paired-pulse facilitation (PPF) and studied the changes in paired-pulse ratio (PPR) before and after the addition of specific KV blockers to determine whether particular KV subtypes were located pre- or postsynaptically. Initially, the presence of KV channels was tested by exposing brain slices to tetraethylammonium or 4-aminopyridine; in both cases we observed a decrease in PPR that was dose dependent. Further experiments with tityustoxin, margatoxin, hongotoxin, agitoxin, dendrotoxin, and BDS-I toxins all rendered a reduction in PPR. In contrast heteropodatoxin and phrixotoxin had no effect. Our results reveal that corticostriatal presynaptic KV channels have a complex stoichiometry, including heterologous combinations KV1.1, KV1.2, KV1.3, and KV1.6 isoforms, as well as KV3.4, but not KV4 channels. The variety of KV channels offers a wide spectrum of possibilities to regulate neurotransmitter release, providing fine-tuning mechanisms to modulate synaptic strength. PMID:27379187

A Tri-network Model of Human Semantic Processing

PubMed Central

Xu, Yangwen; He, Yong; Bi, Yanchao

2017-01-01

Humans process the meaning of the world via both verbal and nonverbal modalities. It has been established that widely distributed cortical regions are involved in semantic processing, yet the global wiring pattern of this brain system has not been considered in the current neurocognitive semantic models. We review evidence from the brain-network perspective, which shows that the semantic system is topologically segregated into three brain modules. Revisiting previous region-based evidence in light of these new network findings, we postulate that these three modules support multimodal experiential representation, language-supported representation, and semantic control. A tri-network neurocognitive model of semantic processing is proposed, which generates new hypotheses regarding the network basis of different types of semantic processes. PMID:28955266

Dietary Selenium Supplementation Modulates Growth of Brain Metastatic Tumors and Changes the Expression of Adhesion Molecules in Brain Microvessels.

PubMed

Wrobel, Jagoda K; Wolff, Gretchen; Xiao, Rijin; Power, Ronan F; Toborek, Michal

2016-08-01

Various dietary agents can modulate tumor invasiveness. The current study explored whether selenoglycoproteins (SeGPs) extracted from selenium-enriched yeast affect tumor cell homing and growth in the brain. Mice were fed diets enriched with specific SeGPs (SeGP40 or SeGP65, 1 mg/kg Se each), glycoproteins (GP40 or GP65, 0.2-0.3 mg/kg Se each) or a control diet (0.2-0.3 mg/kg Se) for 12 weeks. Then, murine Lewis lung carcinoma cells were infused into the brain circulation. Analyses were performed at early (48 h) and late stages (3 weeks) post tumor cell infusion. Imaging of tumor progression in the brain revealed that mice fed SeGP65-enriched diet displayed diminished metastatic tumor growth, fewer extravasating tumor cells and smaller metastatic lesions. While administration of tumor cells resulted in a significant upregulation of adhesion molecules in the early stage of tumor progression, overexpression of VCAM-1 (vascular call adhesion molecule-1) and ALCAM (activated leukocyte cell adhesion molecule) messenger RNA (mRNA) was diminished in SeGP65 supplemented mice. Additionally, mice fed SeGP65 showed decreased expression of acetylated NF-κB p65, 48 h post tumor cell infusion. The results indicate that tumor progression in the brain can be modulated by specific SeGPs. Selenium-containing compounds were more effective than their glycoprotein controls, implicating selenium as a potential negative regulator of metastatic process.

DBMap: a TreeMap-based framework for data navigation and visualization of brain research registry

NASA Astrophysics Data System (ADS)

Zhang, Ming; Zhang, Hong; Tjandra, Donny; Wong, Stephen T. C.

2003-05-01

The purpose of this study is to investigate and apply a new, intuitive and space-conscious visualization framework to facilitate efficient data presentation and exploration of large-scale data warehouses. We have implemented the DBMap framework for the UCSF Brain Research Registry. Such a novel utility would facilitate medical specialists and clinical researchers in better exploring and evaluating a number of attributes organized in the brain research registry. The current UCSF Brain Research Registry consists of a federation of disease-oriented database modules, including Epilepsy, Brain Tumor, Intracerebral Hemorrphage, and CJD (Creuzfeld-Jacob disease). These database modules organize large volumes of imaging and non-imaging data to support Web-based clinical research. While the data warehouse supports general information retrieval and analysis, there lacks an effective way to visualize and present the voluminous and complex data stored. This study investigates whether the TreeMap algorithm can be adapted to display and navigate categorical biomedical data warehouse or registry. TreeMap is a space constrained graphical representation of large hierarchical data sets, mapped to a matrix of rectangles, whose size and color represent interested database fields. It allows the display of a large amount of numerical and categorical information in limited real estate of computer screen with an intuitive user interface. The paper will describe, DBMap, the proposed new data visualization framework for large biomedical databases. Built upon XML, Java and JDBC technologies, the prototype system includes a set of software modules that reside in the application server tier and provide interface to backend database tier and front-end Web tier of the brain registry.

Interaction between total body gamma-irradiation and choline deficiency triggers immediate modulation of choline and choline-containing moieties.

PubMed

Batra, Vipen; Kislay, Binita; Devasagayam, Thomas Paul Asir

2011-12-01

The objective of this study was to examine the effect of 60Co-gamma (γ) radiation on acute phase modulation, if any, of choline and choline-containing moieties in choline-deficient subjects. Corresponding results could provide information that might be useful in the management of adverse effects of γ-radiation. Male Swiss mice maintained on a choline-sufficient diet (CSD) and choline-free diet (CFD) based on AIN-93M formula, were subjected to whole body γ-irradiation (2-6 Gy). Liver, serum and brain samples from each group were then tested for: (i) Alterations in choline and choline-containing moieties such as phosphatidylcholine (PC) and sphingomyeline (SM); and (ii) modulation of choline profile modulating enzymes such as phospholipase D (PLD) and total sphingomyelinase (t-SMase). Liver and brain samples were also subjected to histo-pathological examinations. No significant changes were observed in folate, choline, choline-containing moieties and choline-modulating enzymes in choline-sufficient mice. In contrast, interaction between cytotoxic effects of γ-radiation and choline deficiency modulated choline and choline-containing moieties. Feeding CFD reduced hepatic concentrations of choline, PC and SM whereas PLD and t-SMase activities were significantly raised. The decrease in liver choline and choline-containing moieties was accompanied by an increase in blood choline concentration. Despite choline deficiency, the level of choline and acetylcholine synthesizing enzyme choline acetyltransfease (ChAT) significantly increased in the brain. We propose that choline deprivation and γ-radiation interact to modulate choline reserves of hepatic tissue, which might release choline to blood. Our studies also clearly showed that interaction between choline deficiency and γ-radiation might substantially enhance liver adipogenesis.

To Modulate and Be Modulated: Estrogenic Influences on Auditory Processing of Communication Signals within a Socio-Neuro-Endocrine Framework

PubMed Central

Yoder, Kathleen M.; Vicario, David S.

2012-01-01

Gonadal hormones modulate behavioral responses to sexual stimuli, and communication signals can also modulate circulating hormone levels. In several species, these combined effects appear to underlie a two-way interaction between circulating gonadal hormones and behavioral responses to socially salient stimuli. Recent work in songbirds has shown that manipulating local estradiol levels in the auditory forebrain produces physiological changes that affect discrimination of conspecific vocalizations and can affect behavior. These studies provide new evidence that estrogens can directly alter auditory processing and indirectly alter the behavioral response to a stimulus. These studies show that: 1. Local estradiol action within an auditory area is necessary for socially-relevant sounds to induce normal physiological responses in the brains of both sexes; 2. These physiological effects occur much more quickly than predicted by the classical time-frame for genomic effects; 3. Estradiol action within the auditory forebrain enables behavioral discrimination among socially-relevant sounds in males; and 4. Estradiol is produced locally in the male brain during exposure to particular social interactions. The accumulating evidence suggests a socio-neuro-endocrinology framework in which estradiol is essential to auditory processing, is increased by a socially relevant stimulus, acts rapidly to shape perception of subsequent stimuli experienced during social interactions, and modulates behavioral responses to these stimuli. Brain estrogens are likely to function similarly in both songbird sexes because aromatase and estrogen receptors are present in both male and female forebrain. Estrogenic modulation of perception in songbirds and perhaps other animals could fine-tune male advertising signals and female ability to discriminate them, facilitating mate selection by modulating behaviors. Keywords: Estrogens, Songbird, Social Context, Auditory Perception PMID:22201281

High Performance Composites. "Designed" Materials for the New Millennium. 2nd Module in a Series on Advanced Materials. Resources in Technology.

ERIC Educational Resources Information Center

Jacobs, James A.

1994-01-01

This learning module on composites such as polymer matrix, metal matrix, ceramic matrix, particulate, and laminar includes a design brief giving context, objectives, evaluation, student outcomes, and quiz. (SK)

Weight gain in anorexia nervosa does not ameliorate the faecal microbiota, branched chain fatty acid profiles, and gastrointestinal complaints

PubMed Central

Mack, Isabelle; Cuntz, Ulrich; Grämer, Claudia; Niedermaier, Sabrina; Pohl, Charlotte; Schwiertz, Andreas; Zimmermann, Kurt; Zipfel, Stephan; Enck, Paul; Penders, John

2016-01-01

The gut microbiota not only influences host metabolism but can also affect brain function and behaviour through the microbiota-gut-brain axis. To explore the potential role of the intestinal microbiota in anorexia nervosa (AN), we comprehensively investigated the faecal microbiota and short-chain fatty acids in these patients before (n = 55) and after weight gain (n = 44) in comparison to normal-weight participants (NW, n = 55) along with dietary intake and gastrointestinal complaints. We show profound microbial perturbations in AN patients as compared to NW participants, with higher levels of mucin-degraders and members of Clostridium clusters I, XI and XVIII and reduced levels of the butyrate-producing Roseburia spp. Branched-chain fatty acid concentrations, being markers for protein fermentation, were elevated. Distinct perturbations in microbial community compositions were observed for individual restrictive and binge/purging AN-subtypes. Upon weight gain, microbial richness increased, however perturbations in intestinal microbiota and short chain fatty acid profiles in addition to several gastrointestinal symptoms did not recover. These insights provide new leads to modulate the intestinal microbiota in order to improve the outcomes of the standard therapy. PMID:27229737

Intestinal microbiota in pathophysiology and management of irritable bowel syndrome

PubMed Central

Lee, Kang Nyeong; Lee, Oh Young

2014-01-01

Irritable bowel syndrome (IBS) is a functional bowel disorder without any structural or metabolic abnormalities that sufficiently explain the symptoms, which include abdominal pain and discomfort, and bowel habit changes such as diarrhea and constipation. Its pathogenesis is multifactorial: visceral hypersensitivity, dysmotility, psychosocial factors, genetic or environmental factors, dysregulation of the brain-gut axis, and altered intestinal microbiota have all been proposed as possible causes. The human intestinal microbiota are composed of more than 1000 different bacterial species and 1014 cells, and are essential for the development, function, and homeostasis of the intestine, and for individual health. The putative mechanisms that explain the role of microbiota in the development of IBS include altered composition or metabolic activity of the microbiota, mucosal immune activation and inflammation, increased intestinal permeability and impaired mucosal barrier function, sensory-motor disturbances provoked by the microbiota, and a disturbed gut-microbiota-brain axis. Therefore, modulation of the intestinal microbiota through dietary changes, and use of antibiotics, probiotics, and anti-inflammatory agents has been suggested as strategies for managing IBS symptoms. This review summarizes and discusses the accumulating evidence that intestinal microbiota play a role in the pathophysiology and management of IBS. PMID:25083061

Orientation-modulated attention effect on visual evoked potential: Application for PIN system using brain-computer interface.

PubMed

Wilaiprasitporn, Theerawit; Yagi, Tohru

2015-01-01

This research demonstrates the orientation-modulated attention effect on visual evoked potential. We combined this finding with our previous findings about the motion-modulated attention effect and used the result to develop novel visual stimuli for a personal identification number (PIN) application based on a brain-computer interface (BCI) framework. An electroencephalography amplifier with a single electrode channel was sufficient for our application. A computationally inexpensive algorithm and small datasets were used in processing. Seven healthy volunteers participated in experiments to measure offline performance. Mean accuracy was 83.3% at 13.9 bits/min. Encouraged by these results, we plan to continue developing the BCI-based personal identification application toward real-time systems.

Towards a neural basis of music perception.

PubMed

Koelsch, Stefan; Siebel, Walter A

2005-12-01

Music perception involves complex brain functions underlying acoustic analysis, auditory memory, auditory scene analysis, and processing of musical syntax and semantics. Moreover, music perception potentially affects emotion, influences the autonomic nervous system, the hormonal and immune systems, and activates (pre)motor representations. During the past few years, research activities on different aspects of music processing and their neural correlates have rapidly progressed. This article provides an overview of recent developments and a framework for the perceptual side of music processing. This framework lays out a model of the cognitive modules involved in music perception, and incorporates information about the time course of activity of some of these modules, as well as research findings about where in the brain these modules might be located.

Driving the need to feed: Insight into the collaborative interaction between ghrelin and endocannabinoid systems in modulating brain reward systems.

PubMed

Edwards, Alexander; Abizaid, Alfonso

2016-07-01

Independent stimulation of either the ghrelin or endocannabinoid system promotes food intake and increases adiposity. Given the similar distribution of their receptors in feeding associated brain regions and organs involved in metabolism, it is not surprising that evidence of their interaction and its importance in modulating energy balance has emerged. This review documents the relationship between ghrelin and endocannabinoid systems within the periphery and hypothalamus (HYP) before presenting evidence suggesting that these two systems likewise work collaboratively within the ventral tegmental area (VTA) to modulate non-homeostatic feeding. Mechanisms, consistent with current evidence and local infrastructure within the VTA, will be proposed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aging and sequential modulations of poorer strategy effects: An EEG study in arithmetic problem solving.

PubMed

Hinault, Thomas; Lemaire, Patrick; Phillips, Natalie

2016-01-01

This study investigated age-related differences in electrophysiological signatures of sequential modulations of poorer strategy effects. Sequential modulations of poorer strategy effects refer to decreased poorer strategy effects (i.e., poorer performance when the cued strategy is not the best) on current problem following poorer strategy problems compared to after better strategy problems. Analyses on electrophysiological (EEG) data revealed important age-related changes in time, frequency, and coherence of brain activities underlying sequential modulations of poorer strategy effects. More specifically, sequential modulations of poorer strategy effects were associated with earlier and later time windows (i.e., between 200- and 550 ms and between 850- and 1250 ms). Event-related potentials (ERPs) also revealed an earlier onset in older adults, together with more anterior and less lateralized activations. Furthermore, sequential modulations of poorer strategy effects were associated with theta and alpha frequencies in young adults while these modulations were found in delta frequency and theta inter-hemispheric coherence in older adults, consistent with qualitatively distinct patterns of brain activity. These findings have important implications to further our understanding of age-related differences and similarities in sequential modulations of cognitive control processes during arithmetic strategy execution. Copyright © 2015 Elsevier B.V. All rights reserved.

Disrupted functional connectome in antisocial personality disorder.

PubMed

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen; Wang, Wei; Shen, Dinggang

2017-08-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD.

Disrupted functional connectome in antisocial personality disorder

PubMed Central

Jiang, Weixiong; Shi, Feng; Liao, Jian; Liu, Huasheng; Wang, Tao; Shen, Celina; Shen, Hui; Hu, Dewen

2017-01-01

Studies on antisocial personality disorder (ASPD) subjects focus on brain functional alterations in relation to antisocial behaviors. Neuroimaging research has identified a number of focal brain regions with abnormal structures or functions in ASPD. However, little is known about the connections among brain regions in terms of inter-regional whole-brain networks in ASPD patients, as well as possible alterations of brain functional topological organization. In this study, we employ resting-state functional magnetic resonance imaging (R-fMRI) to examine functional connectome of 32 ASPD patients and 35 normal controls by using a variety of network properties, including small-worldness, modularity, and connectivity. The small-world analysis reveals that ASPD patients have increased path length and decreased network efficiency, which implies a reduced ability of global integration of whole-brain functions. Modularity analysis suggests ASPD patients have decreased overall modularity, merged network modules, and reduced intra- and inter-module connectivities related to frontal regions. Also, network-based statistics show that an internal sub-network, composed of 16 nodes and 16 edges, is significantly affected in ASPD patients, where brain regions are mostly located in the fronto-parietal control network. These results suggest that ASPD is associated with both reduced brain integration and segregation in topological organization of functional brain networks, particularly in the fronto-parietal control network. These disruptions may contribute to disturbances in behavior and cognition in patients with ASPD. Our findings may provide insights into a deeper understanding of functional brain networks of ASPD. PMID:27541949

Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces.

PubMed

Benyamini, Miri; Zacksenhouse, Miriam

2015-01-01

Recent experiments with brain-machine-interfaces (BMIs) indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus, we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal.

Optimal feedback control successfully explains changes in neural modulations during experiments with brain-machine interfaces

PubMed Central

Benyamini, Miri; Zacksenhouse, Miriam

2015-01-01

Recent experiments with brain-machine-interfaces (BMIs) indicate that the extent of neural modulations increased abruptly upon starting to operate the interface, and especially after the monkey stopped moving its hand. In contrast, neural modulations that are correlated with the kinematics of the movement remained relatively unchanged. Here we demonstrate that similar changes are produced by simulated neurons that encode the relevant signals generated by an optimal feedback controller during simulated BMI experiments. The optimal feedback controller relies on state estimation that integrates both visual and proprioceptive feedback with prior estimations from an internal model. The processing required for optimal state estimation and control were conducted in the state-space, and neural recording was simulated by modeling two populations of neurons that encode either only the estimated state or also the control signal. Spike counts were generated as realizations of doubly stochastic Poisson processes with linear tuning curves. The model successfully reconstructs the main features of the kinematics and neural activity during regular reaching movements. Most importantly, the activity of the simulated neurons successfully reproduces the observed changes in neural modulations upon switching to brain control. Further theoretical analysis and simulations indicate that increasing the process noise during normal reaching movement results in similar changes in neural modulations. Thus, we conclude that the observed changes in neural modulations during BMI experiments can be attributed to increasing process noise associated with the imperfect BMI filter, and, more directly, to the resulting increase in the variance of the encoded signals associated with state estimation and the required control signal. PMID:26042002

Frequency-dependent tACS modulation of BOLD signal during rhythmic visual stimulation.

PubMed

Chai, Yuhui; Sheng, Jingwei; Bandettini, Peter A; Gao, Jia-Hong

2018-05-01

Transcranial alternating current stimulation (tACS) has emerged as a promising tool for modulating cortical oscillations. In previous electroencephalogram (EEG) studies, tACS has been found to modulate brain oscillatory activity in a frequency-specific manner. However, the spatial distribution and hemodynamic response for this modulation remains poorly understood. Functional magnetic resonance imaging (fMRI) has the advantage of measuring neuronal activity in regions not only below the tACS electrodes but also across the whole brain with high spatial resolution. Here, we measured fMRI signal while applying tACS to modulate rhythmic visual activity. During fMRI acquisition, tACS at different frequencies (4, 8, 16, and 32 Hz) was applied along with visual flicker stimulation at 8 and 16 Hz. We analyzed the blood-oxygen-level-dependent (BOLD) signal difference between tACS-ON vs tACS-OFF, and different frequency combinations (e.g., 4 Hz tACS, 8 Hz flicker vs 8 Hz tACS, 8 Hz flicker). We observed significant tACS modulation effects on BOLD responses when the tACS frequency matched the visual flicker frequency or the second harmonic frequency. The main effects were predominantly seen in regions that were activated by the visual task and targeted by the tACS current distribution. These findings bridge different scientific domains of tACS research and demonstrate that fMRI could localize the tACS effect on stimulus-induced brain rhythms, which could lead to a new approach for understanding the high-level cognitive process shaped by the ongoing oscillatory signal. © 2018 Wiley Periodicals, Inc.

Circadian regulation of slow waves in human sleep: Topographical aspects

PubMed Central

Lazar, Alpar S.; Lazar, Zsolt I.; Dijk, Derk-Jan

2015-01-01

Slow waves (SWs, 0.5–4 Hz) in field potentials during sleep reflect synchronized alternations between bursts of action potentials and periods of membrane hyperpolarization of cortical neurons. SWs decline during sleep and this is thought to be related to a reduction of synaptic strength in cortical networks and to be central to sleep's role in maintaining brain function. A central assumption in current concepts of sleep function is that SWs during sleep, and associated recovery processes, are independent of circadian rhythmicity. We tested this hypothesis by quantifying all SWs from 12 EEG derivations in 34 participants in whom 231 sleep periods were scheduled across the circadian cycle in a 10-day forced-desynchrony protocol which allowed estimation of the separate circadian and sleep-dependent modulation of SWs. Circadian rhythmicity significantly modulated the incidence, amplitude, frequency and the slope of the SWs such that the peaks of the circadian rhythms in these slow-wave parameters were located during the biological day. Topographical analyses demonstrated that the sleep-dependent modulation of SW characteristics was most prominent in frontal brain areas whereas the circadian effect was similar to or greater than the sleep-dependent modulation over the central and posterior brain regions. The data demonstrate that circadian rhythmicity directly modulates characteristics of SWs thought to be related to synaptic plasticity and that this modulation depends on topography. These findings have implications for the understanding of local sleep regulation and conditions such as ageing, depression, and neurodegeneration which are associated with changes in SWs, neural plasticity and circadian rhythmicity. PMID:25979664

Heparanase Mechanisms in Melanoma Brain Metastasis

DTIC Science & Technology

2015-10-01

and ultimately affecting the modulation of BMM. 4 2. KEYWORDS: Brain-metastatic melanoma (BMM), Heparanase (HPSE), Exosomes , proteomic profiling...levels of exosomes , microvescicles that were found to be significantly implicated in the metastatic cancer events, notably to brain (6). Exosomes ...microenvironment. Thus, exosomes isolated from our melanoma/BMM cell models were interrogated for HPSE, MicroRNAs, and for protein expression contents by

Cathodal Transcranial Direct Current Stimulation of the Right Wernicke's Area Improves Comprehension in Subacute Stroke Patients

ERIC Educational Resources Information Center

You, Dae Sang; Kim, Dae-Yul; Chun, Min Ho; Jung, Seung Eun; Park, Sung Jong

2011-01-01

Previous studies have shown the appearance of right-sided language-related brain activity in right-handed patients after a stroke. Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been shown to modulate excitability in the brain. Moreover, rTMS and…

More than a drainage fluid: the role of CSF in signaling in the brain and other effects on brain tissue.

PubMed

Illes, Sebastian

2017-01-01

Current progress in neuroscience demonstrates that the brain is not an isolated organ and is influenced by the systemic environment and extracerebral processes within the body. In view of this new concept, blood and cerebrospinal fluid (CSF) are important body fluids linking extracerebral and intracerebral processes. For decades, substantial evidence has been accumulated indicating that CSF modulates brain states and influences behavior as well as cognition. This chapter provides an overview of how CSF directly modulates the function of different types of brain cells, such as neurons, neural stem cells, and CSF-contacting cells. Alterations in CSF content occur in most pathologic central nervous system (CNS) conditions. In a classic view, the function of CSF is to drain waste products and detrimental factors derived from diseased brain parenchyma. This chapter presents examples for how intra- and extracerebral pathologic processes lead to alterations in the CSF content. Current knowledge about how pathologically altered CSF influences the functionality of brain cells will be presented. Thereby, it becomes evident that CSF has more than a drainage function and has a causal role for the etiology and pathogenesis of different CNS diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Electro-acupuncture at different acupoints modulating the relative specific brain functional network

NASA Astrophysics Data System (ADS)

Fang, Jiliang; Wang, Xiaoling; Wang, Yin; Liu, Hesheng; Hong, Yang; Liu, Jun; Zhou, Kehua; Wang, Lei; Xue, Chao; Song, Ming; Liu, Baoyan; Zhu, Bing

2010-11-01

Objective: The specific brain effects of acupoint are important scientific concern in acupuncture. However, previous acupuncture fMRI studies focused on acupoints in muscle layer on the limb. Therefore, researches on acupoints within connective tissue at trunk are warranted. Material and Methods: Brain effects of acupuncture on abdomen at acupoints Guanyuan (CV4) and Zhongwan (CV12) were tested using fMRI on 21 healthy volunteers. The data acquisition was performed at resting state, during needle retention, electroacupuncture (EA) and post-EA resting state. Needling sensations were rated after every electroacupuncture (EA) procedure. The needling sensations and the brain functional activity and connectivity were compared between CV4 and CV12 using SPSS, SPM2 and the local and remote connectivity maps. Results and conclusion: EA at CV4 and CV12 induced apparent deactivation effects in the limbic-paralimbic-neocortical network. The default mode of the brain was modified by needle retention and EA, respectively. The functional brain network was significantly changed post EA. However, the minor differences existed between these two acupoints. The results demonstrated similarity between functional brain network mode of acupuncture modulation and functional circuits of emotional and cognitive regulation. Acupuncture may produce analgesia, anti-anxiety and anti-depression via the limbic-paralimbic-neocortical network (LPNN).

Glutamate-Mediated Blood-Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery.

PubMed

Vazana, Udi; Veksler, Ronel; Pell, Gaby S; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio; Friedman, Alon

2016-07-20

The blood-brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood-brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood-brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood-brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood-brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. In this study, we reveal a new mechanism that governs blood-brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. Copyright © 2016 the authors 0270-6474/16/367727-13$15.00/0.

Glutamate-Mediated Blood–Brain Barrier Opening: Implications for Neuroprotection and Drug Delivery

PubMed Central

Vazana, Udi; Veksler, Ronel; Pell, Gaby S.; Prager, Ofer; Fassler, Michael; Chassidim, Yoash; Roth, Yiftach; Shahar, Hamutal; Zangen, Abraham; Raccah, Ruggero; Onesti, Emanuela; Ceccanti, Marco; Colonnese, Claudio; Santoro, Antonio; Salvati, Maurizio; D'Elia, Alessandro; Nucciarelli, Valter; Inghilleri, Maurizio

2016-01-01

The blood–brain barrier is a highly selective anatomical and functional interface allowing a unique environment for neuro-glia networks. Blood–brain barrier dysfunction is common in most brain disorders and is associated with disease course and delayed complications. However, the mechanisms underlying blood–brain barrier opening are poorly understood. Here we demonstrate the role of the neurotransmitter glutamate in modulating early barrier permeability in vivo. Using intravital microscopy, we show that recurrent seizures and the associated excessive glutamate release lead to increased vascular permeability in the rat cerebral cortex, through activation of NMDA receptors. NMDA receptor antagonists reduce barrier permeability in the peri-ischemic brain, whereas neuronal activation using high-intensity magnetic stimulation increases barrier permeability and facilitates drug delivery. Finally, we conducted a double-blind clinical trial in patients with malignant glial tumors, using contrast-enhanced magnetic resonance imaging to quantitatively assess blood–brain barrier permeability. We demonstrate the safety of stimulation that efficiently increased blood–brain barrier permeability in 10 of 15 patients with malignant glial tumors. We suggest a novel mechanism for the bidirectional modulation of brain vascular permeability toward increased drug delivery and prevention of delayed complications in brain disorders. SIGNIFICANCE STATEMENT In this study, we reveal a new mechanism that governs blood–brain barrier (BBB) function in the rat cerebral cortex, and, by using the discovered mechanism, we demonstrate bidirectional control over brain endothelial permeability. Obviously, the clinical potential of manipulating BBB permeability for neuroprotection and drug delivery is immense, as we show in preclinical and proof-of-concept clinical studies. This study addresses an unmet need to induce transient BBB opening for drug delivery in patients with malignant brain tumors and effectively facilitate BBB closure in neurological disorders. PMID:27445149

A Hypothesis for the Composition of the Tardigrade Brain and its Implications for Panarthropod Brain Evolution.

PubMed

Smith, Frank W; Bartels, Paul J; Goldstein, Bob

2017-09-01

Incredibly disparate brain types are found in Metazoa, which raises the question of how this disparity evolved. Ecdysozoa includes representatives that exhibit ring-like brains-the Cycloneuralia-and representatives that exhibit ganglionic brains-the Panarthropoda (Euarthropoda, Onychophora, and Tardigrada). The evolutionary steps leading to these distinct brain types are unclear. Phylogenomic analyses suggest that the enigmatic Tardigrada is a closely related outgroup of a Euarthropoda + Onychophora clade; as such, the brains of tardigrades may provide insight into the evolution of ecdysozoan brains. Recently, evolutionarily salient questions have arisen regarding the composition of the tardigrade brain. To address these questions, we investigated brain anatomy in four tardigrade species-Hypsibius dujardini, Milnesium n. sp., Echiniscus n. sp., and Batillipes n. sp.-that together span Tardigrada. Our results suggest that general brain morphology is conserved across Tardigrada. Based on our results we present a hypothesis that proposes direct parallels between the tardigrade brain and the segmental trunk ganglia of the tardigrade ventral nervous system. In this hypothesis, brain neuropil nearly circumscribes the tardigrade foregut. We suggest that the tardigrade brain retains aspects of an ancestral cycloneuralian brain, while exhibiting ganglionic structure characteristic of euarthropods and onychophorans. © The Author 2017. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.All rights reserved. For permissions please email: journals.permissions@oup.com.

Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women

PubMed Central

de Jong, Peter J.; Georgiadis, Janniko R.

2014-01-01

Lifetime experiences shape people’s attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile–vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-‘hot’ vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-‘hot’) associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli. PMID:23051899

The Synapse Project: Engagement in mentally challenging activities enhances neural efficiency.

PubMed

McDonough, Ian M; Haber, Sara; Bischof, Gérard N; Park, Denise C

2015-01-01

Correlational and limited experimental evidence suggests that an engaged lifestyle is associated with the maintenance of cognitive vitality in old age. However, the mechanisms underlying these engagement effects are poorly understood. We hypothesized that mental effort underlies engagement effects and used fMRI to examine the impact of high-challenge activities (digital photography and quilting) compared with low-challenge activities (socializing or performing low-challenge cognitive tasks) on neural function at pretest, posttest, and one year after the engagement program. In the scanner, participants performed a semantic-classification task with two levels of difficulty to assess the modulation of brain activity in response to task demands. The High-Challenge group, but not the Low-Challenge group, showed increased modulation of brain activity in medial frontal, lateral temporal, and parietal cortex-regions associated with attention and semantic processing-some of which were maintained a year later. This increased modulation stemmed from decreases in brain activity during the easy condition for the High-Challenge group and was associated with time committed to the program, age, and cognition. Sustained engagement in cognitively demanding activities facilitated cognition by increasing neural efficiency. Mentally-challenging activities may be neuroprotective and an important element to maintaining a healthy brain into late adulthood.

Subcortical BOLD responses during visual sexual stimulation vary as a function of implicit porn associations in women.

PubMed

Borg, Charmaine; de Jong, Peter J; Georgiadis, Janniko R

2014-02-01

Lifetime experiences shape people's attitudes toward sexual stimuli. Visual sexual stimulation (VSS), for instance, may be perceived as pleasurable by some, but as disgusting or ambiguous by others. VSS depicting explicit penile-vaginal penetration (PEN) is relevant in this respect, because the act of penetration is a core sexual activity. In this study, 20 women without sexual complaints participated. We used functional magnetic resonance imaging and a single-target implicit association task to investigate how brain responses to PEN were modulated by the initial associations in memory (PEN-'hot' vs PEN-disgust) with such hardcore pornographic stimuli. Many brain areas responded to PEN in the same way they responded to disgust stimuli, and PEN-induced brain activity was prone to modulation by subjective disgust ratings toward PEN stimuli. The relative implicit PEN-disgust (relative to PEN-'hot') associations exclusively modulated PEN-induced brain responses: comparatively negative (PEN-disgust) implicit associations with pornography predicted the strongest PEN-related responses in the basal forebrain (including nucleus accumbens and bed nucleus of stria terminalis), midbrain and amygdala. Since these areas are often implicated in visual sexual processing, the present findings should be taken as a warning: apparently their involvement may also indicate a negative or ambivalent attitude toward sexual stimuli.

Evidence of successful modulation of brain activation and subjective experience during reappraisal of negative emotion in unmedicated depression.

PubMed

Dillon, Daniel Gerard; Pizzagalli, Diego Andrea

2013-05-30

Functional magnetic resonance imaging (fMRI) was used to examine cognitive regulation of negative emotion in 12 unmedicated patients with major depressive disorder (MDD) and 24 controls. The participants used reappraisal to increase (real condition) and reduce (photo condition) the personal relevance of negative and neutral pictures during fMRI as valence ratings were collected; passive viewing (look condition) served as a baseline. Reappraisal was not strongly affected by MDD. Ratings indicated that both groups successfully reappraised negative emotional experience. Both groups also showed better memory for negative vs. neutral pictures 2 weeks later. Across groups, increased brain activation was observed on negative/real vs. negative/look and negative/photo trials in left dorsolateral prefrontal cortex (DLPFC), rostral anterior cingulate, left parietal cortex, caudate, and right amygdala. Depressive severity was inversely correlated with activation modulation in the left DLPFC, right amygdala, and right cerebellum during negative reappraisal. The lack of group differences suggests that depressed adults can modulate the brain activation and subjective experience elicited by negative pictures when given clear instructions. However, the negative relationship between depression severity and effects of reappraisal on brain activation indicates that group differences may be detectable in larger samples of more severely depressed participants. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Synapse Project: Engagement in mentally challenging activities enhances neural efficiency

PubMed Central

McDonough, Ian M.; Haber, Sara; Bischof, Gérard N.; Park, Denise C.

2015-01-01

Purpose: Correlational and limited experimental evidence suggests that an engaged lifestyle is associated with the maintenance of cognitive vitality in old age. However, the mechanisms underlying these engagement effects are poorly understood. We hypothesized that mental effort underlies engagement effects and used fMRI to examine the impact of high-challenge activities (digital photography and quilting) compared with low-challenge activities (socializing or performing low-challenge cognitive tasks) on neural function at pretest, posttest, and one year after the engagement program. Methods: In the scanner, participants performed a semantic-classification task with two levels of difficulty to assess the modulation of brain activity in response to task demands. Results: The High-Challenge group, but not the Low-Challenge group, showed increased modulation of brain activity in medial frontal, lateral temporal, and parietal cortex—regions associated with attention and semantic processing—some of which were maintained a year later. This increased modulation stemmed from decreases in brain activity during the easy condition for the High-Challenge group and was associated with time committed to the program, age, and cognition. Conclusions: Sustained engagement in cognitively demanding activities facilitated cognition by increasing neural efficiency. Mentally-challenging activities may be neuroprotective and an important element to maintaining a healthy brain into late adulthood. PMID:26484698

The lipid habitats of neurotransmitter receptors in brain.

PubMed

Borroni, María Virginia; Vallés, Ana Sofía; Barrantes, Francisco J

2016-11-01

Neurotransmitter receptors, the macromolecules specialized in decoding the chemical signals encrypted in the chemical signaling mechanism in the nervous system, occur either at the somatic cell surface of chemically excitable cells or at specialized subcellular structures, the synapses. Synapses have lipid compositions distinct from the rest of the cell membrane, suggesting that neurotransmitter receptors and their scaffolding and adaptor protein partners require specific lipid habitats for optimal operation. In this review we discuss some paradigmatic cases of neurotransmitter receptor-lipid interactions, highlighting the chemical nature of the intervening lipid species and providing examples of the receptor mechanisms affected by interaction with lipids. The focus is on the effects of cholesterol, glycerophospholipids and covalent fatty acid acylation on neurotransmitter receptors. We also briefly discuss the role of lipid phase states involving lateral heterogeneities of the host membrane known to modulate membrane transport, protein sorting and signaling. Modulation of neurotransmitter receptors by lipids occurs at multiple levels, affecting a wide span of activities including their trafficking, sorting, stability, residence lifetime at the cell surface, endocytosis, and recycling, among other important functional properties at the synapse. Copyright © 2016 Elsevier B.V. All rights reserved.

Membrane cholesterol effect on the 5-HT2A receptor: Insights into the lipid-induced modulation of an antipsychotic drug target.

PubMed

Ramírez-Anguita, Juan Manuel; Rodríguez-Espigares, Ismael; Guixà-González, Ramon; Bruno, Agostino; Torrens-Fontanals, Mariona; Varela-Rial, Alejandro; Selent, Jana

2018-01-01

The serotonin 5-hydroxytryptamine 2A (5-HT 2A ) receptor is a G-protein-coupled receptor (GPCR) relevant for the treatment of CNS disorders. In this regard, neuronal membrane composition in the brain plays a crucial role in the modulation of the receptor functioning. Since cholesterol is an essential component of neuronal membranes, we have studied its effect on the 5-HT 2A receptor dynamics through all-atom MD simulations. We find that the presence of cholesterol in the membrane increases receptor conformational variability in most receptor segments. Importantly, detailed structural analysis indicates that conformational variability goes along with the destabilization of hydrogen bonding networks not only within the receptor but also between receptor and lipids. In addition to increased conformational variability, we also find receptor segments with reduced variability. Our analysis suggests that this increased stabilization is the result of stabilizing effects of tightly bound cholesterol molecules to the receptor surface. Our finding contributes to a better understanding of membrane-induced alterations of receptor dynamics and points to cholesterol-induced stabilizing and destabilizing effects on the conformational variability of GPCRs. © 2017 International Union of Biochemistry and Molecular Biology, Inc.

The effect of fish oil supplementation on brain DHA and EPA content and fatty acid profile in mice.

PubMed

Valentini, Kelly J; Pickens, C Austin; Wiesinger, Jason A; Fenton, Jenifer I

2017-12-18

Supplementation with omega-3 (n-3) fatty acids may improve cognitive performance and protect against cognitive decline. However, changes in brain phospholipid fatty acid composition after supplementation with n-3 fatty acids are poorly described. The purpose of this study was to feed increasing n-3 fatty acids and characterise the changes in brain phospholipid fatty acid composition and correlate the changes with red blood cells (RBCs) and plasma in mice. Increasing dietary docosahexaenoic (DHA) and eicosapentaenoic acid (EPA) did not alter brain DHA. Brain EPA increased and total n-6 polyunsaturated fatty acids decreased across treatment groups, and correlated with fatty acid changes in the RBC (r > 0.7). Brain cis-monounsaturated fatty acids oleic and nervonic acid (p < .01) and saturated fatty acids arachidic, behenic, and lignoceric acid (p < .05) also increased. These brain fatty acid changes upon increasing n-3 intake should be further investigated to determine their effects on cognition and neurodegenerative disease.

Integrated Computer-Aided Manufacturing (ICAM) Architecture Part 2. Volume 6. Dynamics Modeling Manual (IDEF2)

DTIC Science & Technology

1981-06-01

design of manufacturing systems, "ilidation and verification of ICAM modules, integration of ICAM modules and the orderly transition of ICAM modules into...Function Model of "Manufacture Product" (MFGO) VIII - Composite Function Model of " Design Product" (DESIGNO) IX - Composite Information Model of...User Interface Requirements; and the Architecture of Design . This work was performed during the period of 29 September 1978 through 10

Changing Brain Networks Through Non-invasive Neuromodulation

PubMed Central

To, Wing Ting; De Ridder, Dirk; Hart Jr., John; Vanneste, Sven

2018-01-01

Background/Objective: Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method: This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion: Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks. PMID:29706876

Remodeling Functional Connectivity in Multiple Sclerosis: A Challenging Therapeutic Approach.

PubMed

Stampanoni Bassi, Mario; Gilio, Luana; Buttari, Fabio; Maffei, Pierpaolo; Marfia, Girolama A; Restivo, Domenico A; Centonze, Diego; Iezzi, Ennio

2017-01-01

Neurons in the central nervous system are organized in functional units interconnected to form complex networks. Acute and chronic brain damage disrupts brain connectivity producing neurological signs and/or symptoms. In several neurological diseases, particularly in Multiple Sclerosis (MS), structural imaging studies cannot always demonstrate a clear association between lesion site and clinical disability, originating the "clinico-radiological paradox." The discrepancy between structural damage and disability can be explained by a complex network perspective. Both brain networks architecture and synaptic plasticity may play important roles in modulating brain networks efficiency after brain damage. In particular, long-term potentiation (LTP) may occur in surviving neurons to compensate network disconnection. In MS, inflammatory cytokines dramatically interfere with synaptic transmission and plasticity. Importantly, in addition to acute and chronic structural damage, inflammation could contribute to reduce brain networks efficiency in MS leading to worse clinical recovery after a relapse and worse disease progression. These evidence suggest that removing inflammation should represent the main therapeutic target in MS; moreover, as synaptic plasticity is particularly altered by inflammation, specific strategies aimed at promoting LTP mechanisms could be effective for enhancing clinical recovery. Modulation of plasticity with different non-invasive brain stimulation (NIBS) techniques has been used to promote recovery of MS symptoms. Better knowledge of features inducing brain disconnection in MS is crucial to design specific strategies to promote recovery and use NIBS with an increasingly tailored approach.

Changing Brain Networks Through Non-invasive Neuromodulation.

PubMed

To, Wing Ting; De Ridder, Dirk; Hart, John; Vanneste, Sven

2018-01-01

Background/Objective : Non-invasive neuromodulation techniques, such as repetitive Transcranial Magnetic Stimulation (rTMS) and transcranial Direct Current Stimulation (tDCS), have increasingly been investigated for their potential as treatments for neurological and psychiatric disorders. Despite widespread dissemination of these techniques, the underlying therapeutic mechanisms and the ideal stimulation site for a given disorder remain unknown. Increasing evidence support the possibility of non-invasive neuromodulation affecting a brain network rather than just the local stimulation target. In this article, we present evidence in a clinical setting to support the idea that non-invasive neuromodulation changes brain networks. Method : This article addresses the idea that non-invasive neuromodulation modulates brain networks, rather than just the local stimulation target, using neuromodulation studies in tinnitus and major depression as examples. We present studies that support this hypothesis from different perspectives. Main Results/Conclusion : Studies stimulating the same brain region, such as the dorsolateral prefrontal cortex (DLPFC), have shown to be effective for several disorders and studies using different stimulation sites for the same disorder have shown similar results. These findings, as well as results from studies investigating brain network connectivity on both macro and micro levels, suggest that non-invasive neuromodulation affects a brain network rather than just the local stimulation site targeted. We propose that non-invasive neuromodulation should be approached from a network perspective and emphasize the therapeutic potential of this approach through the modulation of targeted brain networks.

Disentangling the co-structure of multilayer interaction networks: degree distribution and module composition in two-layer bipartite networks.

PubMed

Astegiano, Julia; Altermatt, Florian; Massol, François

2017-11-13

Species establish different interactions (e.g. antagonistic, mutualistic) with multiple species, forming multilayer ecological networks. Disentangling network co-structure in multilayer networks is crucial to predict how biodiversity loss may affect the persistence of multispecies assemblages. Existing methods to analyse multilayer networks often fail to consider network co-structure. We present a new method to evaluate the modular co-structure of multilayer networks through the assessment of species degree co-distribution and network module composition. We focus on modular structure because of its high prevalence among ecological networks. We apply our method to two Lepidoptera-plant networks, one describing caterpillar-plant herbivory interactions and one representing adult Lepidoptera nectaring on flowers, thereby possibly pollinating them. More than 50% of the species established either herbivory or visitation interactions, but not both. These species were over-represented among plants and lepidopterans, and were present in most modules in both networks. Similarity in module composition between networks was high but not different from random expectations. Our method clearly delineates the importance of interpreting multilayer module composition similarity in the light of the constraints imposed by network structure to predict the potential indirect effects of species loss through interconnected modular networks.

The modulation of brain functional connectivity with manual acupuncture in healthy subjects: An electroencephalograph case study

NASA Astrophysics Data System (ADS)

Yi, Guo-Sheng; Wang, Jiang; Han, Chun-Xiao; Deng, Bin; Wei, Xi-Le; Li, Nuo

2013-02-01

Manual acupuncture is widely used for pain relief and stress control. Previous studies on acupuncture have shown its modulatory effects on the functional connectivity associated with one or a few preselected brain regions. To investigate how manual acupuncture modulates the organization of functional networks at a whole-brain level, we acupuncture at ST36 of a right leg to obtain electroencephalograph (EEG) signals. By coherence estimation, we determine the synchronizations between all pairwise combinations of EEG channels in three acupuncture states. The resulting synchronization matrices are converted into functional networks by applying a threshold, and the clustering coefficients and path lengths are computed as a function of threshold. The results show that acupuncture can increase functional connections and synchronizations between different brain areas. For a wide range of thresholds, the clustering coefficient during acupuncture and post-acupuncture period is higher than that during the pre-acupuncture control period, whereas the characteristic path length is shorter. We provide further support for the presence of “small-world" network characteristics in functional networks by using acupuncture. These preliminary results highlight the beneficial modulations of functional connectivity by manual acupuncture, which could contribute to the understanding of the effects of acupuncture on the entire brain, as well as the neurophysiological mechanisms underlying acupuncture. Moreover, the proposed method may be a useful approach to the further investigation of the complexity of patterns of interrelations between EEG channels.

Exposure of Adolescent Mice to Delta-9-Tetrahydrocannabinol Induces Long-Lasting Modulation of Pro- and Anti-Inflammatory Cytokines in Hypothalamus and Hippocampus Similar to that Observed for Peripheral Macrophages.

PubMed

Moretti, Sarah; Franchi, Silvia; Castelli, Mara; Amodeo, Giada; Somaini, Lorenzo; Panerai, Alberto; Sacerdote, Paola

2015-06-01

Cannabis use is frequent among adolescents. Its main component, delta-9-tetrahydrocannabinol (THC), affects the immune system. We recently demonstrated that chronic exposure of adolescent mice to THC suppressed immunity immediately after treatment but that after a washout period THC induced a long-lasting opposite modulation towards a proinflammatory and T-helper-1 phenotype in adulthood. The main objective of this study was to investigate whether the same effect was also present in brain regions such as the hypothalamus and hippocampus. Thirty-three-day-old adolescent and 80-day-old adult male mice were used. Acute THC administration induced a similar reduction of macrophage proinflammatory cytokines and an IL-10 increase in adult and adolescent mice. THC did not affect brain cytokines in adult mice, but a proinflammatory cytokine decrease was evident in the adolescent brain. A similar effect was present in the hypothalamus and hippocampus after 10 days' THC administration. In contrast, when brain cytokines were measured 47 days after the final THC administration, we observed an inverted effect in adult mice treated as adolescents, i.e., IL-1β and TNF-α increased and IL-10 decreased, indicating a shift toward neuroinflammation. These data suggest that THC exposure in adolescence has long-lasting effects on brain cytokines that parallel those present in the periphery. This modulation may affect vulnerability to immune and behavioural diseases in adulthood.

Pathophysiological implications of neurovascular P450 in brain disorders

PubMed Central

Ghosh, Chaitali; Hossain, Mohammed; Solanki, Jesal; Dadas, Aaron; Marchi, Nicola; Janigro, Damir

2016-01-01

Over the past decades, the significance of cytochrome P450 (CYP) enzymes has expanded beyond their role as peripheral drug metabolizers in the liver and gut. CYP enzymes are also functionally active at the neurovascular interface. CYP expression is modulated by disease states, impacting cellular functions, detoxification, and reactivity to toxic stimuli and brain drug biotransformation. Unveiling the physiological and molecular complexity of brain P450 enzymes will improve our understanding of the mechanisms underlying brain drug availability, pharmacological efficacy, and neurotoxic adverse effects from pharmacotherapy targeting brain disorders. PMID:27312874

27-Hydroxycholesterol contributes to disruptive effects on learning and memory by modulating cholesterol metabolism in the rat brain.

PubMed

Zhang, D-D; Yu, H-L; Ma, W-W; Liu, Q-R; Han, J; Wang, H; Xiao, R

2015-08-06

Cholesterol metabolism is important for neuronal function in the central nervous system (CNS). The oxysterol 27-hydroxycholesterol (27-OHC) is a cholesterol metabolite that crosses the blood-brain barrier (BBB) and may be a useful substitutive marker for neurodegenerative diseases. However, the effects of 27-OHC on learning and memory and the underlying mechanisms are unclear. To determine this mechanism, we investigated learning and memory and cholesterol metabolism in rat brain following the injection of various doses of 27-OHC into the caudal vein. We found that 27-OHC increased cholesterol levels and upregulated the expression of liver X receptor-α (LXR-α) and adenosine triphosphate (ATP)-binding cassette transporter protein family member A1 (ABCA1). In addition, 27-OHC decreased the expression of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CR) and low-density lipoprotein receptor (LDLR) in rat brain tissues. These findings suggest that 27-OHC may negatively modulate cognitive effects and cholesterol metabolism in the brain. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach.

PubMed

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-18

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

Evidence that Meningeal Mast Cells Can Worsen Stroke Pathology in Mice

PubMed Central

Arac, Ahmet; Grimbaldeston, Michele A.; Nepomuceno, Andrew R.B.; Olayiwola, Oluwatobi; Pereira, Marta P.; Nishiyama, Yasuhiro; Tsykin, Anna; Goodall, Gregory J.; Schlecht, Ulrich; Vogel, Hannes; Tsai, Mindy; Galli, Stephen J.; Bliss, Tonya M.; Steinberg, Gary K.

2015-01-01

Stroke is the leading cause of adult disability and the fourth most common cause of death in the United States. Inflammation is thought to play an important role in stroke pathology, but the factors that promote inflammation in this setting remain to be fully defined. An understudied but important factor is the role of meningeal-located immune cells in modulating brain pathology. Although different immune cells traffic through meningeal vessels en route to the brain, mature mast cells do not circulate but are resident in the meninges. With the use of genetic and cell transfer approaches in mice, we identified evidence that meningeal mast cells can importantly contribute to the key features of stroke pathology, including infiltration of granulocytes and activated macrophages, brain swelling, and infarct size. We also obtained evidence that two mast cell-derived products, interleukin-6 and, to a lesser extent, chemokine (C-C motif) ligand 7, can contribute to stroke pathology. These findings indicate a novel role for mast cells in the meninges, the membranes that envelop the brain, as potential gatekeepers for modulating brain inflammation and pathology after stroke. PMID:25134760

Hierarchical organization of functional connectivity in the mouse brain: a complex network approach

NASA Astrophysics Data System (ADS)

Bardella, Giampiero; Bifone, Angelo; Gabrielli, Andrea; Gozzi, Alessandro; Squartini, Tiziano

2016-08-01

This paper represents a contribution to the study of the brain functional connectivity from the perspective of complex networks theory. More specifically, we apply graph theoretical analyses to provide evidence of the modular structure of the mouse brain and to shed light on its hierarchical organization. We propose a novel percolation analysis and we apply our approach to the analysis of a resting-state functional MRI data set from 41 mice. This approach reveals a robust hierarchical structure of modules persistent across different subjects. Importantly, we test this approach against a statistical benchmark (or null model) which constrains only the distributions of empirical correlations. Our results unambiguously show that the hierarchical character of the mouse brain modular structure is not trivially encoded into this lower-order constraint. Finally, we investigate the modular structure of the mouse brain by computing the Minimal Spanning Forest, a technique that identifies subnetworks characterized by the strongest internal correlations. This approach represents a faster alternative to other community detection methods and provides a means to rank modules on the basis of the strength of their internal edges.

Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer's disease.

PubMed

Roh, Jee Hoon; Jiang, Hong; Finn, Mary Beth; Stewart, Floy R; Mahan, Thomas E; Cirrito, John R; Heda, Ashish; Snider, B Joy; Li, Mingjie; Yanagisawa, Masashi; de Lecea, Luis; Holtzman, David M

2014-12-15

Age-related aggregation of amyloid-β (Aβ) is an upstream pathological event in Alzheimer's disease (AD) pathogenesis, and it disrupts the sleep-wake cycle. The amount of sleep declines with aging and to a greater extent in AD. Poor sleep quality and insufficient amounts of sleep have been noted in humans with preclinical evidence of AD. However, how the amount and quality of sleep affects Aβ aggregation is not yet well understood. Orexins (hypocretins) initiate and maintain wakefulness, and loss of orexin-producing neurons causes narcolepsy. We tried to determine whether orexin release or secondary changes in sleep via orexin modulation affect Aβ pathology. Amyloid precursor protein (APP)/Presenilin 1 (PS1) transgenic mice, in which the orexin gene is knocked out, showed a marked decrease in the amount of Aβ pathology in the brain with an increase in sleep time. Focal overexpression of orexin in the hippocampus in APP/PS1 mice did not alter the total amount of sleep/wakefulness and the amount of Aβ pathology. In contrast, sleep deprivation or increasing wakefulness by rescue of orexinergic neurons in APP/PS1 mice lacking orexin increased the amount of Aβ pathology in the brain. Collectively, modulation of orexin and its effects on sleep appear to modulate Aβ pathology in the brain. © 2014 Roh et al.

How emotional abilities modulate the influence of early life stress on hippocampal functioning.

PubMed

Aust, Sabine; Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R; Heuser, Isabella; Bajbouj, Malek

2014-07-01

Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual's degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Self-regulation of primary motor cortex activity with motor imagery induces functional connectivity modulation: A real-time fMRI neurofeedback study.

PubMed

Makary, Meena M; Seulgi, Eun; Kyungmo Park

2017-07-01

Recent developments in data acquisition of functional magnetic resonance imaging (fMRI) have led to rapid preprocessing and analysis of brain activity in a quasireal-time basis, what so called real-time fMRI neurofeedback (rtfMRI-NFB). This information is fed back to subjects allowing them to gain a voluntary control over their own region-specific brain activity. Forty-one healthy participants were randomized into an experimental (NFB) group, who received a feedback directly proportional to their brain activity from the primary motor cortex (M1), and a control (CTRL) group who received a sham feedback. The M1 ROI was functionally localized during motor execution and imagery tasks. A resting-state functional run was performed before and after the neurofeedback training to investigate the default mode network (DMN) modulation after training. The NFB group revealed increased DMN functional connectivity after training to the cortical and subcortical sensory/motor areas (M1/S1 and caudate nucleus, respectively), which may be associated with sensorimotor processing of learning in the resting state. These results show that motor imagery training through rtfMRI-NFB could modulate the DMN functional connectivity to motor-related areas, suggesting that this modulation potentially subserved the establishment of motor learning in the NFB group.

LRP in amyloid-beta production and metabolism.

PubMed

Bu, Guojun; Cam, Judy; Zerbinatti, Celina

2006-11-01

Amyloid-beta peptide (Abeta) production and accumulation in the brain is a central event in the pathogenesis of Alzheimer's disease (AD). Recent studies have shown that apolipoprotein E (apoE) receptors, members of the low-density lipoprotein receptor (LDLR) family, modulate Abeta production as well as Abeta cellular uptake. Abeta is derived from proteolytic processing of the amyloid precursor protein (APP), which interacts with several members of the LDLR family. Studies from our laboratory have focused on two members of the LDLR family, the LDLR-related protein (LRP) and LRP1B. Our in vitro studies have shown that while LRP's rapid endocytosis facilitates APP endocytic trafficking and processing to Abeta, LRP1B's slow endocytosis inhibits these processes. In addition to modulating APP endocytic trafficking, LRP's rapid endocytosis also facilitates Abeta cellular uptake by binding to Abeta either directly or via LRP ligands such as apoE. Our in vivo studies using transgenic mice have shown that overexpression of LRP in central nervous system (CNS) neurons increases soluble brain Abeta and this increase correlates with deficits in memory. Together our studies demonstrate that members of the LDLR family modulate APP processing and Abeta metabolism by several independent mechanisms. Understanding the pathways that modulate brain Abeta metabolism may enable the rational design of molecular medicine to treat AD.

Distinct Patterns of Neural Activity during Memory Formation of Nonwords versus Words

PubMed Central

Otten, Leun J.; Sveen, Josefin; Quayle, Angela H.

2008-01-01

Research into the neural underpinnings of memory formation has focused on the encoding of familiar verbal information. Here, we address how the brain supports the encoding of novel information that does not have meaning. Electrical brain activity was recorded from the scalps of healthy young adults while they performed an incidental encoding task (syllable judgments) on separate series of words and ‘nonwords’ (nonsense letter strings that are orthographically legal and pronounceable). Memory for the items was then probed with a recognition memory test. For words as well as nonwords, event-related potentials differed depending on whether an item would subsequently be remembered or forgotten. However, the polarity and timing of the effect varied across item type. For words, subsequently remembered items showed the usually observed positive-going, frontally-distributed modulation from around 600 ms after word onset. For nonwords, by contrast, a negative-going, spatially widespread modulation predicted encoding success from 1000 ms onwards. Nonwords also showed a modulation shortly after item onset. These findings imply that the brain supports the encoding of familiar and unfamiliar letter strings in qualitatively different ways, including the engagement of distinct neural activity at different points in time. The processing of semantic attributes plays an important role in the encoding of words and the associated positive frontal modulation. PMID:17958481

Validation of a Virtual Reality Balance Module for Use in Clinical Concussion Assessment and Management

PubMed Central

Teel, Elizabeth F.; Slobounov, Semyon M.

2014-01-01

Objective To determine the criterion and content validity of a virtual reality (VR) balance module for use in clinical practice. Design Retrospective, VR balance module completed by participants during concussion baseline or assessment testing session. Setting A Pennsylvania State University research laboratory Participants A total of 60 control and 28 concussed students and athletes from the Pennsylvania State University Interventions None Main Outcome Measures This study examined: (1) the relationship between VR composite balance scores (final, stationary, yaw, pitch, and roll) and area of the center-of-pressure (eyes open and closed) scores and (2) group differences (normal volunteers and concussed student-athletes) on VR composite balance scores. Results With the exception of the stationary composite score, all other VR balance composite scores were significantly correlated with the center of pressure (COP) data obtained from a force platform. Significant correlations for the eyes open conditions ranged from r= −.273 to −.704 and from r= −.353 to −.876 for the eyes closed condition. When examining group differences on the VR balance composite modules, the concussed group did significantly (p<.01) worse on all measures compared to the control group. Conclusions The VR balance module met or exceeded the criterion and content validity standard set by current balance tools and may be appropriate for use in a clinical concussion setting. PMID:24905539

Neurophysiology of hypnosis.

