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Sample records for brain states promoting

  1. Histamine from brain resident MAST cells promotes wakefulness and modulates behavioral states.

    Directory of Open Access Journals (Sweden)

    Sachiko Chikahisa

    Full Text Available Mast cell activation and degranulation can result in the release of various chemical mediators, such as histamine and cytokines, which significantly affect sleep. Mast cells also exist in the central nervous system (CNS. Since up to 50% of histamine contents in the brain are from brain mast cells, mediators from brain mast cells may significantly influence sleep and other behaviors. In this study, we examined potential involvement of brain mast cells in sleep/wake regulations, focusing especially on the histaminergic system, using mast cell deficient (W/W(v mice. No significant difference was found in the basal amount of sleep/wake between W/W(v mice and their wild-type littermates (WT, although W/W(v mice showed increased EEG delta power and attenuated rebound response after sleep deprivation. Intracerebroventricular injection of compound 48/80, a histamine releaser from mast cells, significantly increased histamine levels in the ventricular region and enhanced wakefulness in WT mice, while it had no effect in W/W(v mice. Injection of H1 antagonists (triprolidine and mepyramine significantly increased the amounts of slow-wave sleep in WT mice, but not in W/W(v mice. Most strikingly, the food-seeking behavior observed in WT mice during food deprivation was completely abolished in W/W(v mice. W/W(v mice also exhibited higher anxiety and depression levels compared to WT mice. Our findings suggest that histamine released from brain mast cells is wake-promoting, and emphasizes the physiological and pharmacological importance of brain mast cells in the regulation of sleep and fundamental neurobehavior.

  2. Central thalamic deep brain stimulation to promote recovery from chronic posttraumatic minimally conscious state: challenges and opportunities.

    Science.gov (United States)

    Giacino, Joseph; Fins, Joseph J; Machado, Andre; Schiff, Nicholas D

    2012-07-01

    Central thalamic deep brain stimulation (CT-DBS) may have therapeutic potential to improve behavioral functioning in patients with severe traumatic brain injury (TBI), but its use remains experimental. Current research suggests that the central thalamus plays a critical role in modulating arousal during tasks requiring sustained attention, working memory, and motor function. The aim of the current article is to review the methodology used in the CT-DBS protocol developed by our group, outline the challenges we encountered and offer suggestions for future DBS trials in this population. RATIONAL FOR CT-DBS IN TBI:  CT-DBS may therefore be able to stimulate these functions by eliciting action potentials that excite thalamocortical and thalamostriatal pathways. Because patients in chronic minimally conscious state (MCS) have a very low probability of regaining functional independence, yet often have significant sparing of cortical connectivity, they may represent a particularly appropriate target group for CT-DBS. PIlOT STUDY RESULTS:  We have conducted a series of single-subject studies of CT-DBS in patients with chronic posttraumatic MCS, with 24-month follow-up. Outcomes were measured using the Coma Recovery Scale-Revised as well as a battery of secondary outcome measures to capture more granular changes. Findings from our index case suggest that CT-DBS can significantly increase functional communication, motor performance, feeding, and object naming in the DBS on state, with performance in some domains remaining above baseline even after DBS was turned off. The use of CT-DBS in patients in MCS, however, presents challenges at almost every step, including during surgical planning, outcome measurement, and postoperative care. Additionally, given the difficulties of obtaining informed consent from patients in MCS and the experimental nature of the treatment, a robust, scientifically rooted ethical framework is resented for pursuing this line of work. © 2012

  3. Brain states and hypnosis research.

    Science.gov (United States)

    Posner, Michael I; Rothbart, Mary K

    2011-06-01

    Research in cognitive neuroscience now considers the state of the brain prior to the task an important aspect of performance. Hypnosis seems to alter the brain state in a way which allows external input to dominate over internal goals. We examine how normal development may illuminate the hypnotic state. Copyright © 2009 Elsevier Inc. All rights reserved.

  4. Training brain networks and states.

    Science.gov (United States)

    Tang, Yi-Yuan; Posner, Michael I

    2014-07-01

    Brain training refers to practices that alter the brain in a way that improves cognition, and performance in domains beyond those involved in the training. We argue that brain training includes network training through repetitive practice that exercises specific brain networks and state training, which changes the brain state in a way that influences many networks. This opinion article considers two widely used methods - working memory training (WMT) and meditation training (MT) - to demonstrate the similarities and differences between network and state training. These two forms of training involve different areas of the brain and different forms of generalization. We propose a distinction between network and state training methods to improve understanding of the most effective brain training. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Research project: "Promotion of optimum brain ageing"

    CERN Multimedia

    IT Department

    2009-01-01

    The Rehabilitation and Geriatrics Department of the Geneva University Hospitals (HUG) has signed a research protocol with CERN with a view to promoting better understanding of the mechanisms that trigger Alzheimer’s disease. Alzheimer’s disease is a form of dementia associated with memory loss, inability to make plans and spatial disorientation. With 24 million sufferers worldwide at present, a figure that is predicted to rise to 29 million by 2020, it represents a major challenge for the coming decades. Prevention is a key factor in slowing the alarming spread of this disease. Delaying the onset of the disease could reduce the total number of cases by 50%. Why CERN? CERN is an international research organisation with a workforce that is predominantly male (a section of the population that has been little studied so far) and has a high level of education. Moreover, its pensioners are easy to reach since the majority live in the Geneva area. The aim of the study is to ev...

  6. Stress Impact on Resting State Brain Networks.

    Science.gov (United States)

    Soares, José Miguel; Sampaio, Adriana; Ferreira, Luís Miguel; Santos, Nadine Correia; Marques, Paulo; Marques, Fernanda; Palha, Joana Almeida; Cerqueira, João José; Sousa, Nuno

    2013-01-01

    Resting state brain networks (RSNs) are spatially distributed large-scale networks, evidenced by resting state functional magnetic resonance imaging (fMRI) studies. Importantly, RSNs are implicated in several relevant brain functions and present abnormal functional patterns in many neuropsychiatric disorders, for which stress exposure is an established risk factor. Yet, so far, little is known about the effect of stress in the architecture of RSNs, both in resting state conditions or during shift to task performance. Herein we assessed the architecture of the RSNs using functional magnetic resonance imaging (fMRI) in a cohort of participants exposed to prolonged stress (participants that had just finished their long period of preparation for the medical residence selection exam), and respective gender- and age-matched controls (medical students under normal academic activities). Analysis focused on the pattern of activity in resting state conditions and after deactivation. A volumetric estimation of the RSNs was also performed. Data shows that stressed participants displayed greater activation of the default mode (DMN), dorsal attention (DAN), ventral attention (VAN), sensorimotor (SMN), and primary visual (VN) networks than controls. Importantly, stressed participants also evidenced impairments in the deactivation of resting state-networks when compared to controls. These functional changes are paralleled by a constriction of the DMN that is in line with the pattern of brain atrophy observed after stress exposure. These results reveal that stress impacts on activation-deactivation pattern of RSNs, a finding that may underlie stress-induced changes in several dimensions of brain activity.

  7. Stress Impact on Resting State Brain Networks.

    Directory of Open Access Journals (Sweden)

    José Miguel Soares

    Full Text Available Resting state brain networks (RSNs are spatially distributed large-scale networks, evidenced by resting state functional magnetic resonance imaging (fMRI studies. Importantly, RSNs are implicated in several relevant brain functions and present abnormal functional patterns in many neuropsychiatric disorders, for which stress exposure is an established risk factor. Yet, so far, little is known about the effect of stress in the architecture of RSNs, both in resting state conditions or during shift to task performance. Herein we assessed the architecture of the RSNs using functional magnetic resonance imaging (fMRI in a cohort of participants exposed to prolonged stress (participants that had just finished their long period of preparation for the medical residence selection exam, and respective gender- and age-matched controls (medical students under normal academic activities. Analysis focused on the pattern of activity in resting state conditions and after deactivation. A volumetric estimation of the RSNs was also performed. Data shows that stressed participants displayed greater activation of the default mode (DMN, dorsal attention (DAN, ventral attention (VAN, sensorimotor (SMN, and primary visual (VN networks than controls. Importantly, stressed participants also evidenced impairments in the deactivation of resting state-networks when compared to controls. These functional changes are paralleled by a constriction of the DMN that is in line with the pattern of brain atrophy observed after stress exposure. These results reveal that stress impacts on activation-deactivation pattern of RSNs, a finding that may underlie stress-induced changes in several dimensions of brain activity.

  8. Transcranial brain stimulation to promote functional recovery after stroke

    DEFF Research Database (Denmark)

    Raffin, Estelle; Siebner, Hartwig R

    2014-01-01

    PURPOSE OF REVIEW: Noninvasive brain stimulation (NIBS) is increasingly used to enhance the recovery of function after stroke. The purpose of this review is to highlight and discuss some unresolved questions that need to be addressed to better understand and exploit the potential of NIBS...... therapeutic efficacy. SUMMARY: This review addressed six questions: How does NIBS facilitate the recovery of function after stroke? Which brain regions should be targeted by NIBS? Is there a particularly effective NIBS modality that should be used? Does the location of the stroke influence the therapeutic...... response? How often should NIBS be repeated? Is the functional state of the brain during or before NIBS relevant to therapeutic efficacy of NIBS? We argue that these questions need to be tackled to obtain sufficient mechanistic understanding of how NIBS facilitates the recovery of function. This knowledge...

  9. Deep brain stimulation in the globus pallidus externa promotes sleep.

    Science.gov (United States)

    Qiu, M H; Chen, M C; Wu, J; Nelson, D; Lu, J

    2016-05-13

    The basal ganglia, a network of subcortical structures, play a critical role in movements, sleep and mental behavior. Basal ganglia disorders such as Parkinson's disease and Huntington's disease affect sleep. Deep brain stimulation (DBS) to treat motor symptoms in Parkinson's disease can ameliorate sleep disturbances. Our series of previous studies lead the hypothesis that dopamine, acting on D2 receptors on the striatopallidal terminals, enhances activity in the globus pallidus externa (GPe) and promotes sleep. Here, we tested if DBS in the GPe promotes sleep in rats. We found that unilateral DBS (180 Hz at 100 μA) in the GPe in rats significantly increased both non-rapid eye movement and rapid eye movement sleep compared to sham DBS stimulation. The EEG power spectrum of sleep induced by DBS was similar to that of the baseline sleep, and sleep latency was not affected by DBS. The GPe is potentially a better site for DBS to treat both insomnia and motor disorders caused by basal ganglia dysfunction. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  10. 77 FR 64031 - United States-Peru Trade Promotion Agreement

    Science.gov (United States)

    2012-10-18

    ... 178 RIN 1515-AD79 United States-Peru Trade Promotion Agreement AGENCIES: U.S. Customs and Border... States-Peru Trade Promotion Agreement. DATES: Final rule effective November 19, 2012. FOR FURTHER... implement the preferential tariff treatment and other customs-related provisions of the United States-Peru...

  11. State-dependencies of learning across brain scales

    Science.gov (United States)

    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

  12. Changes in cognitive state alter human functional brain networks

    Directory of Open Access Journals (Sweden)

    Malaak Nasser Moussa

    2011-08-01

    Full Text Available The study of the brain as a whole system can be accomplished using network theory principles. Research has shown that human functional brain networks during a resting state exhibit small-world properties and high degree nodes, or hubs, localized to brain areas consistent with the default mode network (DMN. However, the study of brain networks across different tasks and or cognitive states has been inconclusive. Research in this field is important because the underpinnings of behavioral output are inherently dependent on whether or not brain networks are dynamic. This is the first comprehensive study to evaluate multiple network metrics at a voxel-wise resolution in the human brain at both the whole brain and regional level under various conditions: resting state, visual stimulation, and multisensory (auditory and visual stimulation. Our results show that despite global network stability, functional brain networks exhibit considerable task-induced changes in connectivity, efficiency, and community structure at the regional level.

  13. Brain states and hypnosis research✩,✩✩

    Science.gov (United States)

    Posner, Michael I.; Rothbart, Mary K.

    2011-01-01

    Research in cognitive neuroscience now considers the state of the brain prior to the task an important aspect of performance. Hypnosis seems to alter the brain state in a way which allows external input to dominate over internal goals. We examine how normal development may illuminate the hypnotic state. PMID:20060745

  14. Brain states and hypnosis research✩,✩✩

    OpenAIRE

    Posner, Michael I.; Rothbart, Mary K.

    2010-01-01

    Research in cognitive neuroscience now considers the state of the brain prior to the task an important aspect of performance. Hypnosis seems to alter the brain state in a way which allows external input to dominate over internal goals. We examine how normal development may illuminate the hypnotic state.

  15. Quality of Life Following Brain Injury: Perspectives from Brain Injury Association of America State Affiliates

    Science.gov (United States)

    Degeneffe, Charles Edmund; Tucker, Mark

    2012-01-01

    Objective: to examine the perspectives of brain injury professionals concerning family members' feelings about the quality of life experienced by individuals with brain injuries. Participants: participating in the study were 28 individuals in leadership positions with the state affiliates of the Brain Injury Association of America (BIAA). Methods:…

  16. Cyclic and sleep-like spontaneous alternations of brain state under urethane anaesthesia.

    Directory of Open Access Journals (Sweden)

    Elizabeth A Clement

    Full Text Available BACKGROUND: Although the induction of behavioural unconsciousness during sleep and general anaesthesia has been shown to involve overlapping brain mechanisms, sleep involves cyclic fluctuations between different brain states known as active (paradoxical or rapid eye movement: REM and quiet (slow-wave or non-REM: nREM stages whereas commonly used general anaesthetics induce a unitary slow-wave brain state. METHODOLOGY/PRINCIPAL FINDINGS: Long-duration, multi-site forebrain field recordings were performed in urethane-anaesthetized rats. A spontaneous and rhythmic alternation of brain state between activated and deactivated electroencephalographic (EEG patterns was observed. Individual states and their transitions resembled the REM/nREM cycle of natural sleep in their EEG components, evolution, and time frame ( approximately 11 minute period. Other physiological variables such as muscular tone, respiration rate, and cardiac frequency also covaried with forebrain state in a manner identical to sleep. The brain mechanisms of state alternations under urethane also closely overlapped those of natural sleep in their sensitivity to cholinergic pharmacological agents and dependence upon activity in the basal forebrain nuclei that are the major source of forebrain acetylcholine. Lastly, stimulation of brainstem regions thought to pace state alternations in sleep transiently disrupted state alternations under urethane. CONCLUSIONS/SIGNIFICANCE: Our results suggest that urethane promotes a condition of behavioural unconsciousness that closely mimics the full spectrum of natural sleep. The use of urethane anaesthesia as a model system will facilitate mechanistic studies into sleep-like brain states and their alternations. In addition, it could also be exploited as a tool for the discovery of new molecular targets that are designed to promote sleep without compromising state alternations.

  17. Health Promotion in General Medical Practice in Ogun State ...

    African Journals Online (AJOL)

    This study was carried out among general medical practitioners in Ogun state to assess their attitude to and practice of health promotion in clinical practice. Although 91.1% of them indicated that health promotion is very important in clinical practice, only a quarter or less of them routinely asked or counseled their patients ...

  18. A regulatory toolbox of MiniPromoters to drive selective expression in the brain

    Science.gov (United States)

    Portales-Casamar, Elodie; Swanson, Douglas J.; Liu, Li; de Leeuw, Charles N.; Banks, Kathleen G.; Ho Sui, Shannan J.; Fulton, Debra L.; Ali, Johar; Amirabbasi, Mahsa; Arenillas, David J.; Babyak, Nazar; Black, Sonia F.; Bonaguro, Russell J.; Brauer, Erich; Candido, Tara R.; Castellarin, Mauro; Chen, Jing; Chen, Ying; Cheng, Jason C. Y.; Chopra, Vik; Docking, T. Roderick; Dreolini, Lisa; D'Souza, Cletus A.; Flynn, Erin K.; Glenn, Randy; Hatakka, Kristi; Hearty, Taryn G.; Imanian, Behzad; Jiang, Steven; Khorasan-zadeh, Shadi; Komljenovic, Ivana; Laprise, Stéphanie; Liao, Nancy Y.; Lim, Jonathan S.; Lithwick, Stuart; Liu, Flora; Liu, Jun; Lu, Meifen; McConechy, Melissa; McLeod, Andrea J.; Milisavljevic, Marko; Mis, Jacek; O'Connor, Katie; Palma, Betty; Palmquist, Diana L.; Schmouth, Jean-François; Swanson, Magdalena I.; Tam, Bonny; Ticoll, Amy; Turner, Jenna L.; Varhol, Richard; Vermeulen, Jenny; Watkins, Russell F.; Wilson, Gary; Wong, Bibiana K. Y.; Wong, Siaw H.; Wong, Tony Y. T.; Yang, George S.; Ypsilanti, Athena R.; Jones, Steven J. M.; Holt, Robert A.; Goldowitz, Daniel; Wasserman, Wyeth W.; Simpson, Elizabeth M.

    2010-01-01

    The Pleiades Promoter Project integrates genomewide bioinformatics with large-scale knockin mouse production and histological examination of expression patterns to develop MiniPromoters and related tools designed to study and treat the brain by directed gene expression. Genes with brain expression patterns of interest are subjected to bioinformatic analysis to delineate candidate regulatory regions, which are then incorporated into a panel of compact human MiniPromoters to drive expression to brain regions and cell types of interest. Using single-copy, homologous-recombination “knockins” in embryonic stem cells, each MiniPromoter reporter is integrated immediately 5′ of the Hprt locus in the mouse genome. MiniPromoter expression profiles are characterized in differentiation assays of the transgenic cells or in mouse brains following transgenic mouse production. Histological examination of adult brains, eyes, and spinal cords for reporter gene activity is coupled to costaining with cell-type–specific markers to define expression. The publicly available Pleiades MiniPromoter Project is a key resource to facilitate research on brain development and therapies. PMID:20807748

  19. Viral Vector-Based Dissection of Marmoset GFAP Promoter in Mouse and Marmoset Brains.

    Directory of Open Access Journals (Sweden)

    Yoichiro Shinohara

    Full Text Available Adeno-associated virus (AAV vectors are small in diameter, diffuse easily in the brain, and represent a highly efficient means by which to transfer a transgene to the brain of a large animal. A major demerit of AAV vectors is their limited accommodation capacity for transgenes. Thus, a compact promoter is useful when delivering large transgenes via AAV vectors. In the present study, we aimed to identify the shortest astrocyte-specific GFAP promoter region that could be used for AAV-vector-mediated transgene expression in the marmoset brain. The 2.0-kb promoter region upstream of the GFAP gene was cloned from the marmoset genome, and short promoters (1.6 kb, 1.4 kb, 0.6 kb, 0.3 kb and 0.2 kb were obtained by progressively deleting the original 2.0-kb promoter from the 5' end. The short promoters were screened in the mouse cerebellum in terms of their strength and astrocyte specificity. We found that the 0.3-kb promoter maintained 40% of the strength of the original 2.0-kb promoter, and approximately 90% of its astrocyte specificity. These properties were superior to those of the 1.4-kb, 0.6-kb (20% promoter strength and 0.2-kb (70% astrocyte specificity promoters. Then, we verified whether the 0.3-kb GFAP promoter retained astrocyte specificity in the marmoset cerebral cortex. Injection of viral vectors carrying the 0.3-kb marmoset GFAP promoter specifically transduced astrocytes in both the cerebral cortex and cerebellar cortex of the marmoset. These results suggest that the compact 0.3-kb promoter region serves as an astrocyte-specific promoter in the marmoset brain, which permits us to express a large gene by AAV vectors that have a limited accommodation capacity.

  20. Hierarchical Functional Modularity in the Resting-State Human Brain

    NARCIS (Netherlands)

    Ferrarini, L.; Veer, I.M.; Baerends, E.; van Tol, M.J.; Renken, R.J.; van der Wee, N.J.A.; Veltman, D.J.; Aleman, A.; Zitman, F.G.; Penninx, B.W.J.H.; van Buchem, M.A.; Reiber, J.H.C.; Rombouts, S.A.R.B.; Milles, J.

    2009-01-01

    Functional magnetic resonance imaging (fMRI) studies have shown that anatomically distinct brain regions are functionally connected during the resting state. Basic topological properties in the brain functional connectivity (BFC) map have highlighted the BFC's small-world topology. Modularity, a

  1. Hierarchical Functional Modularity in the Resting-State Human Brain

    NARCIS (Netherlands)

    Ferrarini, Luca; Veer, Ilya M.; Baerends, Evelinda; van Tol, Marie-Jose; Renken, Remco J.; van der Wee, Nic J. A.; Veltman, Dirk. J.; Aleman, Andre; Zitman, Frans G.; Penninx, Brenda W. J. H.; van Buchem, Mark A.; Reiber, Johan H. C.; Rombouts, Serge A. R. B.; Milles, Julien

    Functional magnetic resonance imaging (fMRI) studies have shown that anatomically distinct brain regions are functionally connected during the resting state. Basic topological properties in the brain functional connectivity (BFC) map have highlighted the BFC's small-world topology. Modularity, a

  2. Does State Merit-Based Aid Stem Brain Drain?

    Science.gov (United States)

    Zhang, Liang; Ness, Erik C.

    2010-01-01

    In this study, the authors use college enrollment and migration data to test the brain drain hypothesis. Their results suggest that state merit scholarship programs do indeed stanch the migration of "best and brightest" students to other states. In the aggregate and on average, the implementation of state merit aid programs increases the…

  3. 20 Ways To Promote Brain-Based Teaching and Learning.

    Science.gov (United States)

    Prigge, Debra J.

    2002-01-01

    Based on current knowledge about cognitive processes, this article presents strategies for preparing the learner, managing the environment to motivate students, gaining and keeping learner attention, and increasing memory and recall by making learning personally relevant to students. Resources are listed for brain-based teaching and learning. (CR)

  4. Variability of Brain Death Policies in the United States.

    Science.gov (United States)

    Greer, David M; Wang, Hilary H; Robinson, Jennifer D; Varelas, Panayiotis N; Henderson, Galen V; Wijdicks, Eelco F M

    2016-02-01

    Brain death is the irreversible cessation of function of the entire brain, and it is a medically and legally accepted mechanism of death in the United States and worldwide. Significant variability may exist in individual institutional policies regarding the determination of brain death. It is imperative that brain death be diagnosed accurately in every patient. The American Academy of Neurology (AAN) issued new guidelines in 2010 on the determination of brain death. To evaluate if institutions have adopted the new AAN guidelines on the determination of brain death, leading to policy changes. Fifty-two organ procurement organizations provided US hospital policies pertaining to the criteria for determining brain death. Organizations were instructed to procure protocols specific to brain death (ie, not cardiac death or organ donation procedures). Data analysis was conducted from June 26, 2012, to July 1, 2015. Policies were evaluated for summary statistics across the following 5 categories of data: who is qualified to perform the determination of brain death, what are the necessary prerequisites for testing, details of the clinical examination, details of apnea testing, and details of ancillary testing. We compared these data with the standards in the 2010 AAN update on practice parameters for brain death. A total of 508 unique hospital policies were obtained, representing the majority of hospitals in the United States that would be eligible and equipped to evaluate brain death in a patient. Of these, 492 provided adequate data for analysis. Although improvement with AAN practice parameters was readily apparent, there remained significant variability across all 5 categories of data, such as excluding the absence of hypotension (276 of 491 policies [56.2%]) and hypothermia (181 of 228 policies [79.4%]), specifying all aspects of the clinical examination and apnea testing, and specifying appropriate ancillary tests and how they were to be performed. Of the 492 policies

  5. Estimating direction in brain-behavior interactions: Proactive and reactive brain states in driving.

    Science.gov (United States)

    Garcia, Javier O; Brooks, Justin; Kerick, Scott; Johnson, Tony; Mullen, Tim R; Vettel, Jean M

    2017-04-15

    Conventional neuroimaging analyses have ascribed function to particular brain regions, exploiting the power of the subtraction technique in fMRI and event-related potential analyses in EEG. Moving beyond this convention, many researchers have begun exploring network-based neurodynamics and coordination between brain regions as a function of behavioral parameters or environmental statistics; however, most approaches average evoked activity across the experimental session to study task-dependent networks. Here, we examined on-going oscillatory activity as measured with EEG and use a methodology to estimate directionality in brain-behavior interactions. After source reconstruction, activity within specific frequency bands (delta: 2-3Hz; theta: 4-7Hz; alpha: 8-12Hz; beta: 13-25Hz) in a priori regions of interest was linked to continuous behavioral measurements, and we used a predictive filtering scheme to estimate the asymmetry between brain-to-behavior and behavior-to-brain prediction using a variant of Granger causality. We applied this approach to a simulated driving task and examined directed relationships between brain activity and continuous driving performance (steering behavior or vehicle heading error). Our results indicated that two neuro-behavioral states may be explored with this methodology: a Proactive brain state that actively plans the response to the sensory information and is characterized by delta-beta activity, and a Reactive brain state that processes incoming information and reacts to environmental statistics primarily within the alpha band. Published by Elsevier Inc.

  6. Alteration of brain insulin and leptin signaling promotes energy homeostasis impairment and neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Taouis Mohammed

    2011-09-01

    Full Text Available The central nervous system (CNS controls vital functions, by efficiently coordinating peripheral and central cascades of signals and networks in a coordinated manner. Historically, the brain was considered to be an insulin-insensitive tissue. But, new findings demonstrating that insulin is present in different regions of themammalian brain, in particular the hypothalamus and the hippocampus. Insulin acts through specific receptors and dialogues with numerous peptides, neurotransmitters and adipokines such as leptin. The cross-talk between leptin and insulin signaling pathways at the hypothalamic level is clearly involved in the control of energy homeostasis. Both hormones are anorexigenic through their action on hypothalamic arcuate nucleus by inducing the expression of anorexigenic neuropetides such as POMC (pro-opiomelanocortin, the precursor of aMSH and reducing the expression of orexigenic neuropeptide such as NPY (Neuropeptide Y. Central defect of insulin and leptin signaling predispose to obesity (leptin-resistant state and type-2 diabetes (insulin resistant state. Obesity and type-2 diabetes are associated to deep alterations in energy homeostasis control but also to other alterations of CNS functions as the predisposition to neurodegenerative diseases such as Alzheimer’s disease (AD. AD is a neurodegenerative disorder characterized by distinct hallmarks within the brain. Postmortem observation of AD brains showed the presence of parenchymal plaques due to the accumulation of the amyloid beta (AB peptide and neurofibrillary tangles. These accumulations result from the hyperphosphorylation of tau (a mictrotubule-interacting protein. Both insulin and leptin have been described to modulate tau phosphorylation and therefore in leptin and insulin resistant states may contribute to AD. The concentrations of leptin and insulin cerebrospinal fluid are decreased type2 diabetes and obese patients. In addition, the concentration of insulin in the

  7. Error probability of intracranial brain computer interfaces under non-task elicited brain states.

    Science.gov (United States)

    Torres Valderrama, Aldemar; Paclik, Pavel; Vansteensel, Mariska J; Aarnoutse, Erik J; Ramsey, Nick F

    2012-12-01

    Intracranial brain computer interfaces (BCIs) can be connected to the user's cortex permanently. The interfaces response when fed with non-task elicited brain activity becomes important as design criterion: ideally intracranial BCIs should remain silent. We study their error probability in the form of false alarms. Using electrocorticograms recorded during task and non-task brain states, we compute false alarms, investigate their origin and introduce strategies to reduce them, using signal detection theory, classifier cascading and adaptation concepts. We show that the incessant dynamics of the brain is prone to spontaneously produce signals, the spectral and topographical characteristics of which can resemble those associated with common control tasks, generating brain state classification errors. In addition to hit and bit rates, response of BCIs to non-task brain states constitutes an important measure of BCI performance. Static classification cascading reduces considerably false positives during no-task brain states. False alarms in intracranial BCIs are undesirable and could have dangerous consequences for the users. Designs which effectively incorporate the error correction strategies discussed in this paper, could be more successful when taken from the laboratory or acute care setting and used in the real world. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  8. Resting state brain networks and their implications in neurodegenerative disease

    Science.gov (United States)

    Sohn, William S.; Yoo, Kwangsun; Kim, Jinho; Jeong, Yong

    2012-10-01

    Neurons are the basic units of the brain, and form network by connecting via synapses. So far, there have been limited ways to measure the brain networks. Recently, various imaging modalities are widely used for this purpose. In this paper, brain network mapping using resting state fMRI will be introduced with several applications including neurodegenerative disease such as Alzheimer's disease, frontotemporal lobar degeneration and Parkinson's disease. The resting functional connectivity using intrinsic functional connectivity in mouse is useful since we can take advantage of perturbation or stimulation of certain nodes of the network. The study of brain connectivity will open a new era in understanding of brain and diseases thus will be an essential foundation for future research.

  9. Static and Dynamic Factors Promoting Resilience following Traumatic Brain Injury: A Brief Review.

    Science.gov (United States)

    Holland, Jessica N; Schmidt, Adam T

    2015-01-01

    Traumatic brain injury (TBI) is the greatest contributing cause of death and disability among children and young adults in the United States. The current paper briefly summarizes contemporary literature on factors that can improve outcomes (i.e., promote resilience) for children and adults following TBI. For the purpose of this paper, the authors divided these factors into static or unmodifiable factors (i.e., age, sex, intellectual abilities/education, and preinjury psychiatric history) and dynamic or modifiable factors (i.e., socioeconomic status, family functioning/social support, nutrition, and exercise). Drawing on human and animal studies, the research reviewed indicated that these various factors can improve outcomes in multiple domains of functioning (e.g., cognition, emotion regulation, health and wellness, behavior, etc.) following a TBI. However, many of these factors have not been studied across populations, have been limited to preclinical investigations, have been limited in their scope or follow-up, or have not involved a thorough evaluation of outcomes. Thus, although promising, continued research is vital in the area of factors promoting resilience following TBI in children and adults.