PubMed

Vanhaudenhuyse, A; Laureys, S; Faymonville, M-E

2014-10-01

We here review behavioral, neuroimaging and electrophysiological studies of hypnosis as a state, as well as hypnosis as a tool to modulate brain responses to painful stimulations. Studies have shown that hypnotic processes modify internal (self awareness) as well as external (environmental awareness) brain networks. Brain mechanisms underlying the modulation of pain perception under hypnotic conditions involve cortical as well as subcortical areas including anterior cingulate and prefrontal cortices, basal ganglia and thalami. Combined with local anesthesia and conscious sedation in patients undergoing surgery, hypnosis is associated with improved peri- and postoperative comfort of patients and surgeons. Finally, hypnosis can be considered as a useful analogue for simulating conversion and dissociation symptoms in healthy subjects, permitting better characterization of these challenging disorders by producing clinically similar experiences. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Emotion and sex of facial stimuli modulate conditional automaticity in behavioral and neuronal interference in healthy men.

PubMed

Kohn, Nils; Fernández, Guillén

2017-12-06

Our surrounding provides a host of sensory input, which we cannot fully process without streamlining and automatic processing. Levels of automaticity differ for different cognitive and affective processes. Situational and contextual interactions between cognitive and affective processes in turn influence the level of automaticity. Automaticity can be measured by interference in Stroop tasks. We applied an emotional version of the Stroop task to investigate how stress as a contextual factor influences the affective valence-dependent level of automaticity. 120 young, healthy men were investigated for behavioral and brain interference following a stress induction or control procedure in a counter-balanced cross-over-design. Although Stroop interference was always observed, sex and emotion of the face strongly modulated interference, which was larger for fearful and male faces. These effects suggest higher automaticity when processing happy and also female faces. Supporting behavioral patterns, brain data show lower interference related brain activity in executive control related regions in response to happy and female faces. In the absence of behavioral stress effects, congruent compared to incongruent trials (reverse interference) showed little to no deactivation under stress in response to happy female and fearful male trials. These congruency effects are potentially based on altered context- stress-related facial processing that interact with sex-emotion stereotypes. Results indicate that sex and facial emotion modulate Stroop interference in brain and behavior. These effects can be explained by altered response difficulty as a consequence of the contextual and stereotype related modulation of automaticity. Copyright © 2017 Elsevier Ltd. All rights reserved.

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study

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

Lee, Katrina, E-mail: Trinabena23@gmail.com; Lenards, Nishele; Holson, Janice

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient's neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to themore » hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient's data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain.« less

Oxytocin selectively modulates brain response to stimuli probing social synchrony.

PubMed

Levy, Jonathan; Goldstein, Abraham; Zagoory-Sharon, Orna; Weisman, Omri; Schneiderman, Inna; Eidelman-Rothman, Moranne; Feldman, Ruth

2016-01-01

The capacity to act collectively within groups has led to the survival and thriving of Homo sapiens. A central group collaboration mechanism is "social synchrony," the coordination of behavior during joint action among affiliative members, which intensifies under threat. Here, we tested brain response to vignettes depicting social synchrony among combat veterans trained for coordinated action and following life-threatening group experience, versus controls, as modulated by oxytocin (OT), a neuropeptide supporting social synchrony. Using a randomized, double-blind, within-subject design, 40 combat-trained and control male veterans underwent magnetoencephalography (MEG) twice following OT/placebo administration while viewing two social vignettes rated as highly synchronous: pleasant male social gathering and coordinated unit during combat. Both vignettes activated a wide response across the social brain in the alpha band; the combat scene triggered stronger activations. Importantly, OT effects were modulated by prior experience. Among combat veterans, OT attenuated the increased response to combat stimuli in the posterior superior temporal sulcus (pSTS) - a hub of social perception, action observation, and mentalizing - and enhanced activation in the inferior parietal lobule (IPL) to the pleasant social scene. Among controls, OT enhanced inferior frontal gyrus (IFG) response to combat cues, demonstrating selective OT effects on mirror-neuron and mentalizing networks. OT-enhanced mirror network activity was dampened in veterans reporting higher posttraumatic symptoms. Results demonstrate that the social brain responds online, via modulation of alpha rhythms, to stimuli probing social synchrony, particularly those involving threat to survival, and OT's enhancing versus anxiolytic effects are sensitive to salient experiences within social groups. Copyright © 2015 Elsevier Inc. All rights reserved.

The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus.

PubMed

Fumagalli, Fabio; Calabrese, Francesca; Luoni, Alessia; Shahid, Mohammed; Racagni, Giorgio; Riva, Marco A

2012-02-01

Brain derived neurotrophic factor (BDNF) is a key mediator of brain plasticity. The modulation of its expression and function is important for cognition and represents a key strategy to enhance neuronal resilience. Within this context, there exists a close interaction between glutamatergic neurotransmission and BDNF activity towards regulating cellular homeostasis and plasticity. The aim of the current study was to investigate the ability of the AMPA receptor potentiator Org 26576 to modulate BDNF expression in selected brain regions under basal conditions or in response to an acute swim stress. Rats subjected to a single intraperitoneal injection with Org 26576 (10mg/kg) or saline were exposed to a swim stress session (5 min) and sacrificed 15 min after the end of stress. Real-time PCR assay was used to determine changes in BDNF transcription in different brain regions. Total BDNF mRNA levels were significantly increased in the hippocampus of animals exposed to the combination of Org 26576 and stress whereas, in prefrontal and frontal cortices, BDNF mRNA levels were modulated by the acute stress, independently from drug treatment. The analysis of BDNF transcripts in the hippocampus revealed a major contribution of exons I and IV. Our results suggest that AMPA receptor potentiation by Org 26576 exerts a positive modulatory influence on BDNF expression during ongoing neuronal activity. Given that these mechanisms are critical for neuronal plasticity, we hypothesized that such changes may facilitate learning/coping mechanisms associated with a mild stressful experience. Copyright © 2011 Elsevier Ltd. All rights reserved.

Extraction of Carbon Dioxide and Hydrogen from Seawater By an Electrolytic Cation Exchange Module (E-CEM) Part 5: E-CEM Effluent Discharge Composition as a Function of Electrode Water Composition

DTIC Science & Technology

2017-08-01

Naval Research Laboratory Washington, DC 20375-5320 NRL/MR/6360--17-9743 Extraction of Carbon Dioxide and Hydrogen from Seawater by an Electrolytic...Cation Exchange Module (E-CEM) Part V: E-CEM Effluent Discharge Composition as a Function of Electrode Water Composition August 1, 2017 Approved for...Office of Naval Research Arlington, Virginia Dennis r. HarDy Nova Research Inc. Alexandria, Virginia i REPORT DOCUMENTATION PAGE Form

Validation of a virtual reality balance module for use in clinical concussion assessment and management.

PubMed

Teel, Elizabeth F; Slobounov, Semyon M

2015-03-01

To determine the criterion and content validity of a virtual reality (VR) balance module for use in clinical practice. Retrospective, VR balance module completed by participants during concussion baseline or assessment testing session. A Pennsylvania State University research laboratory. A total of 60 control and 28 concussed students and athletes from the Pennsylvania State University. None. This study examined: (1) the relationship between VR composite balance scores (final, stationary, yaw, pitch, and roll) and area of the center-of-pressure (eyes open and closed) scores and (2) group differences (normal volunteers and concussed student-athletes) on VR composite balance scores. With the exception of the stationary composite score, all other VR balance composite scores were significantly correlated with the center of pressure data obtained from a force platform. Significant correlations ranged from r = -0.273 to -0.704 for the eyes open conditions and from r = -0.353 to -0.876 for the eyes closed condition. When examining group differences on the VR balance composite modules, the concussed group did significantly (P < 0.01) worse on all measures compared with the control group. The VR balance module met or exceeded the criterion and content validity standard set by the current balance tools and may be appropriate for use in a clinical concussion setting. Virtual reality balance module is a valid tool for concussion assessment in clinical settings. This novel type of balance assessment may be more sensitive to concussion diagnoses, especially later (7-10 days) in the recovery phase than current clinical balance tools.

Sexually dimorphic brain fatty acid composition in low and high fat diet-fed mice.

PubMed

Rodriguez-Navas, Carlos; Morselli, Eugenia; Clegg, Deborah J

2016-08-01

In this study, we analyzed the fatty acid profile of brains and plasma from male and female mice fed chow or a western-style high fat diet (WD) for 16 weeks to determine if males and females process fatty acids differently. Based on the differences in fatty acids observed in vivo, we performed in vitro experiments on N43 hypothalamic neuronal cells to begin to elucidate how the fatty acid milieu may impact brain inflammation. Using a comprehensive mass spectrometry fatty acid analysis, which includes a profile for 52 different fatty acid isomers, we assayed the plasma and brain fatty acid composition of age-matched male and female mice maintained on chow or a WD. Additionally, using the same techniques, we determined the fatty acid composition of N43 hypothalamic cells following exposure to palmitic and linoleic acid, alone or in combination. Our data demonstrate there is a sexual dimorphism in brain fatty acid content both following the consumption of the chow diet, as well as the WD, with males having an increased percentage of saturated fatty acids and reductions in ω6-polyunsaturated fatty acids when compared to females. Interestingly, we did not observe a sexual dimorphism in fatty acid content in the plasma of the same mice. Furthermore, exposure of N43 cells to the ω6-PUFA linoleic acid, which is higher in female brains when compared to males, reduces palmitic acid-induced inflammation. Our data suggest male and female brains, and not plasma, differ in their fatty acid profile. This is the first time, to our knowledge, lipidomic analyses has been used to directly test the hypothesis there is a sexual dimorphism in brain and plasma fatty acid composition following consumption of the chow diet, as well as following exposure to the WD.

Differences in gut microbial composition correlate with regional brain volumes in irritable bowel syndrome.

PubMed

Labus, Jennifer S; Hollister, Emily B; Jacobs, Jonathan; Kirbach, Kyleigh; Oezguen, Numan; Gupta, Arpana; Acosta, Jonathan; Luna, Ruth Ann; Aagaard, Kjersti; Versalovic, James; Savidge, Tor; Hsiao, Elaine; Tillisch, Kirsten; Mayer, Emeran A

2017-05-01

Preclinical and clinical evidence supports the concept of bidirectional brain-gut microbiome interactions. We aimed to determine if subgroups of irritable bowel syndrome (IBS) subjects can be identified based on differences in gut microbial composition, and if there are correlations between gut microbial measures and structural brain signatures in IBS. Behavioral measures, stool samples, and structural brain images were collected from 29 adult IBS and 23 healthy control subjects (HCs). 16S ribosomal RNA (rRNA) gene sequencing was used to profile stool microbial communities, and various multivariate analysis approaches were used to quantitate microbial composition, abundance, and diversity. The metagenomic content of samples was inferred from 16S rRNA gene sequence data using Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt). T1-weighted brain images were acquired on a Siemens Allegra 3T scanner, and morphological measures were computed for 165 brain regions. Using unweighted Unifrac distances with hierarchical clustering on microbial data, samples were clustered into two IBS subgroups within the IBS population (IBS1 (n = 13) and HC-like IBS (n = 16)) and HCs (n = 23) (AUROC = 0.96, sensitivity 0.95, specificity 0.67). A Random Forest classifier provided further support for the differentiation of IBS1 and HC groups. Microbes belonging to the genera Faecalibacterium, Blautia, and Bacteroides contributed to this subclassification. Clinical features distinguishing the groups included a history of early life trauma and duration of symptoms (greater in IBS1), but not self-reported bowel habits, anxiety, depression, or medication use. Gut microbial composition correlated with structural measures of brain regions including sensory- and salience-related regions, and with a history of early life trauma. The results confirm previous reports of gut microbiome-based IBS subgroups and identify for the first time brain structural alterations associated with these subgroups. They provide preliminary evidence for the involvement of specific microbes and their predicted metabolites in these correlations.

Pharmacological benefits of selective modulation of cannabinoid receptor type 2 (CB2) in experimental Alzheimer's disease.

PubMed

Jayant, Shalini; Sharma, Brij Mohan; Bansal, Rani; Sharma, Bhupesh

2016-01-01

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that pervasively affects the population across the world. Currently, there is no effective treatment available for this and existing drugs merely slow the progression of cognitive function decline. Thus, massive effort is required to find an intended therapeutic target to overcome this condition. The present study has been framed to investigate the ameliorative role of selective modulator of cannabinoid receptor type 2 (CB2), 1-phenylisatin in experimental AD condition. We have induced experimental AD in mice by using two induction models viz., intracerebroventricular (i.c.v.) administration of streptozotocin (STZ) and aluminum trichloride (AlCl3)+d-galactose. Morris water maze (MWM) and attentional set shifting test (ASST) were used to assess learning and memory. Hematoxylin-eosin and Congo red staining were used to examine the structural variation in brain. Brain oxidative stress (thiobarbituric acid reactive substance and glutathione), nitric oxide levels (nitrites/nitrates), acetyl cholinesterase activity, myeloperoxidase and calcium levels were also estimated. i.c.v. STZ as well as AlCl3+d-galactose have impaired spatial and reversal learning with executive functioning, increased brain oxidative and nitrosative stress, cholinergic activity, inflammation and calcium levels. Furthermore, these agents have also enhanced the burden of Aβ plaque in the brain. Treatment with 1-phenylisatin and donepezil attenuated i.c.v. STZ as well as AlCl3+d-galactose induced impairment of learning-memory, brain biochemistry and brain damage. Hence, this study concludes that CB2 receptor modulation can be a potential therapeutic target for the management of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

A 1-minute full brain MR exam using a multicontrast EPI sequence.

PubMed

Skare, Stefan; Sprenger, Tim; Norbeck, Ola; Rydén, Henric; Blomberg, Lars; Avventi, Enrico; Engström, Mathias

2018-06-01

A new multicontrast echo-planar imaging (EPI)-based sequence is proposed for brain MRI, which can directly generate six MR contrasts (T 1 -FLAIR, T 2 -w, diffusion-weighted (DWI), apparent diffusion coefficient (ADC), T2*-w, T 2 -FLAIR) in 1 min with full brain coverage. This could enable clinical MR clinical screening in similar time as a conventional CT exam but with more soft-tissue information. Eleven sequence modules were created as dynamic building blocks for the sequence. Two EPI readout modules were reused throughout the sequence and were prepended by other modules to form the desired MR contrasts. Two scan protocols were optimized with scan times of 55-75 s. Motion experiments were carried out on two volunteers to investigate the robustness against head motion. Scans on patients were carried out and compared to conventional clinical images. The pulse sequence is found to be robust against motion given its single-shot nature of each contrast. For excessive out-of-plane head motion, the T 1 -FLAIR and T 2 -FLAIR contrasts suffer from incomplete inversion. Despite lower signal-to-noise ratio (SNR) and resolution, the 1-min multicontrast EPI data show promising correspondence with conventional diagnostic scans on patients. A 1 min multicontrast brain MRI scan based on EPI readouts has been presented in this feasibility study. Preliminary data show potential for clinical brain MRI use with minimal bore time for the patient. Such short examination time could be useful (e.g., for screening and acute stroke). The sequence may also help planning conventional brain MRI scans if run at the beginning of an examination. Magn Reson Med 79:3045-3054, 2018. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

Neural Representation of Subjective Sexual Arousal in Men and Women.

PubMed

Parada, Mayte; Gérard, Marina; Larcher, Kevin; Dagher, Alain; Binik, Yitzchak M

2016-10-01

Studies investigating brain indices of sexual arousal have begun to elucidate the brain's role in processing subjective arousal; however, most research has focused on men, used discrete ratings of subjective arousal, and used stimuli too short to induce significant arousal in women. To examine brain regions modulated by changes in subjective sexual arousal (SSA) rating intensity in men and women. Two groups (20 men, 20 women) viewed movie clips (erotic or humorous) while continuously evaluating changes in their SSA using a Likert-like scale (0 = not aroused, 10 = most aroused) and answering discrete questions about liking the movies and wanting sexual stimulation. Brain activity was measured using functional magnetic resonance imaging. Blood oxygen level-dependent responses and continuous and discrete measurements of sexual arousal. Erotic movies induced significant SSA in men and women. No sex difference in mean SSA was found in response to the erotic movies on continuous or discrete measurements. Several brain regions were correlated with changes in SSA. Parametric modulation with rating intensity showed a specific group of regions within the parietal lobe that showed significant differences in activity among low, medium, and high SSA. Multiple regions were concordant with changes in SSA; however, a subset of regions in men and women was modulated by SSA intensity, a subset previously linked to attentional processes, monitoring of internal body representation, and processing of sensory information from the genitals. This study highlights that similar brain regions are activated during subjective assessment of sexual arousal in men and women. The data further highlight the fact that SSA is a complex phenomenon made up of multiple interoceptive and attentional processes. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Enhancing Motor Network Activity Using Real-Time Functional MRI Neurofeedback of Left Premotor Cortex

PubMed Central

Marins, Theo F.; Rodrigues, Erika C.; Engel, Annerose; Hoefle, Sebastian; Basílio, Rodrigo; Lent, Roberto; Moll, Jorge; Tovar-Moll, Fernanda

2015-01-01

Neurofeedback by functional magnetic resonance imaging (fMRI) is a technique of potential therapeutic relevance that allows individuals to be aware of their own neurophysiological responses and to voluntarily modulate the activity of specific brain regions, such as the premotor cortex (PMC), important for motor recovery after brain injury. We investigated (i) whether healthy human volunteers are able to up-regulate the activity of the left PMC during a right hand finger tapping motor imagery (MI) task while receiving continuous fMRI-neurofeedback, and (ii) whether successful modulation of brain activity influenced non-targeted motor control regions. During the MI task, participants of the neurofeedback group (NFB) received ongoing visual feedback representing the level of fMRI responses within their left PMC. Control (CTL) group participants were shown similar visual stimuli, but these were non-contingent on brain activity. Both groups showed equivalent levels of behavioral ratings on arousal and MI, before and during the fMRI protocol. In the NFB, but not in CLT group, brain activation during the last run compared to the first run revealed increased activation in the left PMC. In addition, the NFB group showed increased activation in motor control regions extending beyond the left PMC target area, including the supplementary motor area, basal ganglia and cerebellum. Moreover, in the last run, the NFB group showed stronger activation in the left PMC/inferior frontal gyrus when compared to the CTL group. Our results indicate that modulation of PMC and associated motor control areas can be achieved during a single neurofeedback-fMRI session. These results contribute to a better understanding of the underlying mechanisms of MI-based neurofeedback training, with direct implications for rehabilitation strategies in severe brain disorders, such as stroke. PMID:26733832

A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory.

PubMed

Kim, Kamin; Ekstrom, Arne D; Tandon, Nitin

2016-10-01

Electrical stimulation of the brain is a unique tool to perturb endogenous neural signals, allowing us to evaluate the necessity of given neural processes to cognitive processing. An important issue, gaining increasing interest in the literature, is whether and how stimulation can be employed to selectively improve or disrupt declarative memory processes. Here, we provide a comprehensive review of both invasive and non-invasive stimulation studies aimed at modulating memory performance. The majority of past studies suggest that invasive stimulation of the hippocampus impairs memory performance; similarly, most non-invasive studies show that disrupting frontal or parietal regions also impairs memory performance, suggesting that these regions also play necessary roles in declarative memory. On the other hand, a handful of both invasive and non-invasive studies have also suggested modest improvements in memory performance following stimulation. These studies typically target brain regions connected to the hippocampus or other memory "hubs," which may affect endogenous activity in connected areas like the hippocampus, suggesting that to augment declarative memory, altering the broader endogenous memory network activity is critical. Together, studies reporting memory improvements/impairments are consistent with the idea that a network of distinct brain "hubs" may be crucial for successful memory encoding and retrieval rather than a single primary hub such as the hippocampus. Thus, it is important to consider neurostimulation from the network perspective, rather than from a purely localizationalist viewpoint. We conclude by proposing a novel approach to neurostimulation for declarative memory modulation that aims to facilitate interactions between multiple brain "nodes" underlying memory rather than considering individual brain regions in isolation. Copyright © 2016. Published by Elsevier Inc.

Toward an Open-Ended BCI: A User-Centered Coadaptive Design.

PubMed

Dhindsa, Kiret; Carcone, Dean; Becker, Suzanna

2017-10-01

Brain-computer interfaces (BCIs) allow users to control a device by interpreting their brain activity. For simplicity, these devices are designed to be operated by purposefully modulating specific predetermined neurophysiological signals, such as the sensorimotor rhythm. However, the ability to modulate a given neurophysiological signal is highly variable across individuals, contributing to the inconsistent performance of BCIs for different users. These differences suggest that individuals who experience poor BCI performance with one class of brain signals might have good results with another. In order to take advantage of individual abilities as they relate to BCI control, we need to move beyond the current approaches. In this letter, we explore a new BCI design aimed at a more individualized and user-focused experience, which we call open-ended BCI. Individual users were given the freedom to discover their own mental strategies as opposed to being trained to modulate a given brain signal. They then underwent multiple coadaptive training sessions with the BCI. Our first open-ended BCI performed similarly to comparable BCIs while accommodating a wider variety of mental strategies without a priori knowledge of the specific brain signals any individual might use. Post hoc analysis revealed individual differences in terms of which sensory modality yielded optimal performance. We found a large and significant effect of individual differences in background training and expertise, such as in musical training, on BCI performance. Future research should be focused on finding more generalized solutions to user training and brain state decoding methods to fully utilize the abilities of different individuals in an open-ended BCI. Accounting for each individual's areas of expertise could have important implications on BCI training and BCI application design.

Remembering what could have happened: Neural correlates of episodic counterfactual thinking

PubMed Central

De Brigard, F; Addis, D.R.; Ford, J.H.; Schacter, D.L.; Giovanello, K.S

2014-01-01

Recent evidence suggests that our capacities to remember the past and to imagine what might happen in the future largely depend on the same core brain network that includes the middle temporal lobe, the posterior cingulate/retrosplenial cortex, the inferior parietal lobe, the medial prefrontal cortex, and the lateral temporal cortex. However, the extent to which regions of this core brain network are also responsible for our capacity to think about what could have happened in our past, yet did not occur (i.e., episodic counterfactual thinking), is still unknown. The present study examined this issue. Using a variation of the experimental recombination paradigm (Addis et al., 2009), participants were asked both to remember personal past events and to envision alternative outcomes to such events while undergoing functional magnetic resonance imaging. Three sets of analyses were performed on the imaging data in order to investigate two related issues. First, a mean-centered spatiotemporal partial least square (PLS) analysis identified a pattern of brain activity across regions of the core network that was common to episodic memory and episodic counterfactual thinking. Second, a non-rotated PLS analysis identified two different patterns of brain activity for likely and unlikely episodic counterfactual thoughts, with the former showing significant overlap with the set of regions engaged during episodic recollection. Finally, a parametric modulation was conducted to explore the differential engagement of brain regions during counterfactual thinking, revealing that areas such as the parahippocampal gyrus and the right hippocampus were modulated by the subjective likelihood of counterfactual simulations. These results suggest that episodic counterfactual thinking engages regions that form the core brain network, and also that the subjective likelihood of our counterfactual thoughts modulates the engagement of different areas within this set of regions. PMID:23376052

The role of expectations, hype and ethics in neuroimaging and neuromodulation futures

PubMed Central

Rusconi, Elena; Mitchener-Nissen, Timothy

2014-01-01

The production of expectations or future-goals for the development of techniques which “read” and modulate brain function, represent an important practical tool for neuroscientists. These visions-of-the-future assist scientists by providing focus for both individual and cross-disciplinary research programs; they encourage the development of new industrial sectors, are used to justify the allocation of government resources and funding, and via the media can help capture the imagination and support of the public. However, such expectations need to be tempered by reality. Over-hyping brain imaging and modulation will lead to disappointment; disappointment that in turn can undermine its potential. Similarly, if neuroscientists focus their attention narrowly on the science without concomitant consideration of its future ethical, legal and social implications, then their expectations may remain unrealized. To develop these arguments herein we introduce the theoretical concept of expectations and the practical consequences of expectations. We contextualize these reflections by referring to brain imaging and modulation studies on deception, which encompass the measurement-suppression-augmentation range. PMID:25400557

Task modulated brain connectivity of the amygdala: a meta-analysis of psychophysiological interactions.

PubMed

Di, Xin; Huang, Jia; Biswal, Bharat B

2017-01-01

Understanding functional connectivity of the amygdala with other brain regions, especially task modulated connectivity, is a critical step toward understanding the role of the amygdala in emotional processes and the interactions between emotion and cognition. The present study performed coordinate-based meta-analysis on studies of task modulated connectivity of the amygdala which used psychophysiological interaction (PPI) analysis. We first analyzed 49 PPI studies on different types of tasks using activation likelihood estimation (ALE) meta-analysis. Widespread cortical and subcortical regions showed consistent task modulated connectivity with the amygdala, including the medial frontal cortex, bilateral insula, anterior cingulate, fusiform gyrus, parahippocampal gyrus, thalamus, and basal ganglia. These regions were in general overlapped with those showed coactivations with the amygdala, suggesting that these regions and amygdala are not only activated together, but also show different levels of interactions during tasks. Further analyses with subsets of PPI studies revealed task specific functional connectivities with the amygdala that were modulated by fear processing, face processing, and emotion regulation. These results suggest a dynamic modulation of connectivity upon task demands, and provide new insights on the functions of the amygdala in different affective and cognitive processes. The meta-analytic approach on PPI studies may offer a framework toward systematical examinations of task modulated connectivity.

Effective connectivity of ascending and descending frontal-thalamic pathways during sustained attention: Complex brain network interactions in adolescence

PubMed Central

Jagtap, Pranav; Diwadkar, Vaibhav A.

2016-01-01

Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals (Dynamic Causal Modeling; DCM) to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian Model Selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: While positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. PMID:27145923

System and technique for retrieving depth information about a surface by projecting a composite image of modulated light patterns

NASA Technical Reports Server (NTRS)

Hassebrook, Laurence G. (Inventor); Lau, Daniel L. (Inventor); Guan, Chun (Inventor)

2010-01-01

A technique, associated system and program code, for retrieving depth information about at least one surface of an object, such as an anatomical feature. Core features include: projecting a composite image comprising a plurality of modulated structured light patterns, at the anatomical feature; capturing an image reflected from the surface; and recovering pattern information from the reflected image, for each of the modulated structured light patterns. Pattern information is preferably recovered for each modulated structured light pattern used to create the composite, by performing a demodulation of the reflected image. Reconstruction of the surface can be accomplished by using depth information from the recovered patterns to produce a depth map/mapping thereof. Each signal waveform used for the modulation of a respective structured light pattern, is distinct from each of the other signal waveforms used for the modulation of other structured light patterns of a composite image; these signal waveforms may be selected from suitable types in any combination of distinct signal waveforms, provided the waveforms used are uncorrelated with respect to each other. The depth map/mapping to be utilized in a host of applications, for example: displaying a 3-D view of the object; virtual reality user-interaction interface with a computerized device; face--or other animal feature or inanimate object--recognition and comparison techniques for security or identification purposes; and 3-D video teleconferencing/telecollaboration.

System and technique for retrieving depth information about a surface by projecting a composite image of modulated light patterns

NASA Technical Reports Server (NTRS)

Guan, Chun (Inventor); Hassebrook, Laurence G. (Inventor); Lau, Daniel L. (Inventor)

2008-01-01

A technique, associated system and program code, for retrieving depth information about at least one surface of an object. Core features include: projecting a composite image comprising a plurality of modulated structured light patterns, at the object; capturing an image reflected from the surface; and recovering pattern information from the reflected image, for each of the modulated structured light patterns. Pattern information is preferably recovered for each modulated structured light pattern used to create the composite, by performing a demodulation of the reflected image. Reconstruction of the surface can be accomplished by using depth information from the recovered patterns to produce a depth map/mapping thereof. Each signal waveform used for the modulation of a respective structured light pattern, is distinct from each of the other signal waveforms used for the modulation of other structured light patterns of a composite image; these signal waveforms may be selected from suitable types in any combination of distinct signal waveforms, provided the waveforms used are uncorrelated with respect to each other. The depth map/mapping to be utilized in a host of applications, for example: displaying a 3-D view of the object; virtual reality user-interaction interface with a computerized device; face--or other animal feature or inanimate object--recognition and comparison techniques for security or identification purposes; and 3-D video teleconferencing/telecollaboration.

Dosimetric impact of daily setup variations during treatment of canine nasal tumors using intensity-modulated radiation therapy.

PubMed

Deveau, Michael A; Gutiérrez, Alonso N; Mackie, Thomas R; Tomé, Wolfgang A; Forrest, Lisa J

2010-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5 mm (0-10.0 mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9 +/- 3.3 mm. Due to variations, a loss of equivalent uniform dose for target volumes of up to 5.6% was noted which corresponded to a potential loss in tumor control probability of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose and highest normalized dose given to 2% of the volume. Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain.

DOSIMETRIC IMPACT OF DAILY SETUP VARIATIONS DURING TREATMENT OF CANINE NASAL TUMORS USING INTENSITY-MODULATED RADIATION THERAPY

PubMed Central

Deveau, Michael A.; Gutiérrez, Alonso N.; Mackie, Thomas R.; Tomé, Wolfgang A.; Forrest, Lisa J.

2009-01-01

Intensity-modulated radiation therapy (IMRT) can be employed to yield precise dose distributions that tightly conform to targets and reduce high doses to normal structures by generating steep dose gradients. Because of these sharp gradients, daily setup variations may have an adverse effect on clinical outcome such that an adjacent normal structure may be overdosed and/or the target may be underdosed. This study provides a detailed analysis of the impact of daily setup variations on optimized IMRT canine nasal tumor treatment plans when variations are not accounted for due to the lack of image guidance. Setup histories of ten patients with nasal tumors previously treated using helical tomotherapy were replanned retrospectively to study the impact of daily setup variations on IMRT dose distributions. Daily setup shifts were applied to IMRT plans on a fraction-by-fraction basis. Using mattress immobilization and laser alignment, mean setup error magnitude in any single dimension was at least 2.5mm (0-10.0mm). With inclusions of all three translational coordinates, mean composite offset vector was 5.9±3.3mm. Due to variations, a loss of equivalent uniform dose (EUD) for target volumes of up to 5.6% was noted which corresponded to a potential loss in TCP of 39.5%. Overdosing of eyes and brain was noted by increases in mean normalized total dose (NTDmean) and highest normalized dose given to 2% of the volume (NTD2%). Findings suggest that successful implementation of canine nasal IMRT requires daily image guidance to ensure accurate delivery of precise IMRT distributions when non-rigid immobilization techniques are utilized. Unrecognized geographical misses may result in tumor recurrence and/or radiation toxicities to the eyes and brain. PMID:20166402

Modularity of mind and the role of incentive motivation in representing novelty.

PubMed

Anselme, Patrick

2012-07-01

Animal and human brains contain a myriad of mental representations that have to be successfully tracked within fractions of a second in a large number of situations. This retrieval process is hard to explain without postulating the massive modularity of cognition. Assuming that the mind is massively modular, it is then necessary to understand how cognitive modules can efficiently represent dynamic environments-in which some modules may have to deal with change-induced novelty and uncertainty. Novelty of a stimulus is a problem for a module when unknown, significant stimuli do not satisfy the module's processing criteria-or domain specificity-and cannot therefore be included in its database. It is suggested that the brain mechanisms of incentive motivation, recruited when faced with novelty and uncertainty, induce transient variations in the domain specificity of cognitive modules in order to allow them to process information they were not prepared to learn. It is hypothesised that the behavioural transitions leading from exploratory activity to habit formation are correlated with (and possibly caused by) the organism's ability to counter novelty-induced uncertainty.

Brain Iron Homeostasis: From Molecular Mechanisms To Clinical Significance and Therapeutic Opportunities

PubMed Central

Haldar, Swati; Tripathi, Ajai K.; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K.; Singh, Ajay

2014-01-01

Abstract Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders. Antioxid. Redox Signal. 20, 1324–1363. PMID:23815406

Brain iron homeostasis: from molecular mechanisms to clinical significance and therapeutic opportunities.

PubMed

Singh, Neena; Haldar, Swati; Tripathi, Ajai K; Horback, Katharine; Wong, Joseph; Sharma, Deepak; Beserra, Amber; Suda, Srinivas; Anbalagan, Charumathi; Dev, Som; Mukhopadhyay, Chinmay K; Singh, Ajay

2014-03-10

Iron has emerged as a significant cause of neurotoxicity in several neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), sporadic Creutzfeldt-Jakob disease (sCJD), and others. In some cases, the underlying cause of iron mis-metabolism is known, while in others, our understanding is, at best, incomplete. Recent evidence implicating key proteins involved in the pathogenesis of AD, PD, and sCJD in cellular iron metabolism suggests that imbalance of brain iron homeostasis associated with these disorders is a direct consequence of disease pathogenesis. A complete understanding of the molecular events leading to this phenotype is lacking partly because of the complex regulation of iron homeostasis within the brain. Since systemic organs and the brain share several iron regulatory mechanisms and iron-modulating proteins, dysfunction of a specific pathway or selective absence of iron-modulating protein(s) in systemic organs has provided important insights into the maintenance of iron homeostasis within the brain. Here, we review recent information on the regulation of iron uptake and utilization in systemic organs and within the complex environment of the brain, with particular emphasis on the underlying mechanisms leading to brain iron mis-metabolism in specific neurodegenerative conditions. Mouse models that have been instrumental in understanding systemic and brain disorders associated with iron mis-metabolism are also described, followed by current therapeutic strategies which are aimed at restoring brain iron homeostasis in different neurodegenerative conditions. We conclude by highlighting important gaps in our understanding of brain iron metabolism and mis-metabolism, particularly in the context of neurodegenerative disorders.

Molecular Mechanisms of Neuroplasticity: An Expanding Universe.

PubMed

Gulyaeva, N V

2017-03-01

Biochemical processes in synapses and other neuronal compartments underlie neuroplasticity (functional and structural alterations in the brain enabling adaptation to the environment, learning, memory, as well as rehabilitation after brain injury). This basic molecular level of brain plasticity covers numerous specific proteins (enzymes, receptors, structural proteins, etc.) participating in many coordinated and interacting signal and metabolic processes, their modulation forming a molecular basis for brain plasticity. The articles in this issue are focused on different "hot points" in the research area of biochemical mechanisms supporting neuroplasticity.

Preliminary Structural Sizing and Alternative Material Trade Study of CEV Crew Module

NASA Technical Reports Server (NTRS)

Bednarcyk, Brett A.; Arnold, Steve M.; Collier, Craig S.; Yarrington, Phillip W.

2007-01-01

This paper presents the results of a preliminary structural sizing and alternate material trade study for NASA s Crew Exploration Vehicle (CEV) Crew Module (CM). This critical CEV component will house the astronauts during ascent, docking with the International Space Station, reentry, and landing. The alternate material design study considers three materials beyond the standard metallic (aluminum alloy) design that resulted from an earlier NASA Smart Buyer Team analysis. These materials are graphite/epoxy composite laminates, discontinuously reinforced SiC/Al (DRA) composites, and a novel integrated panel material/concept known as WebCore. Using the HyperSizer (Collier Research and Development Corporation) structural sizing software and NASTRAN finite element analysis code, a comparison is made among these materials for the three composite CM concepts considered by the 2006 NASA Engineering and Safety Center Composite Crew Module project.

Microbial endocrinology: Host-microbiota neuroendocrine interactions influencing brain and behavior.

PubMed

Lyte, Mark

2014-01-01

The ability of microorganisms, whether present as commensals within the microbiota or introduced as part of a therapeutic regimen, to influence behavior has been demonstrated by numerous laboratories over the last few years. Our understanding of the mechanisms that are responsible for microbiota-gut-brain interactions is, however, lacking. The complexity of the microbiota is, of course, a contributing factor. Nonetheless, while microbiologists approaching the issue of microbiota-gut-brain interactions in the behavior well recognize such complexity, what is often overlooked is the equal complexity of the host neurophysiological system, especially within the gut which is differentially innervated by the enteric nervous system. As such, in the search for common mechanisms by which the microbiota may influence behavior one may look for mechanisms which are shared by both host and microbiota. Such interkingdom signaling can be found in the shared production of neurochemical mediators that are found in both eukaryotes and prokaryotes. The study of the production and recognition of neurochemicals that are exactly the same in structure to those produced in the vertebrate organisms is known as microbial endocrinology. The examination of the microbiota from the vantage point of host-microbiota neuroendocrine interactions cannot only identify new microbial endocrinology-based mechanisms by which the microbiota can influence host behavior, but also lead to the design of interventions in which the composition of the microbiota may be modulated in order to achieve a specific microbial endocrinology-based profile beneficial to overall host behavior.

Tuna Oil Alleviates d-Galactose Induced Aging in Mice Accompanied by Modulating Gut Microbiota and Brain Protein Expression.

PubMed

Zhang, Dijun; Han, Jiaojiao; Li, Yanyan; Yuan, Bei; Zhou, Jun; Cheong, Lingzhi; Li, Ye; Lu, Chenyang; Su, Xiurong

2018-06-06

To discern whether tuna oil modulates the expression of brain proteins and the gut microbiota structure during aging induced by d-galactose, we generated an aging mouse model with d-galactose treatment, and the mice showed aging and memory deterioration symptoms according to physiological and biochemical indices. Treatment with different doses of tuna oil alleviated the symptoms; the high dose showed a better effect. Subsequently, brain proteomic analysis showed the differentially expressed proteins were involved in damaged synaptic system repairment and signal transduction system enhancement. In addition, tuna oil treatment restored the diversity of gut microbiota, 27 key operational taxonomic units, which were identified using a redundancy analysis and were significantly correlated with at least one physiological index and three proteins or genes. These findings suggest that the combination of proteomics and gut microbiota is an effective strategy to gain novel insights regarding the effect of tuna oil treatment on the microbiota-gut-brain axis.

Reconfiguration of brain network architecture to support executive control in aging.

PubMed

Gallen, Courtney L; Turner, Gary R; Adnan, Areeba; D'Esposito, Mark

2016-08-01

Aging is accompanied by declines in executive control abilities and changes in underlying brain network architecture. Here, we examined brain networks in young and older adults during a task-free resting state and an N-back task and investigated age-related changes in the modular network organization of the brain. Compared with young adults, older adults showed larger changes in network organization between resting state and task. Although young adults exhibited increased connectivity between lateral frontal regions and other network modules during the most difficult task condition, older adults also exhibited this pattern of increased connectivity during less-demanding task conditions. Moreover, the increase in between-module connectivity in older adults was related to faster task performance and greater fractional anisotropy of the superior longitudinal fasciculus. These results demonstrate that older adults who exhibit more pronounced network changes between a resting state and task have better executive control performance and greater structural connectivity of a core frontal-posterior white matter pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Noninvasive Electroencephalogram Based Control of a Robotic Arm for Reach and Grasp Tasks

NASA Astrophysics Data System (ADS)

Meng, Jianjun; Zhang, Shuying; Bekyo, Angeliki; Olsoe, Jaron; Baxter, Bryan; He, Bin

2016-12-01

Brain-computer interface (BCI) technologies aim to provide a bridge between the human brain and external devices. Prior research using non-invasive BCI to control virtual objects, such as computer cursors and virtual helicopters, and real-world objects, such as wheelchairs and quadcopters, has demonstrated the promise of BCI technologies. However, controlling a robotic arm to complete reach-and-grasp tasks efficiently using non-invasive BCI has yet to be shown. In this study, we found that a group of 13 human subjects could willingly modulate brain activity to control a robotic arm with high accuracy for performing tasks requiring multiple degrees of freedom by combination of two sequential low dimensional controls. Subjects were able to effectively control reaching of the robotic arm through modulation of their brain rhythms within the span of only a few training sessions and maintained the ability to control the robotic arm over multiple months. Our results demonstrate the viability of human operation of prosthetic limbs using non-invasive BCI technology.

The serotonin receptor 7 and the structural plasticity of brain circuits

PubMed Central

Volpicelli, Floriana; Speranza, Luisa; di Porzio, Umberto; Crispino, Marianna; Perrone-Capano, Carla

2014-01-01

Serotonin (5-hydroxytryptamine, 5-HT) modulates numerous physiological processes in the nervous system. Together with its function as neurotransmitter, 5-HT regulates neurite outgrowth, dendritic spine shape and density, growth cone motility and synapse formation during development. In the mammalian brain 5-HT innervation is virtually ubiquitous and the diversity and specificity of its signaling and function arise from at least 20 different receptors, grouped in 7 classes. Here we will focus on the role 5-HT7 receptor (5-HT7R) in the correct establishment of neuronal cytoarchitecture during development, as also suggested by its involvement in several neurodevelopmental disorders. The emerging picture shows that this receptor is a key player contributing not only to shape brain networks during development but also to remodel neuronal wiring in the mature brain, thus controlling cognitive and emotional responses. The activation of 5-HT7R might be one of the mechanisms underlying the ability of the CNS to respond to different stimuli by modulation of its circuit configuration. PMID:25309369

The effect of the COMT val(158)met polymorphism on neural correlates of semantic verbal fluency.

PubMed

Krug, Axel; Markov, Valentin; Sheldrick, Abigail; Krach, Sören; Jansen, Andreas; Zerres, Klaus; Eggermann, Thomas; Stöcker, Tony; Shah, N Jon; Kircher, Tilo

2009-12-01

Variation in the val(158)met polymorphism of the COMT gene has been found to be associated with cognitive performance. In functional neuroimaging studies, this dysfunction has been linked to signal changes in prefrontal areas. Given the complex modulation and functional heterogeneity of frontal lobe systems, further specification of COMT gene-related phenotypes differing in prefrontally mediated cognitive performance are of major interest. Eighty healthy individuals (54 men, 26 women; mean age 23.3 years) performed an overt semantic verbal fluency task while brain activation was measured with functional magnetic resonance imaging (fMRI). COMT val(158)met genotype was determined and correlated with brain activation measured with fMRI during the task. Although there were no differences in performance, brain activation in the left inferior frontal gyrus [Brodmann area 10] was positively correlated with the number of val alleles in the COMT gene. COMT val(158)met status modulates brain activation during the language production on a semantic level in an area related to executive functions.

TALE transcription factors during early development of the vertebrate brain and eye.

PubMed

Schulte, Dorothea; Frank, Dale

2014-01-01

Our brain's cognitive performance arises from the coordinated activities of billions of nerve cells. Despite a high degree of morphological and functional differences, all neurons of the vertebrate central nervous system (CNS) arise from a common field of multipotent progenitors. Cell fate specification and differentiation are directed by multistep processes that include inductive/external cues, such as the extracellular matrix or growth factors, and cell-intrinsic determinants, such as transcription factors and epigenetic modulators of proteins and DNA. Here we review recent findings implicating TALE-homeodomain proteins in these processes. Although originally identified as HOX-cofactors, TALE proteins also contribute to many physiological processes that do not require HOX-activity. Particular focus is, therefore, given to HOX-dependent and -independent functions of TALE proteins during early vertebrate brain development. Additionally, we provide an overview about known upstream and downstream factors of TALE proteins in the developing vertebrate brain and discuss general concepts of how TALE proteins function to modulate neuronal cell fate specification. Copyright © 2013 Wiley Periodicals, Inc.

Volumetric-modulated arc therapy vs conventional fixed-field intensity-modulated radiotherapy in a whole-ventricular irradiation: A planning comparison study

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

Sakanaka, Katsuyuki; Mizowaki, Takashi, E-mail: mizo@kuhp.kyoto-u.ac.jp; Sato, Sayaka

This study evaluated the dosimetric difference between volumetric-modulated arc therapy (VMAT) and conventional fixed-field intensity-modulated radiotherapy (cIMRT) in whole-ventricular irradiation. Computed tomography simulation data for 13 patients were acquired to create plans for VMAT and cIMRT. In both plans, the same median dose (100% = 24 Gy) was prescribed to the planning target volume (PTV), which comprised a tumor bed and whole ventricles. During optimization, doses to the normal brain and body were reduced, provided that the dose constraints of the target coverage were satisfied. The dose-volume indices of the PTV, normal brain, and body as well as monitor unitsmore » were compared between the 2 techniques by using paired t-tests. The results showed no significant difference in the homogeneity index (0.064 vs 0.065; p = 0.824) of the PTV and conformation number (0.78 vs 0.77; p = 0.065) between the 2 techniques. In the normal brain and body, the dose-volume indices showed no significant difference between the 2 techniques, except for an increase in the volume receiving a low dose in VMAT; the absolute volume of the normal brain and body receiving 1 Gy of radiation significantly increased in VMAT by 1.6% and 8.3%, respectively, compared with that in cIMRT (1044 vs 1028 mL for the normal brain and 3079.2 vs 2823.3 mL for the body; p<0.001). The number of monitor units to deliver a 2.0-Gy fraction was significantly reduced in VMAT compared with that in cIMRT (354 vs 873, respectively; p<0.001). In conclusion, VMAT delivers IMRT to complex target volumes such as whole ventricles with fewer monitor units, while maintaining target coverage and conformal isodose distribution comparable to cIMRT; however, in addition to those characteristics, the fact that the volume of the normal brain and body receiving a low dose would increase in VMAT should be considered.« less

MicroRNA-153 Physiologically Inhibits Expression of Amyloid-β Precursor Protein in Cultured Human Fetal Brain Cells and Is Dysregulated in a Subset of Alzheimer Disease Patients*

PubMed Central

Long, Justin M.; Ray, Balmiki; Lahiri, Debomoy K.

2012-01-01

Regulation of amyloid-β (Aβ) precursor protein (APP) expression is complex. MicroRNAs (miRNAs) are expected to participate in the molecular network that controls this process. The composition of this network is, however, still undefined. Elucidating the complement of miRNAs that regulate APP expression should reveal novel drug targets capable of modulating Aβ production in AD. Here, we investigated the contribution of miR-153 to this regulatory network. A miR-153 target site within the APP 3′-untranslated region (3′-UTR) was predicted by several bioinformatic algorithms. We found that miR-153 significantly reduced reporter expression when co-transfected with an APP 3′-UTR reporter construct. Mutation of the predicted miR-153 target site eliminated this reporter response. miR-153 delivery in both HeLa cells and primary human fetal brain cultures significantly reduced APP expression. Delivery of a miR-153 antisense inhibitor to human fetal brain cultures significantly elevated APP expression. miR-153 delivery also reduced expression of the APP paralog APLP2. High functional redundancy between APP and APLP2 suggests that miR-153 may target biological pathways in which they both function. Interestingly, in a subset of human AD brain specimens with moderate AD pathology, miR-153 levels were reduced. This same subset also exhibited elevated APP levels relative to control specimens. Therefore, endogenous miR-153 inhibits expression of APP in human neurons by specifically interacting with the APP 3′-UTR. This regulatory interaction may have relevance to AD etiology, where low miR-153 levels may drive increased APP expression in a subset of AD patients. PMID:22733824

Cortico-cortical and motor evoked potentials to single and paired-pulse stimuli: An exploratory transcranial magnetic and intracranial electric brain stimulation study.

PubMed

Boulogne, Sébastien; Andre-Obadia, Nathalie; Kimiskidis, Vasilios K; Ryvlin, Philippe; Rheims, Sylvain

2016-11-01

Paired-pulse (PP) paradigms are commonly employed to assess in vivo cortical excitability using transcranial magnetic stimulation (TMS) to stimulate the primary motor cortex and modulate the induced motor evoked potential (MEP). Single-pulse cortical direct electrical stimulation (DES) during intracerebral EEG monitoring allows the investigation of brain connectivity by eliciting cortico-cortical evoked potentials (CCEPs). However, PP paradigm using intracerebral DES has rarely been reported and has never been previously compared with TMS. The work was intended (i) to verify that the well-established modulations of MEPs following PP TMS remain similar using DES in the motor cortex, and (ii) to evaluate if a similar pattern could be observed in distant cortico-cortical connections through modulations of CCEP. Three patients undergoing intracerebral EEG monitoring with electrodes implanted in the central region were studied. Single-pulse DES (1-3 mA, 1 ms, 0.2 Hz) and PP DES using six interstimulus intervals (5, 15, 30, 50, 100, and 200 ms) in the motor cortex with concomitant recording of CCEPs and MEPs in contralateral muscles were performed. Finally, a navigated PP TMS session targeted the intracranial stimulation site to record TMS-induced MEPs in two patients. MEP modulations elicited by PP intracerebral DES proved similar among the three patients and to those obtained by PP TMS. CCEP modulations elicited by PP intracerebral DES usually showed a pattern comparable to that of MEP, although a different pattern could be observed occasionally. PP intracerebral DES seems to involve excitatory and inhibitory mechanisms similar to PP TMS and allows the recording of intracortical inhibition and facilitation modulation on cortico-cortical connections. Hum Brain Mapp 37:3767-3778, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Dynamics of alpha control: Preparatory suppression of posterior alpha oscillations by frontal modulators revealed with combined EEG and event-related optical signal (EROS)

PubMed Central

Mathewson, Kyle E.; Beck, Diane M.; Ro, Tony; Maclin, Edward L.; Low, Kathy A.; Fabiani, Monica; Gratton, Gabriele

2015-01-01

We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously we proposed that alpha (8-12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top-down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently-recorded electroencephalogram (EEG), while subjects performed a visual target-detection task. The pre-target alpha oscillations measured with EEG and EROS from posterior areas were larger for subsequently undetected targets, supporting alpha's inhibitory role. Using EROS, we localized brain correlates of these awareness-related alpha oscillations measured at the scalp to the cuneus and precuneus. Crucially, EROS alpha suppression correlated with posterior EEG alpha power across subjects. Sorting the EROS data based on EEG alpha power quartiles to investigate alpha modulators revealed that suppression of posterior alpha was preceded by increased activity in regions of the dorsal attention network, and decreased activity in regions of the cingulo-opercular network. Cross-correlations revealed the temporal dynamics of activity within these preparatory networks prior to posterior alpha modulation. The novel combination of EEG and EROS afforded localization of the sources and correlates of alpha oscillations and their temporal relationships, supporting our proposal that top-down control from attention networks modulates both posterior alpha and awareness of visual stimuli. PMID:24702458

Non-linear transfer characteristics of stimulation and recording hardware account for spurious low-frequency artifacts during amplitude modulated transcranial alternating current stimulation (AM-tACS).

PubMed

Kasten, Florian H; Negahbani, Ehsan; Fröhlich, Flavio; Herrmann, Christoph S

2018-05-31

Amplitude modulated transcranial alternating current stimulation (AM-tACS) has been recently proposed as a possible solution to overcome the pronounced stimulation artifact encountered when recording brain activity during tACS. In theory, AM-tACS does not entail power at its modulating frequency, thus avoiding the problem of spectral overlap between brain signal of interest and stimulation artifact. However, the current study demonstrates how weak non-linear transfer characteristics inherent to stimulation and recording hardware can reintroduce spurious artifacts at the modulation frequency. The input-output transfer functions (TFs) of different stimulation setups were measured. Setups included recordings of signal-generator and stimulator outputs and M/EEG phantom measurements. 6 th -degree polynomial regression models were fitted to model the input-output TFs of each setup. The resulting TF models were applied to digitally generated AM-tACS signals to predict the frequency of spurious artifacts in the spectrum. All four setups measured for the study exhibited low-frequency artifacts at the modulation frequency and its harmonics when recording AM-tACS. Fitted TF models showed non-linear contributions significantly different from zero (all p < .05) and successfully predicted the frequency of artifacts observed in AM-signal recordings. Results suggest that even weak non-linearities of stimulation and recording hardware can lead to spurious artifacts at the modulation frequency and its harmonics. These artifacts were substantially larger than alpha-oscillations of a human subject in the MEG. Findings emphasize the need for more linear stimulation devices for AM-tACS and careful analysis procedures, taking into account low-frequency artifacts to avoid confusion with effects of AM-tACS on the brain. Copyright © 2018 Elsevier Inc. All rights reserved.

How does the brain process music?

PubMed

Warren, Jason

2008-02-01

The organisation of the musical brain is a major focus of interest in contemporary neuroscience. This reflects the increasing sophistication of tools (especially imaging techniques) to examine brain anatomy and function in health and disease, and the recognition that music provides unique insights into a number of aspects of nonverbal brain function. The emerging picture is complex but coherent, and moves beyond older ideas of music as the province of a single brain area or hemisphere to the concept of music as a 'whole-brain' phenomenon. Music engages a distributed set of cortical modules that process different perceptual, cognitive and emotional components with varying selectivity. 'Why' rather than 'how' the brain processes music is a key challenge for the future.

Modulation of Central Synapses by Astrocyte-Released ATP and Postsynaptic P2X Receptors

PubMed Central

Pankratov, Yuriy

2017-01-01

Communication between neuronal and glial cells is important for neural plasticity. P2X receptors are ATP-gated cation channels widely expressed in the brain where they mediate action of extracellular ATP released by neurons and/or glia. Recent data show that postsynaptic P2X receptors underlie slow neuromodulatory actions rather than fast synaptic transmission at brain synapses. Here, we review these findings with a particular focus on the release of ATP by astrocytes and the diversity of postsynaptic P2X-mediated modulation of synaptic strength and plasticity in the CNS. PMID:28845311

In Vivo Assessment of Neurotransmitters and Modulators with Magnetic Resonance Spectroscopy: Application to Schizophrenia

PubMed Central

Wijtenburg, S. Andrea; Yang, Shaolin; Fischer, Bernard A.; Rowland, Laura M.

2015-01-01

In vivo measurement of neurotransmitters and modulators is now feasible with advanced proton magnetic resonance spectroscopy (1H-MRS) techniques. This review provides a basic tutorial of MRS, describes the methods available to measure brain glutamate, glutamine, γ-aminobutyric acid, glutathione, N-acetylaspartylglutamate, glycine, and serine at magnetic field strengths of 3Tesla or higher, and summarizes the neurochemical findings in schizophrenia. Overall, 1H-MRS holds great promise for producing biomarkers that can serve as treatment targets, prediction of disease onset, or illness exacerbation in schizophrenia and other brain diseases. PMID:25614132

MO-F-CAMPUS-T-02: Optimizing Orientations of Hundreds of Intensity-Modulated Beams to Treat Multiple Brain Targets

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

Ma, L; Dong, P; Larson, D

Purpose: To investigate a new modulated beam orientation optimization (MBOO) approach maximizing treatment planning quality for the state-of-the-art flattening filter free (FFF) beam that has enabled rapid treatments of multiple brain targets. Methods: MBOO selects and optimizes a large number of intensity-modulated beams (400 or more) from all accessible beam angles surrounding a patient’s skull. The optimization algorithm was implemented on a standalone system that interfaced with the 3D Dicom images and structure sets. A standard published data set that consisted of 1 to 12 metastatic brain tumor combinations was selected for MBOO planning. The planning results from various coplanarmore » and non-coplanar configurations via MBOO were then compared with the results obtained from a clinical volume modulated arc therapy (VMAT) delivery system (Truebeam RapidArc, Varian Oncology). Results: When planning a few number of targets (n<4), MBOO produced results equivalent to non-coplanar multi-arc VMAT planning in terms of target volume coverage and normal tissue sparing. For example, the 12-Gy and 4-Gy normal brain volumes for the 3-target plans differed by less than 1 mL ( 3.0 mLvs 3.8 mL; and 35.2 mL vs 36.3 mL, respectively) for MBOO versus VMAT. However, when planning a larger number of targets (n≥4), MBOO significantly reduced the dose to the normal brain as compared to VMAT, though the target volume coverage was equivalent. For example, the 12-Gy and 4-Gy normal brain volumes for the 12-target plans were 10.8 mL vs. 18.0 mL and 217.9 mL vs. 390.0 mL, respectively for the non-coplanar MBOO versus the non-coplanar VMAT treatment plans, yielding a reduction in volume of more than 60% for the case. Conclusion: MBOO is a unique approach for maximizing normal tissue sparing when treating a large number (n≥4) of brain tumors with FFF linear accelerators. Dr Ma and Dr Sahgal are currently on the board of international society of stereotactic radiosurgery. Dr Sahgal has received support for educational presentations from Elekta company.« less

Self-modulation of primary motor cortex activity with motor and motor imagery tasks using real-time fMRI-based neurofeedback

PubMed Central

Berman, Brian D.; Horovitz, Silvina G.; Venkataraman, Gaurav; Hallett, Mark

2011-01-01

Advances in fMRI data acquisition and processing have made it possible to analyze brain activity as rapidly as the images are acquired allowing this information to be fed back to subjects in the scanner. The ability of subjects to learn to volitionally control localized brain activity within motor cortex using such real-time fMRI-based neurofeedback (NF) is actively being investigated as it may have clinical implications for motor rehabilitation after central nervous system injury and brain-computer interfaces. We investigated the ability of fifteen healthy volunteers to use NF to modulate brain activity within the primary motor cortex (M1) during a finger tapping and tapping imagery task. The M1 hand area ROI (ROIm) was functionally localized during finger tapping and a visual representation of BOLD signal changes within the ROIm fed back to the subject in the scanner. Surface EMG was used to assess motor output during tapping and ensure no motor activity was present during motor imagery task. Subjects quickly learned to modulate brain activity within their ROIm during the finger-tapping task, which could be dissociated from the magnitude of the tapping, but did not show a significant increase within the ROIm during the hand motor imagery task at the group level despite strongly activating a network consistent with the performance of motor imagery. The inability of subjects to modulate M1 proper with motor imagery may reflect an inherent difficulty in activating synapses in this area, with or without NF, since such activation may lead to M1 neuronal output and obligatory muscle activity. Future real-time fMRI-based NF investigations involving motor cortex may benefit from focusing attention on cortical regions other than M1 for feedback training or alternative feedback strategies such as measures of functional connectivity within the motor system. PMID:21803163

Brain response to images of food varying in energy density is associated with body composition in 7- to 10-year-old children: Results of an exploratory study.