  10. Static and Dynamic Factors Promoting Resilience following Traumatic Brain Injury: A Brief Review

    Directory of Open Access Journals (Sweden)

    Jessica N. Holland

    2015-01-01

    Full Text Available Traumatic brain injury (TBI is the greatest contributing cause of death and disability among children and young adults in the United States. The current paper briefly summarizes contemporary literature on factors that can improve outcomes (i.e., promote resilience for children and adults following TBI. For the purpose of this paper, the authors divided these factors into static or unmodifiable factors (i.e., age, sex, intellectual abilities/education, and preinjury psychiatric history and dynamic or modifiable factors (i.e., socioeconomic status, family functioning/social support, nutrition, and exercise. Drawing on human and animal studies, the research reviewed indicated that these various factors can improve outcomes in multiple domains of functioning (e.g., cognition, emotion regulation, health and wellness, behavior, etc. following a TBI. However, many of these factors have not been studied across populations, have been limited to preclinical investigations, have been limited in their scope or follow-up, or have not involved a thorough evaluation of outcomes. Thus, although promising, continued research is vital in the area of factors promoting resilience following TBI in children and adults.

  11. Health Promoting Schools: A Way Forward for Bayelsa State, Nigeria

    African Journals Online (AJOL)

    This would make the health promoting schools more visible as well as enhancing access to personal health care for the school community. It would also enable the schools to produce a critical mass of healthy youth who would be able to avail their strength and intellect for the development of their states. Keyword: School ...

  12. 76 FR 68067 - United States-Peru Trade Promotion Agreement

    Science.gov (United States)

    2011-11-03

    ... sections of the Parties' economies; promoting transparency and preventing and combating corruption... references to certain goods originating in Peru for which, like goods originating in Canada, Mexico... States by a resident of Canada, Mexico, Singapore, Chile, Morocco, El Salvador, Guatemala, Honduras...

  13. Motor Skill Acquisition Promotes Human Brain Myelin Plasticity

    Directory of Open Access Journals (Sweden)

    Bimal Lakhani

    2016-01-01

    Full Text Available Experience-dependent structural changes are widely evident in gray matter. Using diffusion weighted imaging (DWI, the neuroplastic effect of motor training on white matter in the brain has been demonstrated. However, in humans it is not known whether specific features of white matter relate to motor skill acquisition or if these structural changes are associated to functional network connectivity. Myelin can be objectively quantified in vivo and used to index specific experience-dependent change. In the current study, seventeen healthy young adults completed ten sessions of visuomotor skill training (10,000 total movements using the right arm. Multicomponent relaxation imaging was performed before and after training. Significant increases in myelin water fraction, a quantitative measure of myelin, were observed in task dependent brain regions (left intraparietal sulcus [IPS] and left parieto-occipital sulcus. In addition, the rate of motor skill acquisition and overall change in myelin water fraction in the left IPS were negatively related, suggesting that a slower rate of learning resulted in greater neuroplastic change. This study provides the first evidence for experience-dependent changes in myelin that are associated with changes in skilled movements in healthy young adults.

  14. Assessing state-level active living promotion using network analysis.

    Science.gov (United States)

    Buchthal, Opal Vanessa; Taniguchi, Nicole; Iskandar, Livia; Maddock, Jay

    2013-01-01

    Physical inactivity is a growing problem in the United States, one that is being addressed through the development of active living communities. However, active living promotion requires collaboration among organizations that may not have previously shared goals. A network analysis was conducted to assess Hawaii's active living promotion network. Twenty-six organizations playing a significant role in promoting active living in Hawaii were identified and surveyed about their frequency of contact, level of collaboration, and funding flow with other agencies. A communication network was identified linking all agencies. This network had many long pathways, impeding information flow. The Department of Health (DOH) and the State Nutrition and Physical Activity Coalition (NPAC) were central nodes, but DOH connected state agencies while NPAC linked county and voluntary organizations. Within the network, information sharing was common, but collaboration and formal partnership were low. Linkages between county and state agencies, between counties, and between state agencies with different core agendas were particularly low. Results suggest that in the early stages of development, active living networks may be divided by geography and core missions, requiring work to bridge these divides. Network mapping appears helpful in identifying areas for network development.

  15. P1 interneurons promote a persistent internal state that enhances inter-male aggression in Drosophila

    Science.gov (United States)

    Hoopfer, Eric D; Jung, Yonil; Inagaki, Hidehiko K; Rubin, Gerald M; Anderson, David J

    2015-01-01

    How brains are hardwired to produce aggressive behavior, and how aggression circuits are related to those that mediate courtship, is not well understood. A large-scale screen for aggression-promoting neurons in Drosophila identified several independent hits that enhanced both inter-male aggression and courtship. Genetic intersections revealed that 8-10 P1 interneurons, previously thought to exclusively control male courtship, were sufficient to promote fighting. Optogenetic experiments indicated that P1 activation could promote aggression at a threshold below that required for wing extension. P1 activation in the absence of wing extension triggered persistent aggression via an internal state that could endure for minutes. High-frequency P1 activation promoted wing extension and suppressed aggression during photostimulation, whereas aggression resumed and wing extension was inhibited following photostimulation offset. Thus, P1 neuron activation promotes a latent, internal state that facilitates aggression and courtship, and controls the overt expression of these social behaviors in a threshold-dependent, inverse manner. DOI: http://dx.doi.org/10.7554/eLife.11346.001 PMID:26714106

  16. Prompt recognition of brain states by their EEG signals

    DEFF Research Database (Denmark)

    Peters, B.O.; Pfurtscheller, G.; Flyvbjerg, H.

    1997-01-01

    Brain states corresponding to intention of movement of left and right index finger and right foot are classified by a ''committee'' of artificial neural networks processing individual channels of 56-electrode electroencephalograms (EEGs). Correct recognition is achieved in 83% of cases not previo......Brain states corresponding to intention of movement of left and right index finger and right foot are classified by a ''committee'' of artificial neural networks processing individual channels of 56-electrode electroencephalograms (EEGs). Correct recognition is achieved in 83% of cases...... not previously seen by the system on the basis of 1 sec long EEGs....

  17. Resting-state brain organization revealed by functional covariance networks.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Zhang

    Full Text Available BACKGROUND: Brain network studies using techniques of intrinsic connectivity network based on fMRI time series (TS-ICN and structural covariance network (SCN have mapped out functional and structural organization of human brain at respective time scales. However, there lacks a meso-time-scale network to bridge the ICN and SCN and get insights of brain functional organization. METHODOLOGY AND PRINCIPAL FINDINGS: We proposed a functional covariance network (FCN method by measuring the covariance of amplitude of low-frequency fluctuations (ALFF in BOLD signals across subjects, and compared the patterns of ALFF-FCNs with the TS-ICNs and SCNs by mapping the brain networks of default network, task-positive network and sensory networks. We demonstrated large overlap among FCNs, ICNs and SCNs and modular nature in FCNs and ICNs by using conjunctional analysis. Most interestingly, FCN analysis showed a network dichotomy consisting of anti-correlated high-level cognitive system and low-level perceptive system, which is a novel finding different from the ICN dichotomy consisting of the default-mode network and the task-positive network. CONCLUSION: The current study proposed an ALFF-FCN approach to measure the interregional correlation of brain activity responding to short periods of state, and revealed novel organization patterns of resting-state brain activity from an intermediate time scale.

  18. An Overview of State Policies Supporting Worksite Health Promotion Programs.

    Science.gov (United States)

    VanderVeur, Jennifer; Gilchrist, Siobhan; Matson-Koffman, Dyann

    2017-05-01

    Worksite health promotion (WHP) programs can reduce the occurrence of cardiovascular disease risk factors. State law can encourage employers and employer-provided insurance companies to offer comprehensive WHP programs. This research examines state law authorizing WHP programs. Quantitative content analysis. Worksites or workplaces. United States (and the District of Columbia). State law in effect in 2013 authorizing WHP programs. Frequency and distribution of states with WHP laws. To determine the content of the laws for analysis and coding, we identified 18 policy elements, 12 from the Centers for Disease Control and Prevention's Worksite Health ScoreCard (HSC) and 6 additional supportive WHP strategies. We used these strategies as key words to search for laws authorizing WHP programs or select WHP elements. We calculated the number and type of WHP elements for each state with WHP laws and selected two case examples from states with comprehensive WHP laws. Twenty-four states authorized onsite WHP programs, 29 authorized WHP through employer-provided insurance plans, and 18 authorized both. Seven states had a comprehensive WHP strategy, addressing 8 or more of 12 HSC elements. The most common HSC elements were weight management, tobacco cessation, and physical activity. Most states had laws encouraging the adoption of WHP programs. Massachusetts and Maine are implementing comprehensive WHP laws but studies evaluating their health impact are needed.

  19. Restoring Responsibility : Promoting Justice, Therapy and Reform Through Direct Brain Interventions

    NARCIS (Netherlands)

    Vincent, N.A.

    Direct brain intervention based mental capacity restoration techniques—for instance, psycho-active drugs—are sometimes used in criminal cases to promote the aims of justice. For instance, they might be used to restore a person’s competence to stand trial in order to assess the degree of their

  20. [State dependent modification of auditory brain stem potentials].

    Science.gov (United States)

    Maier, R; Rebentisch, E

    1984-11-01

    It is well known, amplitudes and latencies of auditory brain stem potentials are almost independent of viligance state. Contrary to that, simple cognitive requirements effect amplitude changes (enhancement of variance, amplitude reduction) in a part 2/3) of the subjects.

  1. Brain imaging of pain: state of the art

    Directory of Open Access Journals (Sweden)

    Morton DL

    2016-09-01

    Full Text Available Debbie L Morton, Javin S Sandhu, Anthony KP Jones Human Pain Research Group, Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK Abstract: Pain is a complex sensory and emotional experience that is heavily influenced by prior experience and expectations of pain. Before the development of noninvasive human brain imaging, our grasp of the brain’s role in pain processing was limited to data from postmortem studies, direct recording of brain activity, patient experience and stimulation during neurosurgical procedures, and animal models of pain. Advances made in neuroimaging have bridged the gap between brain activity and the subjective experience of pain and allowed us to better understand the changes in the brain that are associated with both acute and chronic pain. Additionally, cognitive influences on pain such as attention, anticipation, and fear can now be directly observed, allowing for the interpretation of the neural basis of the psychological modulation of pain. The use of functional brain imaging to measure changes in endogenous neurochemistry has increased our understanding of how states of increased resilience and vulnerability to pain are maintained. Keywords: fMRI, PET, EEG, arthritis, fibromyalgia

  2. Computing the Social Brain Connectome Across Systems and States.

    Science.gov (United States)

    Alcalá-López, Daniel; Smallwood, Jonathan; Jefferies, Elizabeth; Van Overwalle, Frank; Vogeley, Kai; Mars, Rogier B; Turetsky, Bruce I; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B; Bzdok, Danilo

    2017-05-18

    Social skills probably emerge from the interaction between different neural processing levels. However, social neuroscience is fragmented into highly specialized, rarely cross-referenced topics. The present study attempts a systematic reconciliation by deriving a social brain definition from neural activity meta-analyses on social-cognitive capacities. The social brain was characterized by meta-analytic connectivity modeling evaluating coactivation in task-focused brain states and physiological fluctuations evaluating correlations in task-free brain states. Network clustering proposed a functional segregation into (1) lower sensory, (2) limbic, (3) intermediate, and (4) high associative neural circuits that together mediate various social phenomena. Functional profiling suggested that no brain region or network is exclusively devoted to social processes. Finally, nodes of the putative mirror-neuron system were coherently cross-connected during tasks and more tightly coupled to embodied simulation systems rather than abstract emulation systems. These first steps may help reintegrate the specialized research agendas in the social and affective sciences. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    Fuqing Zhou

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

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

    Science.gov (United States)

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

    2016-01-01

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

  5. Stop state classification in intracortical brain-machine-interface.

    Science.gov (United States)

    Tze Hui Koh; Libedinsky, Camilo; Cuntai Guan; Kai Keng Ang; So, Rosa Q

    2017-07-01

    Invasive brain-machine-interface (BMI) has the prospect to empower tetraplegic patients with independent mobility through the use of brain-controlled wheelchairs. For the practical and long-term use of such control systems, the system has to distinguish between stop and movement states and has to be robust to overcome non-stationarity in the brain signals. In this work, we investigates the non-stationarity of the stop state on neural data collected from a macaque trained to control a robotic platform to stop and move in left, right, forward directions We then propose a hybrid approach that employs both random forest and linear discriminant analysis (LDA). Using this approach, we performed offline decoding on 8 days of data collected over the course of three months during joystick control of the robotic platform. We compared the results of using the proposed approach with the use of LDA alone to perform direct classifications of stop, left, right and forward. The results showed an average performance increment of 22.7% using the proposed hybrid approach. The results yielded significant improvements during sessions where LDA showed a heavy bias towards the stop state. This suggests that the proposed hybrid approach addresses the non-stationarity in the stop state and subsequently facilitates a more accurate decoding of the movement states.

  6. Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimers Disease

    Science.gov (United States)

    2015-12-01

    Alricsson M (2012) Physical exercise ameliorates deficits induced by traumatic brain injury. Acta Neurol Scand 125, 293-302. [19] Qu C, Mahmood A...AWARD NUMBER: W81XWH-12-1-0582 TITLE: Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer’s...COVERED 09/25/2012-09/24/2015 4. TITLE AND SUBTITLE Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for

  7. Brain communication in the locked-in state.

    Science.gov (United States)

    De Massari, Daniele; Ruf, Carolin A; Furdea, Adrian; Matuz, Tamara; van der Heiden, Linda; Halder, Sebastian; Silvoni, Stefano; Birbaumer, Niels

    2013-06-01

    Patients in the completely locked-in state have no means of communication and they represent the target population for brain-computer interface research in the last 15 years. Although different paradigms have been tested and different physiological signals used, to date no sufficiently documented completely locked-in state patient was able to control a brain-computer interface over an extended time period. We introduce Pavlovian semantic conditioning to enable basic communication in completely locked-in state. This novel paradigm is based on semantic conditioning for online classification of neuroelectric or any other physiological signals to discriminate between covert (cognitive) 'yes' and 'no' responses. The paradigm comprised the presentation of affirmative and negative statements used as conditioned stimuli, while the unconditioned stimulus consisted of electrical stimulation of the skin paired with affirmative statements. Three patients with advanced amyotrophic lateral sclerosis participated over an extended time period, one of which was in a completely locked-in state, the other two in the locked-in state. The patients' level of vigilance was assessed through auditory oddball procedures to study the correlation between vigilance level and the classifier's performance. The average online classification accuracies of slow cortical components of electroencephalographic signals were around chance level for all the patients. The use of a non-linear classifier in the offline classification procedure resulted in a substantial improvement of the accuracy in one locked-in state patient achieving 70% correct classification. A reliable level of performance in the completely locked-in state patient was not achieved uniformly throughout the 37 sessions despite intact cognitive processing capacity, but in some sessions communication accuracies up to 70% were achieved. Paradigm modifications are proposed. Rapid drop of vigilance was detected suggesting attentional

  8. Promoting brain health through exercise and diet in older adults: a physiological perspective.

    Science.gov (United States)

    Jackson, Philippa A; Pialoux, Vincent; Corbett, Dale; Drogos, Lauren; Erickson, Kirk I; Eskes, Gail A; Poulin, Marc J

    2016-08-15

    The rise in incidence of age-related cognitive impairment is a global health concern. Ageing is associated with a number of changes in the brain that, collectively, contribute to the declines in cognitive function observed in older adults. Structurally, the ageing brain atrophies as white and grey matter volumes decrease. Oxidative stress and inflammation promote endothelial dysfunction thereby hampering cerebral perfusion and thus delivery of energy substrates and nutrients. Further, the development of amyloid plaques and neurofibrillary tangles contributes to neuronal loss. Of interest, there are substantial inter-individual differences in the degree to which these physical and functional changes impact upon cognitive function as we grow older. This review describes how engaging in physical activity and cognitive activities and adhering to a Mediterranean style diet promote 'brain health'. From a physiological perspective, we discuss the effects of these modifiable lifestyle behaviours on the brain, and how some recent human trials are beginning to show some promise as to the effectiveness of lifestyle behaviours in combating cognitive impairment. Moreover, we propose that these lifestyle behaviours, through numerous mechanisms, serve to increase brain, cerebrovascular and cognitive reserve, thereby preserving and enhancing cognitive function for longer. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

  9. Cognitive brain responses during circadian wake-promotion: evidence for sleep-pressure-dependent hypothalamic activations.

    Science.gov (United States)

    Reichert, Carolin F; Maire, Micheline; Gabel, Virginie; Viola, Antoine U; Götz, Thomas; Scheffler, Klaus; Klarhöfer, Markus; Berthomier, Christian; Strobel, Werner; Phillips, Christophe; Salmon, Eric; Cajochen, Christian; Schmidt, Christina

    2017-07-17

    The two-process model of sleep-wake regulation posits that sleep-wake-dependent homeostatic processes interact with the circadian timing system to affect human behavior. The circadian timing system is fundamental to maintaining stable cognitive performance, as it counteracts growing homeostatic sleep pressure during daytime. Using magnetic resonance imaging, we explored brain responses underlying working memory performance during the time of maximal circadian wake-promotion under varying sleep pressure conditions. Circadian wake-promoting strength was derived from the ability to sleep during an evening nap. Hypothalamic BOLD activity was positively linked to circadian wake-promoting strength under normal, but not under disproportionally high or low sleep pressure levels. Furthermore, higher hypothalamic activity under normal sleep pressure levels predicted better performance under sleep loss. Our results reappraise the two-process model by revealing a homeostatic-dose-dependent association between circadian wake-promotion and cognition-related hypothalamic activity.

  10. MGMT promoter methylation status in brain metastases from colorectal cancer and corresponding primary tumors.

    Science.gov (United States)

    De Maglio, Giovanna; Casagrande, Mariaelena; Guardascione, Michela; Fontanella, Caterina; Lutrino, Stefania Eufemia; Rihawi, Karim; Pisa, Federica Edith; Tuniz, Francesco; Fasola, Gianpiero; Pizzolitto, Stefano; Aprile, Giuseppe

    2015-01-01

    Brain metastases (BM) from colorectal cancer are usually associated with poor prognosis. The aim of this retrospective study is to evaluate MGMT promoter methylation in BM and their corresponding primary colorectal cancer tumors. MGMT promoter methylation status was assessed by pyrosequencing in 53 consecutive patients resected for BM. A concordance analysis between BM and matched primary tumor was performed in 39 cases. MGMT methylation was found in 34 (64.2%) BM and in 25 corresponding primary tumors (64.1%). Median survival after neurosurgery was independent from MGMT promoter methylation (163 days for those with methylated MGMT versus 193 days for the unmethylated). Epigenetic MGMT promoter methylation was common and the concordance between primary and secondary lesions was high.

  11. Do state breastfeeding laws in the US promote breastfeeding?

    Science.gov (United States)

    Hawkins, Summer Sherburne; Stern, Ariel Dora; Gillman, Matthew W.

    2012-01-01

    Objectives Despite the passage of state laws promoting breastfeeding, a formal evaluation has not yet been conducted to test whether and/or what type of laws may increase breastfeeding. The enactment of breastfeeding laws in different states in the US creates a natural experiment. We examined the impact of state breastfeeding laws on breastfeeding initiation and duration as well as on disparities in these infant feeding practices. Methods Using data from the Pregnancy Risk Assessment Monitoring System, we conducted differences-in-differences models to examine breastfeeding status before and after the institution of laws between 2000 and 2008 among 326,263 mothers from 32 states in the US. For each mother we coded the presence of two types of state breastfeeding laws. Mothers reported whether they ever breastfed or pumped breast milk (breastfeeding initiation) and if so, how long they continued. We defined breastfeeding duration as continuing to breastfeed for ≥4 weeks. Results Breastfeeding initiation was 1.7 percentage points higher in states with new laws to provide break time and private space for breastfeeding employees (p=0.01), particularly among Hispanic mothers (adjusted coefficient 0.058). While there was no overall effect of laws permitting mothers to breastfeed in any location, among Black mothers we observed increases in breastfeeding initiation (adjusted coefficient 0.056). Effects on breastfeeding duration were in the same direction, but slightly weaker. Conclusions State laws that support breastfeeding appear to increase breastfeeding rates. Most of these gains were observed among Hispanic and Black women and women of lower educational attainment suggesting that such state laws may help reduce disparities in breastfeeding. PMID:23087383

  12. Do state breastfeeding laws in the USA promote breast feeding?

    Science.gov (United States)

    Hawkins, Summer Sherburne; Stern, Ariel Dora; Gillman, Matthew W

    2013-03-01

    Despite the passage of state laws promoting breast feeding, a formal evaluation has not yet been conducted to test whether and/or what type of laws may increase breast feeding. The enactment of breastfeeding laws in different states in the USA creates a natural experiment. We examined the impact of state breastfeeding laws on breastfeeding initiation and duration as well as on disparities in these infant feeding practices. Using data from the Pregnancy Risk Assessment Monitoring System, we conducted differences-in-differences models to examine breastfeeding status before and after the institution of laws between 2000 and 2008 among 326 263 mothers from 32 states in the USA. For each mother, we coded the presence of two types of state breastfeeding laws. Mothers reported whether they ever breast fed or pumped breast milk (breastfeeding initiation) and, if so, how long they continued. We defined breastfeeding duration as continuing to breast feed for ≥4 weeks. Breastfeeding initiation was 1.7 percentage points higher in states with new laws to provide break time and private space for breastfeeding employees (p=0.01), particularly among Hispanic mothers (adjusted coefficient 0.058). While there was no overall effect of laws permitting mothers to breast feed in any location, among Black mothers we observed increases in breastfeeding initiation (adjusted coefficient 0.056). Effects on breastfeeding duration were in the same direction, but slightly weaker. State laws that support breast feeding appear to increase breastfeeding rates. Most of these gains were observed among Hispanic and Black women and women of lower educational attainment suggesting that such state laws may help reduce disparities in breast feeding.

  13. A Plastic Temporal Brain Code for Conscious State Generation

    Directory of Open Access Journals (Sweden)

    Birgitta Dresp-Langley

    2009-01-01

    Full Text Available Consciousness is known to be limited in processing capacity and often described in terms of a unique processing stream across a single dimension: time. In this paper, we discuss a purely temporal pattern code, functionally decoupled from spatial signals, for conscious state generation in the brain. Arguments in favour of such a code include Dehaene et al.'s long-distance reverberation postulate, Ramachandran's remapping hypothesis, evidence for a temporal coherence index and coincidence detectors, and Grossberg's Adaptive Resonance Theory. A time-bin resonance model is developed, where temporal signatures of conscious states are generated on the basis of signal reverberation across large distances in highly plastic neural circuits. The temporal signatures are delivered by neural activity patterns which, beyond a certain statistical threshold, activate, maintain, and terminate a conscious brain state like a bar code would activate, maintain, or inactivate the electronic locks of a safe. Such temporal resonance would reflect a higher level of neural processing, independent from sensorial or perceptual brain mechanisms.

  14. Energy landscapes of resting-state brain networks

    Directory of Open Access Journals (Sweden)

    Takamitsu eWatanabe

    2014-02-01

    Full Text Available During rest, the human brain performs essential functions such as memory maintenance, which are associated with resting-state brain networks (RSNs including the default-mode network (DMN and frontoparietal network (FPN. Previous studies based on spiking-neuron network models and their reduced models, as well as those based on imaging data, suggest that resting-state network activity can be captured as attractor dynamics, i.e., dynamics of the brain state toward an attractive state and transitions between different attractors. Here, we analyze the energy landscapes of the RSNs by applying the maximum entropy model, or equivalently the Ising spin model, to human RSN data. We use the previously estimated parameter values to define the energy landscape, and the disconnectivity graph method to estimate the number of local energy minima (equivalent to attractors in attractor dynamics, the basin size, and hierarchical relationships among the different local minima. In both of the DMN and FPN, low-energy local minima tended to have large basins. A majority of the network states belonged to a basin of one of a few local minima. Therefore, a small number of local minima constituted the backbone of each RSN. In the DMN, the energy landscape consisted of two groups of low-energy local minima that are separated by a relatively high energy barrier. Within each group, the activity patterns of the local minima were similar, and different minima were connected by relatively low energy barriers. In the FPN, all dominant energy were separated by relatively low energy barriers such that they formed a single coarse-grained global minimum. Our results indicate that multistable attractor dynamics may underlie the DMN, but not the FPN, and assist memory maintenance with different memory states.

  15. Modulatory interactions of resting-state brain functional connectivity.

    Directory of Open Access Journals (Sweden)

    Xin Di

    Full Text Available The functional brain connectivity studies are generally based on the synchronization of the resting-state functional magnetic resonance imaging (fMRI signals. Functional connectivity measures usually assume a stable relationship over time; however, accumulating studies have reported time-varying properties of strength and spatial distribution of functional connectivity. The present study explored the modulation of functional connectivity between two regions by a third region using the physiophysiological interaction (PPI technique. We first identified eight brain networks and two regions of interest (ROIs representing each of the networks using a spatial independent component analysis. A voxel-wise analysis was conducted to identify regions that showed modulatory interactions (PPI with the two ROIs of each network. Mostly, positive modulatory interactions were observed within regions involved in the same system. For example, the two regions of the dorsal attention network revealed modulatory interactions with the regions related to attention, while the two regions of the extrastriate network revealed modulatory interactions with the regions in the visual cortex. In contrast, the two regions of the default mode network (DMN revealed negative modulatory interactions with the regions in the executive network, and vice versa, suggesting that the activities of one network may be associated with smaller within network connectivity of the competing network. These results validate the use of PPI analysis to study modulation of resting-state functional connectivity by a third region. The modulatory effects may provide a better understanding of complex brain functions.

  16. Brain state dependent activity in the cortex and thalamus.

    Science.gov (United States)

    McCormick, David A; McGinley, Matthew J; Salkoff, David B

    2015-04-01

    Cortical and thalamocortical activity is highly state dependent, varying between patterns that are conducive to accurate sensory-motor processing, to states in which the brain is largely off-line and generating internal rhythms irrespective of the outside world. The generation of rhythmic activity occurs through the interaction of stereotyped patterns of connectivity together with intrinsic membrane and synaptic properties. One common theme in the generation of rhythms is the interaction of a positive feedback loop (e.g., recurrent excitation) with negative feedback control (e.g., inhibition, adaptation, or synaptic depression). The operation of these state-dependent activities has wide ranging effects from enhancing or blocking sensory-motor processing to the generation of pathological rhythms associated with psychiatric or neurological disorders. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. ABERRANT SPLICING OF A BRAIN-ENRICHED ALTERNATIVE EXON ELIMINATES TUMOR SUPPRESSOR FUNCTION AND PROMOTES ONCOGENE FUNCTION DURING BRAIN TUMORIGENESIS

    Science.gov (United States)

    Bredel, Markus; Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; Elverfeldt, Dominik v.; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.

    2014-01-01

    BACKGROUND: Tissue-specific alternative splicing is known to be critical to emergence of tissue identity during development, yet its role in malignant transformation is undefined. Tissue-specific splicing involves evolutionary-conserved, alternative exons, which represent only a minority of total alternative exons. Many, however, have functional features that influence activity in signaling pathways to profound biological effect. Given that tissue-specific splicing has a determinative role in brain development and the enrichment of genes containing tissue-specific exons for proteins with roles in signaling and development, it is thus plausible that changes in such exons could rewire normal neurogenesis towards malignant transformation. METHODS: We used integrated molecular genetic and cell biology analyses, computational biology, animal modeling, and clinical patient profiles to characterize the effect of aberrant splicing of a brain-enriched alternative exon in the membrane-binding tumor suppressor Annexin A7 (ANXA7) on oncogene regulation and brain tumorigenesis. RESULTS: We show that aberrant splicing of a tissue-specific cassette exon in ANXA7 diminishes endosomal targeting and consequent termination of the signal of the EGFR oncoprotein during brain tumorigenesis. Splicing of this exon is mediated by the ribonucleoprotein Polypyrimidine Tract-Binding Protein 1 (PTBP1), which is normally repressed during brain development but, we find, is excessively expressed in glioblastomas through either gene amplification or loss of a neuron-specific microRNA, miR-124. Silencing of PTBP1 attenuates both malignancy and angiogenesis in a stem cell-derived glioblastoma animal model characterized by a high native propensity to generate tumor endothelium or vascular pericytes to support tumor growth. We show that EGFR amplification and PTBP1 overexpression portend a similarly poor clinical outcome, further highlighting the importance of PTBP1-mediated activation of EGFR

  18. Ancestral Circuits for the Coordinated Modulation of Brain State.

    Science.gov (United States)

    Lovett-Barron, Matthew; Andalman, Aaron S; Allen, William E; Vesuna, Sam; Kauvar, Isaac; Burns, Vanessa M; Deisseroth, Karl

    2017-11-30

    Internal states of the brain profoundly influence behavior. Fluctuating states such as alertness can be governed by neuromodulation, but the underlying mechanisms and cell types involved are not fully understood. We developed a method to globally screen for cell types involved in behavior by integrating brain-wide activity imaging with high-content molecular phenotyping and volume registration at cellular resolution. We used this method (MultiMAP) to record from 22 neuromodulatory cell types in behaving zebrafish during a reaction-time task that reports alertness. We identified multiple monoaminergic, cholinergic, and peptidergic cell types linked to alertness and found that activity in these cell types was mutually correlated during heightened alertness. We next recorded from and controlled homologous neuromodulatory cells in mice; alertness-related cell-type dynamics exhibited striking evolutionary conservation and modulated behavior similarly. These experiments establish a method for unbiased discovery of cellular elements underlying behavior and reveal an evolutionarily conserved set of diverse neuromodulatory systems that collectively govern internal state. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Integrating Health Promotion Into Physical Therapy Practice to Improve Brain Health and Prevent Alzheimer Disease.

    Science.gov (United States)

    McGough, Ellen; Kirk-Sanchez, Neva; Liu-Ambrose, Teresa

    2017-07-01

    Alzheimer disease is the most common cause of dementia, and brain pathology appears years before symptoms are evident. Primary prevention through health promotion can incorporate lifestyle improvement across the lifespan. Risk factor assessment and identifying markers of disease might also trigger preventive measures needed for high-risk individuals and groups. Many potential risk factors are modifiable through exercise, and may be responsive to early intervention strategies to reduce the downward slope toward disability. Through the use of common clinical tests to identify cognitive and noncognitive functional markers of disease, detection and intervention can occur at earlier stages, including preclinical stages of disease. Physical activity and exercise interventions to address modifiable risk factors and impairments can play a pivotal role in the prevention and delay of functional decline, ultimately reducing the incidence of dementia. This article discusses prevention, prediction, plasticity, and participation in the context of preserving brain health and preventing Alzheimer disease and related dementias in aging adults. Rehabilitation professionals have opportunities to slow disease progression through research, practice, and education initiatives. From a clinical perspective, interventions that target brain health through lifestyle changes and exercise interventions show promise for preventing stroke and associated neurovascular diseases in addition to dementia. Physical therapists are well positioned to integrate primary health promotion into practice for the prevention of dementia and other neurological conditions in older adults.

  20. Activated and deactivated functional brain areas in the Deqi state

    OpenAIRE

    Huang, Yong; Zeng, Tongjun; Zhang, Guifeng; Li, Ganlong; Lu, Na; Lai, Xinsheng; Lu, Yangjia; Chen, Jiarong

    2012-01-01

    We compared the activities of functional regions of the brain in the Deqi versus non-Deqi state, as reported by physicians and subjects during acupuncture. Twelve healthy volunteers received sham and true needling at the Waiguan (TE5) acupoint. Real-time cerebral functional MRI showed that compared with non-sensation after sham needling, true needling activated Brodmann areas 3, 6, 8, 9, 10, 11, 13, 20, 21, 37, 39, 40, 43, and 47, the head of the caudate nucleus, the parahippocampal gyrus, th...

  1. Brain-derived neurotrophic factor promoter methylation and cortical thickness in recurrent major depressive disorder.

    Science.gov (United States)

    Na, Kyoung-Sae; Won, Eunsoo; Kang, June; Chang, Hun Soo; Yoon, Ho-Kyoung; Tae, Woo Suk; Kim, Yong-Ku; Lee, Min-Soo; Joe, Sook-Haeng; Kim, Hyun; Ham, Byung-Joo

    2016-02-15

    Recent studies have reported that methylation of the brain-derived neurotrophic factor (BDNF) gene promoter is associated with major depressive disorder (MDD). This study aimed to investigate the association between cortical thickness and methylation of BDNF promoters as well as serum BDNF levels in MDD. The participants consisted of 65 patients with recurrent MDD and 65 age- and gender-matched healthy controls. Methylation of BDNF promoters and cortical thickness were compared between the groups. The right medial orbitofrontal, right lingual, right lateral occipital, left lateral orbitofrontal, left pars triangularis, and left lingual cortices were thinner in patients with MDD than in healthy controls. Among the MDD group, right pericalcarine, right medical orbitofrontal, right rostral middle frontal, right postcentral, right inferior temporal, right cuneus, right precuneus, left frontal pole, left superior frontal, left superior temporal, left rostral middle frontal and left lingual cortices had inverse correlations with methylation of BDNF promoters. Higher levels of BDNF promoter methylation may be closely associated with the reduced cortical thickness among patients with MDD. Serum BDNF levels were significantly lower in MDD, and showed an inverse relationship with BDNF methylation only in healthy controls. Particularly the prefrontal and occipital cortices seem to indicate key regions in which BDNF methylation has a significant effect on structure.

  2. Regional differences in gene expression and promoter usage in aged human brains

    KAUST Repository

    Pardo, Luba M.

    2013-02-19

    To characterize the promoterome of caudate and putamen regions (striatum), frontal and temporal cortices, and hippocampi from aged human brains, we used high-throughput cap analysis of gene expression to profile the transcription start sites and to quantify the differences in gene expression across the 5 brain regions. We also analyzed the extent to which methylation influenced the observed expression profiles. We sequenced more than 71 million cap analysis of gene expression tags corresponding to 70,202 promoter regions and 16,888 genes. More than 7000 transcripts were differentially expressed, mainly because of differential alternative promoter usage. Unexpectedly, 7% of differentially expressed genes were neurodevelopmental transcription factors. Functional pathway analysis on the differentially expressed genes revealed an overrepresentation of several signaling pathways (e.g., fibroblast growth factor and wnt signaling) in hippocampus and striatum. We also found that although 73% of methylation signals mapped within genes, the influence of methylation on the expression profile was small. Our study underscores alternative promoter usage as an important mechanism for determining the regional differences in gene expression at old age.

  3. GM-CSF is not essential for experimental autoimmune encephalomyelitis but promotes brain-targeted disease.

    Science.gov (United States)

    Pierson, Emily R; Goverman, Joan M

    2017-04-06

    Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of multiple sclerosis to identify pathogenic cytokines that could be therapeutic targets. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is the only cytokine reported to be essential for EAE. We investigated the role of GM-CSF in EAE in C3HeB/FeJ mice that uniquely exhibit extensive brain and spinal cord inflammation. Unexpectedly, GM-CSF-deficient C3HeB/FeJ mice were fully susceptible to EAE because IL-17 activity compensated for the loss of GM-CSF during induction of spinal cord-targeted disease. In contrast, both GM-CSF and IL-17 were needed to fully overcome the inhibitory influence of IFN-γ on the induction of inflammation in the brain. Both GM-CSF and IL-17 independently promoted neutrophil accumulation in the brain, which was essential for brain-targeted disease. These results identify a GM-CSF/IL-17/IFN-γ axis that regulates inflammation in the central nervous system and suggest that a combination of cytokine-neutralizing therapies may be needed to dampen central nervous system autoimmunity.

  4. The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study

    NARCIS (Netherlands)

    Bosma, I.; Stam, C. J.; Douw, L.; Bartolomei, F.; Heimans, J. J.; van Dijk, B. W.; Postma, T. J.; Klein, M.; Reijneveld, J. C.

    2008-01-01

    In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity

  5. The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study

    NARCIS (Netherlands)

    Bosma, I.; Stam, C.; Douw, L.; Bartolomei, F.; Heimans, J.; Dijk, van B.; Postma, T.; Klein, M.; Reijneveld, J.

    2008-01-01

    Purpose: In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain

  6. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia

    Science.gov (United States)

    Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

    2012-01-01

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia. PMID:25337108

  7. Constraint-induced movement therapy promotes brain functional reorganization in stroke patients with hemiplegia.

    Science.gov (United States)

    Wang, Wenqing; Wang, Aihui; Yu, Limin; Han, Xuesong; Jiang, Guiyun; Weng, Changshui; Zhang, Hongwei; Zhou, Zhiqiang

    2012-11-15

    Stroke patients with hemiplegia exhibit flexor spasms in the upper limb and extensor spasms in the lower limb, and their movement patterns vary greatly. Constraint-induced movement therapy is an upper limb rehabilitation technique used in stroke patients with hemiplegia; however, studies of lower extremity rehabilitation are scarce. In this study, stroke patients with lower limb hemiplegia underwent conventional Bobath therapy for 4 weeks as baseline treatment, followed by constraint-induced movement therapy for an additional 4 weeks. The 10-m maximum walking speed and Berg balance scale scores significantly improved following treatment, and lower extremity motor function also improved. The results of functional MRI showed that constraint-induced movement therapy alleviates the reduction in cerebral functional activation in patients, which indicates activation of functional brain regions and a significant increase in cerebral blood perfusion. These results demonstrate that constraint-induced movement therapy promotes brain functional reorganization in stroke patients with lower limb hemiplegia.

  8. Resting-State Functional Connectivity in the Infant Brain: Methods, Pitfalls, and Potentiality

    Directory of Open Access Journals (Sweden)

    Chandler R. L. Mongerson

    2017-08-01

    Full Text Available Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Postnatal brain plasticity is associated with increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Resting-state functional magnetic resonance imaging (rs-fMRI has emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD signal at rest that reflect baseline neuronal activity. Over the past decade, its application has expanded to infant populations providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal states. However, many methodological issues of rs-fMRI analysis need to be resolved prior to standardization of the technique to infant populations. As a primary goal, this methodological manuscript will (1 present a robust methodological protocol to extract and assess resting-state networks in early infancy using independent component analysis (ICA, such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature; (2 review the current methodological challenges and ethical considerations associated with emerging field of infant rs-fMRI analysis; and (3 discuss the significance of rs-fMRI application in infants for future investigations of neurodevelopment in the context of early life stressors and pathological processes. The overarching goal is to catalyze efforts toward development of robust, infant-specific acquisition, and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used.

  9. Acute Effects of Modafinil on Brain Resting State Networks in Young Healthy Subjects

    Science.gov (United States)

    Pieramico, Valentina; Ferretti, Antonio; Macchia, Antonella; Tommasi, Marco; Saggino, Aristide; Ciavardelli, Domenico; Manna, Antonietta; Navarra, Riccardo; Cieri, Filippo; Stuppia, Liborio; Tartaro, Armando; Sensi, Stefano L.

    2013-01-01

    Background There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects. Methodology A single dose (100 mg) of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven’s Advanced Progressive Matrices II set (APM) before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI) was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI) was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306. Principal Findings Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; pmodafinil has cognitive enhancing properties and provide functional connectivity data to support these effects. Trial Registration ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306. PMID:23935959

  10. Promoting social plasticity in developmental disorders with non invasive brain stimulation techniques

    Directory of Open Access Journals (Sweden)

    Paulo Sérgio Boggio

    2015-09-01

    Full Text Available Being socially connected directly impacts our basic needs and survival. People with deficits in social cognition might exhibit abnormal behaviors and face many challenges in our highly social-dependent world. These challenges and limitations are associated with a substantial economical and subjective impact. As many conditions where social cognition is affected are highly prevalent, more treatments have to be developed. Based on recent research, we review studies where noninvasive neuromodulatory techniques have been used to promote Social Plasticity in developmental disorders. We focused on three populations where non-invasive brain stimulation seems to be a promising approach in inducing social plasticity: Schizophrenia, Autism Spectrum Disorder (ASD and Williams Syndrome (WS. There are still very few studies directly evaluating the effects of transcranial direct current stimulation (tDCS and transcranial magnetic stimulation (TMS in the social cognition of these populations. However, when considering the promising preliminary evidences presented in this review and the limited amount of clinical interventions available for treating social cognition deficits in these populations today, it is clear that the social neuroscientist arsenal may profit from non-invasive brain stimulation techniques for rehabilitation and promotion of social plasticity.

  11. Promoting social plasticity in developmental disorders with non-invasive brain stimulation techniques.

    Science.gov (United States)

    Boggio, Paulo S; Asthana, Manish K; Costa, Thiago L; Valasek, Cláudia A; Osório, Ana A C

    2015-01-01

    Being socially connected directly impacts our basic needs and survival. People with deficits in social cognition might exhibit abnormal behaviors and face many challenges in our highly social-dependent world. These challenges and limitations are associated with a substantial economical and subjective impact. As many conditions where social cognition is affected are highly prevalent, more treatments have to be developed. Based on recent research, we review studies where non-invasive neuromodulatory techniques have been used to promote Social Plasticity in developmental disorders. We focused on three populations where non-invasive brain stimulation seems to be a promising approach in inducing social plasticity: Schizophrenia, Autism Spectrum Disorder (ASD) and Williams Syndrome (WS). There are still very few studies directly evaluating the effects of transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS) in the social cognition of these populations. However, when considering the promising preliminary evidences presented in this review and the limited amount of clinical interventions available for treating social cognition deficits in these populations today, it is clear that the social neuroscientist arsenal may profit from non-invasive brain stimulation techniques for rehabilitation and promotion of social plasticity.

  12. Lineage-specific splicing of a brain-enriched alternative exon promotes glioblastoma progression

    Science.gov (United States)

    Ferrarese, Roberto; Harsh, Griffith R.; Yadav, Ajay K.; Bug, Eva; Maticzka, Daniel; Reichardt, Wilfried; Dombrowski, Stephen M.; Miller, Tyler E.; Masilamani, Anie P.; Dai, Fangping; Kim, Hyunsoo; Hadler, Michael; Scholtens, Denise M.; Yu, Irene L.Y.; Beck, Jürgen; Srinivasasainagendra, Vinodh; Costa, Fabrizio; Baxan, Nicoleta; Pfeifer, Dietmar; von Elverfeldt, Dominik; Backofen, Rolf; Weyerbrock, Astrid; Duarte, Christine W.; He, Xiaolin; Prinz, Marco; Chandler, James P.; Vogel, Hannes; Chakravarti, Arnab; Rich, Jeremy N.; Carro, Maria S.; Bredel, Markus

    2014-01-01

    Tissue-specific alternative splicing is critical for the emergence of tissue identity during development, yet the role of this process in malignant transformation is undefined. Tissue-specific splicing involves evolutionarily conserved, alternative exons that represent only a minority of the total alternative exons identified. Many of these conserved exons have functional features that influence signaling pathways to profound biological effect. Here, we determined that lineage-specific splicing of a brain-enriched cassette exon in the membrane-binding tumor suppressor annexin A7 (ANXA7) diminishes endosomal targeting of the EGFR oncoprotein, consequently enhancing EGFR signaling during brain tumor progression. ANXA7 exon splicing was mediated by the ribonucleoprotein PTBP1, which is normally repressed during neuronal development. PTBP1 was highly expressed in glioblastomas due to loss of a brain-enriched microRNA (miR-124) and to PTBP1 amplification. The alternative ANXA7 splicing trait was present in precursor cells, suggesting that glioblastoma cells inherit the trait from a potential tumor-initiating ancestor and that these cells exploit this trait through accumulation of mutations that enhance EGFR signaling. Our data illustrate that lineage-specific splicing of a tissue-regulated alternative exon in a constituent of an oncogenic pathway eliminates tumor suppressor functions and promotes glioblastoma progression. This paradigm may offer a general model as to how tissue-specific regulatory mechanisms can reprogram normal developmental processes into oncogenic ones. PMID:24865424

  13. Why and how physical activity promotes experience-induced brain plasticity

    Directory of Open Access Journals (Sweden)

    Gerd eKempermann

    2010-12-01

    Full Text Available Adult hippocampal neurogenesis is an unusual case of brain plasticity, since new neurons (and not just neurites and synapses are added to the network in an activity-dependent way. At the behavioral level the plasticity-inducing stimuli include both physical and cognitive activity. In reductionistic animal studies these types of activity can be studied separately in paradigms like voluntary wheel running and environmental enrichment. In both of these, adult neurogenesis is increased but the net effect is primarily due to different mechanisms at the cellular level. Locomotion appears to stimulate the precursor cells, from which adult neurogenesis originates, to increased proliferation and maintenance over time, whereas environmental enrichment, as well as learning, predominantly promotes survival of immature neurons, that is the progeny of the proliferating precursor cells. Surprisingly, these effects are additive: boosting the potential for adult neurogenesis by physical activity increases the recruitment of cells following cognitive stimulation in an enriched environment. Why is that? We argue that locomotion actually serves as an intrinsic feedback mechanism, signaling to the brain, including its neural precursor cells, that the likelihood of cognitive challenges increases. In the wild (other than in front of a TV, no separation of physical and cognitive activity occurs. Physical activity might thus be much more than a generally healthy garnish to leading an active life but an evolutionarily fundamental aspect of activity, which is needed to provide the brain and its systems of plastic adaptation with the appropriate regulatory input and feedback.

  14. Metabolic resting-state brain networks in health and disease.

    Science.gov (United States)

    Spetsieris, Phoebe G; Ko, Ji Hyun; Tang, Chris C; Nazem, Amir; Sako, Wataru; Peng, Shichun; Ma, Yilong; Dhawan, Vijay; Eidelberg, David

    2015-02-24

    The delineation of resting state networks (RSNs) in the human brain relies on the analysis of temporal fluctuations in functional MRI signal, representing a small fraction of total neuronal activity. Here, we used metabolic PET, which maps nonfluctuating signals related to total activity, to identify and validate reproducible RSN topographies in healthy and disease populations. In healthy subjects, the dominant (first component) metabolic RSN was topographically similar to the default mode network (DMN). In contrast, in Parkinson's disease (PD), this RSN was subordinated to an independent disease-related pattern. Network functionality was assessed by quantifying metabolic RSN expression in cerebral blood flow PET scans acquired at rest and during task performance. Consistent task-related deactivation of the "DMN-like" dominant metabolic RSN was observed in healthy subjects and early PD patients; in contrast, the subordinate RSNs were activated during task performance. Network deactivation was reduced in advanced PD; this abnormality was partially corrected by dopaminergic therapy. Time-course comparisons of DMN loss in longitudinal resting metabolic scans from PD and Alzheimer's disease subjects illustrated that significant reductions appeared later for PD, in parallel with the development of cognitive dysfunction. In contrast, in Alzheimer's disease significant reductions in network expression were already present at diagnosis, progressing over time. Metabolic imaging can directly provide useful information regarding the resting organization of the brain in health and disease.

  15. Emotional brain states carry over and enhance future memory formation.

    Science.gov (United States)

    Tambini, Arielle; Rimmele, Ulrike; Phelps, Elizabeth A; Davachi, Lila

    2017-02-01

    Emotional arousal can produce lasting, vivid memories for emotional experiences, but little is known about whether emotion can prospectively enhance memory formation for temporally distant information. One mechanism that may support prospective memory enhancements is the carry-over of emotional brain states that influence subsequent neutral experiences. Here we found that neutral stimuli encountered by human subjects 9-33 min after exposure to emotionally arousing stimuli had greater levels of recollection during delayed memory testing compared to those studied before emotional and after neutral stimulus exposure. Moreover, multiple measures of emotion-related brain activity showed evidence of reinstatement during subsequent periods of neutral stimulus encoding. Both slow neural fluctuations (low-frequency connectivity) and transient, stimulus-evoked activity predictive of trial-by-trial memory formation present during emotional encoding were reinstated during subsequent neutral encoding. These results indicate that neural measures of an emotional experience can persist in time and bias how new, unrelated information is encoded and recollected.

  16. Resting-state functional brain networks in Parkinson's disease.

    Science.gov (United States)

    Baggio, Hugo C; Segura, Bàrbara; Junque, Carme

    2015-10-01

    The network approach is increasingly being applied to the investigation of normal brain function and its impairment. In the present review, we introduce the main methodological approaches employed for the analysis of resting-state neuroimaging data in Parkinson's disease studies. We then summarize the results of recent studies that used a functional network perspective to evaluate the changes underlying different manifestations of Parkinson's disease, with an emphasis on its cognitive symptoms. Despite the variability reported by many studies, these methods show promise as tools for shedding light on the pathophysiological substrates of different aspects of Parkinson's disease, as well as for differential diagnosis, treatment monitoring and establishment of imaging biomarkers for more severe clinical outcomes. © 2015 John Wiley & Sons Ltd.

  17. What should be the roles of conscious States and brain States in theories of mental activity?

    Science.gov (United States)

    Dulany, Donelson E

    2011-01-01

    Answers to the title's question have been influenced by a history in which an early science of consciousness was rejected by behaviourists on the argument that this entails commitment to ontological dualism and "free will" in the sense of indeterminism. This is, however, a confusion of theoretical assertions with metaphysical assertions. Nevertheless, a legacy within computational and information-processing views of mind rejects or de-emphasises a role for consciousness. This paper sketches a mentalistic metatheory in which conscious states are the sole carriers of symbolic representations, and thus have a central role in the explanation of mental activity and action-while specifying determinism and materialism as useful working assumptions. A mentalistic theory of causal learning, experimentally examined with phenomenal reports, is followed by examination of these questions: Are there common roles for phenomenal reports and brain imaging? Is there defensible evidence for unconscious brain states carrying symbolic representations? Are there interesting dissociations within consciousness?

  18. Detecting Mild Traumatic Brain Injury Using Resting State Magnetoencephalographic Connectivity.

    Directory of Open Access Journals (Sweden)

    Vasily A Vakorin

    2016-12-01

    Full Text Available Accurate means to detect mild traumatic brain injury (mTBI using objective and quantitative measures remain elusive. Conventional imaging typically detects no abnormalities despite post-concussive symptoms. In the present study, we recorded resting state magnetoencephalograms (MEG from adults with mTBI and controls. Atlas-guided reconstruction of resting state activity was performed for 90 cortical and subcortical regions, and calculation of inter-regional oscillatory phase synchrony at various frequencies was performed. We demonstrate that mTBI is associated with reduced network connectivity in the delta and gamma frequency range (>30 Hz, together with increased connectivity in the slower alpha band (8-12 Hz. A similar temporal pattern was associated with correlations between network connectivity and the length of time between the injury and the MEG scan. Using such resting state MEG network synchrony we were able to detect mTBI with 88% accuracy. Classification confidence was also correlated with clinical symptom severity scores. These results provide the first evidence that imaging of MEG network connectivity, in combination with machine learning, has the potential to accurately detect and determine the severity of mTBI.

  19. Brain activation and inhibition after acupuncture at Taichong and Taixi: resting-state functional magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Shao-qun Zhang

    2015-01-01

    Full Text Available Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture at Taichong (LR3 and Taixi (KI3 using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture at Taichong and Taixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic resonance imaging, which revealed that the amplitude of low-frequency fluctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus (Brodmann area 18/19, inferior occipital gyrus (Brodmann area 18 and cuneus (Brodmann area 18, but decreased mainly in the gyrus rectus of the frontal lobe (Brodmann area 11, inferior frontal gyrus (Brodmann area 44 and the center of the posterior lobe of the cerebellum. The present findings indicate that acupuncture at Taichong and Taixi specifically promote blood flow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory.

  20. Brain activation and inhibition after acupuncture at Taichong and Taixi: resting-state functional magnetic resonance imaging.

    Science.gov (United States)

    Zhang, Shao-Qun; Wang, Yan-Jie; Zhang, Ji-Ping; Chen, Jun-Qi; Wu, Chun-Xiao; Li, Zhi-Peng; Chen, Jia-Rong; Ouyang, Huai-Liang; Huang, Yong; Tang, Chun-Zhi

    2015-02-01

    Acupuncture can induce changes in the brain. However, the majority of studies to date have focused on a single acupoint at a time. In the present study, we observed activity changes in the brains of healthy volunteers before and after acupuncture at Taichong (LR3) and Taixi (KI3) using resting-state functional magnetic resonance imaging. Fifteen healthy volunteers underwent resting-state functional magnetic resonance imaging of the brain 15 minutes before acupuncture, then received acupuncture at Taichong and Taixi using the nail-pressing needle insertion method, after which the needle was retained in place for 30 minutes. Fifteen minutes after withdrawal of the needle, the volunteers underwent a further session of resting-state functional magnetic resonance imaging, which revealed that the amplitude of low-frequency fluctuation, a measure of spontaneous neuronal activity, increased mainly in the cerebral occipital lobe and middle occipital gyrus (Brodmann area 18/19), inferior occipital gyrus (Brodmann area 18) and cuneus (Brodmann area 18), but decreased mainly in the gyrus rectus of the frontal lobe (Brodmann area 11), inferior frontal gyrus (Brodmann area 44) and the center of the posterior lobe of the cerebellum. The present findings indicate that acupuncture at Taichong and Taixi specifically promote blood flow and activation in the brain areas related to vision, emotion and cognition, and inhibit brain areas related to emotion, attention, phonological and semantic processing, and memory.

  1. Early-life exercise may promote lasting brain and metabolic health through gut bacterial metabolites.

    Science.gov (United States)

    Mika, Agnieszka; Fleshner, Monika

    2016-02-01

    The 100 trillion microorganisms residing within our intestines contribute roughly 5 million additional genes to our genetic gestalt, thus posing the potential to influence many aspects of our physiology. Microbial colonization of the gut shortly after birth is vital for the proper development of immune, neural and metabolic systems, while sustaining a balanced, diverse gut flora populated with beneficial bacteria is necessary for maintaining optimal function of these systems. Although symbiotic host-microbial interactions are important throughout the lifespan, these interactions can have greater and longer lasting impacts during certain critical developmental periods. A better understanding of these sensitive periods is necessary to improve the impact and effectiveness of health-promoting interventions that target the microbial ecosystem. We have recently reported that exercise initiated in early life increases gut bacterial species involved in promoting psychological and metabolic health. In this review, we emphasize the ability of exercise during this developmentally receptive time to promote optimal brain and metabolic function across the lifespan through microbial signals.

  2. β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

    Directory of Open Access Journals (Sweden)

    Teppei Fujioka

    2017-02-01

    Full Text Available Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

  3. Human platelet-rich plasma promotes axon growth in brain-spinal cord coculture.

    Science.gov (United States)

    Takeuchi, Michiko; Kamei, Naosuke; Shinomiya, Rikuo; Sunagawa, Toru; Suzuki, Osami; Kamoda, Hiroto; Ohtori, Seiji; Ochi, Mitsuo

    2012-08-22

    Platelet-rich plasma (PRP) contains several growth factors, including platelet-derived growth factor (PDGF), transforming growth factor-β1 (TGF-β1), insulin-like growth factor-1 (IGF-1), and vascular endothelial growth factor (VEGF), that are associated with repair processes after central nervous system injury. Although PRP have been applied to some regenerative therapies, the regeneration effects of PRP on spinal cord injury have not been reported. This study applied a rat organ coculture system to examine the ability of PRP to enhance axonal growth in spinal cord tissues and to identify the growth factors in PRP that contribute to the regulation of axon growth. PRP from human peripheral blood was added to organ cocultures. Furthermore, neutralizing antibodies against PDGF-AB, TGF-β1, IGF-1, or VEGF were added to the cocultures with PRP. Axon growth from the brain cortex into the spinal cord was assessed quantitatively using anterograde axon tracing with DiI. Addition of PRP to the cocultures promoted axon growth, and the axon growth was significantly suppressed by the addition of neutralizing antibodies against IGF-1 and VEGF, but not PDGF-AB. In contrast, axon growth was promoted significantly by the addition of neutralizing antibodies against TGF-β1. These findings indicate that PRP promotes axon growth in spinal cord tissues through mechanisms associated with IGF-1 and VEGF, and that TGF-β1 in PRP exerts negative effects on axon growth.

  4. Touch-based Brain Computer Interfaces: State of the art

    NARCIS (Netherlands)

    Erp, J.B.F. van; Brouwer, A.M.

    2014-01-01

    Brain Computer Interfaces (BCIs) rely on the user's brain activity to control equipment or computer devices. Many BCIs are based on imagined movement (called active BCIs) or the fact that brain patterns differ in reaction to relevant or attended stimuli in comparison to irrelevant or unattended

  5. Plasticity of resting state brain networks in recovery from stress

    Science.gov (United States)

    Soares, José M.; Sampaio, Adriana; Marques, Paulo; Ferreira, Luís M.; Santos, Nadine C.; Marques, Fernanda; Palha, Joana A.; Cerqueira, João J.; Sousa, Nuno

    2013-01-01

    Chronic stress has been widely reported to have deleterious impact in multiple biological systems. Specifically, structural and functional remodeling of several brain regions following prolonged stress exposure have been described; importantly, some of these changes are eventually reversible. Recently, we showed the impact of stress on resting state networks (RSNs), but nothing is known about the plasticity of RSNs after recovery from stress. Herein, we examined the “plasticity” of RSNs, both at functional and structural levels, by comparing the same individuals before and after recovery from the exposure to chronic stress; results were also contrasted with a control group. Here we show that the stressed individuals after recovery displayed a decreased resting functional connectivity in the default mode network (DMN), ventral attention network (VAN), and sensorimotor network (SMN) when compared to themselves immediately after stress; however, this functional plastic recovery was only partial as when compared with the control group, as there were still areas of increased connectivity in dorsal attention network (DAN), SMN and primary visual network (VN) in participants recovered from stress. Data also shows that participants after recovery from stress displayed increased deactivations in DMN, SMN, and auditory network (AN), to levels similar to those of controls, showing a normalization of the deactivation pattern in RSNs after recovery from stress. In contrast, structural changes (volumetry) of the brain areas involving these networks are absent after the recovery period. These results reveal plastic phenomena in specific RSNs and a functional remodeling of the activation-deactivation pattern following recovery from chronic-stress, which is not accompanied by significant structural plasticity. PMID:24416009

  6. Intra-Arterial Administration of Multipotent Mesenchymal Stromal Cells Promotes Functional Recovery of the Brain After Traumatic Brain Injury.

    Science.gov (United States)

    Silachev, D N; Plotnikov, E Yu; Babenko, V A; Danilina, T I; Zorov, L D; Pevzner, I B; Zorov, D B; Sukhikh, G T

    2015-08-01

    We compared the efficiency of delivery of multipotent mesenchymal stem cells into the brain after their intravenous and intra-arterial injection. Analysis of the therapeutic effects of cells after experimental traumatic brain injury revealed improvement of the neurological status and motor functions of the damaged hemisphere, the effect being more pronounced after intraarterial injection of cells. Intra-arterial administration was followed by rapid infiltration of the cells into the brain tissue and their number considerably surpassed that after intravenous infusion. Targeted delivery of multipotent mesenchymal stromal cells into the brain after their injection into the carotid arteries substantially potentiated their neuroprotective effects in traumatic brain injury.

  7. Resting-state fMRI: a window into human brain plasticity.

    Science.gov (United States)

    Guerra-Carrillo, Belén; Mackey, Allyson P; Bunge, Silvia A

    2014-10-01

    Although brain plasticity is greatest in the first few years of life, the brain continues to be shaped by experience throughout adulthood. Advances in fMRI have enabled us to examine the plasticity of large-scale networks using blood oxygen level-dependent (BOLD) correlations measured at rest. Resting-state functional connectivity analysis makes it possible to measure task-independent changes in brain function and therefore could provide unique insights into experience-dependent brain plasticity in humans. Here, we evaluate the hypothesis that resting-state functional connectivity reflects the repeated history of co-activation between brain regions. To this end, we review resting-state fMRI studies in the sensory, motor, and cognitive learning literature. This body of research provides evidence that the brain's resting-state functional architecture displays dynamic properties in young adulthood. © The Author(s) 2014.

  8. Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia.

    Science.gov (United States)

    Mori, Marco Aurélio; Meyer, Erika; Soares, Ligia Mendes; Milani, Humberto; Guimarães, Francisco Silveira; de Oliveira, Rúbia Maria Weffort

    2017-04-03

    This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice. Using a multi-tiered behavioral testing battery during 21days, we found that BCCAO mice exhibited long-lasting functional deficits reflected by increase in anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like behavior (day 21). Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO. In addition, ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels. CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals. Collectively, the present results demonstrate that short-term CBD treatment results in global functional recovery in ischemic mice and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Strategies to promote differentiation of newborn neurons into mature functional cells in Alzheimer brain.