PubMed

Fearnbach, S Nicole; English, Laural K; Lasschuijt, Marlou; Wilson, Stephen J; Savage, Jennifer S; Fisher, Jennifer O; Rolls, Barbara J; Keller, Kathleen L

2016-08-01

Energy balance is regulated by a multifaceted system of physiological signals that influence energy intake and expenditure. Therefore, variability in the brain's response to food may be partially explained by differences in levels of metabolically active tissues throughout the body, including fat-free mass (FFM) and fat mass (FM). The purpose of this study was to test the hypothesis that children's body composition would be related to their brain response to food images varying in energy density (ED), a measure of energy content per weight of food. Functional magnetic resonance imaging (fMRI) was used to measure brain response to High (>1.5kcal/g) and Low (<1.5kcal/g) ED food images, and Control images, in 36 children ages 7-10years. Body composition was measured using bioelectrical impedance analysis. Multi-subject random effects general linear model (GLM) and two-factor repeated measures analysis of variance (ANOVA) were used to test for main effects of ED (High ED vs. Low ED) in a priori defined brain regions of interest previously implicated in energy homeostasis and reward processing. Pearson's correlations were then calculated between activation in these regions for various contrasts (High ED-Low ED, High ED-Control, Low ED-Control) and child body composition (FFM index, FM index, % body fat). Relative to Low ED foods, High ED foods elicited greater BOLD activation in the left thalamus. In the right substantia nigra, BOLD activation for the contrast of High ED-Low ED foods was positively associated with child FFM. There were no significant results for the High ED-Control or Low ED-Control contrasts. Our findings support literature on FFM as an appetitive driver, such that greater amounts of lean mass were associated with greater activation for High ED foods in an area of the brain associated with dopamine signaling and reward (substantia nigra). These results confirm our hypothesis that brain response to foods varying in energy content is related to measures of child body composition. Copyright © 2016 Elsevier Inc. All rights reserved.

Relation of visual creative imagery manipulation to resting-state brain oscillations.

PubMed

Cai, Yuxuan; Zhang, Delong; Liang, Bishan; Wang, Zengjian; Li, Junchao; Gao, Zhenni; Gao, Mengxia; Chang, Song; Jiao, Bingqing; Huang, Ruiwang; Liu, Ming

2018-02-01

Visual creative imagery (VCI) manipulation is the key component of visual creativity; however, it remains largely unclear how it occurs in the brain. The present study investigated the brain neural response to VCI manipulation and its relation to intrinsic brain activity. We collected functional magnetic resonance imaging (fMRI) datasets related to a VCI task and a control task as well as pre- and post-task resting states in sequential sessions. A general linear model (GLM) was subsequently used to assess the specific activation of the VCI task compared with the control task. The changes in brain oscillation amplitudes across the pre-, on-, and post-task states were measured to investigate the modulation of the VCI task. Furthermore, we applied a Granger causal analysis (GCA) to demonstrate the dynamic neural interactions that underlie the modulation effect. We determined that the VCI task specifically activated the left inferior frontal gyrus pars triangularis (IFGtriang) and the right superior frontal gyrus (SFG), as well as the temporoparietal areas, including the left inferior temporal gyrus, right precuneus, and bilateral superior parietal gyrus. Furthermore, the VCI task modulated the intrinsic brain activity of the right IFGtriang (0.01-0.08 Hz) and the left caudate nucleus (0.2-0.25 Hz). Importantly, an inhibitory effect (negative) may exist from the left SFG to the right IFGtriang in the on-VCI task state, in the frequency of 0.01-0.08 Hz, whereas this effect shifted to an excitatory effect (positive) in the subsequent post-task resting state. Taken together, the present findings provide experimental evidence for the existence of a common mechanism that governs the brain activity of many regions at resting state and whose neural activity may engage during the VCI manipulation task, which may facilitate an understanding of the neural substrate of visual creativity.

Effects of load and maintenance duration on the time course of information encoding and retrieval in working memory: from perceptual analysis to post-categorization processes.

PubMed

Pinal, Diego; Zurrón, Montserrat; Díaz, Fernando

2014-01-01

information encoding, maintenance, and retrieval; these are supported by brain activity in a network of frontal, parietal and temporal regions. Manipulation of WM load and duration of the maintenance period can modulate this activity. Although such modulations have been widely studied using the event-related potentials (ERP) technique, a precise description of the time course of brain activity during encoding and retrieval is still required. Here, we used this technique and principal component analysis to assess the time course of brain activity during encoding and retrieval in a delayed match to sample task. We also investigated the effects of memory load and duration of the maintenance period on ERP activity. Brain activity was similar during information encoding and retrieval and comprised six temporal factors, which closely matched the latency and scalp distribution of some ERP components: P1, N1, P2, N2, P300, and a slow wave. Changes in memory load modulated task performance and yielded variations in frontal lobe activation. Moreover, the P300 amplitude was smaller in the high than in the low load condition during encoding and retrieval. Conversely, the slow wave amplitude was higher in the high than in the low load condition during encoding, and the same was true for the N2 amplitude during retrieval. Thus, during encoding, memory load appears to modulate the processing resources for context updating and post-categorization processes, and during retrieval it modulates resources for stimulus classification and context updating. Besides, despite the lack of differences in task performance related to duration of the maintenance period, larger N2 amplitude and stronger activation of the left temporal lobe after long than after short maintenance periods were found during information retrieval. Thus, results regarding the duration of maintenance period were complex, and future work is required to test the time-based decay theory predictions.

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases.

PubMed

Yarandi, Shadi S; Peterson, Daniel A; Treisman, Glen J; Moran, Timothy H; Pasricha, Pankaj J

2016-04-30

Gut microbiome is an integral part of the Gut-Brain axis. It is becoming increasingly recognized that the presence of a healthy and diverse gut microbiota is important to normal cognitive and emotional processing. It was known that altered emotional state and chronic stress can change the composition of gut microbiome, but it is becoming more evident that interaction between gut microbiome and central nervous system is bidirectional. Alteration in the composition of the gut microbiome can potentially lead to increased intestinal permeability and impair the function of the intestinal barrier. Subsequently, neuro-active compounds and metabolites can gain access to the areas within the central nervous system that regulate cognition and emotional responses. Deregulated inflammatory response, promoted by harmful microbiota, can activate the vagal system and impact neuropsychological functions. Some bacteria can produce peptides or short chain fatty acids that can affect gene expression and inflammation within the central nervous system. In this review, we summarize the evidence supporting the role of gut microbiota in modulating neuropsychological functions of the central nervous system and exploring the potential underlying mechanisms.

Reward sensitivity modulates brain activity in the prefrontal cortex, ACC and striatum during task switching.

PubMed

Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Ventura-Campos, Noelia; Bustamante, Juan C; Costumero, Víctor; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

2015-01-01

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies.

Reward Sensitivity Modulates Brain Activity in the Prefrontal Cortex, ACC and Striatum during Task Switching

PubMed Central

Fuentes-Claramonte, Paola; Ávila, César; Rodríguez-Pujadas, Aina; Ventura-Campos, Noelia; Bustamante, Juan C.; Costumero, Víctor; Rosell-Negre, Patricia; Barrós-Loscertales, Alfonso

2015-01-01

Current perspectives on cognitive control acknowledge that individual differences in motivational dispositions may modulate cognitive processes in the absence of reward contingencies. This work aimed to study the relationship between individual differences in Behavioral Activation System (BAS) sensitivity and the neural underpinnings involved in processing a switching cue in a task-switching paradigm. BAS sensitivity was hypothesized to modulate brain activity in frontal regions, ACC and the striatum. Twenty-eight healthy participants underwent fMRI while performing a switching task, which elicited activity in fronto-striatal regions during the processing of the switch cue. BAS sensitivity was negatively associated with activity in the lateral prefrontal cortex, anterior cingulate cortex and the ventral striatum. Combined with previous results, our data indicate that BAS sensitivity modulates the neurocognitive processes involved in task switching in a complex manner depending on task demands. Therefore, individual differences in motivational dispositions may influence cognitive processing in the absence of reward contingencies. PMID:25875640

Investigation of the low-level modulated light action

NASA Astrophysics Data System (ADS)

Antonov, Sergei N.; Sotnikov, V. N.; Koreneva, L. G.

1994-07-01

Now there exists no clear complete knowledge about mechanisms and pathways by which low level laser bioactivation works. Modulated laser light action has been investigated two new ways: dynamical infrared thermography and computing image of living brain. These ways permit observation in real time laser action on peripheral blood flow, reflex reactions to functional probes, thermoregulation mechanisms as well as brain electrical activity changes of humans. We have designed a universal apparatus which produced all regimes of the output laser light. It has a built-in He-Ne laser with an acousto-optic modulator and an infrared GaAs laser. The device provided spatial combination of both the light beams and permitted us to irradiate an object both separately and simultaneously. This research shows that the most effective frequencies range from several to dozens of hertz. The duty factor and frequency scanning are also important. On the basis of these results in Russian clinics new treatment methods using modulated light are applied in practical neurology, gynecology, etc.

Descending pain modulation in irritable bowel syndrome (IBS): a systematic review and meta-analysis.

PubMed

Chakiath, Rosemary J; Siddall, Philip J; Kellow, John E; Hush, Julia M; Jones, Mike P; Marcuzzi, Anna; Wrigley, Paul J

2015-12-10

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. While abdominal pain is a dominant symptom of IBS, many sufferers also report widespread hypersensitivity and present with other chronic pain conditions. The presence of widespread hypersensitivity and extra-intestinal pain conditions suggests central nervous dysfunction. While central nervous system dysfunction may involve the spinal cord (central sensitisation) and brain, this review will focus on one brain mechanism, descending pain modulation. We will conduct a comprehensive search for the articles indexed in the databases Ovid MEDLINE, Ovid Embase, Ovid PsycINFO and Cochrane Central Register of Controlled Trial (CENTRAL) from their inception to August 2015, that report on any aspect of descending pain modulation in irritable bowel syndrome. Two independent reviewers will screen studies for eligibility, assess risk of bias and extract relevant data. Results will be tabulated and, if possible, a meta-analysis will be carried out. The systematic review outlined in this protocol aims to summarise current knowledge regarding descending pain modulation in IBS. PROSPERO CRD42015024284.

Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms.

PubMed

Clemente-Perez, Alexandra; Makinson, Stefanie Ritter; Higashikubo, Bryan; Brovarney, Scott; Cho, Frances S; Urry, Alexander; Holden, Stephanie S; Wimer, Matthew; Dávid, Csaba; Fenno, Lief E; Acsády, László; Deisseroth, Karl; Paz, Jeanne T

2017-06-06

Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers. We dissociated the connectivity, physiology, and circuit functions of neurons within rodent nRT, based on parvalbumin (PV) and somatostatin (SOM) expression, and validated the existence of such populations in human nRT. We found that PV, but not SOM, cells are rhythmogenic, and that PV and SOM neurons are connected to and modulate distinct thalamocortical circuits. Notably, PV, but not SOM, neurons modulate somatosensory behavior and disrupt seizures. These results provide a conceptual framework for how nRT may gate incoming information to modulate brain-wide rhythms. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Emotional Modulation of Learning and Memory: Pharmacological Implications.

PubMed

LaLumiere, Ryan T; McGaugh, James L; McIntyre, Christa K

2017-07-01

Memory consolidation involves the process by which newly acquired information becomes stored in a long-lasting fashion. Evidence acquired over the past several decades, especially from studies using post-training drug administration, indicates that emotional arousal during the consolidation period influences and enhances the strength of the memory and that multiple different chemical signaling systems participate in this process. The mechanisms underlying the emotional influences on memory involve the release of stress hormones and activation of the basolateral amygdala, which work together to modulate memory consolidation. Moreover, work suggests that this amygdala-based memory modulation occurs with numerous types of learning and involves interactions with many different brain regions to alter consolidation. Additionally, studies suggest that emotional arousal and amygdala activity in particular influence synaptic plasticity and associated proteins in downstream brain regions. This review considers the historical understanding for memory modulation and cellular consolidation processes and examines several research areas currently using this foundational knowledge to develop therapeutic treatments. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging.

PubMed

Phillips, Cristy

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors-including physical activity, cognitive engagement, and diet-are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging.

Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental Engagement, and Diet Promote Cognitive Health during Aging

PubMed Central

2017-01-01

The number of the elderly across the globe will approximate 2.1 billion by 2050. Juxtaposed against this burgeoning segment of the population is evidence that nonpathological aging is associated with an increased risk for cognitive decline in a variety of domains, changes that can cause mild disability even before the onset of dementia. Given that pharmacological treatments that mitigate dementia are still outstanding, alternative therapeutic options are being investigated increasingly. The results from translational studies have shown that modifiable lifestyle factors—including physical activity, cognitive engagement, and diet—are a key strategy for maintaining brain health during aging. Indeed, a multiplicity of studies has demonstrated relationships between lifestyle factors, brain structure and function, and cognitive function in aging adults. For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and antioxidant defense) in the brain whereas cognitive engagement enhances brain and cognitive reserve. The aims of this review are to evaluate the relationship between modifiable lifestyle factors, neuroplasticity, and optimal brain health during aging; to identify putative mechanisms that contribute positive brain aging; and to highlight future directions for scientists and clinicians. Undoubtedly, the translation of cutting-edge knowledge derived from the field of cognitive neuroscience will advance our understanding and enhance clinical treatment interventions as we endeavor to promote brain health during aging. PMID:28695017

Delay-correlation landscape reveals characteristic time delays of brain rhythms and heart interactions

NASA Astrophysics Data System (ADS)

Lin, Aijing; Liu, Kang K. L.; Bartsch, Ronny P.; Ivanov, Plamen Ch.

2016-05-01

Within the framework of `Network Physiology', we ask a fundamental question of how modulations in cardiac dynamics emerge from networked brain-heart interactions. We propose a generalized time-delay approach to identify and quantify dynamical interactions between physiologically relevant brain rhythms and the heart rate. We perform empirical analysis of synchronized continuous EEG and ECG recordings from 34 healthy subjects during night-time sleep. For each pair of brain rhythm and heart interaction, we construct a delay-correlation landscape (DCL) that characterizes how individual brain rhythms are coupled to the heart rate, and how modulations in brain and cardiac dynamics are coordinated in time. We uncover characteristic time delays and an ensemble of specific profiles for the probability distribution of time delays that underly brain-heart interactions. These profiles are consistently observed in all subjects, indicating a universal pattern. Tracking the evolution of DCL across different sleep stages, we find that the ensemble of time-delay profiles changes from one physiologic state to another, indicating a strong association with physiologic state and function. The reported observations provide new insights on neurophysiological regulation of cardiac dynamics, with potential for broad clinical applications. The presented approach allows one to simultaneously capture key elements of dynamic interactions, including characteristic time delays and their time evolution, and can be applied to a range of coupled dynamical systems.

Simulated driving and brain imaging: combining behavior, brain activity, and virtual reality.

PubMed

Carvalho, Kara N; Pearlson, Godfrey D; Astur, Robert S; Calhoun, Vince D

2006-01-01

Virtual reality in the form of simulated driving is a useful tool for studying the brain. Various clinical questions can be addressed, including both the role of alcohol as a modulator of brain function and regional brain activation related to elements of driving. We reviewed a study of the neural correlates of alcohol intoxication through the use of a simulated-driving paradigm and wished to demonstrate the utility of recording continuous-driving behavior through a new study using a programmable driving simulator developed at our center. Functional magnetic resonance imaging data was collected from subjects while operating a driving simulator. Independent component analysis (ICA) was used to analyze the data. Specific brain regions modulated by alcohol, and relationships between behavior, brain function, and alcohol blood levels were examined with aggregate behavioral measures. Fifteen driving epochs taken from two subjects while also recording continuously recorded driving variables were analyzed with ICA. Preliminary findings reveal that four independent components correlate with various aspects of behavior. An increase in braking while driving was found to increase activation in motor areas, while cerebellar areas showed signal increases during steering maintenance, yet signal decreases during steering changes. Additional components and significant findings are further outlined. In summary, continuous behavioral variables conjoined with ICA may offer new insight into the neural correlates of complex human behavior.

Brain networks and their origins. Comment on “Understanding brain networks and brain organization” by Luiz Pessoa

NASA Astrophysics Data System (ADS)

Cisek, Paul

2014-09-01

Nearly every textbook on psychology or neuroscience contains theories of function described with box and arrow diagrams. Sometimes, the boxes stand for purely theoretical constructs, such as attention or working memory, and sometimes they also correspond to specific brain regions or systems, such as parietal or prefrontal cortex, and the arrows between them to known anatomical pathways. It is common for scientists (present company included) to summarize their theories in this way and to think of the brain as a set of interacting modules with clearly distinguishable functions.

Modulation of Cholinergic Pathways and Inflammatory Mediators in Blast-Induced Traumatic Brain Injury

DTIC Science & Technology

2013-01-01

matic brain injury (TBI). Centrally acting acetylcholinesterase (AChE) inhibitors are also being considered as potential therapeutic candidates...repeated blast exposures [12]. AChE inhibitors are possible therapeutic candidates against Alzheimer’s disease and TBI [13–15]. In this study, we...esterase inhibitor , as described earlier [12,17–19]. Brain AChE activity was expressed as milliunits/mg protein. 2.3. Microarray analysis Various

Optimization of Treatment Geometry to Reduce Normal Brain Dose in Radiosurgery of Multiple Brain Metastases with Single-Isocenter Volumetric Modulated Arc Therapy.

PubMed

Wu, Qixue; Snyder, Karen Chin; Liu, Chang; Huang, Yimei; Zhao, Bo; Chetty, Indrin J; Wen, Ning

2016-09-30

Treatment of patients with multiple brain metastases using a single-isocenter volumetric modulated arc therapy (VMAT) has been shown to decrease treatment time with the tradeoff of larger low dose to the normal brain tissue. We have developed an efficient Projection Summing Optimization Algorithm to optimize the treatment geometry in order to reduce dose to normal brain tissue for radiosurgery of multiple metastases with single-isocenter VMAT. The algorithm: (a) measures coordinates of outer boundary points of each lesion to be treated using the Eclipse Scripting Application Programming Interface, (b) determines the rotations of couch, collimator, and gantry using three matrices about the cardinal axes, (c) projects the outer boundary points of the lesion on to Beam Eye View projection plane, (d) optimizes couch and collimator angles by selecting the least total unblocked area for each specific treatment arc, and (e) generates a treatment plan with the optimized angles. The results showed significant reduction in the mean dose and low dose volume to normal brain, while maintaining the similar treatment plan qualities on the thirteen patients treated previously. The algorithm has the flexibility with regard to the beam arrangements and can be integrated in the treatment planning system for clinical application directly.

The motilin agonist erythromycin increases hunger by modulating homeostatic and hedonic brain circuits in healthy women: a randomized, placebo-controlled study.

PubMed

Zhao, Dongxing; Meyer-Gerspach, Anne Christin; Deloose, Eveline; Iven, Julie; Weltens, Nathalie; Depoortere, Inge; O'daly, Owen; Tack, Jan; Van Oudenhove, Lukas

2018-01-29

The motilin agonist, erythromycin, induces gastric phase III of the migrating motor complex, which in turn generates hunger peaks. To identify the brain mechanisms underlying these orexigenic effects, 14 healthy women participated in a randomized, placebo-controlled crossover study. Functional magnetic resonance brain images were acquired for 50 minutes interprandially. Intravenous infusion of erythromycin (40 mg) or saline started 10 minutes after the start of scanning. Blood samples (for glucose and hormone levels) and hunger ratings were collected at fixed timepoints. Thirteen volunteers completed the study, without any adverse events. Brain regions involved in homeostatic and hedonic control of appetite and food intake responded to erythromycin, including pregenual anterior cingulate cortex, anterior insula cortex, orbitofrontal cortex, amygdala, caudate, pallidum and putamen bilaterally, right accumbens, hypothalamus, and midbrain. Octanoylated ghrelin levels decreased, whereas both glucose and insulin increased after erythromycin. Hunger were higher after erythromycin, and these differences covaried with the brain response in most of the abovementioned regions. The motilin agonist erythromycin increases hunger by modulating neurocircuitry related to homeostatic and hedonic control of appetite and feeding. These results confirm recent behavioural findings identifying motilin as a key orexigenic hormone in humans, and identify the brain mechanisms underlying its effect.

Gliovascular and cytokine interactions modulate brain endothelial barrier in vitro.

PubMed

Chaitanya, Ganta V; Cromer, Walter E; Wells, Shannon R; Jennings, Merilyn H; Couraud, P Olivier; Romero, Ignacio A; Weksler, Babette; Erdreich-Epstein, Anat; Mathis, J Michael; Minagar, Alireza; Alexander, J Steven

2011-11-23

The glio-vascular unit (G-unit) plays a prominent role in maintaining homeostasis of the blood-brain barrier (BBB) and disturbances in cells forming this unit may seriously dysregulate BBB. The direct and indirect effects of cytokines on cellular components of the BBB are not yet unclear. The present study compares the effects of cytokines and cytokine-treated astrocytes on brain endothelial barrier. 3-dimensional transwell co-cultures of brain endothelium and related-barrier forming cells with astrocytes were used to investigate gliovascular barrier responses to cytokines during pathological stresses. Gliovascular barrier was measured using trans-endothelial electrical resistance (TEER), a sensitive index of in vitro barrier integrity. We found that neither TNF-α, IL-1β or IFN-γ directly reduced barrier in human or mouse brain endothelial cells or ECV-304 barrier (independent of cell viability/metabolism), but found that astrocyte exposure to cytokines in co-culture significantly reduced endothelial (and ECV-304) barrier. These results indicate that the barrier established by human and mouse brain endothelial cells (and other cells) may respond positively to cytokines alone, but that during pathological conditions, cytokines dysregulate the barrier forming cells indirectly through astrocyte activation involving reorganization of junctions, matrix, focal adhesion or release of barrier modulating factors (e.g. oxidants, MMPs). © 2011 Chaitanya et al; licensee BioMed Central Ltd.

Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

PubMed

Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

2017-01-01

Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

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.

A subject-independent pattern-based Brain-Computer Interface

PubMed Central

Ray, Andreas M.; Sitaram, Ranganatha; Rana, Mohit; Pasqualotto, Emanuele; Buyukturkoglu, Korhan; Guan, Cuntai; Ang, Kai-Keng; Tejos, Cristián; Zamorano, Francisco; Aboitiz, Francisco; Birbaumer, Niels; Ruiz, Sergio

2015-01-01

While earlier Brain-Computer Interface (BCI) studies have mostly focused on modulating specific brain regions or signals, new developments in pattern classification of brain states are enabling real-time decoding and modulation of an entire functional network. The present study proposes a new method for real-time pattern classification and neurofeedback of brain states from electroencephalographic (EEG) signals. It involves the creation of a fused classification model based on the method of Common Spatial Patterns (CSPs) from data of several healthy individuals. The subject-independent model is then used to classify EEG data in real-time and provide feedback to new individuals. In a series of offline experiments involving training and testing of the classifier with individual data from 27 healthy subjects, a mean classification accuracy of 75.30% was achieved, demonstrating that the classification system at hand can reliably decode two types of imagery used in our experiments, i.e., happy emotional imagery and motor imagery. In a subsequent experiment it is shown that the classifier can be used to provide neurofeedback to new subjects, and that these subjects learn to “match” their brain pattern to that of the fused classification model in a few days of neurofeedback training. This finding can have important implications for future studies on neurofeedback and its clinical applications on neuropsychiatric disorders. PMID:26539089

Nanobiotechnology-based delivery strategies: New frontiers in brain tumor targeted therapies.

PubMed

Mangraviti, Antonella; Gullotti, David; Tyler, Betty; Brem, Henry

2016-10-28

Despite recent technological advancements and promising preclinical experiments, brain tumor patients are still met with limited treatment options. Some of the barriers to clinical improvements include the systemic toxicity of cytotoxic compounds, the impedance of the blood brain barrier (BBB), and the lack of therapeutic agents that can selectively target the intracranial tumor environment. To overcome such barriers, a number of chemotherapeutic agents and nucleic acid-based therapies are rapidly being synthesized and tested as new brain tumor-targeted delivery strategies. Novel carriers include liposomal and polymeric nanoparticles, wafers, microchips, microparticle-based nanoplatforms and cells-based vectors. Strong preclinical results suggest that these nanotechnologies are set to transform the therapeutic paradigm for brain tumor treatment. In addition to new tumoricidal agents, parallel work is also being conducted on the BBB front. Preclinical testing of chemical and physical modulation strategies is yielding improved intracranial concentrations. New diagnostic and therapeutic imaging techniques, such as high-intensity focused ultrasound and MRI-guided focused ultrasound, are being used to modulate the BBB in a more precise and non-invasive manner. This review details some of the tremendous advances that are being explored in current brain tumor targeted therapies, including local implant development, nanobiotechnology-based delivery strategies, and techniques of BBB manipulation. Copyright © 2016 Elsevier B.V. All rights reserved.

Counteracting radio frequency inhomogeneity in the human brain at 7 Tesla using strongly modulating pulses.

PubMed

Boulant, N; Mangin, J-F; Amadon, A

2009-05-01

We report flip angle and spoiled gradient echo measurements at 7 Tesla on human brains in three-dimensional imaging, using strongly modulating pulses to counteract the transmitted radiofrequency inhomogeneity problem. Compared with the standard square pulse results, three points of improvement are demonstrated, namely: (i) the removal of the bright center (typical at high fields when using a quadrature head coil), (ii) the substantial gain of signal in the regions of low B(1) intensity, and (iii) an increased 35% signal uniformity over the whole brain at the flip angle where maximum contrast between white and gray matter occurs. We also find by means of simulations that standard BIR-4 adiabatic pulses need several times more energy to reach a similar performance at the same field strength. (c) 2009 Wiley-Liss, Inc.

Plasmin-dependent modulation of the blood–brain barrier: a major consideration during tPA-induced thrombolysis?

PubMed Central

Niego, Be'eri; Medcalf, Robert L

2014-01-01

Plasmin, the principal downstream product of tissue-type plasminogen activator (tPA), is known for its potent fibrin-degrading capacity but is also recognized for many non-fibrinolytic activities. Curiously, plasmin has not been conclusively linked to blood–brain barrier (BBB) disruption during recombinant tPA (rtPA)-induced thrombolysis in ischemic stroke. This is surprising given the substantial involvement of tPA in the modulation of BBB permeability and the co-existence of tPA and plasminogen in both blood and brain throughout the ischemic event. Here, we review the work that argues a role for plasmin together with endogenous tPA or rtPA in BBB alteration, presenting the overall controversy around the topic yet creating a rational case for an involvement of plasmin in this process. PMID:24896566

Network analysis reveals that bacteria and fungi form modules that correlate independently with soil parameters.

PubMed

de Menezes, Alexandre B; Prendergast-Miller, Miranda T; Richardson, Alan E; Toscas, Peter; Farrell, Mark; Macdonald, Lynne M; Baker, Geoff; Wark, Tim; Thrall, Peter H

2015-08-01

Network and multivariate statistical analyses were performed to determine interactions between bacterial and fungal community terminal restriction length polymorphisms as well as soil properties in paired woodland and pasture sites. Canonical correspondence analysis (CCA) revealed that shifts in woodland community composition correlated with soil dissolved organic carbon, while changes in pasture community composition correlated with moisture, nitrogen and phosphorus. Weighted correlation network analysis detected two distinct microbial modules per land use. Bacterial and fungal ribotypes did not group separately, rather all modules comprised of both bacterial and fungal ribotypes. Woodland modules had a similar fungal : bacterial ribotype ratio, while in the pasture, one module was fungal dominated. There was no correspondence between pasture and woodland modules in their ribotype composition. The modules had different relationships to soil variables, and these contrasts were not detected without the use of network analysis. This study demonstrated that fungi and bacteria, components of the soil microbial communities usually treated as separate functional groups as in a CCA approach, were co-correlated and formed distinct associations in these adjacent habitats. Understanding these distinct modular associations may shed more light on their niche space in the soil environment, and allow a more realistic description of soil microbial ecology and function. © 2014 Society for Applied Microbiology and John Wiley & Sons Ltd.

Quantification of brain lipids by FTIR spectroscopy and partial least squares regression

NASA Astrophysics Data System (ADS)

Dreissig, Isabell; Machill, Susanne; Salzer, Reiner; Krafft, Christoph

2009-01-01

Brain tissue is characterized by high lipid content. Its content decreases and the lipid composition changes during transformation from normal brain tissue to tumors. Therefore, the analysis of brain lipids might complement the existing diagnostic tools to determine the tumor type and tumor grade. Objective of this work is to extract lipids from gray matter and white matter of porcine brain tissue, record infrared (IR) spectra of these extracts and develop a quantification model for the main lipids based on partial least squares (PLS) regression. IR spectra of the pure lipids cholesterol, cholesterol ester, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, sphingomyelin, galactocerebroside and sulfatide were used as references. Two lipid mixtures were prepared for training and validation of the quantification model. The composition of lipid extracts that were predicted by the PLS regression of IR spectra was compared with lipid quantification by thin layer chromatography.