    Science.gov (United States)

    Schaeffer, Evelin L; Novaes, Barbara A; da Silva, Emanuelle R; Skaf, Heni D; Mendes-Neto, Alvaro G

    2009-10-01

    Adult neurogenesis occurs in the subgranular zone (SGZ) and subventricular zone (SVZ). New SGZ neurons migrate into the granule cell layer of the dentate gyrus (DG). New SVZ neurons seem to enter the association neocortex and entorhinal cortex besides the olfactory bulb. Alzheimer disease (AD) is characterized by neuron loss in the hippocampus (DG and CA1 field), entorhinal cortex, and association neocortex, which underlies the learning and memory deficits. We hypothesized that, if the AD brain can support neurogenesis, strategies to stimulate the neurogenesis process could have therapeutic value in AD. We reviewed the literature on: (a) the functional significance of adult-born neurons; (b) the occurrence of endogenous neurogenesis in AD; and (c) strategies to stimulate the adult neurogenesis process. We found that: (a) new neurons in the adult DG contribute to memory function; (b) new neurons are generated in the SGZ and SVZ of AD brains, but they fail to differentiate into mature neurons in the target regions; and (c) numerous strategies (Lithium, Glatiramer Acetate, nerve growth factor, environmental enrichment) can enhance adult neurogenesis and promote maturation of newly generated neurons. Such strategies might help to compensate for the loss of neurons and improve the memory function in AD.

  10. Hydrogel-delivered brain-derived neurotrophic factor promotes tissue repair and recovery after stroke.

    Science.gov (United States)

    Cook, Douglas J; Nguyen, Cynthia; Chun, Hyun N; L Llorente, Irene; Chiu, Abraham S; Machnicki, Michal; Zarembinski, Thomas I; Carmichael, S Thomas

    2017-03-01

    Stroke is the leading cause of adult disability. Systemic delivery of candidate neural repair therapies is limited by the blood-brain barrier and off-target effects. We tested a bioengineering approach for local depot release of BDNF from the infarct cavity for neural repair in chronic periods after stroke. The brain release levels of a hyaluronic acid hydrogel + BDNF were tested in several stroke models in mouse (strains C57Bl/6, DBA) and non-human primate ( Macaca fascicularis) and tracked with MRI. The behavioral recovery effects of hydrogel + BDNF and the effects on tissue repair outcomes were determined. Hydrogel-delivered BDNF diffuses from the stroke cavity into peri-infarct tissue over 3 weeks in two mouse stroke models, compared with 1 week for direct BDNF injection. Hydrogel delivery of BDNF promotes recovery of motor function. Mapping of motor system connections indicates that hydrogel-BDNF induces axonal sprouting within existing cortical and cortico-striatal systems. Pharmacogenetic studies show that hydrogel-BDNF induces the initial migration of immature neurons into the peri-infarct cortex and their long-term survival. In chronic stroke in the non-human primate, hydrogel-released BDNF can be detected up to 2 cm from the infarct, a distance relevant to human functional recovery in stroke. The hydrogel can be tracked by MRI in mouse and primate.

  11. Granulocyte colony-stimulating factor promotes behavioral recovery in a mouse model of traumatic brain injury.

    Science.gov (United States)

    Song, Shijie; Kong, Xiaoyuan; Acosta, Sandra; Sava, Vasyl; Borlongan, Cesar; Sanchez-Ramos, Juan

    2016-05-01

    Hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) represent a novel approach for treatment of traumatic brain injury (TBI). After mild controlled cortical impact (CCI), mice were treated with G-CSF (100 μg/kg) for 3 consecutive days. The primary behavioral endpoint was performance on the radial arm water maze (RAWM), assessed 7 and 14 days after CCI. Secondary endpoints included 1) motor performance on a rotating cylinder (rotarod), 2) measurement of microglial and astroglial response, 3) hippocampal neurogenesis, and 4) measures of neurotrophic factors (brain-derived neurotrophic factor [BDNF] and glial cell line-derived neurotrophic factor [GDNF]) and cytokines in brain homogenates. G-CSF-treated animals performed significantly better than vehicle-treated mice in the RAWM at 1 and 2 weeks but not on the rotarod. Cellular changes found in the G-CSF group included increased hippocampal neurogenesis as well as astrocytosis and microgliosis in both the striatum and the hippocampus. Neurotrophic factors GDNF and BDNF, elaborated by activated microglia and astrocytes, were increased in G-CSF-treated mice. These factors along with G-CSF itself are known to promote hippocampal neurogenesis and inhibit apoptosis and likely contributed to improvement in the hippocampal-dependent learning task. Six cytokines that were modulated by G-CSF treatment following CCI were elevated on day 3, but only one of them remained altered by day 7, and all of them were no different from vehicle controls by day 14. The pro- and anti-inflammatory cytokines modulated by G-CSF administration interact in a complex and incompletely understood network involving both damage and recovery processes, underscoring the dual role of inflammation after TBI. © 2016 Wiley Periodicals, Inc.

  12. State-Dependent Changes of Connectivity Patterns and Functional Brain Network Topology in Autism Spectrum Disorder

    Science.gov (United States)

    Barttfeld, Pablo; Wicker, Bruno; Cukier, Sebastian; Navarta, Silvana; Lew, Sergio; Leiguarda, Ramon; Sigman, Mariano

    2012-01-01

    Anatomical and functional brain studies have converged to the hypothesis that autism spectrum disorders (ASD) are associated with atypical connectivity. Using a modified resting-state paradigm to drive subjects' attention, we provide evidence of a very marked interaction between ASD brain functional connectivity and cognitive state. We show that…

  13. Brain Network Reconfiguration and Perceptual Decoupling During an Absorptive State of Consciousness.

    Science.gov (United States)

    Hove, Michael J; Stelzer, Johannes; Nierhaus, Till; Thiel, Sabrina D; Gundlach, Christopher; Margulies, Daniel S; Van Dijk, Koene R A; Turner, Robert; Keller, Peter E; Merker, Björn

    2016-07-01

    Trance is an absorptive state of consciousness characterized by narrowed awareness of external surroundings and has long been used-for example, by shamans-to gain insight. Shamans across cultures often induce trance by listening to rhythmic drumming. Using functional magnetic resonance imaging (fMRI), we examined the brain-network configuration associated with trance. Experienced shamanic practitioners (n = 15) listened to rhythmic drumming, and either entered a trance state or remained in a nontrance state during 8-min scans. We analyzed changes in network connectivity. Trance was associated with higher eigenvector centrality (i.e., stronger hubs) in 3 regions: posterior cingulate cortex (PCC), dorsal anterior cingulate cortex (dACC), and left insula/operculum. Seed-based analysis revealed increased coactivation of the PCC (a default network hub involved in internally oriented cognitive states) with the dACC and insula (control-network regions involved in maintaining relevant neural streams). This coactivation suggests that an internally oriented neural stream was amplified by the modulatory control network. Additionally, during trance, seeds within the auditory pathway were less connected, possibly indicating perceptual decoupling and suppression of the repetitive auditory stimuli. In sum, trance involved coactive default and control networks, and decoupled sensory processing. This network reconfiguration may promote an extended internal train of thought wherein integration and insight can occur. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Behavioral strategies for assessing and promoting community readiness in brain injury rehabilitation.

    Science.gov (United States)

    Schaub, Chris; Peters, Christina; Peters, Scott

    2012-01-01

    Individuals with acquired brain injuries often display problematic behaviors, such as impulsivity, disinhibition, lack of initiation, isolation, and aggression, that impact their readiness to return to home and/or the community. The occurrence and treatment of these behaviors is often complicated by impairments in cognition and self-awareness, as well as by co-occurring issues including substance abuse. Community reintegration for these individuals is a goal that can be both hazardous and difficult to attain. This article briefly reviews the literature and describes a treatment philosophy and methodology by which an interdisciplinary team can employ evidence-based behavioral principles and procedures to assess and promote behavioral stability toward the goal of community readiness within a residential rehabilitation setting. Assessment includes a comprehensive evaluation of individual strengths and barriers across all disciplines as well as an analysis of the function of problematic behaviors. Based upon these assessments and analyses, integrated interdisciplinary treatment efforts then support the development and implementation of specific strategies and tools to promote community readiness and ultimately reentry. These strategies and tools are intended to provide direction and support to the client and include prompts and cues to self-manage, as well as ways to assist clients and staff to collect and reflect upon relevant data. Additionally, other methods of data collection, techniques to develop self-management skills, and the use of contingencies as part of a community reentry plan are discussed.

  15. Promoting Partnerships for Crime Prevention between State and ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    This study will explore crime prevention partnerships between the state and the private security actors in Botswana, Namibia, South Africa, and Swaziland. Drawing on a literature review and interviews, it will provide the first in-depth analysis of crime prevention partnerships between the state and non-state actors in these ...

  16. Promoting Undergraduate Research at Grand Valley State University

    Science.gov (United States)

    Riemersma, P.; Mekik, F. A.

    2003-12-01

    Grand Valley State University (GVSU) is a relatively young, rapidly growing, predominately undergraduate institution of about 20,000 students located in western Michigan in which undergraduate research plays a vital role in the education of our students. Student research is supported and actively promoted by 1) creating university funding opportunities and taking advantage of small outside funding sources 2) building a tradition of undergraduate research 3) incorporating small research activities into classes and 4) educating students explicitly in how to prepare a professional poster, give a professional talk and write a journal article. As the saying goes, if you have money, the students will come. At GVSU most students recognize the value of a research experience but need income to pay for college expenses. The internally funded Student Summer Scholars program at GVSU provides student salary and faculty stipend for a summer research project (\\6000 per grant). The geology department has also been successful at obtaining grants from the NASA Michigan Space Grant Consortium (\\5,000 plus a 100% GVSU match). We have been successful in using these easier to obtain smaller grants to fund undergraduate projects. In some cases small grants actually allow us to pursue "risky" or otherwise difficult to fund projects. Undergraduate research "counts" at GVSU and once a tradition and critical mass of undergraduate research has been established, it can become self-sustaining. To recognize the achievements of undergraduate research at GVSU, there is an annual Student Scholarship Day in which the students (580 university wide) present the results of their research. Also, by persuading students in our introductory classes (for extra credit) to attend Student Scholarship Day, the students, early in their college career, can see what fellow students can accomplish and student presenters can revel in their role of researcher and educator. Such an event helps to build a tradition

  17. The relationship between promotions committees' identification of problem medical students and subsequent state medical board actions.

    Science.gov (United States)

    Santen, Sally A; Petrusa, Emil; Gruppen, Larry D

    2015-05-01

    Studies have found unprofessional behavior in medical school was associated with disciplinary action by state medical boards. For medical schools, promotions committees are responsible for identifying which students do not demonstrate academic performance and professional behavior acceptable for promotion and graduation. The objective of this study was to determine if student identification by promotions committees during medical school was associated with disciplinary actions by state medical boards later in practice. We reviewed 20 years of promotions committees' records from a single institution and noted students identified by promotions committees for performance or behavioral issues. These were compared with disciplinary action reports from the Federation of State Medical Boards (FSMB) for graduates. Over the two decades, 2,131 students matriculated and 2,078 of these graduated. The promotions committees identified 140 students for poor academic performance or behavioral problems (140/2,078, 6.7 %). Of these, 108 students graduated. FSMB records showed 29 of the 2,078 graduates had sanctions by state boards (29/2,078, 1.4 %). Only four students that had actions by state medical boards were among the 108 graduated students identified by medical school promotions committees (4/108, 3.7 %). Of the students not identified by promotions committees, 25 eventually had disciplinary actions (25/1,970, 1.3 %). The odds of having state medical board action if identified by promotions committees was 3.0 (CI 1.02-8.8, p school promotions committees was later associated with state medical board actions. However, most graduates with state medical board actions were not identified by medical school promotions committees.

  18. Plasticity of brain wave network interactions and evolution across physiologic states

    Science.gov (United States)

    Liu, Kang K. L.; Bartsch, Ronny P.; Lin, Aijing; Mantegna, Rosario N.; Ivanov, Plamen Ch.

    2015-01-01

    Neural plasticity transcends a range of spatio-temporal scales and serves as the basis of various brain activities and physiologic functions. At the microscopic level, it enables the emergence of brain waves with complex temporal dynamics. At the macroscopic level, presence and dominance of specific brain waves is associated with important brain functions. The role of neural plasticity at different levels in generating distinct brain rhythms and how brain rhythms communicate with each other across brain areas to generate physiologic states and functions remains not understood. Here we perform an empirical exploration of neural plasticity at the level of brain wave network interactions representing dynamical communications within and between different brain areas in the frequency domain. We introduce the concept of time delay stability (TDS) to quantify coordinated bursts in the activity of brain waves, and we employ a system-wide Network Physiology integrative approach to probe the network of coordinated brain wave activations and its evolution across physiologic states. We find an association between network structure and physiologic states. We uncover a hierarchical reorganization in the brain wave networks in response to changes in physiologic state, indicating new aspects of neural plasticity at the integrated level. Globally, we find that the entire brain network undergoes a pronounced transition from low connectivity in Deep Sleep and REM to high connectivity in Light Sleep and Wake. In contrast, we find that locally, different brain areas exhibit different network dynamics of brain wave interactions to achieve differentiation in function during different sleep stages. Moreover, our analyses indicate that plasticity also emerges in frequency-specific networks, which represent interactions across brain locations mediated through a specific frequency band. Comparing frequency-specific networks within the same physiologic state we find very different degree of

  19. Plasticity of brain wave network interactions and evolution across physiologic states.

    Science.gov (United States)

    Liu, Kang K L; Bartsch, Ronny P; Lin, Aijing; Mantegna, Rosario N; Ivanov, Plamen Ch

    2015-01-01

    Neural plasticity transcends a range of spatio-temporal scales and serves as the basis of various brain activities and physiologic functions. At the microscopic level, it enables the emergence of brain waves with complex temporal dynamics. At the macroscopic level, presence and dominance of specific brain waves is associated with important brain functions. The role of neural plasticity at different levels in generating distinct brain rhythms and how brain rhythms communicate with each other across brain areas to generate physiologic states and functions remains not understood. Here we perform an empirical exploration of neural plasticity at the level of brain wave network interactions representing dynamical communications within and between different brain areas in the frequency domain. We introduce the concept of time delay stability (TDS) to quantify coordinated bursts in the activity of brain waves, and we employ a system-wide Network Physiology integrative approach to probe the network of coordinated brain wave activations and its evolution across physiologic states. We find an association between network structure and physiologic states. We uncover a hierarchical reorganization in the brain wave networks in response to changes in physiologic state, indicating new aspects of neural plasticity at the integrated level. Globally, we find that the entire brain network undergoes a pronounced transition from low connectivity in Deep Sleep and REM to high connectivity in Light Sleep and Wake. In contrast, we find that locally, different brain areas exhibit different network dynamics of brain wave interactions to achieve differentiation in function during different sleep stages. Moreover, our analyses indicate that plasticity also emerges in frequency-specific networks, which represent interactions across brain locations mediated through a specific frequency band. Comparing frequency-specific networks within the same physiologic state we find very different degree of

  20. Activation of the c-Met pathway mobilizes an inflammatory network in the brain microenvironment to promote brain metastasis of breast cancer

    Science.gov (United States)

    Xing, Fei; Liu, Yin; Sharma, Sambad; Wu, Kerui; Chan, Michael D.; Lo, Hui-Wen; Carpenter, Richard L.; Metheny-Barlow, Linda J.; Zhou, Xiaobo; Qasem, Shadi A.; Pasche, Boris; Watabe, Kounosuke

    2016-01-01

    Brain metastasis is one of the chief causes of mortality in breast cancer patients, but the mechanisms that drive this process remains poorly understood. Here we report that brain metastatic cells expressing high levels of c-Met promote the metastatic process via inflammatory cytokine upregulation and vascular reprogramming. Activated c-Met signaling promoted adhesion of tumor cells to brain endothelial cells and enhanced neovascularization by inducing the secretion of IL-8 and CXCL1. Additionally, stimulation of IL1β secretion by activation of c-Met induced tumor-associated astrocytes to secrete the c-Met ligand HGF. Thus, a feed-forward mechanism of cytokine release initiated and sustained by c-Met fed a vicious cycle which generated a favorable microenvironment for metastatic cells. Reinforcing our results, we found that pterostilbene, a compound that penetrates the blood-brain barrier, could suppress brain metastasis by targeting c-Met signaling. These findings suggest a potential utility of this natural compound for chemoprevention. PMID:27364556

  1. Recursive cluster elimination based support vector machine for disease state prediction using resting state functional and effective brain connectivity.

    Directory of Open Access Journals (Sweden)

    Gopikrishna Deshpande

    2010-12-01

    Full Text Available Brain state classification has been accomplished using features such as voxel intensities, derived from functional magnetic resonance imaging (fMRI data, as inputs to efficient classifiers such as support vector machines (SVM and is based on the spatial localization model of brain function. With the advent of the connectionist model of brain function, features from brain networks may provide increased discriminatory power for brain state classification.In this study, we introduce a novel framework where in both functional connectivity (FC based on instantaneous temporal correlation and effective connectivity (EC based on causal influence in brain networks are used as features in an SVM classifier. In order to derive those features, we adopt a novel approach recently introduced by us called correlation-purged Granger causality (CPGC in order to obtain both FC and EC from fMRI data simultaneously without the instantaneous correlation contaminating Granger causality. In addition, statistical learning is accelerated and performance accuracy is enhanced by combining recursive cluster elimination (RCE algorithm with the SVM classifier. We demonstrate the efficacy of the CPGC-based RCE-SVM approach using a specific instance of brain state classification exemplified by disease state prediction. Accordingly, we show that this approach is capable of predicting with 90.3% accuracy whether any given human subject was prenatally exposed to cocaine or not, even when no significant behavioral differences were found between exposed and healthy subjects.The framework adopted in this work is quite general in nature with prenatal cocaine exposure being only an illustrative example of the power of this approach. In any brain state classification approach using neuroimaging data, including the directional connectivity information may prove to be a performance enhancer. When brain state classification is used for disease state prediction, our approach may aid the

  2. Acute effects of modafinil on brain resting state networks in young healthy subjects.

    Directory of Open Access Journals (Sweden)

    Roberto Esposito

    Full Text Available There is growing debate on the use of drugs that promote cognitive enhancement. Amphetamine-like drugs have been employed as cognitive enhancers, but they show important side effects and induce addiction. In this study, we investigated the use of modafinil which appears to have less side effects compared to other amphetamine-like drugs. We analyzed effects on cognitive performances and brain resting state network activity of 26 healthy young subjects.A single dose (100 mg of modafinil was administered in a double-blind and placebo-controlled study. Both groups were tested for neuropsychological performances with the Raven's Advanced Progressive Matrices II set (APM before and three hours after administration of drug or placebo. Resting state functional magnetic resonance (rs-FMRI was also used, before and after three hours, to investigate changes in the activity of resting state brain networks. Diffusion Tensor Imaging (DTI was employed to evaluate differences in structural connectivity between the two groups. Protocol ID: Modrest_2011; NCT01684306; http://clinicaltrials.gov/ct2/show/NCT01684306.Results indicate that a single dose of modafinil improves cognitive performance as assessed by APM. Rs-fMRI showed that the drug produces a statistically significant increased activation of Frontal Parietal Control (FPC; p<0.04 and Dorsal Attention (DAN; p<0.04 networks. No modifications in structural connectivity were observed.Overall, our findings support the notion that modafinil has cognitive enhancing properties and provide functional connectivity data to support these effects.ClinicalTrials.gov NCT01684306 http://clinicaltrials.gov/ct2/show/NCT01684306.

  3. Transcriptional activity of novel ALDH1L1 promoters in the rat brain following AAV vector-mediated gene transfer

    Directory of Open Access Journals (Sweden)

    Janitha M Mudannayake

    2016-01-01

    Full Text Available Aldehyde dehydrogenase family 1, member L1 (ALDH1L1 is a recently characterized pan-astrocytic marker that is more homogenously expressed throughout the brain than the classic astrocytic marker, glial fibrillary acidic protein. We generated putative promoter sequence variants of the rat ALDH1L1 gene for use in adeno-associated viral vector-mediated gene transfer, with an aim to achieve selective regulation of transgene expression in astrocytes in the rat brain. Unexpectedly, ALDH1L1 promoter variants mediated transcriptional activity exclusively in neurons in the substantia nigra pars compacta as assessed by luciferase reporter expression at 3 weeks postvector infusion. This selectivity for neurons in the substantia nigra pars compacta also persisted in the context of adeno-associated viral serotype 5, 8 or 9 vector-mediated gene delivery. An in vivo promoter comparison showed the highest performing ALDH1L1 promoter variant mediated higher transgene expression than the neuronal-specific synapsin 1 and tyrosine hydroxylase promoters. The ALDH1L1 promoter was also transcriptionally active in dentate granule neurons following intrahippocampal adeno-associated viral vector infusion, whereas transgene expression was detected in both striatal neurons and astrocytes following vector infusion into the striatum. Our results demonstrate the potential suitability of the ALDH1L1 promoter as a new tool in the development of gene therapy and disease modelling applications.

  4. What Should Be the Roles of Conscious States and Brain States in Theories of Mental Activity?**

    Science.gov (United States)

    Dulany, Donelson E.

    2011-01-01

    Answers to the title’s question have been influenced by a history in which an early science of consciousness was rejected by behaviourists on the argument that this entails commitment to ontological dualism and “free will” in the sense of indeterminism. This is, however, a confusion of theoretical assertions with metaphysical assertions. Nevertheless, a legacy within computational and information-processing views of mind rejects or de-emphasises a role for consciousness. This paper sketches a mentalistic metatheory in which conscious states are the sole carriers of symbolic representations, and thus have a central role in the explanation of mental activity and action-while specifying determinism and materialism as useful working assumptions. A mentalistic theory of causal learning, experimentally examined with phenomenal reports, is followed by examination of these questions: Are there common roles for phenomenal reports and brain imaging? Is there defensible evidence for unconscious brain states carrying symbolic representations? Are there interesting dissociations within consciousness? PMID:21694964

  5. Deep brain stimulation and spinal cord stimulation for vegetative state and minimally conscious state.

    Science.gov (United States)

    Yamamoto, Takamitsu; Katayama, Yoichi; Obuchi, Toshiki; Kobayashi, Kazutaka; Oshima, Hideki; Fukaya, Chikashi

    2013-01-01

    On the basis of the findings of the electrophysiological evaluation of vegetative state (VS) and minimally conscious state (MCS), the effect of deep brain stimulation (DBS) was examined according to long-term follow-up results. The results of spinal cord stimulation (SCS) on MCS was also examined and compared with that of DBS. One hundred seven patients in VS and 21 patients in MCS were evaluated neurologically and electrophysiologically over 3 months after the onset of brain injury. Among the 107 VS patients, 21 were treated by DBS. Among the 21 MCS patients, 5 were treated by DBS and 10 by SCS. Eight of the 21 patients recovered from VS and were able to follow verbal instructions. These eight patients showed desynchronization on continuous electroencephalographic frequency analysis. The Vth wave of the auditory brainstem response and N20 of somatosensory evoked potential were recorded even with a prolonged latency, and pain-related P250 was recorded with an amplitude of more than 7 μV. In addition, DBS and SCS induced a marked functional recovery in MCS patients who satisfied the electrophysiological inclusion criteria. DBS for VS and MCS patients and SCS for MCS patients may be useful, when the candidates are selected on the basis of the electrophysiological inclusion criteria. Only 16 (14.9%) of the 107 VS patients and 15 (71.4%) of the 21 MCS patients satisfied the electrophysiological inclusion criteria. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Promoting "Academic Entrepreneurship" in Europe and the United States

    DEFF Research Database (Denmark)

    Tvarnø, Christina D.; Bagley, Constance E.

    2016-01-01

    States (“U.S.”). Our comparative analysis of the EU and U.S. approaches to translational medicine shows that there are lessons to be shared. The EU can apply the experiences from the U.S. Bayh-Dole Act and PPPPs in the United States, and the United States can emulate certain of the open innovation...... aspects of the European Innovative Medicines Initiative and the tighter patenting standards imposed by the European Patent Office. Thus, a secondary purpose of this article is suggesting amendments to the U.S. laws governing the patenting and licensing of government-funded technology to prevent undue...

  7. Pregnancy affects FOS rhythms in brain regions regulating sleep/wake state and body temperature in rats.

    Science.gov (United States)

    Schrader, Jessica A; Smale, Laura; Nunez, Antonio A

    2012-10-22

    Circadian rhythms in behavior and physiology change substantially as female mammals undergo the transition from a non-pregnant to a pregnant state. Here, we examined the possibility that site-specific changes in brain regions known to regulate the sleep/wake cycle and body temperature might reflect altered rhythms in these overt functions. Specifically, we compared daily patterns of immunoreactive FOS in early pregnant and diestrous rats in the medial septum (MS), vertical and horizontal diagonal bands of Broca (VDB and HDB), perifornical lateral hypothalamus (LH), and ventrolateral, medial, and median preoptic areas (VLPO, MPA, and MnPO, respectively). In the pregnant animals, FOS expression was reduced and the daily rhythms of expression were lost or attenuated in the MS, VDB, and LH, areas known to support wakefulness, and in the MPA, a brain region that may coordinate sleep/wake patterns with temperature changes. However, despite the well-documented differences in sleep patterns between diestrous and pregnant rats, reproductive state did not affect FOS expression in the VLPO or MnPO, two brain regions in which FOS expression usually correlates with sleep. These data indicate that plasticity in sleep/wake patterns during early pregnancy may be driven by a reduction in wakefulness-promotion by the brain, rather than by an increase in sleep drive. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. State-of-the-Art Methods for Brain Tissue Segmentation: A Review.

    Science.gov (United States)

    Dora, Lingraj; Agrawal, Sanjay; Panda, Rutuparna; Abraham, Ajith

    2017-01-01

    Brain tissue segmentation is one of the most sought after research areas in medical image processing. It provides detailed quantitative brain analysis for accurate disease diagnosis, detection, and classification of abnormalities. It plays an essential role in discriminating healthy tissues from lesion tissues. Therefore, accurate disease diagnosis and treatment planning depend merely on the performance of the segmentation method used. In this review, we have studied the recent advances in brain tissue segmentation methods and their state-of-the-art in neuroscience research. The review also highlights the major challenges faced during tissue segmentation of the brain. An effective comparison is made among state-of-the-art brain tissue segmentation methods. Moreover, a study of some of the validation measures to evaluate different segmentation methods is also discussed. The brain tissue segmentation, content in terms of methodologies, and experiments presented in this review are encouraging enough to attract researchers working in this field.

  9. Rebalancing brain drain: exploring resource reallocation to address health worker migration and promote global health.

    Science.gov (United States)

    Mackey, Timothy Ken; Liang, Bryan Albert

    2012-09-01

    Global public health is threatened by an imbalance in health worker migration from resource-poor countries to developed countries. This "brain drain" results in health workforce shortages, health system weakening, and economic loss and waste, threatening the well-being of vulnerable populations and effectiveness of global health interventions. Current structural imbalances in resource allocation and global incentive structures have resulted in 57 countries identified by WHO as having a "critical shortage" of health workers. Yet current efforts to strengthen domestic health systems have fallen short in addressing this issue. Instead, global solutions should focus on sustainable forms of equitable resource sharing. This can be accomplished by adoption of mandatory global resource and staff-sharing programs in conjunction with implementation of state-based health services corps. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  10. The Promotion of Moral ideals in Schools; What the State May or May Not Demand

    Science.gov (United States)

    de Ruyter, Doret J.; Steutel, Jan W.

    2013-01-01

    The content and boundaries of moral education the state may require schools to offer is a matter of contention. This article investigates whether the state may obligate schools to promote the pursuit of moral ideals. Moral ideals refer to (a cluster of) characteristics of a person as well as to situations or states that are believed to be morally…

  11. Acupuncture promotes mTOR-independent autophagic clearance of aggregation-prone proteins in mouse brain.

    Science.gov (United States)

    Tian, Tian; Sun, Yanhong; Wu, Huangan; Pei, Jian; Zhang, Jing; Zhang, Yi; Wang, Lu; Li, Bin; Wang, Lihua; Shi, Jiye; Hu, Jun; Fan, Chunhai

    2016-01-21

    Acupuncture has historically been practiced to treat medical disorders by mechanically stimulating specific acupoints with fine needles. Despite its well-documented efficacy, its biological basis remains largely elusive. In this study, we found that mechanical stimulation at the acupoint of Yanglingquan (GB34) promoted the autophagic clearance of α-synuclein (α-syn), a well known aggregation-prone protein closely related to Parkinson's disease (PD), in the substantia nigra par compacta (SNpc) of the brain in a PD mouse model. We found the protein clearance arose from the activation of the autophagy-lysosome pathway (ALP) in a mammalian target of rapamycin (mTOR)-independent approach. Further, we observed the recovery in the activity of dopaminergic neurons in SNpc, and improvement in the motor function at the behavior level of PD mice. Whereas acupuncture and rapamycin, a chemical mTOR inhibitor, show comparable α-syn clearance and therapeutic effects in the PD mouse model, the latter adopts a distinctly different, mTOR-dependent, autophagy induction process. Due to this fundamental difference, acupuncture may circumvent adverse effects of the rapamycin treatment. The newly discovered connection between acupuncture and autophagy not only provides a new route to understanding the molecular mechanism of acupuncture but also sheds new light on cost-effective and safe therapy of neurodegenerative diseases.

  12. 77 FR 59064 - United States-Colombia Trade Promotion Agreement

    Science.gov (United States)

    2012-09-26

    ..., Morocco, El Salvador, Guatemala, Honduras, Nicaragua, the Dominican Republic, Costa Rica, Bahrain, Oman... importer fails to comply with any of the requirements under Subpart T, Part 10, CBP regulations. Export... of a person who completes and issues a certification for a good exported from the United States to...

  13. 78 FR 63052 - United States-Panama Trade Promotion Agreement

    Science.gov (United States)

    2013-10-23

    ..., Chile, Morocco, El Salvador, Guatemala, Honduras, Nicaragua, the Dominican Republic, Costa Rica, Bahrain... with any of the requirements under Subpart S, Part 10, CBP regulations. Export Requirements Section 10... who completes and issues a certification for a good exported from the United States to Panama...