Indicaxanthin from Opuntia ficus-indica Crosses the Blood-Brain Barrier and Modulates Neuronal Bioelectric Activity in Rat Hippocampus at Dietary-Consistent Amounts.

PubMed

Allegra, Mario; Carletti, Fabio; Gambino, Giuditta; Tutone, Marco; Attanzio, Alessandro; Tesoriere, Luisa; Ferraro, Giuseppe; Sardo, Pierangelo; Almerico, Anna Maria; Livrea, Maria Antonia

2015-08-26

Indicaxanthin is a bioactive and bioavailable betalain pigment from the Opuntia ficus-indica fruits. In this in vivo study, kinetic measurements showed that indicaxanthin is revealed in the rat brain within 1 h from oral administration of 2 μmol/kg, an amount compatible with a dietary consumption of cactus pear fruits in humans. A peak (20 ± 2.4 ng of indicaxanthin per whole brain) was measured after 2.5 h; thereafter the molecule disappeared with first order kinetics within 4 h. The potential of indicaxanthin to affect neural activities was in vivo investigated by a microiontophoretic approach. Indicaxanthin, administered in a range between 0.085 ng and 0.34 ng per neuron, dose-dependently modulated the rate of discharge of spontaneously active neurons of the hippocampus, with reduction of the discharge and related changes of latency and duration of the effect. Indicaxanthin (0.34 ng/neuron) showed inhibitory effects on glutamate-induced excitation, indicating activity at the level of glutamatergic synapses. A molecular target of indicaxanthin is suggested by in silico molecular modeling of indicaxanthin with N-methyl-D-aspartate receptor (NMDAR), the most represented of the glutamate receptor family in hippocampus. Therefore, at nutritionally compatible amounts indicaxanthin (i) crosses the rat BBB and accumulates in brain; (ii) can affect the bioelectric activity of hippocampal neurons locally treated with amounts comparable with those measured in the brain; and (iii) modulates glutamate-induced neuronal excitation. The potential of dietary indicaxanthin as a natural neuromodulatory agent deserves further mechanistic and neurophysiologic investigation.

Epoxy Fatty Acids and Inhibition of the Soluble Epoxide Hydrolase Selectively Modulate GABA Mediated Neurotransmission to Delay Onset of Seizures

PubMed Central

Inceoglu, Bora; Zolkowska, Dorota; Yoo, Hyun Ju; Wagner, Karen M.; Yang, Jun; Hackett, Edward; Hwang, Sung Hee; Lee, Kin Sing Stephen; Rogawski, Michael A.; Morisseau, Christophe; Hammock, Bruce D.

2013-01-01

In the brain, seizures lead to release of large amounts of polyunsaturated fatty acids including arachidonic acid (ARA). ARA is a substrate for three major enzymatic routes of metabolism by cyclooxygenase, lipoxygenase and cytochrome P450 enzymes. These enzymes convert ARA to potent lipid mediators including prostanoids, leukotrienes and epoxyeicosatrienoic acids (EETs). The prostanoids and leukotrienes are largely pro-inflammatory molecules that sensitize neurons whereas EETs are anti-inflammatory and reduce the excitability of neurons. Recent evidence suggests a GABA-related mode of action potentially mediated by neurosteroids. Here we tested this hypothesis using models of chemically induced seizures. The level of EETs in the brain was modulated by inhibiting the soluble epoxide hydrolase (sEH), the major enzyme that metabolizes EETs to inactive molecules, by genetic deletion of sEH and by direct administration of EETs into the brain. All three approaches delayed onset of seizures instigated by GABA antagonists but not seizures through other mechanisms. Inhibition of neurosteroid synthesis by finasteride partially blocked the anticonvulsant effects of sEH inhibitors while the efficacy of an inactive dose of neurosteroid allopregnanolone was enhanced by sEH inhibition. Consistent with earlier findings, levels of prostanoids in the brain were elevated. In contrast, levels of bioactive EpFAs were decreased following seizures. Overall these results demonstrate that EETs are natural molecules which suppress the tonic component of seizure related excitability through modulating the GABA activity and that exploration of the EET mediated signaling in the brain could yield alternative approaches to treat convulsive disorders. PMID:24349022

Gray matter volume is associated with rate of subsequent skill learning after a long term training intervention

PubMed Central

Sampaio-Baptista, Cassandra; Scholz, Jan; Jenkinson, Mark; Thomas, Adam G.; Filippini, Nicola; Smit, Gabrielle; Douaud, Gwenaëlle; Johansen-Berg, Heidi

2014-01-01

The ability to predict learning performance from brain imaging data has implications for selecting individuals for training or rehabilitation interventions. Here, we used structural MRI to test whether baseline variations in gray matter (GM) volume correlated with subsequent performance after a long-term training of a complex whole-body task. 44 naïve participants were scanned before undertaking daily juggling practice for 6 weeks, following either a high intensity or a low intensity training regime. To assess performance across the training period participants' practice sessions were filmed. Greater GM volume in medial occipito-parietal areas at baseline correlated with steeper learning slopes. We also tested whether practice time or performance outcomes modulated the degree of structural brain change detected between the baseline scan and additional scans performed immediately after training and following a further 4 weeks without training. Participants with better performance had higher increases in GM volume during the period following training (i.e., between scans 2 and 3) in dorsal parietal cortex and M1. When contrasting brain changes between the practice intensity groups, we did not find any straightforward effects of practice time though practice modulated the relationship between performance and GM volume change in dorsolateral prefrontal cortex. These results suggest that practice time and performance modulate the degree of structural brain change evoked by long-term training regimes. PMID:24680712

Scale invariant rearrangement of resting state networks in the human brain under sustained stimulation.

PubMed

Tommasin, Silvia; Mascali, Daniele; Moraschi, Marta; Gili, Tommaso; Assan, Ibrahim Eid; Fratini, Michela; DiNuzzo, Mauro; Wise, Richard G; Mangia, Silvia; Macaluso, Emiliano; Giove, Federico

2018-06-14

Brain activity at rest is characterized by widely distributed and spatially specific patterns of synchronized low-frequency blood-oxygenation level-dependent (BOLD) fluctuations, which correspond to physiologically relevant brain networks. This network behaviour is known to persist also during task execution, yet the details underlying task-associated modulations of within- and between-network connectivity are largely unknown. In this study we exploited a multi-parametric and multi-scale approach to investigate how low-frequency fluctuations adapt to a sustained n-back working memory task. We found that the transition from the resting state to the task state involves a behaviourally relevant and scale-invariant modulation of synchronization patterns within both task-positive and default mode networks. Specifically, decreases of connectivity within networks are accompanied by increases of connectivity between networks. In spite of large and widespread changes of connectivity strength, the overall topology of brain networks is remarkably preserved. We show that these findings are strongly influenced by connectivity at rest, suggesting that the absolute change of connectivity (i.e., disregarding the baseline) may be not the most suitable metric to study dynamic modulations of functional connectivity. Our results indicate that a task can evoke scale-invariant, distributed changes of BOLD fluctuations, further confirming that low frequency BOLD oscillations show a specialized response and are tightly bound to task-evoked activation. Copyright © 2018. Published by Elsevier Inc.

Methylmercury Increases and Eicosapentaenoic Acid Decreases the Relative Amounts of Arachidonic Acid-Containing Phospholipids in Mouse Brain.

PubMed

Zeng, Ying-Xu; Du, Zhen-Yu; Mjøs, Svein Are; Grung, Bjørn; Midtbø, Lisa K

2016-01-01

The membrane phospholipid composition in mammalian brain can be modified either by nutrients such as dietary fatty acids, or by certain toxic substances such as methylmercury (MeHg), leading to various biological and toxic effects. The present study evaluated the effects of eicosapentaenoic acid (EPA) and MeHg on the composition of the two most abundant membrane phospholipid classes, i.e., phosphatidylcholines (PtdCho) and phosphatidylethanolamines (PtdEtn), in mouse brain by using a two-level factorial design. The intact membrane PtdCho and PtdEtn species were analyzed by liquid chromatography-mass spectrometry. The effects of EPA and MeHg on the PtdCho and PtdEtn composition were evaluated by principal component analysis and ANOVA. The results showed that EPA and MeHg had different effects on the composition of membrane PtdCho and PtdEtn species in brain, where EPA showed strongest impact. EPA led to large reductions in the levels of arachidonic acid (ARA)-containing PtdCho and PtdEtn species in brain, while MeHg tended to elevate the levels of ARA-containing PtdCho and PtdEtn species. EPA also significantly increased the levels of PtdCho and PtdEtn species with n-3 fatty acids. Our results indicate that EPA may to some degree counteract the alterations of the PtdCho and PtdEtn pattern induced by MeHg, and thus alleviate the MeHg neurotoxicity in mouse brain through the inhibition of ARA-derived pro-inflammatory factors. These results may assist in the understanding of the interaction between MeHg, EPA and phospholipids, as well as the risk and benefits of a fish diet.

Social isolation stress-induced oxidative damage in mouse brain and its modulation by majonoside-R2, a Vietnamese ginseng saponin.

PubMed

Huong, Nguyen Thi Thu; Murakami, Yukihisa; Tohda, Michihisa; Watanabe, Hiroshi; Matsumoto, Kinzo

2005-08-01

Stressors with a physical factor such as immobilization, electric foot shock, cold swim, etc., have been shown to produce oxidative damage to membrane lipids in the brain. In this study, we investigated the effect of protracted social isolation stress on lipid peroxidation activity in the mouse brain and elucidated the protective effect of majonoside-R2, a major saponin component of Vietnamese ginseng, in mice exposed to social isolation stress. Thiobarbituric acid reactive substance levels, one of the end products of lipid peroxidation reaction, were increased in the brains of mice subjected to 6-8 weeks of social isolation stress. Measurements of nitric oxide (NO) metabolites (NO(x)(-)) also revealed a significant increase of NO production in the brains of socially isolated mice. Moreover, the depletion of brain glutathione content, an endogenous antioxidant, in socially isolated animals occurred in association with the rise in lipid peroxidation. The intraperitoneal administration of majonoside-R2 (10-50 mg/kg) had no effect on thiobarbituric acid reactive substances (TBARS), NO, or glutathione levels in the brains of group-housed control mice but it significantly suppressed the increase in TBARS and NO levels and the decrease in glutathione levels caused by social isolation stress. These results suggest that mice subjected to 6-8 weeks of social isolation stress produces oxidative damage in the brain partly via enhancement of NO production, and that majonoside-R2 exerts a protective effect by modulating NO and glutathione systems in the brain.

Using Brain–Computer Interfaces and Brain-State Dependent Stimulation as Tools in Cognitive Neuroscience

PubMed Central

Jensen, Ole; Bahramisharif, Ali; Oostenveld, Robert; Klanke, Stefan; Hadjipapas, Avgis; Okazaki, Yuka O.; van Gerven, Marcel A. J.

2011-01-01

Large efforts are currently being made to develop and improve online analysis of brain activity which can be used, e.g., for brain–computer interfacing (BCI). A BCI allows a subject to control a device by willfully changing his/her own brain activity. BCI therefore holds the promise as a tool for aiding the disabled and for augmenting human performance. While technical developments obviously are important, we will here argue that new insight gained from cognitive neuroscience can be used to identify signatures of neural activation which reliably can be modulated by the subject at will. This review will focus mainly on oscillatory activity in the alpha band which is strongly modulated by changes in covert attention. Besides developing BCIs for their traditional purpose, they might also be used as a research tool for cognitive neuroscience. There is currently a strong interest in how brain-state fluctuations impact cognition. These state fluctuations are partly reflected by ongoing oscillatory activity. The functional role of the brain state can be investigated by introducing stimuli in real-time to subjects depending on the actual state of the brain. This principle of brain-state dependent stimulation may also be used as a practical tool for augmenting human behavior. In conclusion, new approaches based on online analysis of ongoing brain activity are currently in rapid development. These approaches are amongst others informed by new insight gained from electroencephalography/magnetoencephalography studies in cognitive neuroscience and hold the promise of providing new ways for investigating the brain at work. PMID:21687463

Focused Ultrasound Immunotherapy for Central Nervous System Pathologies: Challenges and Opportunities

PubMed Central

Curley, Colleen T.; Sheybani, Natasha D.; Bullock, Timothy N.; Price, Richard J.

2017-01-01

Immunotherapy is rapidly emerging as the cornerstone for the treatment of several forms of metastatic cancer, as well as for a host of other pathologies. Meanwhile, several new high-profile studies have uncovered remarkable linkages between the central nervous and immune systems. With these recent developments, harnessing the immune system for the treatment of brain pathologies is a promising strategy. Here, we contend that MR image-guided focused ultrasound (FUS) represents a noninvasive approach that will allow for favorable therapeutic immunomodulation in the setting of the central nervous system. One obstacle to effective immunotherapeutic drug delivery to the brain is the blood brain barrier (BBB), which refers to the specialized structure of brain capillaries that prevents transport of most therapeutics from the blood into brain tissue. When applied in the presence of circulating microbubbles, FUS can safely and transiently open the BBB to facilitate the delivery of immunotherapeutic agents into the brain parenchyma. Furthermore, it has been demonstrated that physical perturbations of the tissue microenvironment via FUS can modulate immune response in both normal and diseased tissue. In this review article, we provide an overview of FUS energy regimens and corresponding tissue bioeffects, followed by a review of the literature pertaining to FUS for therapeutic antibody delivery in normal brain and preclinical models of brain disease. We provide an overview of studies that demonstrate FUS-mediated immune modulation in both the brain and peripheral settings. Finally, we provide remarks on challenges facing FUS immunotherapy and opportunities for future expansion in this area. PMID:29109764

Review of Infant Feeding: Key Features of Breast Milk and Infant Formula

PubMed Central

Martin, Camilia R.; Ling, Pei-Ra; Blackburn, George L.

2016-01-01

Mothers’ own milk is the best source of nutrition for nearly all infants. Beyond somatic growth, breast milk as a biologic fluid has a variety of other benefits, including modulation of postnatal intestinal function, immune ontogeny, and brain development. Although breastfeeding is highly recommended, breastfeeding may not always be possible, suitable or solely adequate. Infant formula is an industrially produced substitute for infant consumption. Infant formula attempts to mimic the nutritional composition of breast milk as closely as possible, and is based on cow’s milk or soymilk. A number of alternatives to cow’s milk-based formula also exist. In this article, we review the nutritional information of breast milk and infant formulas for better understanding of the importance of breastfeeding and the uses of infant formula from birth to 12 months of age when a substitute form of nutrition is required. PMID:27187450

Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs intensity-modulated radiation therapy case study.

PubMed

Lee, Katrina; Lenards, Nishele; Holson, Janice

2016-01-01

The hippocampus is responsible for memory and cognitive function. An ongoing phase II clinical trial suggests that sparing dose to the hippocampus during whole-brain radiation therapy can help preserve a patient׳s neurocognitive function. Progressive research and advancements in treatment techniques have made treatment planning more sophisticated but beneficial for patients undergoing treatment. The aim of this study is to evaluate and compare hippocampal sparing whole-brain (HS-WB) radiation therapy treatment planning techniques using volume-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT). We randomly selected 3 patients to compare different treatment techniques that could be used for reducing dose to the hippocampal region. We created 2 treatment plans, a VMAT and an IMRT, from each patient׳s data set and planned on the Eclipse 11.0 treatment planning system (TPS). A total of 6 plans (3 IMRT and 3 VMAT) were created and evaluated for this case study. The physician contoured the hippocampus as per the Radiation Therapy Oncology Group (RTOG) 0933 protocol atlas. The organs at risk (OR) were contoured and evaluated for the plan comparison, which included the spinal cord, optic chiasm, the right and left eyes, lenses, and optic nerves. Both treatment plans produced adequate coverage on the planning target volume (PTV) while significantly reducing dose to the hippocampal region. The VMAT treatment plans produced a more homogenous dose distribution throughout the PTV while decreasing the maximum point dose to the target. However, both treatment techniques demonstrated hippocampal sparing when irradiating the whole brain. Copyright © 2016 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Changes in the modulation of brain activity during context encoding vs. context retrieval across the adult lifespan.

PubMed

Ankudowich, E; Pasvanis, S; Rajah, M N

2016-10-01

Age-related deficits in context memory may arise from neural changes underlying both encoding and retrieval of context information. Although age-related functional changes in the brain regions supporting context memory begin at midlife, little is known about the functional changes with age that support context memory encoding and retrieval across the adult lifespan. We investigated how age-related functional changes support context memory across the adult lifespan by assessing linear changes with age during successful context encoding and retrieval. Using functional magnetic resonance imaging (fMRI), we compared young, middle-aged and older adults during both encoding and retrieval of spatial and temporal details of faces. Multivariate behavioral partial least squares (B-PLS) analysis of fMRI data identified a pattern of whole-brain activity that correlated with a linear age term and a pattern of whole-brain activity that was associated with an age-by-memory phase (encoding vs. retrieval) interaction. Further investigation of this latter effect identified three main findings: 1) reduced phase-related modulation in bilateral fusiform gyrus, left superior/anterior frontal gyrus and right inferior frontal gyrus that started at midlife and continued to older age, 2) reduced phase-related modulation in bilateral inferior parietal lobule that occurred only in older age, and 3) changes in phase-related modulation in older but not younger adults in left middle frontal gyrus and bilateral parahippocampal gyrus that was indicative of age-related over-recruitment. We conclude that age-related reductions in context memory arise in midlife and are related to changes in perceptual recollection and changes in fronto-parietal retrieval monitoring. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Small molecule modulator of protein disulfide isomerase attenuates mutant huntingtin toxicity and inhibits endoplasmic reticulum stress in a mouse model of Huntington's disease.

PubMed

Zhou, Xiao; Li, Gang; Kaplan, Anna; Gaschler, Michael M; Zhang, Xiaoyan; Hou, Zhipeng; Jiang, Mali; Zott, Roseann; Cremers, Serge; Stockwell, Brent R; Duan, Wenzhen

2018-05-01

Huntington's disease (HD) is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene encoding an elongated polyglutamine tract within the N-terminal of the huntingtin protein (Htt) and leads to Htt misfolding, aberrant protein aggregation, and progressive appearance of disease symptoms. Chronic activation of endoplasmic reticulum (ER) stress by mutant Htt (mHtt) results in cellular dysfunction and ultimately cell death. Protein disulfide isomerase (PDI) is a chaperone protein located in the ER. Our previous studies demonstrated that mHtt caused PDI to accumulate at mitochondria-associated ER membranes and triggered cell death, and that modulating PDI activity using small molecules protected cells again mHtt toxicity in cell and brain slice models of HD. In this study, we demonstrated that PDI is upregulated in the HD human brain, in cell and mouse models. Chronic administration of a reversible, brain penetrable small molecule PDI modulator, LOC14 (20 mg/kg/day), significantly improved motor function, attenuated brain atrophy and extended survival in the N171-82Q HD mice. Moreover, LOC14 preserved medium spiny neuronal marker dopamine- and cyclic-AMP-regulated phosphoprotein of molecular weight 32 000 (DARPP32) levels in the striatum of HD mice. Mechanistic study revealed that LOC14 suppressed mHtt-induced ER stress, indicated by repressing the abnormally upregulated ER stress proteins in HD models. These findings suggest that LOC14 is promising to be further optimized for clinical trials of HD, and modulation of signaling pathways coping with ER stress may constitute an attractive approach to reduce mHtt toxicity and identify new therapeutic targets for treatment of HD.

Seismic Performance of Composite Shear Walls Constructed Using Recycled Aggregate Concrete and Different Expandable Polystyrene Configurations.

PubMed

Liu, Wenchao; Cao, Wanlin; Zhang, Jianwei; Qiao, Qiyun; Ma, Heng

2016-03-02

The seismic performance of recycled aggregate concrete (RAC) composite shear walls with different expandable polystyrene (EPS) configurations was investigated. Six concrete shear walls were designed and tested under cyclic loading to evaluate the effect of fine RAC in designing earthquake-resistant structures. Three of the six specimens were used to construct mid-rise walls with a shear-span ratio of 1.5, and the other three specimens were used to construct low-rise walls with a shear-span ratio of 0.8. The mid-rise and low-rise shear walls consisted of an ordinary recycled concrete shear wall, a composite wall with fine aggregate concrete (FAC) protective layer (EPS modules as the external insulation layer), and a composite wall with sandwiched EPS modules as the insulation layer. Several parameters obtained from the experimental results were compared and analyzed, including the load-bearing capacity, stiffness, ductility, energy dissipation, and failure characteristics of the specimens. The calculation formula of load-bearing capacity was obtained by considering the effect of FAC on composite shear walls as the protective layer. The damage process of the specimen was simulated using the ABAQUS Software, and the results agreed quite well with those obtained from the experiments. The results show that the seismic resistance behavior of the EPS module composite for shear walls performed better than ordinary recycled concrete for shear walls. Shear walls with sandwiched EPS modules had a better seismic performance than those with EPS modules lying outside. Although the FAC protective layer slightly improved the seismic performance of the structure, it undoubtedly slowed down the speed of crack formation and the stiffness degradation of the walls.

Seismic Performance of Composite Shear Walls Constructed Using Recycled Aggregate Concrete and Different Expandable Polystyrene Configurations

PubMed Central

Liu, Wenchao; Cao, Wanlin; Zhang, Jianwei; Qiao, Qiyun; Ma, Heng

2016-01-01

The seismic performance of recycled aggregate concrete (RAC) composite shear walls with different expandable polystyrene (EPS) configurations was investigated. Six concrete shear walls were designed and tested under cyclic loading to evaluate the effect of fine RAC in designing earthquake-resistant structures. Three of the six specimens were used to construct mid-rise walls with a shear-span ratio of 1.5, and the other three specimens were used to construct low-rise walls with a shear-span ratio of 0.8. The mid-rise and low-rise shear walls consisted of an ordinary recycled concrete shear wall, a composite wall with fine aggregate concrete (FAC) protective layer (EPS modules as the external insulation layer), and a composite wall with sandwiched EPS modules as the insulation layer. Several parameters obtained from the experimental results were compared and analyzed, including the load-bearing capacity, stiffness, ductility, energy dissipation, and failure characteristics of the specimens. The calculation formula of load-bearing capacity was obtained by considering the effect of FAC on composite shear walls as the protective layer. The damage process of the specimen was simulated using the ABAQUS Software, and the results agreed quite well with those obtained from the experiments. The results show that the seismic resistance behavior of the EPS module composite for shear walls performed better than ordinary recycled concrete for shear walls. Shear walls with sandwiched EPS modules had a better seismic performance than those with EPS modules lying outside. Although the FAC protective layer slightly improved the seismic performance of the structure, it undoubtedly slowed down the speed of crack formation and the stiffness degradation of the walls. PMID:28773274

Microglia recapitulate a hematopoietic master regulator network in the aging human frontal cortex

PubMed Central

Wehrspaun, Claudia C.; Haerty, Wilfried; Ponting, Chris P.

2015-01-01

Microglia form the immune system of the brain. Previous studies in cell cultures and animal models suggest altered activation states and cellular senescence in the aged brain. Instead, we analyzed 3 transcriptome data sets from the postmortem frontal cortex of 381 control individuals to show that microglia gene markers assemble into a transcriptional module in a gene coexpression network. These markers predominantly represented M1 and M1/M2b activation phenotypes. Expression of genes in this module generally declines over the adult life span. This decrease was more pronounced in microglia surface receptors for microglia and/or neuron crosstalk than in markers for activation state phenotypes. In addition to these receptors for exogenous signals, microglia are controlled by brain-expressed regulatory factors. We identified a subnetwork of transcription factors, including RUNX1, IRF8, PU.1, and TAL1, which are master regulators (MRs) for the age-dependent microglia module. The causal contributions of these MRs on the microglia module were verified using publicly available ChIP-Seq data. Interactions of these key MRs were preserved in a protein-protein interaction network. Importantly, these MRs appear to be essential for regulating microglia homeostasis in the adult human frontal cortex in addition to their crucial roles in hematopoiesis and myeloid cell-fate decisions during embryogenesis. PMID:26002684

BMI not WHR modulates BOLD fMRI responses in a sub-cortical reward network when participants judge the attractiveness of human female bodies.

PubMed

Holliday, Ian E; Longe, Olivia A; Thai, N Jade; Hancock, Peter J B; Tovée, Martin J

2011-01-01

In perceptual terms, the human body is a complex 3d shape which has to be interpreted by the observer to judge its attractiveness. Both body mass and shape have been suggested as strong predictors of female attractiveness. Normally body mass and shape co-vary, and it is difficult to differentiate their separate effects. A recent study suggested that altering body mass does not modulate activity in the reward mechanisms of the brain, but shape does. However, using computer generated female body-shaped greyscale images, based on a Principal Component Analysis of female bodies, we were able to construct images which covary with real female body mass (indexed with BMI) and not with body shape (indexed with WHR), and vice versa. Twelve observers (6 male and 6 female) rated these images for attractiveness during an fMRI study. The attractiveness ratings were correlated with changes in BMI and not WHR. Our primary fMRI results demonstrated that in addition to activation in higher visual areas (such as the extrastriate body area), changing BMI also modulated activity in the caudate nucleus, and other parts of the brain reward system. This shows that BMI, not WHR, modulates reward mechanisms in the brain and we infer that this may have important implications for judgements of ideal body size in eating disordered individuals.

BMI Not WHR Modulates BOLD fMRI Responses in a Sub-Cortical Reward Network When Participants Judge the Attractiveness of Human Female Bodies

PubMed Central

Holliday, Ian E.; Longe, Olivia A.; Thai, N. Jade; Hancock, Peter J. B.; Tovée, Martin J.

2011-01-01

In perceptual terms, the human body is a complex 3d shape which has to be interpreted by the observer to judge its attractiveness. Both body mass and shape have been suggested as strong predictors of female attractiveness. Normally body mass and shape co-vary, and it is difficult to differentiate their separate effects. A recent study suggested that altering body mass does not modulate activity in the reward mechanisms of the brain, but shape does. However, using computer generated female body-shaped greyscale images, based on a Principal Component Analysis of female bodies, we were able to construct images which covary with real female body mass (indexed with BMI) and not with body shape (indexed with WHR), and vice versa. Twelve observers (6 male and 6 female) rated these images for attractiveness during an fMRI study. The attractiveness ratings were correlated with changes in BMI and not WHR. Our primary fMRI results demonstrated that in addition to activation in higher visual areas (such as the extrastriate body area), changing BMI also modulated activity in the caudate nucleus, and other parts of the brain reward system. This shows that BMI, not WHR, modulates reward mechanisms in the brain and we infer that this may have important implications for judgements of ideal body size in eating disordered individuals. PMID:22102883

Asprosin, a fasting-induced glucogenic protein hormone

USDA-ARS?s Scientific Manuscript database

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is t...

Positive Affect Modulates Flexibility and Evaluative Control

ERIC Educational Resources Information Center

van Wouwe, Nelleke C.; Band, Guido P. H.; Ridderinkhof, K. Richard

2011-01-01

The ability to interact with a constantly changing environment requires a balance between maintaining the currently relevant working memory content and being sensitive to potentially relevant new information that should be given priority access to working memory. Mesocortical dopamine projections to frontal brain areas modulate working memory…

Nativism versus Neuroconstructivism: Rethinking the Study of Developmental Disorders

ERIC Educational Resources Information Center

Karmiloff-Smith, Annette

2009-01-01

This article argues that one dominant position in psychology, linguistics, neuroscience, and philosophy about how genetic disorders point to the innate specification of dissociated modules in the human brain should be replaced by a dynamic, neuroconstructivist approach in which genes, brain, cognition, and environment interact multidirectionally.…

Modulation of Brain Activity during Phonological Familiarization

ERIC Educational Resources Information Center

Majerus, S.; Van der Linden, M.; Collette, F.; Laureys, S.; Poncelet, M.; Degueldre, C.; Delfiore, G.; Luxen, A.; Salmon, E.

2005-01-01

We measured brain activity in 12 adults for the repetition of auditorily presented words and nonwords, before and after repeated exposure to their phonological form. The nonword phoneme combinations were either of high (HF) or low (LF) phonotactic frequency. After familiarization, we observed, for both word and nonword conditions, decreased…

Galantamine Facilitates Acquisition of a Trace-Conditioned Eyeblink Response in Healthy, Young Rabbits

ERIC Educational Resources Information Center

Simon, Barbara B.; Knuckley, Bryan; Powell, Donald A.

2004-01-01

Previous work has demonstrated that drugs increasing brain concentrations of acetylcholine can enhance cognition in aging and brain-damaged organisms. The present study assessed whether galantamine (GAL), an allosteric modulator of nicotinic cholinergic receptors and weak acetylcholinesterase inhibitor, could improve acquisition and retention of…

Brain-Behavior Relationships in Reading Acquisition Are Modulated by Socioeconomic Factors

ERIC Educational Resources Information Center

Noble, Kimberly G.; Wolmetz, Michael E.; Ochs, Lisa G.; Farah, Martha J.; McCandliss, Bruce D.

2006-01-01

Functional neuroimaging may provide insights into the achievement gap in reading skill commonly observed across socioeconomic status (SES). Brain activation during reading tasks is known to be associated with individual differences in children's phonological language skills. By selecting children of equivalent phonological skill, yet diverse…

Brains Rule!: A Model Program for Developing Professional Stewardship among Neuroscientists

ERIC Educational Resources Information Center

Zardetto-Smith, Andrea M.; Mu, Keli; Carruth, Laura L.; Frantz, Kyle J.

2006-01-01

Brains Rule! Neuroscience Expositions, funded through a National Institute on Drug Abuse Science Education Drug Abuse Partnership Award, has developed a successful model for informal neuroscience education. Each Exposition is a "reverse science fair" in which neuroscientists present short neuroscience teaching modules to students. This…

Fetal auditory evoked responses to onset of amplitude modulated sounds. A fetal magnetoencephalography (fMEG) study.

PubMed

Draganova, R; Schollbach, A; Schleger, F; Braendle, J; Brucker, S; Abele, H; Kagan, K O; Wallwiener, D; Fritsche, A; Eswaran, H; Preissl, H

2018-06-01

The human fetal auditory system is functional around the 25th week of gestational age when the thalamocortical connections are established. Fetal magnetoencephalography (fMEG) provides evidence for fetal auditory brain responses to pure tones and syllables. Fifty-five pregnant women between 31 and 40 weeks of gestation were included in the study. Fetal MEG was recorded during the presentation of an amplitude modulated tone (AM) with a carrier frequency of 500 Hz to the maternal abdomen modulated by low modulation rates (MRs) - 2/s and 4/s, middle MR - 8/s and high MRs - 27/s, 42/s, 78/s and 91/s. The aim was to determine whether the fetal brain responds differently to envelope slopes and intensity change at the onset of the AM sounds. A significant decrease of the response latencies of transient event-related responses (ERR) to high and middle MRs in comparison to the low MRs was observed. The highest fetal response rate was achieved by modulation rates of 2/s, 4/s and 27/s (70%, 57%, and 86%, respectively). Additionally, a maturation effect of the ERR (response latency vs. gestational age) was observed only for 4/s MR. The significant difference between the response latencies to low, middle, and high MRs suggests that still before birth the fetal brain processes the sound slopes at the onset in different integration time-windows, depending on the time for the intensity increase or stimulus power density at the onset, which is a prerequisite for language acquisition. Copyright © 2018 Elsevier B.V. All rights reserved.

Emotion regulation modulates anticipatory brain activity that predicts emotional memory encoding in women.

PubMed

Galli, Giulia; Griffiths, Victoria A; Otten, Leun J

2014-03-01

It has been shown that the effectiveness with which unpleasant events are encoded into memory is related to brain activity set in train before the events. Here, we assessed whether encoding-related activity before an aversive event can be modulated by emotion regulation. Electrical brain activity was recorded from the scalps of healthy women while they performed an incidental encoding task on randomly intermixed unpleasant and neutral visual scenes. A cue presented 1.5 s before each picture indicated the upcoming valence. In half of the blocks of trials, the instructions emphasized to let emotions arise in a natural way. In the other half, participants were asked to decrease their emotional response by adopting the perspective of a detached observer. Memory for the scenes was probed 1 day later with a recognition memory test. Brain activity before unpleasant scenes predicted later memory of the scenes, but only when participants felt their emotions and did not detach from them. The findings indicate that emotion regulation can eliminate the influence of anticipatory brain activity on memory encoding. This may be relevant for the understanding and treatment of psychiatric diseases with a memory component.

Brain Signal Variability is Parametrically Modifiable

PubMed Central

Garrett, Douglas D.; McIntosh, Anthony R.; Grady, Cheryl L.

2014-01-01

Moment-to-moment brain signal variability is a ubiquitous neural characteristic, yet remains poorly understood. Evidence indicates that heightened signal variability can index and aid efficient neural function, but it is not known whether signal variability responds to precise levels of environmental demand, or instead whether variability is relatively static. Using multivariate modeling of functional magnetic resonance imaging-based parametric face processing data, we show here that within-person signal variability level responds to incremental adjustments in task difficulty, in a manner entirely distinct from results produced by examining mean brain signals. Using mixed modeling, we also linked parametric modulations in signal variability with modulations in task performance. We found that difficulty-related reductions in signal variability predicted reduced accuracy and longer reaction times within-person; mean signal changes were not predictive. We further probed the various differences between signal variance and signal means by examining all voxels, subjects, and conditions; this analysis of over 2 million data points failed to reveal any notable relations between voxel variances and means. Our results suggest that brain signal variability provides a systematic task-driven signal of interest from which we can understand the dynamic function of the human brain, and in a way that mean signals cannot capture. PMID:23749875

Graph theory in brain-to-brain connectivity: A simulation study and an application to an EEG hyperscanning experiment.

PubMed

Toppi, J; Ciaramidaro, A; Vogel, P; Mattia, D; Babiloni, F; Siniatchkin, M; Astolfi, L

2015-08-01

Hyperscanning consists in the simultaneous recording of hemodynamic or neuroelectrical signals from two or more subjects acting in a social context. Well-established methodologies for connectivity estimation have already been adapted to hyperscanning purposes. The extension of graph theory approach to multi-subjects case is still a challenging issue. In the present work we aim to test the ability of the currently used graph theory global indices in describing the properties of a network given by two interacting subjects. The testing was conducted first on surrogate brain-to-brain networks reproducing typical social scenarios and then on real EEG hyperscanning data recorded during a Joint Action task. The results of the simulation study highlighted the ability of all the investigated indexes in modulating their values according to the level of interaction between subjects. However, only global efficiency and path length indexes demonstrated to be sensitive to an asymmetry in the communication between the two subjects. Such results were, then, confirmed by the application on real EEG data. Global efficiency modulated, in fact, their values according to the inter-brain density, assuming higher values in the social condition with respect to the non-social condition.

An imaging genetics approach to understanding social influence

PubMed Central

Falk, Emily B.; Way, Baldwin M.; Jasinska, Agnes J.

2012-01-01

Normative social influences shape nearly every aspect of our lives, yet the biological processes mediating the impact of these social influences on behavior remain incompletely understood. In this Hypothesis, we outline a theoretical framework and an integrative research approach to the study of social influences on the brain and genetic moderators of such effects. First, we review neuroimaging evidence linking social influence and conformity to the brain's reward system. We next review neuroimaging evidence linking social punishment (exclusion) to brain systems involved in the experience of pain, as well as evidence linking exclusion to conformity. We suggest that genetic variants that increase sensitivity to social cues may predispose individuals to be more sensitive to either social rewards or punishments (or potentially both), which in turn increases conformity and susceptibility to normative social influences more broadly. To this end, we review evidence for genetic moderators of neurochemical responses in the brain, and suggest ways in which genes and pharmacology may modulate sensitivity to social influences. We conclude by proposing an integrative imaging genetics approach to the study of brain mediators and genetic modulators of a variety of social influences on human attitudes, beliefs, and actions. PMID:22701416

Large-Scale functional network overlap is a general property of brain functional organization: Reconciling inconsistent fMRI findings from general-linear-model-based analyses

PubMed Central

Xu, Jiansong; Potenza, Marc N.; Calhoun, Vince D.; Zhang, Rubin; Yip, Sarah W.; Wall, John T.; Pearlson, Godfrey D.; Worhunsky, Patrick D.; Garrison, Kathleen A.; Moran, Joseph M.

2016-01-01

Functional magnetic resonance imaging (fMRI) studies regularly use univariate general-linear-model-based analyses (GLM). Their findings are often inconsistent across different studies, perhaps because of several fundamental brain properties including functional heterogeneity, balanced excitation and inhibition (E/I), and sparseness of neuronal activities. These properties stipulate heterogeneous neuronal activities in the same voxels and likely limit the sensitivity and specificity of GLM. This paper selectively reviews findings of histological and electrophysiological studies and fMRI spatial independent component analysis (sICA) and reports new findings by applying sICA to two existing datasets. The extant and new findings consistently demonstrate several novel features of brain functional organization not revealed by GLM. They include overlap of large-scale functional networks (FNs) and their concurrent opposite modulations, and no significant modulations in activity of most FNs across the whole brain during any task conditions. These novel features of brain functional organization are highly consistent with the brain’s properties of functional heterogeneity, balanced E/I, and sparseness of neuronal activity, and may help reconcile inconsistent GLM findings. PMID:27592153

Targeting the brain--surmounting or bypassing the blood-brain barrier.

PubMed

Potschka, Heidrun

2010-01-01

The constituents of the blood-brain barrier, including its efflux transporter system, can efficiently limit brain penetration of potential CNS therapeutics. Effective extrusion from the brain by transporters is a frequent reason for the pharmaceutical industry to exclude novel compounds from further development for CNS therapeutics. Moreover, high transporter expression levels that are present in individual patients or may be generally associated with the pathophysiology seem to be a major cause of therapeutic failure in a variety of CNS diseases including brain tumors, epilepsy, brain HIV infection, and psychiatric disorders. Increasing knowledge of the structure and function of the blood-brain barrier creates a basis for the development of strategies which aim to enhance brain uptake of beneficial pharmaceutical compounds. The different strategies discussed in this review aim to modulate blood-brain barrier function or to bypass constituents of the blood-brain barrier.

[Are Visual Field Defects Reversible? - Visual Rehabilitation with Brains].

PubMed

Sabel, B A

2017-02-01

Visual field defects are considered irreversible because the retina and optic nerve do not regenerate. Nevertheless, there is some potential for recovery of the visual fields. This can be accomplished by the brain, which analyses and interprets visual information and is able to amplify residual signals through neuroplasticity. Neuroplasticity refers to the ability of the brain to change its own functional architecture by modulating synaptic efficacy. This is actually the neurobiological basis of normal learning. Plasticity is maintained throughout life and can be induced by repetitively stimulating (training) brain circuits. The question now arises as to how plasticity can be utilised to activate residual vision for the treatment of visual field loss. Just as in neurorehabilitation, visual field defects can be modulated by post-lesion plasticity to improve vision in glaucoma, diabetic retinopathy or optic neuropathy. Because almost all patients have some residual vision, the goal is to strengthen residual capacities by enhancing synaptic efficacy. New treatment paradigms have been tested in clinical studies, including vision restoration training and non-invasive alternating current stimulation. While vision training is a behavioural task to selectively stimulate "relative defects" with daily vision exercises for the duration of 6 months, treatment with alternating current stimulation (30 min. daily for 10 days) activates and synchronises the entire retina and brain. Though full restoration of vision is not possible, such treatments improve vision, both subjectively and objectively. This includes visual field enlargements, improved acuity and reaction time, improved orientation and vision related quality of life. About 70 % of the patients respond to the therapies and there are no serious adverse events. Physiological studies of the effect of alternating current stimulation using EEG and fMRI reveal massive local and global changes in the brain. These include local activation of the visual cortex and global reorganisation of neuronal brain networks. Because modulation of neuroplasticity can strengthen residual vision, the brain deserves a better reputation in ophthalmology for its role in visual rehabilitation. For patients, there is now more light at the end of the tunnel, because vision loss in some areas of the visual field defect is indeed reversible. Georg Thieme Verlag KG Stuttgart · New York.

Alpha-fetoprotein (AFP) modulates the effect of serum albumin on brain development by restraining the neurotrophic effect of oleic acid.

PubMed

García-García, Alejandro G; Polo-Hernández, Erica; Tabernero, Arantxa; Medina, José M

2015-10-22

We have previously shown that serum albumin controls perinatal rat brain development through the regulation of oleic acid synthesis by astrocytes. In fact, oleic acid synthesized and released by astrocytes promoted neurite growth, neuron migration and the arrangement of prospective synapses. In this work we show that alpha-fetoprotein (AFP) is also present in the brain during embryonic development, its concentrations peaking at E15.5 and at E19.5. However, after E19.5 AFP concentrations plummeted concurrently with a sharp increase in serum albumin concentrations. At E15.5, AFP is present in caudal regions of the brain, particularly in brain areas undergoing differentiation during this period, such as the thalamic reticular nucleus of the thalamus, the hypothalamus, the amygdala and the hippocampus. Albumin was not detected in the brain at E15.5 but stained brain cells substantially on day E19.5, showing a very similar distribution to that of AFP under the same circumstances. The concentrations of free oleic acid in the brain were inversely correlated with those of AFP, suggesting that the signals elicited by AFP and oleic acid can be inversely associated. GAP-43, a marker of axonal growth that is highly expressed by the presence of oleic acid, was not co-localized with AFP except in the marginal zone and areas delimiting the subplate. AFP prevented the increase in GAP-43 expression caused by the presence of oleic acid in neurons in primary culture in vitro and in organotypic cultures of embryonic rat brain ex vivo, suggesting that AFP may modulate the effect of serum albumin on brain development. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Gender differences in healthy aging and Alzheimer's Dementia: A 18 F-FDG-PET study of brain and cognitive reserve.

PubMed

Malpetti, Maura; Ballarini, Tommaso; Presotto, Luca; Garibotto, Valentina; Tettamanti, Marco; Perani, Daniela

2017-08-01

Cognitive reserve (CR) and brain reserve (BR) are protective factors against age-associated cognitive decline and neurodegenerative disorders. Very limited evidence exists about gender effects on brain aging and on the effect of CR on brain modulation in healthy aging and Alzheimer's Dementia (AD). We investigated gender differences in brain metabolic activity and resting-state network connectivity, as measured by 18 F-FDG-PET, in healthy aging and AD, also considering the effects of education and occupation. The clinical and imaging data were retrieved from large datasets of healthy elderly subjects (HE) (225) and AD patients (282). In HE, males showed more extended age-related reduction of brain metabolism than females in frontal medial cortex. We also found differences in brain modulation as metabolic increases induced by education and occupation, namely in posterior associative cortices in HE males and in the anterior limbic-affective and executive networks in HE females. In AD patients, the correlations between education and occupation levels and brain hypometabolism showed gender differences, namely a posterior temporo-parietal association in males and a frontal and limbic association in females, indicating the involvement of different networks. Finally, the metabolic connectivity in both HE and AD aligned with these results, suggesting greater efficiency in the posterior default mode network for males, and in the anterior frontal executive network for females. The basis of these brain gender differences in both aging and AD, obtained exploring cerebral metabolism, metabolic connectivity and the effects of education and occupation, is likely at the intersection between biological and sociodemographic factors. Hum Brain Mapp 38:4212-4227, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Lifestyle and nutritional imbalances associated with Western diseases: causes and consequences of chronic systemic low-grade inflammation in an evolutionary context.

PubMed

Ruiz-Núñez, Begoña; Pruimboom, Leo; Dijck-Brouwer, D A Janneke; Muskiet, Frits A J

2013-07-01

In this review, we focus on lifestyle changes, especially dietary habits, that are at the basis of chronic systemic low grade inflammation, insulin resistance and Western diseases. Our sensitivity to develop insulin resistance traces back to our rapid brain growth in the past 2.5 million years. An inflammatory reaction jeopardizes the high glucose needs of our brain, causing various adaptations, including insulin resistance, functional reallocation of energy-rich nutrients and changing serum lipoprotein composition. The latter aims at redistribution of lipids, modulation of the immune reaction, and active inhibition of reverse cholesterol transport for damage repair. With the advent of the agricultural and industrial revolutions, we have introduced numerous false inflammatory triggers in our lifestyle, driving us to a state of chronic systemic low grade inflammation that eventually leads to typically Western diseases via an evolutionary conserved interaction between our immune system and metabolism. The underlying triggers are an abnormal dietary composition and microbial flora, insufficient physical activity and sleep, chronic stress and environmental pollution. The disturbance of our inflammatory/anti-inflammatory balance is illustrated by dietary fatty acids and antioxidants. The current decrease in years without chronic disease is rather due to "nurture" than "nature," since less than 5% of the typically Western diseases are primary attributable to genetic factors. Resolution of the conflict between environment and our ancient genome might be the only effective manner for "healthy aging," and to achieve this we might have to return to the lifestyle of the Paleolithic era as translated to the 21st century culture. Copyright © 2013 Elsevier Inc. All rights reserved.

Probiotics drive gut microbiome triggering emotional brain signatures.

PubMed

Bagga, Deepika; Reichert, Johanna Louise; Koschutnig, Karl; Aigner, Christoph Stefan; Holzer, Peter; Koskinen, Kaisa; Eichinger, Christine Moissl; Schöpf, Veronika

2018-05-03

Experimental manipulation of the gut microbiome was found to modify emotional and cognitive behavior, neurotransmitter expression and brain function in rodents, but corresponding human data remain scarce. The present double-blind, placebo-controlled randomised study aimed at investigating the effects of 4 weeks' probiotic administration on behavior, brain function and gut microbial composition in healthy volunteers. Forty-five healthy participants divided equally into three groups (probiotic, placebo and no intervention) underwent functional MRI (emotional decision-making and emotional recognition memory tasks). In addition, stool samples were collected to investigate the gut microbial composition. Probiotic administration for 4 weeks was associated with changes in brain activation patterns in response to emotional memory and emotional decision-making tasks, which were also accompanied by subtle shifts in gut microbiome profile. Microbiome composition mirrored self-reported behavioral measures and memory performance. This is the first study reporting a distinct influence of probiotic administration at behavioral, neural, and microbiome levels at the same time in healthy volunteers. The findings provide a basis for future investigations into the role of the gut microbiota and potential therapeutic application of probiotics.

Brain-Mind Operational Architectonics Imaging: Technical and Methodological Aspects

PubMed Central

Fingelkurts, Andrew A; Fingelkurts, Alexander A

2008-01-01

This review paper deals with methodological and technical foundations of the Operational Architectonics framework of brain and mind functioning. This theory provides a framework for mapping and understanding important aspects of the brain mechanisms that constitute perception, cognition, and eventually consciousness. The methods utilized within Operational Architectonics framework allow analyzing with an incredible detail the operational behavior of local neuronal assemblies and their joint activity in the form of unified and metastable operational modules, which constitute the whole hierarchy of brain operations, operations of cognition and phenomenal consciousness. PMID:19526071

New Clinically Feasible 3T MRI Protocol to Discriminate Internal Brain Stem Anatomy.

PubMed

Hoch, M J; Chung, S; Ben-Eliezer, N; Bruno, M T; Fatterpekar, G M; Shepherd, T M

2016-06-01

Two new 3T MR imaging contrast methods, track density imaging and echo modulation curve T2 mapping, were combined with simultaneous multisection acquisition to reveal exquisite anatomic detail at 7 canonical levels of the brain stem. Compared with conventional MR imaging contrasts, many individual brain stem tracts and nuclear groups were directly visualized for the first time at 3T. This new approach is clinically practical and feasible (total scan time = 20 minutes), allowing better brain stem anatomic localization and characterization. © 2016 by American Journal of Neuroradiology.

Noninvasive near-infrared topography of human brain activity using intensity modulation spectroscopy

NASA Astrophysics Data System (ADS)

Yamashita, Yuichi; Maki, Atsushi; Ito, Yoshitoshi; Watanabe, Eiju; Mayanagi, Yoshiaki; Koizumi, Hideaki

1996-04-01

We describe the functional topography of human brain activity due to motor stimulation by using near-infrared spectroscopy. Finger motion by each hand was used as the motor stimulation, and activity in the left fronto-central region of the brain was measured. A greater change in oxyhemoglobin concentration due to brain activity during the stimulation was obtained for the right hand than for the left hand. Localization of the activity was obtained by topographically mapping the measured changes for ten positions within the region.

Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid beta peptide.

PubMed

Hama, E; Saido, T C

2005-01-01

We recently demonstrated that amyloid beta peptide (Abeta) is catabolized primarily by a neutral endopeptidase, neprilysin, in the brain and that a neuropeptide, somatostatin (SST), regulates brain Abeta level via modulation of neprilysin activity. Because SST expression in the brain declines upon aging in various mammals including rodents, apes and humans, we hypothesize that the aging-dependent reduction of SST triggers accumulation of Abeta in the brain by suppressing neprilysin action. This hypothesis accounts for the fact that aging is the predominant risk factor for Sporadic Alzheimer's disease.

First and second generation γ-secretase modulators (GSMs) modulate amyloid-β (Aβ) peptide production through different mechanisms.

PubMed

Borgegard, Tomas; Juréus, Anders; Olsson, Fredrik; Rosqvist, Susanne; Sabirsh, Alan; Rotticci, Didier; Paulsen, Kim; Klintenberg, Rebecka; Yan, Hongmei; Waldman, Magnus; Stromberg, Kia; Nord, Johan; Johansson, Jonas; Regner, Anna; Parpal, Santiago; Malinowsky, David; Radesater, Ann-Cathrin; Li, Tingsheng; Singh, Rajeshwar; Eriksson, Hakan; Lundkvist, Johan

2012-04-06

γ-Secretase-mediated cleavage of amyloid precursor protein (APP) results in the production of Alzheimer disease-related amyloid-β (Aβ) peptides. The Aβ42 peptide in particular plays a pivotal role in Alzheimer disease pathogenesis and represents a major drug target. Several γ-secretase modulators (GSMs), such as the nonsteroidal anti-inflammatory drugs (R)-flurbiprofen and sulindac sulfide, have been suggested to modulate the Alzheimer-related Aβ production by targeting the APP. Here, we describe novel GSMs that are selective for Aβ modulation and do not impair processing of Notch, EphB2, or EphA4. The GSMs modulate Aβ both in cell and cell-free systems as well as lower amyloidogenic Aβ42 levels in the mouse brain. Both radioligand binding and cellular cross-competition experiments reveal a competitive relationship between the AstraZeneca (AZ) GSMs and the established second generation GSM, E2012, but a noncompetitive interaction between AZ GSMs and the first generation GSMs (R)-flurbiprofen and sulindac sulfide. The binding of a (3)H-labeled AZ GSM analog does not co-localize with APP but overlaps anatomically with a γ-secretase targeting inhibitor in rodent brains. Combined, these data provide compelling evidence of a growing class of in vivo active GSMs, which are selective for Aβ modulation and have a different mechanism of action compared with the original class of GSMs described.

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive ‘mild’ blast-related traumatic brain injury†

PubMed Central

Han, Kihwan; Mac Donald, Christine L.; Johnson, Ann M.; Barnes, Yolanda; Wierzechowski, Linda; Zonies, David; Oh, John; Flaherty, Stephen; Fang, Raymond; Raichle, Marcus E.; Brody, David L.

2013-01-01

Blast-related traumatic brain injury (TBI) has been one of the “signature injuries” of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive ‘mild’ blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20 minutes of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90 days post-injury and 65 subjects underwent a follow-up scan 6 to 12 months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI patients served as a validation dataset. The second independent cohort underwent an initial scan within 30 days post-injury. 75% of scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p < 0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p = 0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p = 0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p = 0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required. PMID:23968735

Mapping Language Function in the Brain: A Review of the Recent Literature.

ERIC Educational Resources Information Center

Crafton, Robert E.; Kido, Elissa

2000-01-01

Considers the potential importance of brain study for composition instruction, briefly describes functional imaging techniques, and reviews the findings of recent brain-mapping studies investigating the neurocognitive systems involved in language function. Presents a review of the recent literature and considers the possible implications of this…

The Brain Melanocortin System, Sympathetic Control, and Obesity Hypertension

PubMed Central

do Carmo, Jussara M.; Wang, Zhen; Hall, John E.

2014-01-01

Excess weight gain is the most significant, preventable cause of increased blood pressure (BP) in patients with primary (essential) hypertension and increases the risk for cardiovascular and renal diseases. In this review, we discuss the role of the brain melanocortin system in causing increased sympathetic activity in obesity and other forms of hypertension. In addition, we highlight potential mechanisms by which the brain melanocortin system modulates metabolic and cardiovascular functions. PMID:24789984

Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury.

PubMed

McBride, Devin W; Wang, Yuechun; Adam, Loic; Oudin, Guillaume; Louis, Jean-Sébastien; Tang, Jiping; Zhang, John H

2016-01-01

No matter how carefully a neurosurgical procedure is performed, it is intrinsically linked to postoperative deficits resulting in delayed healing caused by direct trauma, hemorrhage, and brain edema, termed surgical brain injury (SBI). Cerebral edema occurs several hours after SBI and is a major contributor to patient morbidity, resulting in increased postoperative care. Currently, the correlation between functional recovery and brain edema after SBI remains unknown. Here we examine the correlation between neurological function and brain water content in rats 42 h after SBI. SBI was induced in male Sprague-Dawley rats via frontal lobectomy. Twenty-four hours post-ictus animals were subjected to four neurobehavior tests: composite Garcia neuroscore, beam walking test, corner turn test, and beam balance test. Animals were then sacrificed for right-frontal brain water content measurement via the wet-dry method. Right-frontal lobe brain water content was found to significantly correlate with neurobehavioral deficits in the corner turn and beam balance tests: the number of left turns (percentage of total turns) for the corner turn test and distance traveled for the beam balance test were both inversely proportional with brain water content. No correlation was observed for the composite Garcia neuroscore or the beam walking test.

Health Instruction Packages: Respiratory Therapy.

ERIC Educational Resources Information Center

Lavich, Margot; And Others

Text, illustrations, and exercises are utilized in these four learning modules to teach respiratory therapy students a variety of job-related skills. The first module, "Anatomy and Physiology of the Central Controls of Respiration" by Margot Lavich, describes the functions of the five centers of the brain that control respiration and…

Significant modulation of mitochondrial electron transport system by nicotine in various rat brain regions

USDA-ARS?s Scientific Manuscript database

The mitochondrion is the organelle responsible for generation of most usable energy in a cell. It also plays an important role in a series of physiological processes such as apoptosis and proliferation. Although previous studies have demonstrated that nicotine modulates the morphology and function ...

Activation of Phosphoinositide Metabolism by Cholinergic Agents.

DTIC Science & Technology

1992-03-15

most notably calcium. Cholinergic agonist-induced seizures; Brain second messenger systems; Neurotransmitter/ Neuromodulator interactions; RAV; Lab...have been described: modulation by protein kinase C and modulation by neurotransmitter (or neuromodulator ) interactions. Agents which stimulate...phosphoinositide hydrolysis that has been identified consists of interactions among neurotransmitter systems or neuromodulators . Perhaps those most widely

Obesity development in neuron-specific lipoprotein lipase deficient mice is not responsive to increased dietary fat content or change in fat composition.

PubMed

Wang, Hong; Taussig, Matthew D; DiPatrizio, Nicholas V; Bruce, Kimberley; Piomelli, Daniele; Eckel, Robert H

2016-07-01

We have previously reported that mice with neuron-specific LPL deficiency (NEXLPL-/-) become obese by 16weeks of age on chow. Moreover, these mice had reduced uptake of triglyceride (TG)-rich lipoprotein-derived fatty acids and lower levels of n-3 long chain polyunsaturated fatty acids (n-3 PUFAs) in the hypothalamus. Here, we asked whether increased dietary fat content or altered dietary composition could modulate obesity development in NEXLPL-/- mice. Male NEXLPL-/- mice and littermate controls (WT) were randomly assigned one of three synthetic diets; a high carbohydrate diet (HC, 10% fat), a high-fat diet (HF, 45% fat), or a HC diet supplemented with n-3 PUFAs (HCn-3, 10% fat, Lovaza, GSK®). After 42weeks of HC feeding, body weight and fat mass were increased in the NEXLPL-/- mice compared to WT. WT mice fed a HF diet displayed typical diet-induced obesity, but weight gain was only marginal in HF-fed NEXLPL-/- mice, with no significant difference in body composition. Dietary n-3 PUFA supplementation did not prevent obesity in NEXLPL-/- mice, but was associated with differential modifications in hypothalamic gene expression and PUFA concentration compared to WT mice. Our findings suggest that neuronal LPL is involved in the regulation of body weight and composition in response to either the change in quantity (HF feeding) or quality (n-3 PUFA-enriched) of dietary fat. The precise role of LPL in lipid sensing in the brain requires further investigation. Copyright © 2016 Elsevier Inc. All rights reserved.

Brain correlates of music-evoked emotions.

PubMed

Koelsch, Stefan

2014-03-01

Music is a universal feature of human societies, partly owing to its power to evoke strong emotions and influence moods. During the past decade, the investigation of the neural correlates of music-evoked emotions has been invaluable for the understanding of human emotion. Functional neuroimaging studies on music and emotion show that music can modulate activity in brain structures that are known to be crucially involved in emotion, such as the amygdala, nucleus accumbens, hypothalamus, hippocampus, insula, cingulate cortex and orbitofrontal cortex. The potential of music to modulate activity in these structures has important implications for the use of music in the treatment of psychiatric and neurological disorders.