  14. Brain activation by music in patients in a vegetative or minimally conscious state following diffuse brain injury.

    Science.gov (United States)

    Okumura, Yuka; Asano, Yoshitaka; Takenaka, Shunsuke; Fukuyama, Seisuke; Yonezawa, Shingo; Kasuya, Yukinori; Shinoda, Jun

    2014-01-01

    The aim of this study was to objectively evaluate the brain activity potential of patients with impaired consciousness in a chronic stage of diffuse brain injury (DBI) using functional MRI (fMRI) following music stimulation (MS). Two patients in a minimally conscious state (MCS) and five patients in a vegetative state (VS) due to severe DBI were enrolled along with 21 healthy adults. This study examined the brain regions activated by music and assessed topographical differences of the MS-activated brain among healthy adults and these patients. MS was shown to activate the bilateral superior temporal gyri (STG) of both healthy adults and patients in an MCS. In four of five patients in a VS, however, no significant activation in STG could be induced by the same MS. The remaining patient in a VS displayed the same MS-induced brain activation in STG as healthy adults and patients in an MCS and this patient's status also improved to an MCS 4 months after the study. The presence of STG activation by MS may predict a possible improvement of patients in a VS to MCS and fMRI employing MS may be a useful modality to objectively evaluate consciousness in these patients.

  15. An evaluation of the left-brain vs. right-brain hypothesis with resting state functional connectivity magnetic resonance imaging.

    Science.gov (United States)

    Nielsen, Jared A; Zielinski, Brandon A; Ferguson, Michael A; Lainhart, Janet E; Anderson, Jeffrey S

    2013-01-01

    Lateralized brain regions subserve functions such as language and visuospatial processing. It has been conjectured that individuals may be left-brain dominant or right-brain dominant based on personality and cognitive style, but neuroimaging data has not provided clear evidence whether such phenotypic differences in the strength of left-dominant or right-dominant networks exist. We evaluated whether strongly lateralized connections covaried within the same individuals. Data were analyzed from publicly available resting state scans for 1011 individuals between the ages of 7 and 29. For each subject, functional lateralization was measured for each pair of 7266 regions covering the gray matter at 5-mm resolution as a difference in correlation before and after inverting images across the midsagittal plane. The difference in gray matter density between homotopic coordinates was used as a regressor to reduce the effect of structural asymmetries on functional lateralization. Nine left- and 11 right-lateralized hubs were identified as peaks in the degree map from the graph of significantly lateralized connections. The left-lateralized hubs included regions from the default mode network (medial prefrontal cortex, posterior cingulate cortex, and temporoparietal junction) and language regions (e.g., Broca Area and Wernicke Area), whereas the right-lateralized hubs included regions from the attention control network (e.g., lateral intraparietal sulcus, anterior insula, area MT, and frontal eye fields). Left- and right-lateralized hubs formed two separable networks of mutually lateralized regions. Connections involving only left- or only right-lateralized hubs showed positive correlation across subjects, but only for connections sharing a node. Lateralization of brain connections appears to be a local rather than global property of brain networks, and our data are not consistent with a whole-brain phenotype of greater "left-brained" or greater "right-brained" network strength

  16. An evaluation of the left-brain vs. right-brain hypothesis with resting state functional connectivity magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Jared A Nielsen

    Full Text Available Lateralized brain regions subserve functions such as language and visuospatial processing. It has been conjectured that individuals may be left-brain dominant or right-brain dominant based on personality and cognitive style, but neuroimaging data has not provided clear evidence whether such phenotypic differences in the strength of left-dominant or right-dominant networks exist. We evaluated whether strongly lateralized connections covaried within the same individuals. Data were analyzed from publicly available resting state scans for 1011 individuals between the ages of 7 and 29. For each subject, functional lateralization was measured for each pair of 7266 regions covering the gray matter at 5-mm resolution as a difference in correlation before and after inverting images across the midsagittal plane. The difference in gray matter density between homotopic coordinates was used as a regressor to reduce the effect of structural asymmetries on functional lateralization. Nine left- and 11 right-lateralized hubs were identified as peaks in the degree map from the graph of significantly lateralized connections. The left-lateralized hubs included regions from the default mode network (medial prefrontal cortex, posterior cingulate cortex, and temporoparietal junction and language regions (e.g., Broca Area and Wernicke Area, whereas the right-lateralized hubs included regions from the attention control network (e.g., lateral intraparietal sulcus, anterior insula, area MT, and frontal eye fields. Left- and right-lateralized hubs formed two separable networks of mutually lateralized regions. Connections involving only left- or only right-lateralized hubs showed positive correlation across subjects, but only for connections sharing a node. Lateralization of brain connections appears to be a local rather than global property of brain networks, and our data are not consistent with a whole-brain phenotype of greater "left-brained" or greater "right-brained

  17. [The current state of the brain-computer interface problem].

    Science.gov (United States)

    Shurkhay, V A; Aleksandrova, E V; Potapov, A A; Goryainov, S A

    2015-01-01

    It was only 40 years ago that the first PC appeared. Over this period, rather short in historical terms, we have witnessed the revolutionary changes in lives of individuals and the entire society. Computer technologies are tightly connected with any field, either directly or indirectly. We can currently claim that computers are manifold superior to a human mind in terms of a number of parameters; however, machines lack the key feature: they are incapable of independent thinking (like a human). However, the key to successful development of humankind is collaboration between the brain and the computer rather than competition. Such collaboration when a computer broadens, supplements, or replaces some brain functions is known as the brain-computer interface. Our review focuses on real-life implementation of this collaboration.

  18. Altered resting state brain networks in Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Martin Göttlich

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

  19. Modeling epileptic brain states using EEG spectral analysis and topographic mapping.

    Science.gov (United States)

    Direito, Bruno; Teixeira, César; Ribeiro, Bernardete; Castelo-Branco, Miguel; Sales, Francisco; Dourado, António

    2012-09-30

    Changes in the spatio-temporal behavior of the brain electrical activity are believed to be associated to epileptic brain states. We propose a novel methodology to identify the different states of the epileptic brain, based on the topographic mapping of the time varying relative power of delta, theta, alpha, beta and gamma frequency sub-bands, estimated from EEG. Using normalized-cuts segmentation algorithm, points of interest are identified in the topographic mappings and their trajectories over time are used for finding out relations with epileptogenic propagations in the brain. These trajectories are used to train a Hidden Markov Model (HMM), which models the different epileptic brain states and the transition among them. Applied to 10 patients suffering from focal seizures, with a total of 30 seizures over 497.3h of data, the methodology shows good results (an average point-by-point accuracy of 89.31%) for the identification of the four brain states--interictal, preictal, ictal and postictal. The results suggest that the spatio-temporal dynamics captured by the proposed methodology are related to the epileptic brain states and transitions involved in focal seizures. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Brain Organization into Resting State Networks Emerges at Criticality on a Model of the Human Connectome

    Science.gov (United States)

    Haimovici, Ariel; Tagliazucchi, Enzo; Balenzuela, Pablo; Chialvo, Dante R.

    2013-04-01

    The relation between large-scale brain structure and function is an outstanding open problem in neuroscience. We approach this problem by studying the dynamical regime under which realistic spatiotemporal patterns of brain activity emerge from the empirically derived network of human brain neuroanatomical connections. The results show that critical dynamics unfolding on the structural connectivity of the human brain allow the recovery of many key experimental findings obtained from functional magnetic resonance imaging, such as divergence of the correlation length, the anomalous scaling of correlation fluctuations, and the emergence of large-scale resting state networks.

  1. Modulation of brain resting-state networks by sad mood induction

    National Research Council Canada - National Science Library

    Harrison, Ben J; Pujol, Jesus; Ortiz, Hector; Fornito, Alex; Pantelis, Christos; Yücel, Murat

    2008-01-01

    ...) signal observed in functional MRI resting-state studies. In humans, these slow BOLD variations are thought to reflect an underlying or intrinsic form of brain functional connectivity in discrete neuroanatomical systems...

  2. 78 FR 9929 - Current Traumatic Brain Injury State Implementation Partnership Grantees; Non-Competitive One...

    Science.gov (United States)

    2013-02-12

    ... HUMAN SERVICES Health Resources and Services Administration Current Traumatic Brain Injury State... State Departments of Health, Rehabilitation, Human Services, Education, Transportation, or Labor. This...,000 Oregon State Department of Education H21MC06769 OR 249,999 249,999 Texas Health & Human Services...

  3. Worksite health promotion research: challenges, current state and future directions

    Directory of Open Access Journals (Sweden)

    Georg F. Bauer

    2007-12-01

    Full Text Available

    Background: Worksite health promotion (WHP addresses diverse individual and work-related health determinants. Thus, multiple, non-standardized interventions as well as company outcomes other than health have to be considered in WHP research.

    Methods: The article builds primarily on published research reviews in WHP and related fields. It discusses key practical and research challenges of the workplace setting. The evidence available on the effectiveness of WHP is summarised and conclusions are drawn for future WHP practice and research.

    Results: WHP research on health-oriented, behavioural interventions shows that the level of evidence ranges from suggestive to acceptable for key prevention areas such as physical activity, nutrition, fitness, smoking, alcohol and stress. Such interventions are effective if key conditions are met. Future research is needed on long-term effects, on multi-component programs and on programs, which address environmental determinants of health behaviour as well. Research on work-related determinants of health shows the economic and public health relevance of WHP interventions. Reviews of work-oriented, organisational interventions show that they produce a range of individual and organisational outcomes. However, due to the complexity of the organisational context, the generalisability and predictability of such outcomes remain limited.

    Conclusions: WHP research shows success factors of WHP and provides evidence of its effectiveness. In future, the evidence base should be expanded by developing adaptive, company-driven intervention approaches which allow for continuous optimisation of companies from a health perspective. Also, approaches for active dissemination of such a systemic-salutogenic occupational health management approach should be developed to increase the public health impact of WHP.

  4. 3 CFR 8341 - Proclamation 8341 of January 16, 2009. To Implement the United States-Peru Trade Promotion...

    Science.gov (United States)

    2010-01-01

    ... the United States-Peru Trade Promotion Agreement and for Other Purposes 8341 Proclamation 8341... States-Peru Trade Promotion Agreement and for Other PurposesBy the President of the United States of... Promotion Agreement (the “Agreement”), and on June 24 and June 25, 2007, the Parties to the Agreement signed...

  5. Serpins Promote Cancer Cell Survival and Vascular Cooption in Brain Metastasis

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C.; Jin, Xin; Chen, Qing; Zhang, Xiang H.-F.; Lee, Derek J.; Chaft, Jamie E.; Kris, Mark G.; Huse, Jason T.; Brogi, Edi; Massagué, Joan

    2014-01-01

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM that metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its deleterious consequences. By protecting cancer cells from death signals and fostering vascular cooption, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. PMID:24581498

  6. The Brain: Its Relationship to Learning, Emotional States, and Behavior

    Science.gov (United States)

    Armstrong, Terry

    1977-01-01

    Outlines findings of contemporary neuro-scientists studying the biological basis of human learning and behavior. Areas of research discussed are: (1) the center of human emotion--the limbic system; (2) brain rhythms; and (3) the molecular basis of learning. (CS)

  7. Human TFIID binds to core promoter DNA in a reorganized structural state

    Science.gov (United States)

    Cianfrocco, Michael A.; Kassavetis, George A.; Grob, Patricia; Fang, Jie; Juven-Gershon, Tamar; Kadonaga, James T.; Nogales, Eva

    2012-01-01

    A mechanistic description of metazoan transcription is essential for understanding the molecular processes that govern cellular decisions. To provide structural insights into the DNA recognition step of transcription initiation, we used single particle electron microscopy to visualize human TFIID with promoter DNA. This analysis revealed that TFIID co-exists in two predominant and distinct structural states that differ by a 100Å translocation of TFIID’s lobe A. The transition between these structural states is modulated by TFIIA, as the presence of TFIIA and promoter DNA facilitates the formation of a novel rearranged state of TFIID capable of promoter recognition and binding. DNA-labeling and footprinting, together with cryo-EM studies, mapped the locations of the TATA, Inr, MTE, and DPE promoter motifs within the TFIID-TFIIA-DNA structure. The existence of two structurally and functionally distinct forms of TFIID suggests that the different conformers may serve as specific targets for the action of regulatory factors. PMID:23332750

  8. Glymphatic clearance controls state-dependent changes in brain lactate concentration

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Lu, Minh Lon; Yang, Ezra

    2017-01-01

    accumulation of lactate in cervical, but not in inguinal lymph nodes when mice were anesthetized. Thus, our study suggests that brain lactate is an excellent biomarker of the sleep-wake cycle and increases further during sleep deprivation, because brain lactate is inversely correlated with glymphatic......Brain lactate concentration is higher during wakefulness than in sleep. However, it is unknown why arousal is linked to an increase in brain lactate and why lactate declines within minutes of sleep. Here, we show that the glymphatic system is responsible for state-dependent changes in brain lactate...... concentration. Suppression of glymphatic function via acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, or changes in body position reduced the decline in brain lactate normally observed when awake mice transition into sleep or anesthesia. Concurrently, the same manipulations diminished...

  9. Deep Learning for Brain MRI Segmentation: State of the Art and Future Directions.

    Science.gov (United States)

    Akkus, Zeynettin; Galimzianova, Alfiia; Hoogi, Assaf; Rubin, Daniel L; Erickson, Bradley J

    2017-08-01

    Quantitative analysis of brain MRI is routine for many neurological diseases and conditions and relies on accurate segmentation of structures of interest. Deep learning-based segmentation approaches for brain MRI are gaining interest due to their self-learning and generalization ability over large amounts of data. As the deep learning architectures are becoming more mature, they gradually outperform previous state-of-the-art classical machine learning algorithms. This review aims to provide an overview of current deep learning-based segmentation approaches for quantitative brain MRI. First we review the current deep learning architectures used for segmentation of anatomical brain structures and brain lesions. Next, the performance, speed, and properties of deep learning approaches are summarized and discussed. Finally, we provide a critical assessment of the current state and identify likely future developments and trends.

  10. Brain and muscle Arnt-like 1 promotes skeletal muscle regeneration through satellite cell expansion

    Energy Technology Data Exchange (ETDEWEB)

    Chatterjee, Somik [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yin, Hongshan [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Cardiovascular Medicine, Third Affiliated Hospital, Hebei Medical University, Shijiazhuang 050051, Hebei (China); Nam, Deokhwa [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Li, Yong [Department of Pediatric Surgery, Center for Stem Cell Research and Regenerative Medicine, University of Texas Health Science Center at Houston, Houston, TX 77030 (United States); Ma, Ke, E-mail: kma@houstonmethodist.org [Center for Diabetes Research, Department of Medicine, Houston Methodist Research Institute, Houston, TX 77030 (United States)

    2015-02-01

    Circadian clock is an evolutionarily conserved timing mechanism governing diverse biological processes and the skeletal muscle possesses intrinsic functional clocks. Interestingly, although the essential clock transcription activator, Brain and muscle Arnt-like 1 (Bmal1), participates in maintenance of muscle mass, little is known regarding its role in muscle growth and repair. In this report, we investigate the in vivo function of Bmal1 in skeletal muscle regeneration using two muscle injury models. Bmal1 is highly up-regulated by cardiotoxin injury, and its genetic ablation significantly impairs regeneration with markedly suppressed new myofiber formation and attenuated myogenic induction. A similarly defective regenerative response is observed in Bmal1-null mice as compared to wild-type controls upon freeze injury. Lack of satellite cell expansion accounts for the regeneration defect, as Bmal1{sup −/−} mice display significantly lower satellite cell number with nearly abolished induction of the satellite cell marker, Pax7. Furthermore, satellite cell-derived primary myoblasts devoid of Bmal1 display reduced growth and proliferation ex vivo. Collectively, our results demonstrate, for the first time, that Bmal1 is an integral component of the pro-myogenic response that is required for muscle repair. This mechanism may underlie its role in preserving adult muscle mass and could be targeted therapeutically to prevent muscle-wasting diseases. - Highlights: • Bmal1 is highly inducible by muscle injury and myogenic stimuli. • Genetic ablation of Bmal1 significantly impairs muscle regeneration. • Bmal1 promotes satellite cell expansion during muscle regeneration. • Bmal1-deficient primary myoblasts display attenuated growth and proliferation.

  11. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  12. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Science.gov (United States)

    Zhang, Kuan; Zhou, Yanzhao; Zhao, Tong; Wu, Liying; Huang, Xin; Wu, Kuiwu; Xu, Lun; Li, Dahu; Liu, Shuhong; Zhao, Yongqi; Fan, Ming; Zhu, Lingling

    2015-01-01

    Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG) of the hippocampus and the sub-ventricular zone (SVZ) of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCs)in vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr) and DG (approximately 10 Torr) were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr). Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  13. Detecting brain dynamics during resting state: a tensor based evolutionary clustering approach

    Science.gov (United States)

    Al-sharoa, Esraa; Al-khassaweneh, Mahmood; Aviyente, Selin

    2017-08-01

    Human brain is a complex network with connections across different regions. Understanding the functional connectivity (FC) of the brain is important both during resting state and task; as disruptions in connectivity patterns are indicators of different psychopathological and neurological diseases. In this work, we study the resting state functional connectivity networks (FCNs) of the brain from fMRI BOLD signals. Recent studies have shown that FCNs are dynamic even during resting state and understanding the temporal dynamics of FCNs is important for differentiating between different conditions. Therefore, it is important to develop algorithms to track the dynamic formation and dissociation of FCNs of the brain during resting state. In this paper, we propose a two step tensor based community detection algorithm to identify and track the brain network community structure across time. First, we introduce an information-theoretic function to reduce the dynamic FCN and identify the time points that are similar topologically to combine them into a tensor. These time points will be used to identify the different FC states. Second, a tensor based spectral clustering approach is developed to identify the community structure of the constructed tensors. The proposed algorithm applies Tucker decomposition to the constructed tensors and extract the orthogonal factor matrices along the connectivity mode to determine the common subspace within each FC state. The detected community structure is summarized and described as FC states. The results illustrate the dynamic structure of resting state networks (RSNs), including the default mode network, somatomotor network, subcortical network and visual network.

  14. Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation

    Directory of Open Access Journals (Sweden)

    Alireza eGharabaghi

    2014-03-01

    Full Text Available Motor recovery after stroke is an unsolved challenge despite intensive rehabilitation training programs. Brain stimulation techniques have been explored in addition to traditional rehabilitation training to increase the excitability of the stimulated motor cortex. This modulation of cortical excitability augments the response to afferent input during motor exercises, thereby enhancing skilled motor learning by long-term potentiation-like plasticity. Recent approaches examined brain stimulation applied concurrently with voluntary movements to induce more specific use-dependent neural plasticity during motor training for neurorehabilitation. Unfortunately, such approaches are not applicable for the many severely affected stroke patients lacking residual hand function. These patients require novel activity-dependent stimulation paradigms based on intrinsic brain activity. Here, we report on such brain state-dependent stimulation (BSDS combined with haptic feedback provided by a robotic hand orthosis. Transcranial magnetic stimulation of the motor cortex and haptic feedback to the hand were controlled by sensorimotor desynchronization during motor-imagery and applied within a brain-machine interface environment in one healthy subject and one patient with severe hand paresis in the chronic phase after stroke. BSDS significantly increased the excitability of the stimulated motor cortex in both healthy and post-stroke conditions, an effect not observed in non-BSDS protocols. This feasibility study suggests that closing the loop between intrinsic brain state, cortical stimulation and haptic feedback provides a novel neurorehabilitation strategy for stroke patients lacking residual hand function, a proposal that warrants further investigation in a larger cohort of stroke patients.

  15. The promotion of moral ideals in schools; what the state may or may not demand

    NARCIS (Netherlands)

    de Ruyter, D.J.; Steutel, J.W.

    2013-01-01

    The content and boundaries of moral education the state may require schools to offer is a matter of contention. This article investigates whether the state may obligate schools to promote the pursuit of moral ideals. Moral ideals refer to (a cluster of) characteristics of a person as well as to

  16. Developing a state-wide infrastructure for safe sleep promotion.

    Science.gov (United States)

    Ahlers-Schmidt, Carolyn R; Schunn, Christy; Kuhlmann, Stephanie; Kuhlmann, Zachary; Engel, Matthew

    2017-08-01

    Sleep-related deaths are the third leading cause of infant death in Kansas. This manuscript describes implementation of an infrastructure of regional trainers to educate on the American Academy of Pediatrics safe sleep recommendations. Prospective evaluation of training program on knowledge transfer. Instructors were recruited from throughout the state of Kansas and trained to provide safe sleep education in their communities. Instructors were a mix of healthcare workers and community members. Their trainees encompassed both professionals and caregivers. Instructors attended a 2-day training, including completing 18-item pre and post-training knowledge tests, a training evaluation survey, and performing a portion of the structured safe sleep presentation and crib demonstration for feedback. Instructors were evaluated before and after training. After conducting trainings in their region, instructors submitted trainees' pre and post-test results. Scores were compared using t-test. Twenty-three instructors were trained. Scores averaged 13.5 (SD=2.4) for the pre-test and 15.3 (SD=2.4) for the post-test. Those scoring sleep education at 21 events to a total of 378 trainees. Trainee scores averaged 11.4 (SD=2.7) on the pre-test and increased to 13.9 (SD=2.5) on the post-test (Psleep instructors can be trained to disseminate safe sleep guidelines; however, only half provided at least 1 training within 1 year. Future recommendations include over-recruiting potential instructors, incorporating trainings into existing positions or otherwise incentivizing trainers. Copyright © 2017 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

  17. Immanuel Kant's mind and the brain's resting state.

    Science.gov (United States)

    Northoff, Georg

    2012-07-01

    The early philosopher Immanuel Kant suggested that the mind’s intrinsic features are intimately linked to the extrinsic stimuli of the environment it processes. Currently, the field faces an analogous problem with regard to the brain. Kant’s ideas may provide novel insights into how the brain’s intrinsic features must be so that they can be linked to the neural processing of extrinsic stimuli to enable the latter’s association with consciousness and self.

  18. Neural Stem Cell Transplantation Promotes Functional Recovery from Traumatic Brain Injury via Brain Derived Neurotrophic Factor-Mediated Neuroplasticity.

    Science.gov (United States)

    Xiong, Liu-Lin; Hu, Yue; Zhang, Piao; Zhang, Zhuo; Li, Li-Hong; Gao, Guo-Dong; Zhou, Xin-Fu; Wang, Ting-Hua

    2017-04-18

    Traumatic brain injury (TBI) induces cognitive impairments, motor and behavioral deficits. Previous evidences have suggested that neural stem cell (NSC) transplantation could facilitate functional recovery from brain insults, but their underlying mechanisms remains to be elucidated. Here, we established TBI model by an electromagnetic-controlled cortical impact device in the rats. Then, 5 μl NSCs (5.0 × 10 5 /μl), derived from green fluorescent protein (GFP) transgenic mouse, was transplanted into the traumatic brain regions of rats at 24 h after injury. After differentiation of the NSCs was determined using immunohistochemistry, neurological severity scores (NSS) and rotarod test were conducted to detect the neurological behavior. Western blot and RT-PCR as well as ELASA were used to evaluate the expression of synaptophysin and brain-derived neurotrophic factor (BDNF). In order to elucidate the role of BDNF on the neural recovery after NSC transplantation, BDNF knockdown in NSC was performed and transplanted into the rats with TBI, and potential mechanism for BDNF knockdown in the NSC was analyzed using microassay analysis. Meanwhile, BDNF antibody blockade was conducted to further confirm the effect of BDNF on neural activity. As a result, an increasing neurological function improvement was seen in NSC transplanted rats, which was associated with the upregulation of synaptophysin and BDNF expression. Moreover, transplantation of BDNF knockdown NSCs and BDNF antibody block reduced not only the level of synaptophysin but also exacerbated neurological function deficits. Microassay analysis showed that 14 genes such as Wnt and Gsk3-β were downregulated after BDNF knockdown. The present data therefore showed that BDNF-mediated neuroplasticity underlie the mechanism of NSC transplantation for the treatment of TBI in adult rats.

  19. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate.

    Science.gov (United States)

    Sleiman, Sama F; Henry, Jeffrey; Al-Haddad, Rami; El Hayek, Lauretta; Abou Haidar, Edwina; Stringer, Thomas; Ulja, Devyani; Karuppagounder, Saravanan S; Holson, Edward B; Ratan, Rajiv R; Ninan, Ipe; Chao, Moses V

    2016-06-02

    Exercise induces beneficial responses in the brain, which is accompanied by an increase in BDNF, a trophic factor associated with cognitive improvement and the alleviation of depression and anxiety. However, the exact mechanisms whereby physical exercise produces an induction in brain Bdnf gene expression are not well understood. While pharmacological doses of HDAC inhibitors exert positive effects on Bdnf gene transcription, the inhibitors represent small molecules that do not occur in vivo. Here, we report that an endogenous molecule released after exercise is capable of inducing key promoters of the Mus musculus Bdnf gene. The metabolite β-hydroxybutyrate, which increases after prolonged exercise, induces the activities of Bdnf promoters, particularly promoter I, which is activity-dependent. We have discovered that the action of β-hydroxybutyrate is specifically upon HDAC2 and HDAC3, which act upon selective Bdnf promoters. Moreover, the effects upon hippocampal Bdnf expression were observed after direct ventricular application of β-hydroxybutyrate. Electrophysiological measurements indicate that β-hydroxybutyrate causes an increase in neurotransmitter release, which is dependent upon the TrkB receptor. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF.

  20. Subacute intranasal administration of tissue plasminogen activator promotes neuroplasticity and improves functional recovery following traumatic brain injury in rats.

    Directory of Open Access Journals (Sweden)

    Yuling Meng

    Full Text Available Traumatic brain injury (TBI is a major cause of death and long-term disability worldwide. To date, there are no effective pharmacological treatments for TBI. Recombinant human tissue plasminogen activator (tPA is the effective drug for the treatment of acute ischemic stroke. In addition to its thrombolytic effect, tPA is also involved in neuroplasticity in the central nervous system. However, tPA has potential adverse side effects when administered intravenously including brain edema and hemorrhage. Here we report that tPA, administered by intranasal delivery during the subacute phase after TBI, provides therapeutic benefit. Animals with TBI were treated intranasally with saline or tPA initiated 7 days after TBI. Compared with saline treatment, subacute intranasal tPA treatment significantly 1 improved cognitive (Morris water maze test and sensorimotor (footfault and modified neurological severity score functional recovery in rats after TBI, 2 reduced the cortical stimulation threshold evoking ipsilateral forelimb movement, 3 enhanced neurogenesis in the dentate gyrus and axonal sprouting of the corticospinal tract originating from the contralesional cortex into the denervated side of the cervical gray matter, and 4 increased the level of mature brain-derived neurotrophic factor. Our data suggest that subacute intranasal tPA treatment improves functional recovery and promotes brain neurogenesis and spinal cord axonal sprouting after TBI, which may be mediated, at least in part, by tPA/plasmin-dependent maturation of brain-derived neurotrophic factor.

  1. Cancer-associated fibroblast promote transmigration through endothelial brain cells in three-dimensional in vitro models.

    Science.gov (United States)

    Choi, Yoon Pyo; Lee, Joo Hyun; Gao, Ming-Qing; Kim, Baek Gil; Kang, Suki; Kim, Se Hoon; Cho, Nam Hoon

    2014-11-01

    Brain metastases are associated with high morbidity as well as with poor prognosis and survival in breast cancer patients. Despite its clinical importance, metastasis of breast cancer cells through the blood-brain barrier (BBB) is poorly understood. The objective of our study was to investigate whether cancer-associated fibroblasts (CAFs) play crucial roles in breast cancer brain metastasis. Using a cell adhesion assays, in vitro BBB permeability and transmigration assays and soft agar colony formation assays, we investigated the physical roles of CAFs in breast cancer brain metastasis. We also performed immunofluorescence, flow cytometric analysis, Droplet Digital PCR and Simon™ Simple Western System to confirm changes in expression levels. We established two novel three-dimensional (3D) culture systems using a perpendicular slide chamber and applying 3D embedded culture method to reflect brain metastasis conditions. With a newly developed device, CAFs was proven to promote cell adhesion to human brain microvascular endothelial cells, in vitro BBB permeability and transmigration and colony formation of breast cancer cells. Furthermore, CAFs enhanced the invasive migration of breast cancer cells in two kinds of 3D cultures. These 3D models also reliably recapitulate the initial steps of BBB transmigration, micro-metastasis and colonization. Expression of integrin α5β1 and αvβ3, c-MET and α2,6-siayltransferase was increased in breast cancer cells that migrated through the BBB. In conclusion, based on our in vitro BBB and co-culture models, our data suggest that CAFs may play a role in breast cancer brain metastasis. © 2014 UICC.

  2. Contributions of training to the promotion of health in State Health Services: comparative analysis in eight states in Mexico

    Directory of Open Access Journals (Sweden)

    Jacqueline Elizabeth Alcalde-Rabanal

    2013-05-01

    Full Text Available Objective. To evaluate the results of the training provided by the National Public Health Institute (INSP per its abbreviation in Spanish in health promotion to institutional staff of local health services during 2007 and 2008. Materials and methods. A non-experimental evaluative research with comparison group was conducted, in which quantitative and qualitative methods were used. Results. In states intervened a better conceptualization of health promotion, social  participation and components of the Health Promotion Operating Model was observed; participatory action research was the basic strategy to work in the community and management showed a tendency to be more participatory and inclusive. Conclusion. A better conceptualization of health promotion has allowed health personnel develop more sustainable work processes in the community and has driven the search for consent and participatory management.

  3. The metastasis-promoting S100A4 protein confers neuroprotection in brain injury

    DEFF Research Database (Denmark)

    Dmytriyeva, Oksana; Pankratova, Stanislava; Owczarek, Sylwia

    2012-01-01

    Identification of novel pro-survival factors in the brain is paramount for developing neuroprotective therapies. The multifunctional S100 family proteins have important roles in many human diseases and are also upregulated by brain injury. However, S100 functions in the nervous system remain...