Aroused with heart: Modulation of heartbeat evoked potential by arousal induction and its oscillatory correlates

PubMed Central

Luft, Caroline Di Bernardi; Bhattacharya, Joydeep

2015-01-01

Recent studies showed that the visceral information is constantly processed by the brain, thereby potentially influencing cognition. One index of such process is the heartbeat evoked potential (HEP), an ERP component related to the cortical processing of the heartbeat. The HEP is sensitive to a number of factors such as motivation, attention, pain, which are associated with higher levels of arousal. However, the role of arousal and its associated brain oscillations on the HEP has not been characterized, yet it could underlie the previous findings. Here we analysed the effects of high- (HA) and low-arousal (LA) induction on the HEP. Further, we investigated the brain oscillations and their role in the HEP in response to HA and LA inductions. As compared to LA, HA was associated with a higher HEP and lower alpha oscillations. Interestingly, individual differences in the HEP modulation by arousal induction were correlated with alpha oscillations. In particular, participants with higher alpha power during the arousal inductions showed a larger HEP in response to HA compared to LA. In summary, we demonstrated that arousal induction affects the cortical processing of heartbeats; and that the alpha oscillations may modulate this effect. PMID:26503014

Social hierarchy modulates neural responses of empathy for pain

PubMed Central

Feng, Chunliang; Li, Zhihao; Feng, Xue; Wang, Lili; Tian, Tengxiang

2016-01-01

Recent evidence indicates that empathic responses to others’ pain are modulated by various situational and individual factors. However, few studies have examined how empathy and underlying brain functions are modulated by social hierarchies, which permeate human society with an enormous impact on social behavior and cognition. In this study, social hierarchies were established based on incidental skill in a perceptual task in which all participants were mediumly ranked. Afterwards, participants were scanned with functional magnetic resonance imaging while watching inferior-status or superior-status targets receiving painful or non-painful stimulation. The results revealed that painful stimulation applied to inferior-status targets induced higher activations in the anterior insula (AI) and anterior medial cingulate cortex (aMCC), whereas these empathic brain activations were significantly attenuated in response to superior-status targets’ pain. Further, this neural empathic bias to inferior-status targets was accompanied by stronger functional couplings of AI with brain regions important in emotional processing (i.e. thalamus) and cognitive control (i.e. middle frontal gyrus). Our findings indicate that emotional sharing with others’ pain is shaped by relative positions in a social hierarchy such that underlying empathic neural responses are biased toward inferior-status compared with superior-status individuals. PMID:26516169

Characterizing Variability of Modular Brain Connectivity with Constrained Principal Component Analysis

PubMed Central

Hirayama, Jun-ichiro; Hyvärinen, Aapo; Kiviniemi, Vesa; Kawanabe, Motoaki; Yamashita, Okito

2016-01-01

Characterizing the variability of resting-state functional brain connectivity across subjects and/or over time has recently attracted much attention. Principal component analysis (PCA) serves as a fundamental statistical technique for such analyses. However, performing PCA on high-dimensional connectivity matrices yields complicated “eigenconnectivity” patterns, for which systematic interpretation is a challenging issue. Here, we overcome this issue with a novel constrained PCA method for connectivity matrices by extending the idea of the previously proposed orthogonal connectivity factorization method. Our new method, modular connectivity factorization (MCF), explicitly introduces the modularity of brain networks as a parametric constraint on eigenconnectivity matrices. In particular, MCF analyzes the variability in both intra- and inter-module connectivities, simultaneously finding network modules in a principled, data-driven manner. The parametric constraint provides a compact module-based visualization scheme with which the result can be intuitively interpreted. We develop an optimization algorithm to solve the constrained PCA problem and validate our method in simulation studies and with a resting-state functional connectivity MRI dataset of 986 subjects. The results show that the proposed MCF method successfully reveals the underlying modular eigenconnectivity patterns in more general situations and is a promising alternative to existing methods. PMID:28002474

Practice reduces task relevant variance modulation and forms nominal trajectory

NASA Astrophysics Data System (ADS)

Osu, Rieko; Morishige, Ken-Ichi; Nakanishi, Jun; Miyamoto, Hiroyuki; Kawato, Mitsuo

2015-12-01

Humans are capable of achieving complex tasks with redundant degrees of freedom. Much attention has been paid to task relevant variance modulation as an indication of online feedback control strategies to cope with motor variability. Meanwhile, it has been discussed that the brain learns internal models of environments to realize feedforward control with nominal trajectories. Here we examined trajectory variance in both spatial and temporal domains to elucidate the relative contribution of these control schemas. We asked subjects to learn reaching movements with multiple via-points, and found that hand trajectories converged to stereotyped trajectories with the reduction of task relevant variance modulation as learning proceeded. Furthermore, variance reduction was not always associated with task constraints but was highly correlated with the velocity profile. A model assuming noise both on the nominal trajectory and motor command was able to reproduce the observed variance modulation, supporting an expression of nominal trajectories in the brain. The learning-related decrease in task-relevant modulation revealed a reduction in the influence of optimal feedback around the task constraints. After practice, the major part of computation seems to be taken over by the feedforward controller around the nominal trajectory with feedback added only when it becomes necessary.

S187. SEARCHING FOR BRAIN CO-EXPRESSION MODULES THAT CONTRIBUTE DISPROPORTIONATELY TO THE COMMON POLYGENIC RISK FOR SCHIZOPHRENIA

PubMed Central

Costas, Javier; Paramo, Mario; Arrojo, Manuel

2018-01-01

Abstract Background Genomic research has revealed that schizophrenia is a highly polygenic disease. Recent estimates indicate that at least 71% of genomic segments of 1 Mb include one or more risk loci for schizophrenia (Loh et al., Nature Genet 2015). This extremely high polygenicity represents a challenge to decipher the biological basis of schizophrenia, as it is expected that any set of SNPs with enough size will be associated with the disorder. Among the different gene sets available for study (such as those from Gene Ontology, KEGG pathway, Reactome pathways or protein protein interaction datasets), those based on brain co-expression networks represent putative functional relationships in the relevant tissue. The aim of this work was to identify brain co-expression networks that contribute disproportionately to the common polygenic risk for schizophrenia to get more insight on schizophrenia etiopathology. Methods We analyzed a case -control dataset consisting of 582 schizophrenia patients from Galicia, NW Spain, and 591 ancestrally matched controls, genotyped with the Illumina PsychArray. Using as discovery sample the summary results from the largest GWAS of schizophrenia to date (Psychiatric Genomics Consortium, SCZ2), we generated polygenic risk scores (PRS) in our sample based on SNPs located at genes belonging to brain co-expression modules determined by the CommonMind Consortium (Fromer et al., Nature Neurosci 2016). PRS were generated using the clumping procedure of PLINK, considering several different thresholds to select SNPs from the discovery sample. In order to test if any specific module increased risk to schizophrenia more than expected by their size, we generated up to 10,000 random permutations of the same number of SNPs, matched by frequency, distance to nearest gene, number of SNPs in LD and gene density, using SNPsnap. Results As expected, most modules with enough number of independent SNPs belonging to them showed a significant increase in Nagelkerke’s R2 in our case-control sample after the addition of the module-specific PRS in a logistic regression model. Our permutation strategy revealed that most modules did not show an excess of risk, measured by increase in Nagelkerke’s R2, in comparison to equal number of SNPs with similar characteristics. But one module, M2c from Fromer et al., remained highly significant after multiple tests’ correction. Reactome pathways analysis revealed an over-representation of genes involved in “Neuronal System” and “Axon guidance” among genes from this module. Using the same protocol, we detected that the 84 genes from the neuronal system pathway at this module, representing less than 6% of the genes from the module, explained a higher level of risk than expected. “Voltage-gated Potassium channels” and “Neurexins and neuroligins” are overrepresented among the Neuronal System genes from module M2c. Discussion Here, we show that, in spite of the high polygenicity of schizophrenia, it is possible to identify gene sets contributing disproportionately to total risk, as it was the case for the M2c module from Fromer et al. These authors have previously reported that the M2c module was enriched in GWAS signals, as well as CNVs and rare variants associated with schizophrenia. Therefore, this module shows a disproportionately contribution to schizophrenia risk. Study supported by Grant PI14/01020 from Instituto de Salud Carlos III, Ministry of Health, Spanish Government.

Remote modulation of neural activities via near-infrared triggered release of biomolecules.

PubMed

Li, Wei; Luo, Rongcong; Lin, Xudong; Jadhav, Amol D; Zhang, Zicong; Yan, Li; Chan, Chung-Yuan; Chen, Xianfeng; He, Jufang; Chen, Chia-Hung; Shi, Peng

2015-10-01

The capability to remotely control the release of biomolecules provides an unique opportunity to monitor and regulate neural signaling, which spans extraordinary spatial and temporal scales. While various strategies, including local perfusion, molecular "uncaging", or photosensitive polymeric materials, have been applied to achieve controlled releasing of neuro-active substances, it is still challenging to adopt these technologies in many experimental contexts that require a straightforward but versatile loading-releasing mechanism. Here, we develop a synthetic strategy for remotely controllable releasing of neuro-modulating molecules. This platform is based on microscale composite hydrogels that incorporate polypyrrole (PPy) nanoparticles as photo-thermal transducers and is triggered by near-infrared-light (NIR) irradiation. Specifically, we first demonstrate the utility of our technology by recapitulating the "turning assay" and "collapse assay", which involve localized treatment of chemotactic factors (e.g. Netrin or Semaphorin 3A) to subcellular neural elements and have been extensively used in studying axonal pathfinding. On a network scale, the photo-sensitive microgels are also validated for light-controlled releasing of neurotransmitters (e.g. glutamate). A single NIR-triggered release is sufficient to change the dynamics of a cultured hippocampal neuron network. Taking the advantage of NIR's capability to penetrate deep into live tissue, this technology is further shown to work similarly well in vivo, which is evidenced by synchronized spiking activity in response to NIR-triggered delivery of glutamate in rat auditory cortex, demonstrating remote control of brain activity without any genetic modifications. Notably, our nano-composite microgels are capable of delivering various molecules, ranging from small chemicals to large proteins, without involving any crosslinking chemistry. Such great versatility and ease-of-use will likely make our optically-controlled delivery technology a general and important tool in cell biology research. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cooling the injured brain: how does moderate hypothermia influence the pathophysiology of traumatic brain injury.

PubMed

Sahuquillo, Juan; Vilalta, Anna

2007-01-01

Neither any neuroprotective drug has been shown to be beneficial in improving the outcome of severe traumatic brain injury (TBI) nor has any prophylactically-induced moderate hypothermia shown any beneficial effect on outcome in severe TBI, despite the optimism generated by preclinical studies. This contrasts with the paradox that hypothermia still is the most powerful neuroprotective method in experimental models because of its ability to influence the multiple biochemical cascades that are set in motion after TBI. The aim of this short review is to highlight the most recent developments concerning the pathophysiology of severe TBI, to review new data on thermoregulation and induced hypothermia, the regulation of core and brain temperature in mammals and the multiplicity of effects of hypothermia in the pathophysiology of TBI. Many experimental studies in the last decade have again confirmed that moderate hypothermia confers protection against ischemic and non-ischemic brain hypoxia, traumatic brain injury, anoxic injury following resuscitation after cardiac arrest and other neurological insults. Many posttraumatic adverse events that occur in the injured brain at a cellular and molecular level are highly temperature-sensitive and are thus a good target for induced hypothermia. The basic mechanisms through which hypothermia protects the brain are clearly multifactorial and include at least the following: reduction in brain metabolic rate, effects on cerebral blood flow, reduction of the critical threshold for oxygen delivery, blockade of excitotoxic mechanisms, calcium antagonism, preservation of protein synthesis, reduction of brain thermopooling, a decrease in edema formation, modulation of the inflammatory response, neuroprotection of the white matter and modulation of apoptotic cell death. The new developments discussed in this review indicate that, by targeting many of the abnormal neurochemical cascades initiated after TBI, induced hypothermia may modulate neurotoxicity and, consequently, may play a unique role in opening up new therapeutic avenues for treating severe TBI and improving its devastating effects. Furthermore, greater understanding of the pathophysiology of TBI, new data from both basic and clinical research, the good clinical results obtained in randomized clinical trials in cardiac arrest and better and more reliable cooling methods have given hypothermia a second chance in treating TBI patients. A critical evaluation of hypothermia is therefore mandatory to elucidate the reasons for previous failures and to design further multicenter randomized clinical trials that would definitively confirm or refute the potential of this therapeutic modality in the management of severe traumatic brain injuries.

Genes and Social Behavior

PubMed Central

Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

2011-01-01

What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence behavior; and 2) genetic variation influences brain function and social behavior. We also briefly discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. PMID:18988841

Neuronal sources of hedgehog modulate neurogenesis in the adult planarian brain.

PubMed

Currie, Ko W; Molinaro, Alyssa M; Pearson, Bret J

2016-11-19

The asexual freshwater planarian is a constitutive adult, whose central nervous system (CNS) is in a state of constant homeostatic neurogenesis. However, very little is known about the extrinsic signals that act on planarian stem cells to modulate rates of neurogenesis. We have identified two planarian homeobox transcription factors, Smed-nkx2.1 and Smed-arx , which are required for the maintenance of cholinergic, GABAergic, and octopaminergic neurons in the planarian CNS. These very same neurons also produce the planarian hedgehog ligand ( Smed-hh ), which appears to communicate with brain-adjacent stem cells to promote normal levels of neurogenesis. Planarian stem cells nearby the brain express core hh signal transduction genes, and consistent hh signaling levels are required to maintain normal production of neural progenitor cells and new mature cholinergic neurons, revealing an important mitogenic role for the planarian hh signaling molecule in the adult CNS.

MEMORY MODULATION

PubMed Central

Roozendaal, Benno; McGaugh, James L.

2011-01-01

Our memories are not all created equally strong: Some experiences are well remembered while others are remembered poorly, if at all. Research on memory modulation investigates the neurobiological processes and systems that contribute to such differences in the strength of our memories. Extensive evidence from both animal and human research indicates that emotionally significant experiences activate hormonal and brain systems that regulate the consolidation of newly acquired memories. These effects are integrated through noradrenergic activation of the basolateral amygdala which regulates memory consolidation via interactions with many other brain regions involved in consolidating memories of recent experiences. Modulatory systems not only influence neurobiological processes underlying the consolidation of new information, but also affect other mnemonic processes, including memory extinction, memory recall and working memory. In contrast to their enhancing effects on consolidation, adrenal stress hormones impair memory retrieval and working memory. Such effects, as with memory consolidation, require noradrenergic activation of the basolateral amygdala and interactions with other brain regions. PMID:22122145

The effect of constraining eye-contact during dynamic emotional face perception—an fMRI study

PubMed Central

Zurcher, Nicole R.; Lassalle, Amandine; Hippolyte, Loyse; Ward, Noreen; Johnels, Jakob Åsberg

2017-01-01

Abstract Eye-contact modifies how we perceive emotions and modulates activity in the social brain network. Here, using fMRI, we demonstrate that adding a fixation cross in the eye region of dynamic facial emotional stimuli significantly increases activation in the social brain of healthy, neurotypical participants when compared with activation for the exact same stimuli observed in a free-viewing mode. In addition, using PPI analysis, we show that the degree of amygdala connectivity with the rest of the brain is enhanced for the constrained view for all emotions tested except for fear, and that anxiety and alexithymia modulate the strength of amygdala connectivity for each emotion differently. Finally, we show that autistic traits have opposite effects on amygdala connectivity for fearful and angry emotional expressions, suggesting that these emotions should be treated separately in studies investigating facial emotion processing. PMID:28402536

Automated Composites Processing Technology: Film Module

NASA Technical Reports Server (NTRS)

Hulcher, A. Bruce

2004-01-01

NASA's Marshall Space Flight Center (MSFC) has developed a technology that combines a film/adhesive laydown module with fiber placement technology to enable the processing of composite prepreg tow/tape and films, foils or adhesives on the same placement machine. The development of this technology grew out of NASA's need for lightweight, permeation-resistant cryogenic propellant tanks. Autoclave processing of high performance composites results in thermally-induced stresses due to differences in the coefficients of thermal expansion of the fiber and matrix resin components. These stresses, together with the reduction in temperature due to cryogen storage, tend to initiate microcracking within the composite tank wall. One way in which to mitigate this problem is to introduce a thin, crack-resistant polymer film or foil into the tank wall. Investigation into methods to automate the processing of thin film or foil materials into composites led to the development of this technology. The concept employs an automated film supply and feed module that may be designed to fit existing fiber placement machines, or may be designed as integral equipment to new machines. This patent-pending technology can be designed such that both film and foil materials may be processed simultaneously, leading to a decrease in part build cycle time. The module may be designed having a compaction device independent of the host machine, or may utilize the host machine's compactor. The film module functions are controlled by a dedicated system independent of the fiber placement machine controls. The film, foil, or adhesive is processed via pre-existing placement machine run programs, further reducing operational expense.

Sniffer patch laser uncaging response (SPLURgE): an assay of regional differences in allosteric receptor modulation and neurotransmitter clearance

PubMed Central

Christian, Catherine A.

2013-01-01

Allosteric modulators exert actions on neurotransmitter receptors by positively or negatively altering the effective response of these receptors to their respective neurotransmitter. γ-Aminobutyric acid (GABA) type A ionotropic receptors (GABAARs) are major targets for allosteric modulators such as benzodiazepines, neurosteroids, and barbiturates. Analysis of substances that produce similar effects has been hampered by the lack of techniques to assess the localization and function of such agents in brain slices. Here we describe measurement of the sniffer patch laser uncaging response (SPLURgE), which combines the sniffer patch recording configuration with laser photolysis of caged GABA. This methodology enables the detection of allosteric GABAAR modulators endogenously present in discrete areas of the brain slice and allows for the application of exogenous GABA with spatiotemporal control without altering the release and localization of endogenous modulators within the slice. Here we demonstrate the development and use of this technique for the measurement of allosteric modulation in different areas of the thalamus. Application of this technique will be useful in determining whether a lack of modulatory effect on a particular category of neurons or receptors is due to insensitivity to allosteric modulation or a lack of local release of endogenous ligand. We also demonstrate that this technique can be used to investigate GABA diffusion and uptake. This method thus provides a biosensor assay for rapid detection of endogenous GABAAR modulators and has the potential to aid studies of allosteric modulators that exert effects on other classes of neurotransmitter receptors, such as glutamate, acetylcholine, or glycine receptors. PMID:23843428

Sniffer patch laser uncaging response (SPLURgE): an assay of regional differences in allosteric receptor modulation and neurotransmitter clearance.

PubMed

Christian, Catherine A; Huguenard, John R

2013-10-01

Allosteric modulators exert actions on neurotransmitter receptors by positively or negatively altering the effective response of these receptors to their respective neurotransmitter. γ-Aminobutyric acid (GABA) type A ionotropic receptors (GABAARs) are major targets for allosteric modulators such as benzodiazepines, neurosteroids, and barbiturates. Analysis of substances that produce similar effects has been hampered by the lack of techniques to assess the localization and function of such agents in brain slices. Here we describe measurement of the sniffer patch laser uncaging response (SPLURgE), which combines the sniffer patch recording configuration with laser photolysis of caged GABA. This methodology enables the detection of allosteric GABAAR modulators endogenously present in discrete areas of the brain slice and allows for the application of exogenous GABA with spatiotemporal control without altering the release and localization of endogenous modulators within the slice. Here we demonstrate the development and use of this technique for the measurement of allosteric modulation in different areas of the thalamus. Application of this technique will be useful in determining whether a lack of modulatory effect on a particular category of neurons or receptors is due to insensitivity to allosteric modulation or a lack of local release of endogenous ligand. We also demonstrate that this technique can be used to investigate GABA diffusion and uptake. This method thus provides a biosensor assay for rapid detection of endogenous GABAAR modulators and has the potential to aid studies of allosteric modulators that exert effects on other classes of neurotransmitter receptors, such as glutamate, acetylcholine, or glycine receptors.

Reconfiguration of Brain Network Architectures between Resting-State and Complexity-Dependent Cognitive Reasoning.

PubMed

Hearne, Luke J; Cocchi, Luca; Zalesky, Andrew; Mattingley, Jason B

2017-08-30

Our capacity for higher cognitive reasoning has a measurable limit. This limit is thought to arise from the brain's capacity to flexibly reconfigure interactions between spatially distributed networks. Recent work, however, has suggested that reconfigurations of task-related networks are modest when compared with intrinsic "resting-state" network architecture. Here we combined resting-state and task-driven functional magnetic resonance imaging to examine how flexible, task-specific reconfigurations associated with increasing reasoning demands are integrated within a stable intrinsic brain topology. Human participants (21 males and 28 females) underwent an initial resting-state scan, followed by a cognitive reasoning task involving different levels of complexity, followed by a second resting-state scan. The reasoning task required participants to deduce the identity of a missing element in a 4 × 4 matrix, and item difficulty was scaled parametrically as determined by relational complexity theory. Analyses revealed that external task engagement was characterized by a significant change in functional brain modules. Specifically, resting-state and null-task demand conditions were associated with more segregated brain-network topology, whereas increases in reasoning complexity resulted in merging of resting-state modules. Further increments in task complexity did not change the established modular architecture, but affected selective patterns of connectivity between frontoparietal, subcortical, cingulo-opercular, and default-mode networks. Larger increases in network efficiency within the newly established task modules were associated with higher reasoning accuracy. Our results shed light on the network architectures that underlie external task engagement, and highlight selective changes in brain connectivity supporting increases in task complexity. SIGNIFICANCE STATEMENT Humans have clear limits in their ability to solve complex reasoning problems. It is thought that such limitations arise from flexible, moment-to-moment reconfigurations of functional brain networks. It is less clear how such task-driven adaptive changes in connectivity relate to stable, intrinsic networks of the brain and behavioral performance. We found that increased reasoning demands rely on selective patterns of connectivity within cortical networks that emerged in addition to a more general, task-induced modular architecture. This task-driven architecture reverted to a more segregated resting-state architecture both immediately before and after the task. These findings reveal how flexibility in human brain networks is integral to achieving successful reasoning performance across different levels of cognitive demand. Copyright © 2017 the authors 0270-6474/17/378399-13$15.00/0.

Pathophysiology of migraine

PubMed Central

Goadsby, Peter J.

2012-01-01

Migraine is a common disabling brain disorder whose pathophysiology is now being better understood. The study of anatomy and physiology of pain producing structures in the cranium and the central nervous system modulation of the input have led to the conclusion that migraine involves alterations in the sub-cortical aminergic sensory modulatory systems that influence the brain widely. PMID:23024559

Comparative Minicolumnar Morphometry of Three Distinguished Scientists

ERIC Educational Resources Information Center

Casanova, Manuel F.; Switala, Andrew E.; Trippe, Juan; Fitzgerald, Michael

2007-01-01

It has been suggested that the cell minicolumn is the smallest module capable of information processing within the brain. In this case series, photomicrographs of six regions of interests (Brodmann areas 4, 9, 17, 21, 22, and 40) were analyzed by computerized image analysis for minicolumnar morphometry in the brains of three distinguished…

How Different Types of Conceptual Relations Modulate Brain Activation during Semantic Priming

ERIC Educational Resources Information Center

Sachs, Olga; Weis, Susanne; Zellagui, Nadia; Sass, Katharina; Huber, Walter; Zvyagintsev, Mikhail; Mathiak, Klaus; Kircher, Tilo

2011-01-01

Semantic priming, a well-established technique to study conceptual representation, has thus far produced variable fMRI results, both regarding the type of priming effects and their correlation with brain activation. The aims of the current study were (a) to investigate two types of semantic relations--categorical versus associative--under…

Polyphenol- and PUFA-rich walnuts protect against age-associated cognitive decline through epigenetic modulation

USDA-ARS?s Scientific Manuscript database

A demographic shift towards an aging population and the incidence of age-related brain disorders are on the rise worldwide. A rapid decline in brain health with aging is primarily caused by the brain’s exceptionally high demand for energy which drives high oxygen consumption, leading to a subsequent...

The Sodium-Activated Potassium Channel Slack Is Required for Optimal Cognitive Flexibility in Mice

ERIC Educational Resources Information Center

Bausch, Anne E.; Dieter, Rebekka; Nann, Yvette; Hausmann, Mario; Meyerdierks, Nora; Kaczmarek, Leonard K.; Ruth, Peter; Lukowski, Robert

2015-01-01

"Kcnt1" encoded sodium-activated potassium channels (Slack channels) are highly expressed throughout the brain where they modulate the firing patterns and general excitability of many types of neurons. Increasing evidence suggests that Slack channels may be important for higher brain functions such as cognition and normal intellectual…

TauG-guidance of transients in expressive musical performance.

PubMed

Schogler, Benjaman; Pepping, Gert-Jan; Lee, David N

2008-08-01

The sounds in expressive musical performance, and the movements that produce them, offer insight into temporal patterns in the brain that generate expression. To gain understanding of these brain patterns, we analyzed two types of transient sounds, and the movements that produced them, during a vocal duet and a bass solo. The transient sounds studied were inter-tone f (0)(t)-glides (the continuous change in fundamental frequency, f (0)(t), when gliding from one tone to the next), and attack intensity-glides (the continuous rise in sound intensity when attacking, or initiating, a tone). The temporal patterns of the inter-tone f (0)(t)-glides and attack intensity-glides, and of the movements producing them, all conformed to the mathematical function, tau (G)(t) (called tauG), predicted by General Tau Theory, and assumed to be generated in the brain. The values of the parameters of the tau (G)(t) function were modulated by the performers when they modulated musical expression. Thus the tau (G)(t) function appears to be a fundamental of brain activity entailed in the generation of expressive temporal patterns of movement and sound.

Clarifying the Ghrelin System's Ability to Regulate Feeding Behaviours Despite Enigmatic Spatial Separation of the GHSR and Its Endogenous Ligand.

PubMed

Edwards, Alexander; Abizaid, Alfonso

2017-04-19

Ghrelin is a hormone predominantly produced in and secreted from the stomach. Ghrelin is involved in many physiological processes including feeding, the stress response, and in modulating learning, memory and motivational processes. Ghrelin does this by binding to its receptor, the growth hormone secretagogue receptor (GHSR), a receptor found in relatively high concentrations in hypothalamic and mesolimbic brain regions. While the feeding and metabolic effects of ghrelin can be explained by the effects of this hormone on regions of the brain that have a more permeable blood brain barrier (BBB), ghrelin produced within the periphery demonstrates a limited ability to reach extrahypothalamic regions where GHSRs are expressed. Therefore, one of the most pressing unanswered questions plaguing ghrelin research is how GHSRs, distributed in brain regions protected by the BBB, are activated despite ghrelin's predominant peripheral production and poor ability to transverse the BBB. This manuscript will describe how peripheral ghrelin activates central GHSRs to encourage feeding, and how central ghrelin synthesis and ghrelin independent activation of GHSRs may also contribute to the modulation of feeding behaviours.

Characterizing and Modulating Brain Circuitry through Transcranial Magnetic Stimulation Combined with Electroencephalography.

PubMed

Farzan, Faranak; Vernet, Marine; Shafi, Mouhsin M D; Rotenberg, Alexander; Daskalakis, Zafiris J; Pascual-Leone, Alvaro

2016-01-01

The concurrent combination of transcranial magnetic stimulation (TMS) with electroencephalography (TMS-EEG) is a powerful technology for characterizing and modulating brain networks across developmental, behavioral, and disease states. Given the global initiatives in mapping the human brain, recognition of the utility of this technique is growing across neuroscience disciplines. Importantly, TMS-EEG offers translational biomarkers that can be applied in health and disease, across the lifespan, and in humans and animals, bridging the gap between animal models and human studies. However, to utilize the full potential of TMS-EEG methodology, standardization of TMS-EEG study protocols is needed. In this article, we review the principles of TMS-EEG methodology, factors impacting TMS-EEG outcome measures, and the techniques for preventing and correcting artifacts in TMS-EEG data. To promote the standardization of this technique, we provide comprehensive guides for designing TMS-EEG studies and conducting TMS-EEG experiments. We conclude by reviewing the application of TMS-EEG in basic, cognitive and clinical neurosciences, and evaluate the potential of this emerging technology in brain research.

The dynamics of human cognition: Increasing global integration coupled with decreasing segregation found using iEEG.

PubMed

Cruzat, Josephine; Deco, Gustavo; Tauste-Campo, Adrià; Principe, Alessandro; Costa, Albert; Kringelbach, Morten L; Rocamora, Rodrigo

2018-05-15

Cognitive processing requires the ability to flexibly integrate and process information across large brain networks. How do brain networks dynamically reorganize to allow broad communication between many different brain regions in order to integrate information? We record neural activity from 12 epileptic patients using intracranial EEG while performing three cognitive tasks. We assess how the functional connectivity between different brain areas changes to facilitate communication across them. At the topological level, this facilitation is characterized by measures of integration and segregation. Across all patients, we found significant increases in integration and decreases in segregation during cognitive processing, especially in the gamma band (50-90 Hz). We also found higher levels of global synchronization and functional connectivity during task execution, again particularly in the gamma band. More importantly, functional connectivity modulations were not caused by changes in the level of the underlying oscillations. Instead, these modulations were caused by a rearrangement of the mutual synchronization between the different nodes as proposed by the "Communication Through Coherence" Theory. Copyright © 2018 Elsevier Inc. All rights reserved.