  4. State Laws Are Associated with School Lunch Duration and Promotion Practices.

    Science.gov (United States)

    Turner, Lindsey; Leider, Julien; Piekarz-Porter, Elizabeth; Schwartz, Marlene B; Merlo, Caitlin; Brener, Nancy; Chriqui, Jamie F

    2017-10-27

    The changes in school meal programs stemming from the Healthy, Hunger-Free Kids Act of 2010 have expanded interest in strategies that increase student participation in school lunch and reduce plate waste. However, it remains unclear what factors are associated with schools' use of such strategies. This study examines whether state laws are associated with two types of school meal-related practices: (a) using promotional strategies (ie, taste tests, using posters or announcements) and (b) duration of lunch periods. This cross-sectional study utilized the nationally representative 2014 School Health Policies and Practices Study, combined with corresponding state laws gathered by the National Wellness Policy Study. School data were available from 414 public schools in 43 states. Outcome measures included 16 strategies to promote school meals and the amount of time students had to eat lunch after being seated. Multivariate logistic regression and Poisson regression were used to examine associations between state laws and school practices, after accounting for school demographic characteristics. Compared to schools in states with no law about engaging stakeholders in meal programs, schools in states with a law were more likely to conduct taste tests (64% vs 44%, P=0.016), collect suggestions from students (67% vs 50%, P=0.017), and invite family members to a school meal (71% vs 53%, P=0.015). Schools used more promotion strategies in states with a law than in states without a law (mean=10.4 vs 8.8, P=0.003). Schools were more likely to provide students at least 30 minutes to eat lunch after being seated in states with laws that addressed a minimum amount of time for lunch duration (43% vs 27%, P=0.042). State-level policy provisions are associated with school practices. Policy development in more states may support school practices that promote lunch participation and consumption. Copyright © 2017 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All

  5. Brain state and changes of mind: Probing the neural bases of multi-stable perceptual dynamics

    NARCIS (Netherlands)

    Kloosterman, N.A.

    2015-01-01

    The internal state of our brain changes constantly, affecting the way in which the cerebral cortex processes information. Changes of cortical state have traditionally been associated with slow and largely automatic fluctuations of wakefulness and arousal, but they can also occur on a rapid

  6. Stability of whole brain and regional network topology within and between resting and cognitive states.

    Directory of Open Access Journals (Sweden)

    Justyna K Rzucidlo

    Full Text Available BACKGROUND: Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. METHODOLOGY/PRINCIPAL FINDINGS: fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. CONCLUSIONS/SIGNIFICANCE: These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

  7. Stability of whole brain and regional network topology within and between resting and cognitive states.

    Science.gov (United States)

    Rzucidlo, Justyna K; Roseman, Paige L; Laurienti, Paul J; Dagenbach, Dale

    2013-01-01

    Graph-theory based analyses of resting state functional Magnetic Resonance Imaging (fMRI) data have been used to map the network organization of the brain. While numerous analyses of resting state brain organization exist, many questions remain unexplored. The present study examines the stability of findings based on this approach over repeated resting state and working memory state sessions within the same individuals. This allows assessment of stability of network topology within the same state for both rest and working memory, and between rest and working memory as well. fMRI scans were performed on five participants while at rest and while performing the 2-back working memory task five times each, with task state alternating while they were in the scanner. Voxel-based whole brain network analyses were performed on the resulting data along with analyses of functional connectivity in regions associated with resting state and working memory. Network topology was fairly stable across repeated sessions of the same task, but varied significantly between rest and working memory. In the whole brain analysis, local efficiency, Eloc, differed significantly between rest and working memory. Analyses of network statistics for the precuneus and dorsolateral prefrontal cortex revealed significant differences in degree as a function of task state for both regions and in local efficiency for the precuneus. Conversely, no significant differences were observed across repeated sessions of the same state. These findings suggest that network topology is fairly stable within individuals across time for the same state, but also fluid between states. Whole brain voxel-based network analyses may prove to be a valuable tool for exploring how functional connectivity changes in response to task demands.

  8. [Between psyche and brain : State of the art in psychiatry].

    Science.gov (United States)

    Fuchs, T

    2017-05-01

    Since its development around 1800 psychiatry has been oscillating between the poles of the sciences and the humanities, being directed towards subjective experience on the one hand and towards the neural substrate on the other hand. Today, this dualism seems to have been overcome by a naturalism, which identifies subjective experience with neural processes, according to Griesinger's frequently quoted statement "mental diseases are brain diseases". The progress achieved by the neurobiological paradigm on the level of a fundamental science is in contrast to the tendency to isolate mental illnesses from the patients' social relationships and to neglect subjectivity and intersubjectivity in their explanation. What should be searched for is therefore an overarching paradigm that is able to establish psychiatry as a relational medicine in an encompassing sense: as a science and practice of biological, psychological and social relationships and their disorders. Within such a paradigm, the brain may be understood and investigated as the central "relational organ" without reductionist constrictions.

  9. Serpins promote cancer cell survival and vascular co-option in brain metastasis.

    Science.gov (United States)

    Valiente, Manuel; Obenauf, Anna C; Jin, Xin; Chen, Qing; Zhang, Xiang H-F; Lee, Derek J; Chaft, Jamie E; Kris, Mark G; Huse, Jason T; Brogi, Edi; Massagué, Joan

    2014-02-27

    Brain metastasis is an ominous complication of cancer, yet most cancer cells that infiltrate the brain die of unknown causes. Here, we identify plasmin from the reactive brain stroma as a defense against metastatic invasion, and plasminogen activator (PA) inhibitory serpins in cancer cells as a shield against this defense. Plasmin suppresses brain metastasis in two ways: by converting membrane-bound astrocytic FasL into a paracrine death signal for cancer cells, and by inactivating the axon pathfinding molecule L1CAM, which metastatic cells express for spreading along brain capillaries and for metastatic outgrowth. Brain metastatic cells from lung cancer and breast cancer express high levels of anti-PA serpins, including neuroserpin and serpin B2, to prevent plasmin generation and its metastasis-suppressive effects. By protecting cancer cells from death signals and fostering vascular co-option, anti-PA serpins provide a unifying mechanism for the initiation of brain metastasis in lung and breast cancers. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. The influence of low-grade glioma on resting state oscillatory brain activity: a magnetoencephalography study.

    Science.gov (United States)

    Bosma, I; Stam, C J; Douw, L; Bartolomei, F; Heimans, J J; van Dijk, B W; Postma, T J; Klein, M; Reijneveld, J C

    2008-05-01

    In the present MEG-study, power spectral analysis of oscillatory brain activity was used to compare resting state brain activity in both low-grade glioma (LGG) patients and healthy controls. We hypothesized that LGG patients show local as well as diffuse slowing of resting state brain activity compared to healthy controls and that particularly global slowing correlates with neurocognitive dysfunction. Resting state MEG recordings were obtained from 17 LGG patients and 17 age-, sex-, and education-matched healthy controls. Relative spectral power was calculated in the delta, theta, upper and lower alpha, beta, and gamma frequency band. A battery of standardized neurocognitive tests measuring 6 neurocognitive domains was administered. LGG patients showed a slowing of the resting state brain activity when compared to healthy controls. Decrease in relative power was mainly found in the gamma frequency band in the bilateral frontocentral MEG regions, whereas an increase in relative power was found in the theta frequency band in the left parietal region. An increase of the relative power in the theta and lower alpha band correlated with impaired executive functioning, information processing, and working memory. LGG patients are characterized by global slowing of their resting state brain activity and this slowing phenomenon correlates with the observed neurocognitive deficits.

  11. Spin-glass model predicts metastable brain states that diminish in anesthesia

    Directory of Open Access Journals (Sweden)

    Anthony G Hudetz

    2014-12-01

    Full Text Available Patterns of resting state connectivity change dynamically and may represent modes of cognitive information processing. The diversity of connectivity patterns (global brain states reflects the information capacity of the brain and determines the state of consciousness. In this work, computer simulation was used to explore the repertoire of global brain states as a function of cortical activation level. We implemented a modified spin glass model to describe UP/DOWN state transitions of neuronal populations at a mesoscopic scale based on resting state BOLD fMRI data. Resting state fMRI was recorded in 20 participants and mapped to 10,000 cortical regions defined on a group-aligned cortical surface map. Each region represented the population activity of a ~20mm2 area of the cortex. Cross-correlation matrices of the mapped BOLD time courses of the set of regions were calculated and averaged across subjects. In the model, each cortical region was allowed to interact with the 16 other regions that had the highest pair-wise correlation values. All regions stochastically transitioned between UP and DOWN states under the net influence of their 16 pairs. The probability of local state transitions was controlled by a single parameter T corresponding to the level of global cortical activation. To estimate the number of distinct global states, first we ran 10,000 simulations at T=0. Simulations were started from random configurations that converged to one of several distinct patterns. Using hierarchical clustering, at 99% similarity, close to 300 distinct states were found. At intermediate T, metastable state configurations were formed suggesting critical behavior with a sharp increase in the number of metastable states at an optimal T. Both reduced activation (anesthesia, sleep and increased activation (hyper-activation moved the system away from equilibrium, presumably incompatible with conscious mentation. During equilibrium, the diversity of large

  12. Creative music therapy to promote brain structure, function, and neurobehavioral outcomes in preterm infants: a randomized controlled pilot trial protocol.

    Science.gov (United States)

    Haslbeck, Friederike Barbara; Bucher, Hans-Ulrich; Bassler, Dirk; Hagmann, Cornelia

    2017-01-01

    Preterm birth is associated with increased risk of neurological impairment and deficits in cognition, motor function, and behavioral problems. Limited studies indicate that multi-sensory experiences support brain development in preterm infants. Music appears to promote neurobiological processes and neuronal learning in the human brain. Creative music therapy (CMT) is an individualized, interactive therapeutic approach based on the theory and methods of Nordoff and Robbins. CMT may promote brain development in preterm infants via concurrent interaction and meaningful auditory stimulation. We hypothesize that preterm infants who receive creative music therapy during neonatal intensive care admission will have developmental benefits short- and long-term brain function. A prospective, randomized controlled single-center pilot trial involving 60 clinically stable preterm infants under 32 weeks of gestational age is conducted in preparation for a multi-center trial. Thirty infants each are randomized to either standard neonatal intensive care or standard care with CMT. Music therapy intervention is approximately 20 min in duration three times per week. A trained music therapist sings for the infants in lullaby style, individually entrained and adjusted to the infant's rhythm and affect. Primary objectives of this study are feasibility of protocol implementation and investigating the potential mechanism of efficacy for this new intervention. To examine the effect of this new intervention, non-invasive, quantitative magnetic resonance imaging (MRI) methods at corrected age and standardized neurodevelopmental assessments using the Bayley Scales of Infant and Toddler Development third edition at a corrected age of 24 months and Kaufman Assessment Battery for Children at 5 years will be performed. All assessments will be performed and analyzed by blinded experts. To our knowledge, this is the first randomized controlled clinical trial to systematically examine possible

  13. State of the Art: Novel Applications for Deep Brain Stimulation.

    Science.gov (United States)

    Roy, Holly A; Green, Alexander L; Aziz, Tipu Z

    2017-05-17

    Deep brain stimulation (DBS) is a rapidly developing field of neurosurgery with potential therapeutic applications that are relevant to conditions traditionally viewed as beyond the limits of neurosurgery. Our objective, in this review, is to highlight some of the emerging applications of DBS within three distinct but overlapping spheres, namely trauma, neuropsychiatry, and autonomic physiology. An extensive literature review was carried out in MEDLINE, to identify relevant studies and review articles describing applications of DBS in the areas of trauma, neuropsychiatry and autonomic neuroscience. A wide range of applications of DBS in these spheres was identified, some having only been tested in one or two cases, others much better studied. We have identified various avenues for DBS to be applied for patient benefit in cases relevant to trauma, neuropsychiatry and autonomic neuroscience. Further developments in DBS technology and clinical trial design will enable these novel applications to be effectively and rigorously assessed and utilized most effectively. © 2017 International Neuromodulation Society.

  14. Cyclin A2 promotes DNA repair in the brain during both development and aging

    OpenAIRE

    Gygli, Patrick E.; Chang, Joshua C.; Gokozan, Hamza N.; Catacutan, Fay P.; Schmidt, Theresa A.; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S.; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J.

    2016-01-01

    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss resu...

  15. Wellness general of the United States: a creative approach to promote family and community health.

    Science.gov (United States)

    Haber, David

    2002-10-01

    This article offers a creative approach to promote family and community health, beginning with the conversion of the office of Surgeon General of the United States into the Wellness General of the United States. The content ranges from federal initiatives to promote quality health research to individuals and families who will be the beneficiaries at medical clinics and community health programs. The proposal recommends changes to institutions and policies, including junk food taxes, the National Institutes of Health, the United States Preventive Services Task Force, the Healthy People 2010 initiative, the Health Plan Employer Data and Information Set, the Medicare Coverage Advisory Committee, state health mandates, local health plans, community medical clinics, and community health programs. The goal is to stimulate ideas and actions among policymakers, researchers, practitioners, educators, and students.

  16. Soft drink effects on sensorimotor rhythm brain computer interface performance and resting-state spectral power.

    Science.gov (United States)

    Mundahl, John; Jianjun Meng; He, Jeffrey; Bin He

    2016-08-01

    Brain-computer interface (BCI) systems allow users to directly control computers and other machines by modulating their brain waves. In the present study, we investigated the effect of soft drinks on resting state (RS) EEG signals and BCI control. Eight healthy human volunteers each participated in three sessions of BCI cursor tasks and resting state EEG. During each session, the subjects drank an unlabeled soft drink with either sugar, caffeine, or neither ingredient. A comparison of resting state spectral power shows a substantial decrease in alpha and beta power after caffeine consumption relative to control. Despite attenuation of the frequency range used for the control signal, caffeine average BCI performance was the same as control. Our work provides a useful characterization of caffeine, the world's most popular stimulant, on brain signal frequencies and their effect on BCI performance.

  17. Relationship of Topology, Multiscale Phase Synchronization, and State Transitions in Human Brain Networks

    Directory of Open Access Journals (Sweden)

    Minkyung Kim

    2017-06-01

    Full Text Available How the brain reconstitutes consciousness and cognition after a major perturbation like general anesthesia is an important question with significant neuroscientific and clinical implications. Recent empirical studies in animals and humans suggest that the recovery of consciousness after anesthesia is not random but ordered. Emergence patterns have been classified as progressive and abrupt transitions from anesthesia to consciousness, with associated differences in duration and electroencephalogram (EEG properties. We hypothesized that the progressive and abrupt emergence patterns from the unconscious state are associated with, respectively, continuous and discontinuous synchronization transitions in functional brain networks. The discontinuous transition is explainable with the concept of explosive synchronization, which has been studied almost exclusively in network science. We used the Kuramato model, a simple oscillatory network model, to simulate progressive and abrupt transitions in anatomical human brain networks acquired from diffusion tensor imaging (DTI of 82 brain regions. To facilitate explosive synchronization, distinct frequencies for hub nodes with a large frequency disassortativity (i.e., higher frequency nodes linking with lower frequency nodes, or vice versa were applied to the brain network. In this simulation study, we demonstrated that both progressive and abrupt transitions follow distinct synchronization processes at the individual node, cluster, and global network levels. The characteristic synchronization patterns of brain regions that are “progressive and earlier” or “abrupt but delayed” account for previously reported behavioral responses of gradual and abrupt emergence from the unconscious state. The characteristic network synchronization processes observed at different scales provide new insights into how regional brain functions are reconstituted during progressive and abrupt emergence from the unconscious

  18. Is functional integration of resting state brain networks an unspecific biomarker for working memory performance?

    Science.gov (United States)

    Alavash, Mohsen; Doebler, Philipp; Holling, Heinz; Thiel, Christiane M; Gießing, Carsten

    2015-03-01

    Is there one optimal topology of functional brain networks at rest from which our cognitive performance would profit? Previous studies suggest that functional integration of resting state brain networks is an important biomarker for cognitive performance. However, it is still unknown whether higher network integration is an unspecific predictor for good cognitive performance or, alternatively, whether specific network organization during rest predicts only specific cognitive abilities. Here, we investigated the relationship between network integration at rest and cognitive performance using two tasks that measured different aspects of working memory; one task assessed visual-spatial and the other numerical working memory. Network clustering, modularity and efficiency were computed to capture network integration on different levels of network organization, and to statistically compare their correlations with the performance in each working memory test. The results revealed that each working memory aspect profits from a different resting state topology, and the tests showed significantly different correlations with each of the measures of network integration. While higher global network integration and modularity predicted significantly better performance in visual-spatial working memory, both measures showed no significant correlation with numerical working memory performance. In contrast, numerical working memory was superior in subjects with highly clustered brain networks, predominantly in the intraparietal sulcus, a core brain region of the working memory network. Our findings suggest that a specific balance between local and global functional integration of resting state brain networks facilitates special aspects of cognitive performance. In the context of working memory, while visual-spatial performance is facilitated by globally integrated functional resting state brain networks, numerical working memory profits from increased capacities for local processing

  19. Taurine enhances the growth of neural precursors derived from fetal human brain and promotes neuronal specification.

    Science.gov (United States)

    Hernández-Benítez, Reyna; Vangipuram, Sharada D; Ramos-Mandujano, Gerardo; Lyman, William D; Pasantes-Morales, Herminia

    2013-01-01

    Taurine is present at high concentrations in the fetal brain and is required for optimal brain development. Recent studies have reported that taurine causes increased proliferation of neural stem/progenitor neural cells (neural precursor cells, NPCs) obtained from embryonic and adult rodent brain. The present study is the first to show that taurine markedly increases cell numbers in cultures and neuronal generation from human NPCs (hNPCs). hNPCs obtained from 3 fetal brains (14-15 weeks of gestation) were cultured and expanded as neurospheres, which contained 76.3% nestin-positive cells. Taurine (5-20 mM) increased the number of hNPCs in culture, with maximal effect found at 10 mM and 4 days of culture. The taurine-induced increase ranged from 57 to 188% in the 3 brains examined. Taurine significantly enhanced the percentage of neurons formed from hNPCs under differentiating conditions, with increases ranging from 172 to 480% over controls without taurine. Taurine also increased the cell number and neuronal generation in cultures of the immortalized human cell line ReNcell VM. These results suggest that taurine has a positive influence on hNPC growth and neuronal formation. Copyright © 2013 S. Karger AG, Basel.

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

    OpenAIRE

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

    2013-01-01

    Both resting state fMRI (R-fMRI) and task-based fMRI (T-fMRI) have been widely used to study the functional activities of the human brain during task-free and task-performance periods, respectively. However, due to the difficulty in strictly controlling the participating subject's mental status and their cognitive behaviors during R-fMRI/T-fMRI scans, it has been challenging to ascertain whether or not an R-fMRI/T-fMRI scan truly reflects the participant's functional brain states during task-...

  1. Meal Replacement: Calming the Hot-State Brain Network of Appetite

    OpenAIRE

    Brielle ePaolini; Laurienti, Paul J.; James eNorris; W. Jack eRejeski

    2014-01-01

    There is a growing awareness in the field of neuroscience that the self-regulation of eating behavior is driven by complex networks within the brain. These networks may be vulnerable to hot states which people can move into and out of dynamically throughout the course of a day as a function of changes in affect or visceral cues. The goal of the current study was to identify and determine differences in the Hot-state Brain Network of Appetite (HBN-A) that exists after a brief period of food re...

  2. An Integrated Neuroscience and Engineering Approach to Classifying Human Brain-States

    Science.gov (United States)

    2015-12-22

    AFRL-AFOSR-VA-TR-2016-0037 An Integrated Neuroscience and Engineering Approach to Classifying Human Brain-States Adrian Lee UNIVERSITY OF WASHINGTON...FORM TO THE ABOVE ORGANIZATION . 1. REPORT DATE (DD-MM-YYYY)      06-01-2016 2. REPORT TYPE Final Performance 3. DATES COVERED (From - To) 15-09-2012...to 14-09-2015 4. TITLE AND SUBTITLE An Integrated Neuroscience and Engineering Approach to Classifying Human Brain- States 5a.  CONTRACT NUMBER 5b

  3. Does Global Astrocytic Calcium Signaling Participate in Awake Brain State Transitions and Neuronal Circuit Function?

    DEFF Research Database (Denmark)

    Kjaerby, Celia; Rasmussen, Rune; Andersen, Mie

    2017-01-01

    We continuously need to adapt to changing conditions within our surrounding environment, and our brain needs to quickly shift between resting and working activity states in order to allow appropriate behaviors. These global state shifts are intimately linked to the brain-wide release...... look at the development and availability of innovative new methodological tools that are opening up for new ways of visualizing and perturbing astrocyte activity in awake behaving animals. With these new tools at hand, the field of astrocyte research will likely be able to elucidate the causal...... and mechanistic roles of astrocytes in complex behaviors within a very near future....

  4. Dynamic Multiscale Modes of Resting State Brain Activity Detected by Entropy Field Decomposition.

    Science.gov (United States)

    Frank, Lawrence R; Galinsky, Vitaly L

    2016-09-01

    The ability of functional magnetic resonance imaging (FMRI) to noninvasively measure fluctuations in brain activity in the absence of an applied stimulus offers the possibility of discerning functional networks in the resting state of the brain. However, the reconstruction of brain networks from these signal fluctuations poses a significant challenge because they are generally nonlinear and nongaussian and can overlap in both their spatial and temporal extent. Moreover, because there is no explicit input stimulus, there is no signal model with which to compare the brain responses. A variety of techniques have been devised to address this problem, but the predominant approaches are based on the presupposition of statistical properties of complex brain signal parameters, which are unprovable but facilitate the analysis. In this article, we address this problem with a new method, entropy field decomposition, for estimating structure within spatiotemporal data. This method is based on a general information field-theoretic formulation of Bayesian probability theory incorporating prior coupling information that allows the enumeration of the most probable parameter configurations without the need for unjustified statistical assumptions. This approach facilitates the construction of brain activation modes directly from the spatial-temporal correlation structure of the data. These modes and their associated spatial-temporal correlation structure can then be used to generate space-time activity probability trajectories, called functional connectivity pathways, which provide a characterization of functional brain networks.

  5. Assistive technology-based programs to promote communication and leisure activities by three children emerged from a minimal conscious state.

    Science.gov (United States)

    Stasolla, Fabrizio; Caffò, Alessandro O; Damiani, Rita; Perilli, Viviana; Di Leone, Antonia; Albano, Vincenza

    2015-02-01

    This study proposed the use of assistive technology (AT) to promote communication and leisure opportunities by three children with traumatic brain injury (TBI). Furthermore, it assessed the effects of such technology on the indices of positive participation and provided a social validation procedure. Three children emerged from a minimal conscious state and presenting extensive motor disabilities were involved. The intervention program allowed the participants to request and to choice preferred items independently and to perform literacy through a keyboard emulator. A multiple probe design across behaviors with post-intervention check was employed. Outcome measures were correct requests, understandable words, intervals with positive participation, and scores of social validation assessment. Request and choice behaviors and literacy improved significantly during intervention phases. During post-intervention check, all participants consolidated their performance. Moreover, indices of positive participation increased during intervention phases. Scores of social validation assessment showed that the combination of both behaviors was preferable to the same considered separately. AT program showed to be suitable for promoting constructive engagement and literacy behaviors by children with TBI. Future research is needed to generalize this data to a larger sample and to develop new technology for people with different levels of disabilities due to TBI.

  6. Use of Ancillary Tests When Determining Brain Death in Pediatric Patients in the United States.

    Science.gov (United States)

    Lewis, Ariane; Adams, Nellie; Chopra, Arun; Kirschen, Matthew P

    2017-10-01

    Although pediatric brain death guidelines stipulate when ancillary testing should be used during brain death determination, little is known about the way these recommendations are implemented in clinical practice. We conducted a survey of pediatric intensivists and neurologists in the United States on the use of ancillary testing. Although most respondents noted they only performed an ancillary test if the clinical examination and apnea test could not be completed, 20% of 195 respondents performed an ancillary test for other reasons, including (1) to convince a family that objected to the brain death determination that a patient is truly dead (n = 21), (2) personal preference (n = 14), and (3) institutional requirement (n = 5). Our findings suggest that pediatricians use ancillary tests for a variety of reasons during brain death determination. Medical societies and governmental regulatory bodies must reinforce the need for homogeneity in practice.

  7. Relation of visual creative imagery manipulation to resting-state brain oscillations.

    Science.gov (United States)

    Cai, Yuxuan; Zhang, Delong; Liang, Bishan; Wang, Zengjian; Li, Junchao; Gao, Zhenni; Gao, Mengxia; Chang, Song; Jiao, Bingqing; Huang, Ruiwang; Liu, Ming

    2017-03-07

    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.

  8. Structurally-constrained relationships between cognitive states in the human brain.

    Directory of Open Access Journals (Sweden)

    Ann M Hermundstad

    2014-05-01

    Full Text Available The anatomical connectivity of the human brain supports diverse patterns of correlated neural activity that are thought to underlie cognitive function. In a manner sensitive to underlying structural brain architecture, we examine the extent to which such patterns of correlated activity systematically vary across cognitive states. Anatomical white matter connectivity is compared with functional correlations in neural activity measured via blood oxygen level dependent (BOLD signals. Functional connectivity is separately measured at rest, during an attention task, and during a memory task. We assess these structural and functional measures within previously-identified resting-state functional networks, denoted task-positive and task-negative networks, that have been independently shown to be strongly anticorrelated at rest but also involve regions of the brain that routinely increase and decrease in activity during task-driven processes. We find that the density of anatomical connections within and between task-positive and task-negative networks is differentially related to strong, task-dependent correlations in neural activity. The space mapped out by the observed structure-function relationships is used to define a quantitative measure of separation between resting, attention, and memory states. We find that the degree of separation between states is related to both general measures of behavioral performance and relative differences in task-specific measures of attention versus memory performance. These findings suggest that the observed separation between cognitive states reflects underlying organizational principles of human brain structure and function.

  9. Progesterone mediates brain functional connectivity changes during the menstrual cycle - A pilot resting state MRI study

    Directory of Open Access Journals (Sweden)

    Katrin eArelin

    2015-02-01

    Full Text Available The growing interest in intrinsic brain organization has sparked various innovative approaches to generating comprehensive connectivity-based maps of the human brain. Prior reports point to a sexual dimorphism of the structural and functional human connectome. However, it is uncertain whether subtle changes in sex hormones, as occur during the monthly menstrual cycle, substantially impact the functional architecture of the female brain. Here, we performed eigenvector centrality (EC mapping in 32 longitudinal resting state fMRI scans of a single healthy subject without oral contraceptive use, across four menstrual cycles, and assessed estrogen and progesterone levels. To investigate associations between cycle-dependent hormones and brain connectivity, we performed correlation analyses between the EC maps and the respective hormone levels. On the whole brain level, we found a significant positive correlation between progesterone and EC in the bilateral DLPFC and bilateral sensorimotor cortex. In a secondary region-of-interest analysis, we detected a progesterone-modulated increase in functional connectivity of both bilateral DLPFC and bilateral sensorimotor cortex with the hippocampus. Our results suggest that the menstrual cycle substantially impacts intrinsic functional connectivity, particularly in brain areas associated with contextual memory-regulation, such as the hippocampus. These findings are the first to link the subtle hormonal fluctuations that occur during the menstrual cycle, to significant changes in regional functional connectivity in the hippocampus in a longitudinal design, given the limitation of data acquisition in a single subject. Our study demonstrates the feasibility of such a longitudinal rs-fMRI design and illustrates a means of creating a personalized map of the human brain by integrating potential mediators of brain states, such as menstrual cycle phase.

  10. The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs.

    Science.gov (United States)

    Carhart-Harris, Robin L; Leech, Robert; Hellyer, Peter J; Shanahan, Murray; Feilding, Amanda; Tagliazucchi, Enzo; Chialvo, Dante R; Nutt, David

    2014-01-01

    Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neurodynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of "primary states" is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. Indeed, since there is a greater repertoire of connectivity motifs in the psychedelic state than in normal waking consciousness, this implies that primary states may exhibit "criticality," i.e., the property of being poised at a "critical" point in a transition zone between order and disorder where certain phenomena such as power-law scaling appear. Moreover, if primary states are critical, then this suggests that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes normal waking consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organized activity within the default-mode network (DMN) and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled). These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as rapid eye movement (REM) sleep and early psychosis and comparing these with

  11. Behavioral state classification in epileptic brain using intracranial electrophysiology

    Science.gov (United States)

    Kremen, Vaclav; Duque, Juliano J.; Brinkmann, Benjamin H.; Berry, Brent M.; Kucewicz, Michal T.; Khadjevand, Fatemeh; Van Gompel, Jamie; Stead, Matt; St. Louis, Erik K.; Worrell, Gregory A.

    2017-04-01

    Objective. Automated behavioral state classification can benefit next generation implantable epilepsy devices. In this study we explored the feasibility of automated awake (AW) and slow wave sleep (SWS) classification using wide bandwidth intracranial EEG (iEEG) in patients undergoing evaluation for epilepsy surgery. Approach. Data from seven patients (age 34+/- 12 , 4 women) who underwent intracranial depth electrode implantation for iEEG monitoring were included. Spectral power features (0.1-600 Hz) spanning several frequency bands from a single electrode were used to train and test a support vector machine classifier. Main results. Classification accuracy of 97.8  ±  0.3% (normal tissue) and 89.4  ±  0.8% (epileptic tissue) across seven subjects using multiple spectral power features from a single electrode was achieved. Spectral power features from electrodes placed in normal temporal neocortex were found to be more useful (accuracy 90.8  ±  0.8%) for sleep-wake state classification than electrodes located in normal hippocampus (87.1  ±  1.6%). Spectral power in high frequency band features (Ripple (80-250 Hz), Fast Ripple (250-600 Hz)) showed comparable performance for AW and SWS classification as the best performing Berger bands (Alpha, Beta, low Gamma) with accuracy  ⩾90% using a single electrode contact and single spectral feature. Significance. Automated classification of wake and SWS should prove useful for future implantable epilepsy devices with limited computational power, memory, and number of electrodes. Applications include quantifying patient sleep patterns and behavioral state dependent detection, prediction, and electrical stimulation therapies.

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

    Science.gov (United States)

    Fingelkurts, Alexander A.; Fingelkurts, Andrew A.

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rosamond B. Guillermo

    2015-03-01

    Full Text Available Background: Supplementation with complex milk lipids (CML during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01, but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05, but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling.

  14. Service Learning to Promote Brain-Based Learning in Undergraduate Teaching

    Science.gov (United States)

    Nwokah, Eva E.; Leafblad, Stefanie

    2013-01-01

    In this study 44 undergraduate students in a language development course participated in service learning with preschool homeless and low-income children as a course requirement. Students completed a survey, questionnaires, reflective journaling, and small-group debriefing sessions. Based on current views on brain-based learning from cortical…

  15. Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

    Directory of Open Access Journals (Sweden)

    Eric J. Neuberger

    2017-09-01

    Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

  16. Resting state functional MRI in Parkinson's disease: the impact of deep brain stimulation on 'effective' connectivity.

    Science.gov (United States)

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl; Foltynie, Tom

    2014-04-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both 'action' and 'resting' motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the 'effective' connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network-disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses.

  17. Somatic survival and organ donation among brain-dead patients in the state of Qatar.

    Science.gov (United States)

    George, Saibu; Thomas, Merlin; Ibrahim, Wanis H; Abdussalam, Ahmed; Chandra, Prem; Ali, Husain Shabbir; Raza, Tasleem

    2016-10-31

    The Qatari law, as in many other countries, uses brain death as the main criteria for organ donation and cessation of medical support. By contrast, most of the public in Qatar do not agree with the limitation or withdrawal of medical care until the time of cardiac death. The current study aims to examine the duration of somatic survival after brain death, organ donation rate in brain-dead patients as well as review the underlying etiologies and level of support provided in the state of Qatar. This is a retrospective study of all patients diagnosed with brain death over a 10-year period conducted at the largest tertiary center in Qatar (Hamad General Hospital). Among the 53 patients who were diagnosed with brain death during the study period, the median and mean somatic survivals of brain-dead patients in the current study were 3 and 4.5 days respectively. The most common etiology was intracranial hemorrhage (45.3 %) followed by ischemic stroke (17 %). Ischemic stroke patients had a median survival of 11 days. Organ donation was accepted by only two families (6.6 %) of the 30 brain dead patients deemed suitable for organ donation. The average somatic survival of brain-dead patients is less than one week irrespective of supportive measures provided. Organ donation rate was extremely low among brain-dead patients in Qatar. Improved public education may lead to significant improvement in resource utilization as well as organ transplant donors and should be a major target area of future health care policies.

  18. The brain tryptophan hydroxylase activity in the sleep-like states in frog.

    Science.gov (United States)

    Kulikov, A V; Karmanova, I G; Kozlachkova, E Y; Voronova, I P; Popova, N K

    1994-10-01

    The activity of the rate-limiting enzyme of serotonin biosynthesis, tryptophan hydroxylase, was determined in the brain stem in active awake frogs, and frogs in three sleep-like states: with plastic muscle tone (SLS-1), with rigid muscle tone (SLS-2), and with relaxed muscle tone (SLS-3). Significant decrease in the enzyme activity has been found in frogs in SLS-1 and SLS-2 compared to awake animals. The development in frogs a cataleptic-like immobility after treating the animals with rhythmic lighting was accompanied with a decrease in the brain tryptophan hydroxylase activity. These results provide strong evidence for the involvement of the brain serotonin in frogs in the control of evolutionary ancient sleep-like states, probably by the regulation of muscle tone.

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

    OpenAIRE

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

    2013-01-01

    Post-concussion syndrome has been related to axonal damage in patients with mild traumatic brain injury, but little is known about the consequences of injury on brain networks. In the present study, our aim was to characterize changes in functional brain networks following mild traumatic brain injury in patients with post-concussion syndrome using resting-state functional magnetic resonance imaging data. We investigated 17 injured patients with persistent post-concussion syndrome (under the D...

  20. Identification of CiaR Regulated Genes That Promote Group B Streptococcal Virulence and Interaction with Brain Endothelial Cells.

    Science.gov (United States)

    Mu, Rong; Cutting, Andrew S; Del Rosario, Yvette; Villarino, Nicholas; Stewart, Lara; Weston, Thomas A; Patras, Kathryn A; Doran, Kelly S

    2016-01-01

    Group B Streptococcus (GBS) is a major causative agent of neonatal meningitis due to its ability to efficiently cross the blood-brain barrier (BBB) and enter the central nervous system (CNS). It has been demonstrated that GBS can invade human brain microvascular endothelial cells (hBMEC), a primary component of the BBB; however, the mechanism of intracellular survival and trafficking is unclear. We previously identified a two component regulatory system, CiaR/H, which promotes GBS intracellular survival in hBMEC. Here we show that a GBS strain deficient in the response regulator, CiaR, localized more frequently with Rab5, Rab7 and LAMP1 positive vesicles. Further, lysosomes isolated from hBMEC contained fewer viable bacteria following initial infection with the ΔciaR mutant compared to the WT strain. To characterize the contribution of CiaR-regulated genes, we constructed isogenic mutant strains lacking the two most down-regulated genes in the CiaR-deficient mutant, SAN_2180 and SAN_0039. These genes contributed to bacterial uptake and intracellular survival. Furthermore, competition experiments in mice showed that WT GBS had a significant survival advantage over the Δ2180 and Δ0039 mutants in the bloodstream and brain.

  1. The secretome of endothelial progenitor cells promotes brain endothelial cell activity through PI3-kinase and MAP-kinase.

    Science.gov (United States)

    Di Santo, Stefano; Seiler, Stefanie; Fuchs, Anna-Lena; Staudigl, Jennifer; Widmer, Hans Rudolf

    2014-01-01

    Angiogenesis and vascular remodelling are crucial events in tissue repair mechanisms promoted by cell transplantation. Current evidence underscores the importance of the soluble factors secreted by stem cells in tissue regeneration. In the present study we investigated the effects of paracrine factors derived from cultured endothelial progenitor cells (EPC) on rat brain endothelial cell properties and addressed the signaling pathways involved. Endothelial cells derived from rat brain (rBCEC4) were incubated with EPC-derived conditioned medium (EPC-CM). The angiogenic response of rBCEC4 to EPC-CM was assessed as effect on cell number, migration and tubular network formation. In addition, we have compared the outcome of the in vitro experiments with the effects on capillary sprouting from rat aortic rings. The specific PI3K/AKT inhibitor LY294002 and the MEK/ERK inhibitor PD98059 were used to study the involvement of these two signaling pathways in the transduction of the angiogenic effects of EPC-CM. Viable cell number, migration and tubule network formation were significantly augmented upon incubation with EPC-CM. Similar findings were observed for aortic ring outgrowth with significantly longer sprouts. The EPC-CM-induced activities were significantly reduced by the blockage of the PI3K/AKT and MEK/ERK signaling pathways. Similarly to the outcome of the rBCEC4 experiments, inhibition of the PI3K/AKT and MEK/ERK pathways significantly interfered with capillary sprouting induced by EPC-CM. The present study demonstrates that EPC-derived paracrine factors substantially promote the angiogenic response of brain microvascular endothelial cells. In addition, our findings identified the PI3K/AKT and MEK/ERK pathways to play a central role in mediating these effects.

  2. Decreased levels of brain-derived neurotrophic factor in the remitted state of unipolar depressive disorder

    DEFF Research Database (Denmark)

    Hasselbalch, Jacob; Knorr, U; Bennike, B

    2012-01-01

    Decreased levels of peripheral brain-derived neurotrophic factor (BDNF) have been associated with depression. It is uncertain whether abnormally low levels of BDNF in blood are present beyond the depressive state and whether levels of BDNF are associated with the course of clinical illness....

  3. Resting-State Functional MR Imaging: A New Window to the Brain

    NARCIS (Netherlands)

    Barkhof, F.; Haller, S.; Rombouts, S.A.R.B.

    2014-01-01

    Resting-state (RS) functional magnetic resonance (MR) imaging constitutes a novel paradigm that examines spontaneous brain function by using blood oxygen level-dependent contrast in the absence of a task. Spatially distributed networks of temporal synchronization can be detected that can

  4. Dissociative states in dreams and brain chaos: Implications for creative awareness

    Directory of Open Access Journals (Sweden)

    Petr eBob

    2015-09-01

    Full Text Available This article reviews recent findings indicating some common brain processes during dissociative states and dreaming with the aim to outline a perspective that neural chaotic states during dreaming can be closely related to dissociative states that may manifest in dreams scenery. These data are in agreement with various clinical findings that dissociated states can be projected into the dream scenery in REM sleep periods and dreams may represent their specific interactions that may uncover unusual psychological potential of creativity in psychotherapy, art and scientific discoveries.

  5. Decoding brain state transitions in the pedunculopontine nucleus: cooperative phasic and tonic mechanisms

    Directory of Open Access Journals (Sweden)

    Anne ePetzold

    2015-10-01

    Full Text Available Cholinergic neurons of the pedunculopontine nucleus (PPN are most active during the waking state. Their activation is deemed to cause a switch in the global brain activity from sleep to wakefulness, while their sustained discharge may contribute to upholding the waking state and enhancing arousal. Similarly, non-cholinergic PPN neurons are responsive to brain state transitions and their activation may influence some of the same targets of cholinergic neurons, suggesting that they operate in coordination. Yet, it is not clear how the discharge of distinct classes of PPN neurons organize during brain states. Here we monitored the in vivo network activity of PPN neurons in the anesthetized rat across two distinct levels of cortical dynamics and their transitions. We identified a highly structured configuration in PPN network activity during slow-wave activity that was replaced by decorrelated activity during the activated state. During the transition, neurons were predominantly excited (phasically or tonically, but some were inhibited. Identified cholinergic neurons displayed phasic and short latency responses to sensory stimulation, whereas the majority of non-cholinergic showed tonic responses and remained at high discharge rates beyond the state transition. In vitro recordings demonstrate that cholinergic neurons exhibit fast adaptation that prevents them from discharging at high rates over prolonged time periods. Our data shows that PPN neurons have distinct but complementary roles during brain state transitions, where cholinergic neurons provide a fast and transient response to sensory events that drive state transitions, whereas non-cholinergic neurons maintain an elevated firing rate during global activation.

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

    Science.gov (United States)

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

    2015-01-01

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

  7. Large sex differences in chicken behavior and brain gene expression coincide with few differences in promoter DNA-methylation.

    Directory of Open Access Journals (Sweden)

    Daniel Nätt

    Full Text Available While behavioral sex differences have repeatedly been reported across taxa, the underlying epigenetic mechanisms in the brain are mostly lacking. Birds have previously shown to have only limited dosage compensation, leading to high sex bias of Z-chromosome gene expression. In chickens, a male hyper-methylated region (MHM on the Z-chromosome has been associated with a local type of dosage compensation, but a more detailed characterization of the avian methylome is limiting our interpretations. Here we report an analysis of genome wide sex differences in promoter DNA-methylation and gene expression in the brain of three weeks old chickens, and associated sex differences in behavior of Red Junglefowl (ancestor of domestic chickens. Combining DNA-methylation tiling arrays with gene expression microarrays we show that a specific locus of the MHM region, together with the promoter for the zinc finger RNA binding protein (ZFR gene on chromosome 1, is strongly associated with sex dimorphism in gene expression. Except for this, we found few differences in promoter DNA-methylation, even though hundreds of genes were robustly differentially expressed across distantly related breeds. Several of the differentially expressed genes are known to affect behavior, and as suggested from their functional annotation, we found that female Red Junglefowl are more explorative and fearful in a range of tests performed throughout their lives. This paper identifies new sites and, with increased resolution, confirms known sites where DNA-methylation seems to affect sexually dimorphic gene expression, but the general lack of this association is noticeable and strengthens the view that birds do not have dosage compensation.

  8. Carnosinase levels in aging brain: redox state induction and cellular stress response.

    Science.gov (United States)

    Bellia, Francesco; Calabrese, Vittorio; Guarino, Francesca; Cavallaro, Monia; Cornelius, Carolin; De Pinto, Vito; Rizzarelli, Enrico

    2009-11-01

    Carnosinase is a dipeptidase found almost exclusively in brain and serum. Its natural substrate carnosine, present at high concentration in the brain, has been proposed as an antioxidant in vivo. We investigated the role of carnosinase in brain aging to establish a possible correlation with age-related changes in cellular stress response and redox status. In addition, a stable HeLa cell line expressing recombinant human serum carnosinase CN1 was established. The enzyme was purified from transfected cells, and specific antibodies were produced against it. Brain expression of CN1, Hsp72, heme oxygenase-1, and thioredoxin reductase increased with age, with a maximal induction in hippocampus and substantia nigra, followed by cerebellum, cortex, septum, and striatum. Hsps induction was associated with significant changes in total SH groups, GSH redox state, carbonyls, and HNE levels. A positive correlation between decrease in GSH and increase in Hsp72 expression was observed in all brain regions examined during aging. Increased carnosinase activity in the brain can lead to decreased carnosine levels and GSH/GSSG ratio. These results, consistent with the current notion that oxidative stress and cellular damage are characteristic hallmarks of the aging process, sustain the critical role of cellular stress-response mechanisms as possible targets for novel antiaging strategies.

  9. Resting-state functional connectivity imaging of the mouse brain using photoacoustic tomography

    Science.gov (United States)

    Nasiriavanaki, Mohammadreza; Xia, Jun; Wan, Hanlin; Bauer, Adam Q.; Culver, Joseph P.; Wang, Lihong V.

    2014-03-01

    Resting-state functional connectivity (RSFC) imaging is an emerging neuroimaging approach that aims to identify spontaneous cerebral hemodynamic fluctuations and their associated functional connections. Clinical studies have demonstrated that RSFC is altered in brain disorders such as stroke, Alzheimer's, autism, and epilepsy. However, conventional neuroimaging modalities cannot easily be applied to mice, the most widely used model species for human brain disease studies. For instance, functional magnetic resonance imaging (fMRI) of mice requires a very high magnetic field to obtain a sufficient signal-to-noise ratio and spatial resolution. Functional connectivity mapping with optical intrinsic signal imaging (fcOIS) is an alternative method. Due to the diffusion of light in tissue, the spatial resolution of fcOIS is limited, and experiments have been performed using an exposed skull preparation. In this study, we show for the first time, the use of photoacoustic computed tomography (PACT) to noninvasively image resting-state functional connectivity in the mouse brain, with a large field of view and a high spatial resolution. Bilateral correlations were observed in eight regions, as well as several subregions. These findings agreed well with the Paxinos mouse brain atlas. This study showed that PACT is a promising, non-invasive modality for small-animal functional brain imaging.

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

    Science.gov (United States)

    Feng, Tingyong; Feng, Pan; Chen, Zhencai

    2013-07-26

    Investigations of fear conditioning in rodents and humans have illuminated the neural mechanisms of fear acquisition and extinction. However, the neural mechanism of automatic memory consolidation of fear conditioning is still unclear. To address this question, we measured brain activity following fear acquisition using resting-state functional magnetic resonance imaging (rs-fMRI). In the current study, we used a marker of fMRI, amplitude of low-frequency (0.01-0.08Hz) fluctuation (ALFF) to quantify the spontaneous brain activity. Brain activity correlated to fear memory consolidation was observed in parahippocampus, insula, and thalamus in resting-state. Furthermore, after acquired fear conditioning, compared with control group some brain areas showed ALFF increased in ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC) in the experimental group, whereas some brain areas showed decreased ALFF in striatal regions (caudate, putamen). Moreover, the change of ALFF in vmPFC was positively correlated with the subjective fear ratings. These findings suggest that the parahippocampus, insula, and thalamus are the neural substrates of fear memory consolidation. The difference in activity could be attributed to a homeostatic process in which the vmPFC and ACC were involved in the fear recovery process, and change of ALFF in vmPFC predicts subjective fear ratings. Copyright © 2013 Elsevier B.V. All rights reserved.

  11. Music Making as a Tool for Promoting Brain Plasticity across the Life Span

    OpenAIRE

    Wan, Catherine Y.; Schlaug, Gottfried

    2010-01-01

    Playing a musical instrument is an intense, multisensory, and motor experience that usually commences at an early age and requires the acquisition and maintenance of a range of skills over the course of a musician's lifetime. Thus, musicians offer an excellent human model for studying the brain effects of acquiring specialized sensorimotor skills. For example, musicians learn and repeatedly practice the association of motor actions with specific sound and visual patterns (musical notation) wh...

  12. Lateralized Resting-State Functional Brain Network Organization Changes in Heart Failure.

    Directory of Open Access Journals (Sweden)

    Bumhee Park

    Full Text Available Heart failure (HF patients show brain injury in autonomic, affective, and cognitive sites, which can change resting-state functional connectivity (FC, potentially altering overall functional brain network organization. However, the status of such connectivity or functional organization is unknown in HF. Determination of that status was the aim here, and we examined region-to-region FC and brain network topological properties across the whole-brain in 27 HF patients compared to 53 controls with resting-state functional MRI procedures. Decreased FC in HF appeared between the caudate and cerebellar regions, olfactory and cerebellar sites, vermis and medial frontal regions, and precentral gyri and cerebellar areas. However, increased FC emerged between the middle frontal gyrus and sensorimotor areas, superior parietal gyrus and orbito/medial frontal regions, inferior temporal gyrus and lingual gyrus/cerebellar lobe/pallidum, fusiform gyrus and superior orbitofrontal gyrus and cerebellar sites, and within vermis and cerebellar areas; these connections were largely in the right hemisphere (p<0.005; 10,000 permutations. The topology of functional integration and specialized characteristics in HF are significantly changed in regions showing altered FC, an outcome which would interfere with brain network organization (p<0.05; 10,000 permutations. Brain dysfunction in HF extends to resting conditions, and autonomic, cognitive, and affective deficits may stem from altered FC and brain network organization that may contribute to higher morbidity and mortality in the condition. Our findings likely result from the prominent axonal and nuclear structural changes reported earlier in HF; protecting neural tissue may improve FC integrity, and thus, increase quality of life and reduce morbidity and mortality.

  13. Relating resting-state fMRI and EEG whole-brain connectomes across frequency bands

    Science.gov (United States)

    Deligianni, Fani; Centeno, Maria; Carmichael, David W.; Clayden, Jonathan D.

    2014-01-01

    Whole brain functional connectomes hold promise for understanding human brain activity across a range of cognitive, developmental and pathological states. So called resting-state (rs) functional MRI studies have contributed to the brain being considered at a macroscopic scale as a set of interacting regions. Interactions are defined as correlation-based signal measurements driven by blood oxygenation level dependent (BOLD) contrast. Understanding the neurophysiological basis of these measurements is important in conveying useful information about brain function. Local coupling between BOLD fMRI and neurophysiological measurements is relatively well defined, with evidence that gamma (range) frequency EEG signals are the closest correlate of BOLD fMRI changes during cognitive processing. However, it is less clear how whole-brain network interactions relate during rest where lower frequency signals have been suggested to play a key role. Simultaneous EEG-fMRI offers the opportunity to observe brain network dynamics with high spatio-temporal resolution. We utilize these measurements to compare the connectomes derived from rs-fMRI and EEG band limited power (BLP). Merging this multi-modal information requires the development of an appropriate statistical framework. We relate the covariance matrices of the Hilbert envelope of the source localized EEG signal across bands to the covariance matrices derived from rs-fMRI with the means of statistical prediction based on sparse Canonical Correlation Analysis (sCCA). Subsequently, we identify the most prominent connections that contribute to this relationship. We compare whole-brain functional connectomes based on their geodesic distance to reliably estimate the performance of the prediction. The performance of predicting fMRI from EEG connectomes is considerably better than predicting EEG from fMRI across all bands, whereas the connectomes derived in low frequency EEG bands resemble best rs-fMRI connectivity. PMID:25221467

  14. Cyclin A2 promotes DNA repair in the brain during both development and aging.

    Science.gov (United States)

    Gygli, Patrick E; Chang, Joshua C; Gokozan, Hamza N; Catacutan, Fay P; Schmidt, Theresa A; Kaya, Behiye; Goksel, Mustafa; Baig, Faisal S; Chen, Shannon; Griveau, Amelie; Michowski, Wojciech; Wong, Michael; Palanichamy, Kamalakannan; Sicinski, Piotr; Nelson, Randy J; Czeisler, Catherine; Otero, José J

    2016-07-01

    Various stem cell niches of the brain have differential requirements for Cyclin A2. Cyclin A2 loss results in marked cerebellar dysmorphia, whereas forebrain growth is retarded during early embryonic development yet achieves normal size at birth. To understand the differential requirements of distinct brain regions for Cyclin A2, we utilized neuroanatomical, transgenic mouse, and mathematical modeling techniques to generate testable hypotheses that provide insight into how Cyclin A2 loss results in compensatory forebrain growth during late embryonic development. Using unbiased measurements of the forebrain stem cell niche, we parameterized a mathematical model whereby logistic growth instructs progenitor cells as to the cell-types of their progeny. Our data was consistent with prior findings that progenitors proliferate along an auto-inhibitory growth curve. The growth retardation inCCNA2-null brains corresponded to cell cycle lengthening, imposing a developmental delay. We hypothesized that Cyclin A2 regulates DNA repair and that CCNA2-null progenitors thus experienced lengthened cell cycle. We demonstrate that CCNA2-null progenitors suffer abnormal DNA repair, and implicate Cyclin A2 in double-strand break repair. Cyclin A2's DNA repair functions are conserved among cell lines, neural progenitors, and hippocampal neurons. We further demonstrate that neuronal CCNA2 ablation results in learning and memory deficits in aged mice.

  15. GM-CSF promotes migration of human monocytes across the blood brain barrier.

    Science.gov (United States)

    Vogel, Daphne Y S; Kooij, Gijs; Heijnen, Priscilla D A M; Breur, Marjolein; Peferoen, Laura A N; van der Valk, Paul; de Vries, Helga E; Amor, Sandra; Dijkstra, Christine D

    2015-06-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Infiltration of monocytes into the CNS is crucial for disease onset and progression. Animal studies indicate that granulocyte-macrophages colony-stimulating factor (GM-CSF) may play an essential role in this process, possibly by acting on the migratory capacities of myeloid cells across the blood-brain barrier. This study describes the effect of GM-CSF on human monocytes, macrophages, and microglia. Furthermore, the expression of GM-CSF and its receptor was investigated in the CNS under healthy and pathological conditions. We show that GM-CSF enhances monocyte migration across human blood-brain barrier endothelial cells in vitro. Next, immunohistochemical analysis on human brain tissues revealed that GM-CSF is highly expressed by microglia and macrophages in MS lesions. The GM-CSF receptor is expressed by neurons in the rim of combined gray/white matter lesions and astrocytes. Finally, the effect of GM-CSF on human macrophages was determined, revealing an intermediate activation status, with a phenotype similar to that observed in active MS lesions. Together our data indicate that GM-CSF is a powerful stimulator of monocyte migration, and is abundantly present in the inflamed CNS where it may act as an activator of macrophages and microglia. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Steady-state brain glucose transport kinetics re-evaluated with a four-state conformational model

    Directory of Open Access Journals (Sweden)

    João M N Duarte

    2009-10-01

    Full Text Available Glucose supply from blood to brain occurs through facilitative transporter proteins. A near linear relation between brain and plasma glucose has been experimentally determined and described by a reversible model of enzyme kinetics. A conformational four-state exchange model accounting for trans-acceleration and asymmetry of the carrier was included in a recently developed multi-compartmental model of glucose transport. Based on this model, we demonstrate that brain glucose (Gbrain as function of plasma glucose (Gplasma can be described by a single analytical equation namely comprising three kinetic compartments: blood, endothelial cells and brain. Transport was described by four parameters: apparent half saturation constant Kt, apparent maximum rate constant Tmax, glucose consumption rate CMRglc, and the iso-inhibition constant Kii that suggests Gbrain as inhibitor of the isomerisation of the unloaded carrier. Previous published data, where Gbrain was quantified as a function of plasma glucose by either biochemical methods or NMR spectroscopy, were used to determine the aforementioned kinetic parameters. Glucose transport was characterized by Kt ranging from 1.5 to 3.5 mM, Tmax/CMRglc from 4.6 to 5.6, and Kii from 51 to 149 mM. It was noteworthy that Kt was on the order of a few mM, as previously determined from the reversible model. The conformational four-state exchange model of glucose transport into the brain includes both efflux and transport inhibition by Gbrain, predicting that Gbrain eventually approaches a maximum concentration. However, since Kii largely exceeds Gplasma, iso-inhibition is unlikely to be of substantial importance for plasma glucose below 25 mM. As a consequence, the reversible model can account for most experimental observations under euglycaemia and moderate cases of hypo- and hyperglycaemia.

  17. State property tax incentives for promoting ecosystem goods and services from private forest land in the United States: a review and analysis

    Science.gov (United States)

    Michael A. Kilgore; Paul B. Ellefson; Travis J. Funk; Gregory E. Frey

    2017-01-01

    Financial incentives provided by State property tax programs are a means of promoting ecosystem services from private forest land. Identified by this 50-State 2015 review, categories of ecosystem services frequently promoted by such programs are open space and scenic resources, conservation of...

  18. Spontaneous brain oscillations as neural fingerprints of working memory capacities: A resting-state MEG study.

    Science.gov (United States)

    Oswald, Victor; Zerouali, Younes; Boulet-Craig, Aubrée; Krajinovic, Maja; Laverdière, Caroline; Sinnett, Daniel; Jolicoeur, Pierre; Lippé, Sarah; Jerbi, Karim; Robaey, Philippe

    2017-12-01

    Short-term storage and mental information manipulation capacities in the human brain are key to healthy cognition. These brain processes collectively known as working memory (WM) are associated with modulations of rhythmic brain activity across multiple brain areas and frequencies. Yet, it is not clear whether - and, if so, how-intrinsic resting-state neuronal oscillations are related to individual WM capacities, as measured by standard neuropsychological tests. We addressed this question by probing the correlation between resting-state brain activity, recorded with magnetoencephalography (MEG), and verbal and visuo-spatial WM indices obtained from the standardized Wechsler Adult Intelligence Scale (WAIS-IV) and the Wechsler Memory Scale (WMS-IV). To this end, 5-min eyes-open resting-state MEG data were acquired in 28 healthy participants. Source-reconstructed spectral power estimates were then computed in standard frequency bands and their correlation with neuropsychological indices across individuals was assessed using Pearson correlation and cluster-level statistics. We found statistically significant positive correlations between spectral amplitudes measured at rest and standardized scores on both verbal and visuo-spatial WM performance. The correlation clusters primarily involved key medial and dorsolateral components within the parietal and prefrontal regions. In addition, while the correlation in some clusters was frequency selective (e.g., alpha-band oscillations), other areas showed correlations with WM across a wide range of frequencies reflecting a broadband effect. These results provide the first evidence for a positive correlation between neuromagnetic signals measured at rest and WM performance separately assessed by standardized neuropsychological tests. Our results advance our understanding of the link between WM capacities and intrinsic oscillatory dynamics networks. They also suggest that individual differences in baseline spectral power might

  19. Correlation between APOE -491AA promoter in epsilon4 carriers and clinical deterioration in early stage of traumatic brain injury.

    Science.gov (United States)

    Jiang, Yong; Sun, Xiaochuan; Gui, Li; Xia, Yuxian; Tang, Wenyuan; Cao, Yueqing; Gu, Yingjiang

    2007-12-01

    The objective of this work was to investigate the relationship between apolipoprotein E (APOE) promoters (G-219T, C-427T, A-491T) polymorphisms and the clinical deterioration in early stage of traumatic brain injury (TBI) in a cohort of Chinese patients. In this study, we used the cohort of patients which has been reported previously. A total of 110 subjects with TBI (80 males and 30 females, with mean age of 43.87 years) were admitted from December 2003 to May 2004, and demographic and clinical data were collected. The clinical deterioration of patient's condition in acute stage (Hardy-Weinberg Law, and 19 subjects presented with deteriorated clinical condition in acute stage after hospitalization. chi(2) test showed insignificant differences in association of APOE promoter polymorphisms with clinical deterioration (p>0.05). But logistic regression analyses, after adjusting patients' age, injury severity and injury mechanism etc, showed that -491AA (OR=11.681, p=0.009, 95%, CI 1.824-74.790) and APOE epsilon4 were all risk factors, with injury severity and alcohol-drinking as other risk factors. In Chinese population, as a significant but not independent risk factor, only APOE -491AA promoter in epsilon4 carriers is apt to the clinical deterioration and may contribute to the poor outcome after TBI.

  20. Reducing traumatic brain injuries in youth sports: youth sports traumatic brain injury state laws, January 2009-December 2012.

    Science.gov (United States)

    Harvey, Hosea H

    2013-07-01

    I sought to describe current state-wide youth sports traumatic brain injury (TBI) laws and their relationship to prevailing scientific understandings of youth sports TBIs, and to facilitate further research by creating an open-source data set of current laws. I used Westlaw and LexisNexis databases to create a 50-state data set of youth sports TBI laws enacted between January 2009 and December 2012. I collected and coded the text and citations of each law and developed a protocol and codebook to facilitate future research. Forty-four states and Washington, DC, passed youth sports TBI laws between 2009 and 2012. No state's youth sports TBI law focuses on primary prevention. Instead, such laws focus on (1) increasing coaches' and parents' ability to identify and respond to TBIs and (2) reducing the immediate risk of multiple TBIs. Existing youth sports TBI laws were not designed to reduce initial TBIs. Evaluation is required to assess their effectiveness in reducing the risk and consequences of multiple TBIs. Continued research and evaluation of existing laws will be needed to develop a more comprehensive youth TBI-reduction solution.

  1. Meal replacement: calming the hot-state brain network of appetite

    OpenAIRE

    Paolini, Brielle M.; Laurienti, Paul J.; Norris, James; Rejeski, W. Jack

    2014-01-01

    There is a growing awareness in the field of neuroscience that the self-regulation of eating behavior is driven by complex networks within the brain. These networks may be vulnerable to “hot states” which people can move into and out of dynamically throughout the course of a day as a function of changes in affect or visceral cues. The goal of the current study was to identify and determine differences in the Hot-state Brain Network of Appetite (HBN-A) that exists after a brief period of food ...

  2. Can brain state be manipulated to emphasize individual differences in functional connectivity?

    Science.gov (United States)

    Finn, Emily S; Scheinost, Dustin; Finn, Daniel M; Shen, Xilin; Papademetris, Xenophon; Constable, R Todd

    2017-10-15

    While neuroimaging studies typically collapse data from many subjects, brain functional organization varies between individuals, and characterizing this variability is crucial for relating brain activity to behavioral phenotypes. Rest has become the default state for probing individual differences, chiefly because it is easy to acquire and a supposed neutral backdrop. However, the assumption that rest is the optimal condition for individual differences research is largely untested. In fact, other brain states may afford a better ratio of within- to between-subject variability, facilitating biomarker discovery. Depending on the trait or behavior under study, certain tasks may bring out meaningful idiosyncrasies across subjects, essentially enhancing the individual signal in networks of interest beyond what can be measured at rest. Here, we review theoretical considerations and existing work on how brain state influences individual differences in functional connectivity, present some preliminary analyses of within- and between-subject variability across conditions using data from the Human Connectome Project, and outline questions for future study. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  3. Music Composition from the Brain Signal: Representing the Mental State by Music

    Directory of Open Access Journals (Sweden)

    Dan Wu

    2010-01-01

    Full Text Available This paper proposes a method to translate human EEG into music, so as to represent mental state by music. The arousal levels of the brain mental state and music emotion are implicitly used as the bridge between the mind world and the music. The arousal level of the brain is based on the EEG features extracted mainly by wavelet analysis, and the music arousal level is related to the musical parameters such as pitch, tempo, rhythm, and tonality. While composing, some music principles (harmonics and structure were taken into consideration. With EEGs during various sleep stages as an example, the music generated from them had different patterns of pitch, rhythm, and tonality. 35 volunteers listened to the music pieces, and significant difference in music arousal levels was found. It implied that different mental states may be identified by the corresponding music, and so the music from EEG may be a potential tool for EEG monitoring, biofeedback therapy, and so forth.

  4. Music composition from the brain signal: representing the mental state by music.

    Science.gov (United States)

    Wu, Dan; Li, Chaoyi; Yin, Yu; Zhou, Changzheng; Yao, Dezhong

    2010-01-01

    This paper proposes a method to translate human EEG into music, so as to represent mental state by music. The arousal levels of the brain mental state and music emotion are implicitly used as the bridge between the mind world and the music. The arousal level of the brain is based on the EEG features extracted mainly by wavelet analysis, and the music arousal level is related to the musical parameters such as pitch, tempo, rhythm, and tonality. While composing, some music principles (harmonics and structure) were taken into consideration. With EEGs during various sleep stages as an example, the music generated from them had different patterns of pitch, rhythm, and tonality. 35 volunteers listened to the music pieces, and significant difference in music arousal levels was found. It implied that different mental states may be identified by the corresponding music, and so the music from EEG may be a potential tool for EEG monitoring, biofeedback therapy, and so forth.

  5. Spontaneous sleep-like brain state alternations and breathing characteristics in urethane anesthetized mice.

    Directory of Open Access Journals (Sweden)

    Silvia Pagliardini

    Full Text Available Brain state alternations resembling those of sleep spontaneously occur in rats under urethane anesthesia and they are closely linked with sleep-like respiratory changes. Although rats are a common model for both sleep and respiratory physiology, we sought to determine if similar brain state and respiratory changes occur in mice under urethane. We made local field potential recordings from the hippocampus and measured respiratory activity by means of EMG recordings in intercostal, genioglossus, and abdominal muscles. Similar to results in adult rats, urethane anesthetized mice displayed quasi-periodic spontaneous forebrain state alternations between deactivated patterns resembling slow wave sleep (SWS and activated patterns resembling rapid eye movement (REM sleep. These alternations were associated with an increase in breathing rate, respiratory variability, a depression of inspiratory related activity in genioglossus muscle and an increase in expiratory-related abdominal muscle activity when comparing deactivated (SWS-like to activated (REM-like states. These results demonstrate that urethane anesthesia consistently induces sleep-like brain state alternations and correlated changes in respiratory activity across different rodent species. They open up the powerful possibility of utilizing transgenic mouse technology for the advancement and translation of knowledge regarding sleep cycle alternations and their impact on respiration.

  6. Spontaneous sleep-like brain state alternations and breathing characteristics in urethane anesthetized mice.

    Science.gov (United States)

    Pagliardini, Silvia; Gosgnach, Simon; Dickson, Clayton T

    2013-01-01

    Brain state alternations resembling those of sleep spontaneously occur in rats under urethane anesthesia and they are closely linked with sleep-like respiratory changes. Although rats are a common model for both sleep and respiratory physiology, we sought to determine if similar brain state and respiratory changes occur in mice under urethane. We made local field potential recordings from the hippocampus and measured respiratory activity by means of EMG recordings in intercostal, genioglossus, and abdominal muscles. Similar to results in adult rats, urethane anesthetized mice displayed quasi-periodic spontaneous forebrain state alternations between deactivated patterns resembling slow wave sleep (SWS) and activated patterns resembling rapid eye movement (REM) sleep. These alternations were associated with an increase in breathing rate, respiratory variability, a depression of inspiratory related activity in genioglossus muscle and an increase in expiratory-related abdominal muscle activity when comparing deactivated (SWS-like) to activated (REM-like) states. These results demonstrate that urethane anesthesia consistently induces sleep-like brain state alternations and correlated changes in respiratory activity across different rodent species. They open up the powerful possibility of utilizing transgenic mouse technology for the advancement and translation of knowledge regarding sleep cycle alternations and their impact on respiration.

  7. Motorcycle helmet effectiveness in reducing head, face and brain injuries by state and helmet law.

    Science.gov (United States)

    Olsen, Cody S; Thomas, Andrea M; Singleton, Michael; Gaichas, Anna M; Smith, Tracy J; Smith, Gary A; Peng, Justin; Bauer, Michael J; Qu, Ming; Yeager, Denise; Kerns, Timothy; Burch, Cynthia; Cook, Lawrence J

    2016-12-01

    Despite evidence that motorcycle helmets reduce morbidity and mortality, helmet laws and rates of helmet use vary by state in the U.S. We pooled data from eleven states: five with universal laws requiring all motorcyclists to wear a helmet, and six with partial laws requiring only a subset of motorcyclists to wear a helmet. Data were combined in the Crash Outcome Data Evaluation System's General Use Model and included motorcycle crash records probabilistically linked to emergency department and inpatient discharges for years 2005-2008. Medical outcomes were compared between partial and universal helmet law settings. We estimated adjusted relative risks (RR) and 95 % confidence intervals (CIs) for head, facial, traumatic brain, and moderate to severe head/facial injuries associated with helmet use within each helmet law setting using generalized log-binomial regression. Reported helmet use was higher in universal law states (88 % vs. 42 %). Median charges, adjusted for inflation and differences in state-incomes, were higher in partial law states (emergency department $1987 vs. $1443; inpatient $31,506 vs. $25,949). Injuries to the head and face, including traumatic brain injuries, were more common in partial law states. Effectiveness estimates of helmet use were higher in partial law states (adjusted-RR (CI) of head injury: 2.1 (1.9-2.2) partial law single vehicle; 1.4 (1.2, 1.6) universal law single vehicle; 1.8 (1.6-2.0) partial law multi-vehicle; 1.2 (1.1-1.4) universal law multi-vehicle). Medical charges and rates of head, facial, and brain injuries among motorcyclists were lower in universal law states. Helmets were effective in reducing injury in both helmet law settings; lower effectiveness estimates were observed in universal law states.

  8. The entropic brain:A theory of conscious states informed by neuroimaging research with psychedelic drugs

    Directory of Open Access Journals (Sweden)

    Robin Lester Carhart-Harris

    2014-02-01

    Full Text Available Entropy is a dimensionless quantity that is used for measuring uncertainty about the state of a system but it can also imply physical qualities, where high entropy is synonymous with high disorder. Entropy is applied here in the context of states of consciousness and their associated neural dynamics, with a particular focus on the psychedelic state. The psychedelic state is considered an exemplar of a primitive or primary state of consciousness that preceded the development of modern, adult, human, normal waking consciousness. Based on neuroimaging data with psilocybin, a classic psychedelic drug, it is argued that the defining feature of ‘primary states’ is elevated entropy in certain aspects of brain function, such as the repertoire of functional connectivity motifs that form and fragment across time. It is noted that elevated entropy in this sense, is a characteristic of systems exhibiting ‘self-organised criticality’, i.e., a property of systems that gravitate towards a ‘critical’ point in a transition zone between order and disorder in which certain phenomena such as power-law scaling appear. This implies that entropy is suppressed in normal waking consciousness, meaning that the brain operates just below criticality. It is argued that this entropy suppression furnishes consciousness with a constrained quality and associated metacognitive functions, including reality-testing and self-awareness. It is also proposed that entry into primary states depends on a collapse of the normally highly organised activity within the default-mode network (DMN and a decoupling between the DMN and the medial temporal lobes (which are normally significantly coupled. These hypotheses can be tested by examining brain activity and associated cognition in other candidate primary states such as REM sleep and early psychosis and comparing these with non-primary states such as normal waking consciousness and the anaesthetised state.

  9. Urodynamic function during sleep-like brain states in urethane anesthetized rats.

    Science.gov (United States)

    Crook, J; Lovick, T

    2016-01-28

    The aim was to investigate urodynamic parameters and functional excitability of the periaqueductal gray matter (PAG) during changes in sleep-like brain states in urethane anesthetized rats. Simultaneous recordings of detrusor pressure, external urethral sphincter (EUS) electromyogram (EMG), cortical electroencephalogram (EEG), and single-unit activity in the PAG were made during repeated voiding induced by continuous infusion of saline into the bladder. The EEG cycled between synchronized, high-amplitude slow wave activity (SWA) and desynchronized low-amplitude fast activity similar to slow wave and 'activated' sleep-like brain states. During (SWA, 0.5-1.5 Hz synchronized oscillation of the EEG waveform) voiding became more irregular than in the 'activated' brain state (2-5 Hz low-amplitude desynchronized EEG waveform) and detrusor void pressure threshold, void volume threshold and the duration of bursting activity in the external urethral sphincter EMG were raised. The spontaneous firing rate of 23/52 neurons recorded within the caudal PAG and adjacent tegmentum was linked to the EEG state, with the majority of responsive cells (92%) firing more slowly during SWA. Almost a quarter of the cells recorded (12/52) showed phasic changes in firing rate that were linked to the occurrence of voids. Inhibition (n=6), excitation (n=4) or excitation/inhibition (n=2) was seen. The spontaneous firing rate of 83% of the micturition-responsive cells was sensitive to changes in EEG state. In nine of the 12 responsive cells (75%) the responses were reduced during SWA. We propose that during different sleep-like brain states changes in urodynamic properties occur which may be linked to changing excitability of the micturition circuitry in the periaqueductal gray. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. A test-retest dataset for assessing long-term reliability of brain morphology and resting-state brain activity.

    Science.gov (United States)

    Huang, Lijie; Huang, Taicheng; Zhen, Zonglei; Liu, Jia

    2016-03-15

    We present a test-retest dataset for evaluation of long-term reliability of measures from structural and resting-state functional magnetic resonance imaging (sMRI and rfMRI) scans. The repeated scan dataset was collected from 61 healthy adults in two sessions using highly similar imaging parameters at an interval of 103-189 days. However, as the imaging parameters were not completely identical, the reliability estimated from this dataset shall reflect the lower bounds of the true reliability of sMRI/rfMRI measures. Furthermore, in conjunction with other test-retest datasets, our dataset may help explore the impact of different imaging parameters on reliability of sMRI/rfMRI measures, which is especially critical for assessing datasets collected from multiple centers. In addition, intelligence quotient (IQ) was measured for each participant using Raven's Advanced Progressive Matrices. The data can thus be used for purposes other than assessing reliability of sMRI/rfMRI alone. For example, data from each single session could be used to associate structural and functional measures of the brain with the IQ metrics to explore brain-IQ association.

  11. Subchronic administration of phencyclidine produces hypermethylation in the parvalbumin gene promoter in rat brain.

    Science.gov (United States)

    Fachim, Helene A; Srisawat, Umarat; Dalton, Caroline F; Harte, Michael K; Marsh, Samuel; Neill, Joanna C; Reynolds, Gavin P

    2016-09-01

    A deficit in parvalbumin neurons is found in schizophrenia and several animal models of the disease. In this preliminary study, we determined whether one such model, phencyclidine (PCP) administration, results in changes in DNA methylation in the rat Pvalb promoter. DNA from hippocampus and prefrontal cortex from rats, which 6 weeks previously received either 2 mg/kg PCP or vehicle for 7 days, underwent bisulphite pyrosequencing to determine methylation. PCP administration induced significantly greater methylation at one of two Pvalb CpG sites in both prefrontal cortex and hippocampus, while no significant difference was found in long interspersed nucleotide element-1, a global measure of DNA methylation. Subchronic PCP administration results in a specific hypermethylation in the Pvalb promoter which may contribute to parvalbumin deficits in this animal model of psychosis.

  12. Anesthetics rapidly promote synaptogenesis during a critical period of brain development.

    Directory of Open Access Journals (Sweden)

    Mathias De Roo

    Full Text Available Experience-driven activity plays an essential role in the development of brain circuitry during critical periods of early postnatal life, a process that depends upon a dynamic balance between excitatory and inhibitory signals. Since general anesthetics are powerful pharmacological modulators of neuronal activity, an important question is whether and how these drugs can affect the development of synaptic networks. To address this issue, we examined here the impact of anesthetics on synapse growth and dynamics. We show that exposure of young rodents to anesthetics that either enhance GABAergic inhibition or block NMDA receptors rapidly induce a significant increase in dendritic spine density in the somatosensory cortex and hippocampus. This effect is developmentally regulated; it is transient but lasts for several days and is also reproduced by selective antagonists of excitatory receptors. Analyses of spine dynamics in hippocampal slice cultures reveals that this effect is mediated through an increased rate of protrusions formation, a better stabilization of newly formed spines, and leads to the formation of functional synapses. Altogether, these findings point to anesthesia as an important modulator of spine dynamics in the developing brain and suggest the existence of a homeostatic process regulating spine formation as a function of neural activity. Importantly, they also raise concern about the potential impact of these drugs on human practice, when applied during critical periods of development in infants.

  13. Not in one metric: Neuroticism modulates different resting state metrics within distinctive brain regions.

    Science.gov (United States)

    Gentili, Claudio; Cristea, Ioana Alina; Ricciardi, Emiliano; Vanello, Nicola; Popita, Cristian; David, Daniel; Pietrini, Pietro

    2017-06-01

    Neuroticism is a complex personality trait encompassing diverse aspects. Notably, high levels of neuroticism are related to the onset of psychiatric conditions, including anxiety and mood disorders. Personality traits are stable individual features; therefore, they can be expected to be associated with stable neurobiological features, including the Brain Resting State (RS) activity as measured by fMRI. Several metrics have been used to describe RS properties, yielding rather inconsistent results. This inconsistency could be due to the fact that different metrics portray different RS signal properties and that these properties may be differently affected by neuroticism. To explore the distinct effects of neuroticism, we assessed several distinct metrics portraying different RS properties within the same population. Neuroticism was measured in 31 healthy subjects using the Zuckerman-Kuhlman Personality Questionnaire; RS was acquired by high-resolution fMRI. Using linear regression, we examined the modulatory effects of neuroticism on RS activity, as quantified by the Amplitude of low frequency fluctuations (ALFF, fALFF), regional homogeneity (REHO), Hurst Exponent (H), global connectivity (GC) and amygdalae functional connectivity. Neuroticism modulated the different metrics across a wide network of brain regions, including emotional regulatory, default mode and visual networks. Except for some similarities in key brain regions for emotional expression and regulation, neuroticism affected different metrics in different ways. Metrics more related to the measurement of regional intrinsic brain activity (fALFF, ALFF and REHO), or that provide a parsimonious index of integrated and segregated brain activity (HE), were more broadly modulated in regions related to emotions and their regulation. Metrics related to connectivity were modulated across a wider network of areas. Overall, these results show that neuroticism affects distinct aspects of brain resting state activity

  14. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease.

    Science.gov (United States)

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir; Brown, Peter

    2016-05-01

    Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson's disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus-cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise the

  15. Reducing Traumatic Brain Injuries in Youth Sports: Youth Sports Traumatic Brain Injury State Laws, January 2009–December 2012

    Science.gov (United States)

    2013-01-01

    Objectives. I sought to describe current state-wide youth sports traumatic brain injury (TBI) laws and their relationship to prevailing scientific understandings of youth sports TBIs, and to facilitate further research by creating an open-source data set of current laws. Methods. I used Westlaw and LexisNexis databases to create a 50-state data set of youth sports TBI laws enacted between January 2009 and December 2012. I collected and coded the text and citations of each law and developed a protocol and codebook to facilitate future research. Results. Forty-four states and Washington, DC, passed youth sports TBI laws between 2009 and 2012. No state’s youth sports TBI law focuses on primary prevention. Instead, such laws focus on (1) increasing coaches’ and parents’ ability to identify and respond to TBIs and (2) reducing the immediate risk of multiple TBIs. Conclusions. Existing youth sports TBI laws were not designed to reduce initial TBIs. Evaluation is required to assess their effectiveness in reducing the risk and consequences of multiple TBIs. Continued research and evaluation of existing laws will be needed to develop a more comprehensive youth TBI-reduction solution. PMID:23678903

  16. Resting state fMRI entropy probes complexity of brain activity in adults with ADHD.

    Science.gov (United States)

    Sokunbi, Moses O; Fung, Wilson; Sawlani, Vijay; Choppin, Sabine; Linden, David E J; Thome, Johannes

    2013-12-30

    In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of Pentropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders. © 2013 Elsevier Ireland Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Dong Guangheng

    2012-08-01

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

  18. Hemispheric specialization varies with EEG brain resting states and phase of menstrual cycle.

    Science.gov (United States)

    Cacioppo, Stephanie; Bianchi-Demicheli, Francesco; Bischof, Paul; Deziegler, Dominique; Michel, Christoph M; Landis, Theodor

    2013-01-01

    A growing body of behavioral studies has demonstrated that women's hemispheric specialization varies as a function of their menstrual cycle, with hemispheric specialization enhanced during their menstruation period. Our recent high-density electroencephalogram (EEG) study with lateralized emotional versus neutral words extended these behavioral results by showing that hemispheric specialization in men, but not in women under birth-control, depends upon specific EEG resting brain states at stimulus arrival, suggesting that hemispheric specialization may be pre-determined at the moment of the stimulus onset. To investigate whether EEG brain resting state for hemispheric specialization could vary as a function of the menstrual phase, we tested 12 right-handed healthy women over different phases of their menstrual cycle combining high-density EEG recordings and the same lateralized lexical decision paradigm with emotional versus neutral words. Results showed the presence of specific EEG resting brain states, associated with hemispheric specialization for emotional words, at the moment of the stimulus onset during the menstruation period only. These results suggest that the pre-stimulus EEG pattern influencing hemispheric specialization is modulated by the hormonal state.

  19. Decreased activation of subcortical brain areas in the motor fatigue state: an fMRI study

    Directory of Open Access Journals (Sweden)

    Lijuan Hou

    2016-08-01

    Full Text Available One aspect of motor fatigue is the exercise-induced reduction of neural activity to voluntarily drive the muscle or muscle group. Functional magnetic resonance imaging provides access to investigate the neural activation on the whole brain level and studies observed changes of activation intensity after exercise-induced motor fatigue in the sensorimotor cortex. However, in human, little evidence exists to demonstrate the role of subcortical brain regions in motor fatigue, which is contradict to abundant researches in rodent indicating that during simple movement, the activity of the basal ganglia is modulated by the state of motor fatigue. Thus, in present study, we explored the effect of motor fatigue on subcortical areas in human. A series of fMRI data were collected from 11 healthy subjects while they were executing simple motor tasks in two conditions: before and under the motor fatigue state. The results showed that in both conditions, movements evoked activation volumes in the sensorimotor areas, SMA, cerebellum, thalamus and basal ganglia. Of primary importance are the results that the intensity and size of activation volumes in the subcortical areas (i.e. thalamus and basal ganglia areas are significantly decreased during the motor fatigue state, implying that motor fatigue disturbs the motor control processing in a way that both sensorimotor areas and subcortical brain areas are less active. Further study is needed to clarify how subcortical areas contribute to the overall decreased activity of CNS during motor fatigue state.

  20. Handedness- and brain size-related efficiency differences in small-world brain networks: a resting-state functional magnetic resonance imaging study.

    Science.gov (United States)

    Li, Meiling; Wang, Junping; Liu, Feng; Chen, Heng; Lu, Fengmei; Wu, Guorong; Yu, Chunshui; Chen, Huafu

    2015-05-01

    The human brain has been described as a complex network, which integrates information with high efficiency. However, the relationships between the efficiency of human brain functional networks and handedness and brain size remain unclear. Twenty-one left-handed and 32 right-handed healthy subjects underwent a resting-state functional magnetic resonance imaging scan. The whole brain functional networks were constructed by thresholding Pearson correlation matrices of 90 cortical and subcortical regions. Graph theory-based methods were employed to further analyze their topological properties. As expected, all participants demonstrated small-world topology, suggesting a highly efficient topological structure. Furthermore, we found that smaller brains showed higher local efficiency, whereas larger brains showed higher global efficiency, reflecting a suitable efficiency balance between local specialization and global integration of brain functional activity. Compared with right-handers, significant alterations in nodal efficiency were revealed in left-handers, involving the anterior and median cingulate gyrus, middle temporal gyrus, angular gyrus, and amygdala. Our findings indicated that the functional network organization in the human brain was associated with handedness and brain size.

  1. Tobacco Advertising and Promotional Expenditures in Sports and Sporting Events - United States, 1992-2013.

    Science.gov (United States)

    Agaku, Israel T; Odani, Satomi; Sturgis, Stephanie; Harless, Charles; Glover-Kudon, Rebecca

    2016-08-19

    Smokeless tobacco has been actively promoted by tobacco companies using endorsements by major sport figures, and research indicates that tobacco advertising can lead to youth initiation of tobacco use (1,2). Television and radio advertisements for cigarettes and smokeless tobacco have been prohibited since 1969,* and the 1998 Master Settlement Agreement(†) further prohibited tobacco companies from targeting youths with tobacco product advertisements in specified areas. In 2010, the Food and Drug Administration (FDA), under authority of the 2009 Family Smoking Prevention and Tobacco Control Act (FSPTCA), prohibited tobacco-brand sponsorship (i.e., sponsorship of sports and entertainment events or other social or cultural events using the tobacco brand name or anything identifiable with any brand of cigarettes or smokeless tobacco).(§) However, corporate-name tobacco sponsorship (i.e., sponsorship using the name of the corporation that manufactures regulated tobacco products) is still permitted under certain conditions.(¶) To monitor tobacco advertising and promotional activities in sports in the United States, CDC analyzed trends in sports-related marketing expenditures for cigarettes and smokeless tobacco during 1992-2013 using data from the Federal Trade Commission (FTC). During 1992-2013, sports-related marketing expenditures, adjusted by the consumer price index to constant 2013 dollars, decreased significantly for both cigarettes (from $136 million in 1992 to $0 in 2013) and smokeless tobacco (from $34.8 million in 1992 to $2.1 million in 2013). During 2010-2013, after the prohibition of tobacco-brand sponsorship in sports under the FSPTCA, cigarette manufacturers reported no spending (i.e., $0) on sports-related advertising and promotional activities; in contrast, smokeless tobacco manufacturers reported expenditures of $16.3 million on advertising and promoting smokeless tobacco in sports during 2010-2013. These findings indicate that despite prohibitions

  2. Altered spontaneous brain activity in patients with hemifacial spasm: a resting-state functional MRI study.

    Directory of Open Access Journals (Sweden)

    Ye Tu

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

  3. Activation of P2X7 promotes cerebral edema and neurological injury after traumatic brain injury in mice.

    Directory of Open Access Journals (Sweden)

    Donald E Kimbler

    Full Text Available Traumatic brain injury (TBI is a leading cause of death and disability worldwide. Cerebral edema, the abnormal accumulation of fluid within the brain parenchyma, contributes to elevated intracranial pressure (ICP and is a common life-threatening neurological complication following TBI. Unfortunately, neurosurgical approaches to alleviate increased ICP remain controversial and medical therapies are lacking due in part to the absence of viable drug targets. In the present study, genetic inhibition (P2X7-/- mice of the purinergic P2x7 receptor attenuated the expression of the pro-inflammatory cytokine, interleukin-1β (IL-1β and reduced cerebral edema following controlled cortical impact, as compared to wild-type mice. Similarly, brilliant blue G (BBG, a clinically non-toxic P2X7 inhibitor, inhibited IL-1β expression, limited edemic development, and improved neurobehavioral outcomes after TBI. The beneficial effects of BBG followed either prophylactic administration via the drinking water for one week prior to injury or via an intravenous bolus administration up to four hours after TBI, suggesting a clinically-implementable therapeutic window. Notably, P2X7 localized within astrocytic end feet and administration of BBG decreased the expression of glial fibrillary acidic protein (GFAP, a reactive astrocyte marker, and attenuated the expression of aquaporin-4 (AQP4, an astrocytic water channel that promotes cellular edema. Together, these data implicate P2X7 as a novel therapeutic target to prevent secondary neurological injury after TBI, a finding that warrants further investigation.

  4. An AAV promoter-driven neuropeptide Y gene delivery system using Sendai virosomes for neurons and rat brain.

    Science.gov (United States)

    Wu, P; de Fiebre, C M; Millard, W J; King, M A; Wang, S; Bryant, S O; Gao, Y P; Martin, E J; Meyer, E M

    1996-03-01

    An adeno-associated virus (AAV)-derived construct (pJDT95npy) containing rat neuropeptide Y (NPY) cDNA inserted downstream of endogenous AAV promoters was used to investigate AAV-driven NPY expression in postmitotic neurons in vitro and in the brain. NPY mRNA was expressed in NT2/N and rat brain primary neuronal cultures after transfection. There was a corresponding increase in the number of neurons staining for NPY-like immunoreactivity and an increase in NPY release during depolarization in the primary cultures. Injections of Sendai-virosome encapsulated pJDT95npy into neocortex increased NPY-like immunoreactivity in neurons but not glia indicating that the latter cell type did not have the translational, post-translational or storage capacity to accumulate the peptide. Injections into the rat hypothalamic para-ventricular nucleus increased body weight and food intake for 21 days, though NPY-like immunoreactivity remained elevated for at least 50 days. These studies demonstrate that AAV-derived constructs may be useful for delivering genes into post-mitotic neurons, and that Sendai virosomes are effective for delivering these constructs in vivo.

  5. Antipsychotics promote GABAergic interneuron genesis in the adult rat brain: Role of heat-shock protein production.

    Science.gov (United States)

    Kaneta, Hiroo; Ukai, Wataru; Tsujino, Hanako; Furuse, Kengo; Kigawa, Yoshiyasu; Tayama, Masaya; Ishii, Takao; Hashimoto, Eri; Kawanishi, Chiaki

    2017-09-01

    Current antipsychotics reduce positive symptoms and reverse negative symptoms in conjunction with cognitive behavioral issues with the goal of restoring impaired occupational and social functioning. However, limited information is available on their influence on gliogenesis or their neurogenic properties in adult schizophrenia brains, particularly on GABAergic interneuron production. In the present study, we used young adult subventricular zone (SVZ)-derived progenitor cells expressing proteoglycan NG2 cultures to examine the oligodendrocyte and GABAergic interneuron genesis effects of several kinds of antipsychotics on changes in differentiation function induced by exposure to the NMDA receptor antagonist MK-801. We herein demonstrated that antipsychotics promoted or restored changes in the oligodendrocyte/GABAergic interneuron differentiation functions of NG2(+) cells induced by the exposure to MK-801, which was considered to be one of the drug-induced schizophrenia model. We also demonstrated that antipsychotics restored heat-shock protein (HSP) production in NG2(+) cells with differentiation impairment. The antipsychotics olanzapine, aripiprazole, and blonanserin, but not haloperidol increased HSP90 levels, which were reduced by the exposure to MK-801. Our results showed that antipsychotics, particularly those recently synthesized, exerted similar GABAergic interneuron genesis effects on NG2(+) neuronal/glial progenitor cells in the adult rat brain by increasing cellular HSP production, and also suggest that HSP90 may play a crucial role in the pathophysiology of schizophrenia and is a key target for next drug development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. c-myc and N-myc promote active stem cell metabolism and cycling as architects of the developing brain.

    Science.gov (United States)

    Wey, Alice; Knoepfler, Paul S

    2010-06-01

    myc genes are associated with a wide variety of human cancers including most types of nervous system tumors. While the mechanisms by which myc overexpression causes tumorigenesis are multifaceted and have yet to be clearly elucidated, they are at least in part related to endogenous myc function in normal cells. Knockout (KO) of either c-myc or N-myc genes in neural stem and precursor cells (NSC) driven by nestin-cre impairs mouse brain growth and mutation of N-myc also causes microcephaly in humans in Feingold Syndrome. To further define myc function in NSC and nervous system development, we created a double KO (DKO) for c- and N-myc using nestin-cre. The DKO mice display profoundly impaired overall brain growth associated with decreased cell cycling and migration of NSC, which are strikingly decreased in number. The DKO brain also exhibits specific changes in gene expression including downregulation of genes involved in protein and nucleotide metabolism, mitosis, and chromatin structure as well as upregulation of genes associated with differentiation. Together these data support a model of nervous system tumorigenesis in which excess myc aberrantly locks in a developmentally active chromatin state characterized by overactive cell cycling, and metabolism as well as blocked differentiation.

  7. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome

    DEFF Research Database (Denmark)

    Perry, Rachel J; Peng, Liang; Barry, Natasha A

    2016-01-01

    Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota...... in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient-gut...

  8. Acetate mediates a microbiome-brain-β-cell axis to promote metabolic syndrome.

    Science.gov (United States)

    Perry, Rachel J; Peng, Liang; Barry, Natasha A; Cline, Gary W; Zhang, Dongyan; Cardone, Rebecca L; Petersen, Kitt Falk; Kibbey, Richard G; Goodman, Andrew L; Shulman, Gerald I

    2016-06-09

    Obesity, insulin resistance and the metabolic syndrome are associated with changes to the gut microbiota; however, the mechanism by which modifications to the gut microbiota might lead to these conditions is unknown. Here we show that increased production of acetate by an altered gut microbiota in rodents leads to activation of the parasympathetic nervous system, which, in turn, promotes increased glucose-stimulated insulin secretion, increased ghrelin secretion, hyperphagia, obesity and related sequelae. Together, these findings identify increased acetate production resulting from a nutrient-gut microbiota interaction and subsequent parasympathetic activation as possible therapeutic targets for obesity.

  9. Cortical thickness maturation and duration of music training: health-promoting activities shape brain development.

    Science.gov (United States)

    Hudziak, James J; Albaugh, Matthew D; Ducharme, Simon; Karama, Sherif; Spottswood, Margaret; Crehan, Eileen; Evans, Alan C; Botteron, Kelly N

    2014-11-01

    To assess the extent to which playing a musical instrument is associated with cortical thickness development among healthy youths. Participants were part of the National Institutes of Health (NIH) Magnetic Resonance Imaging (MRI) Study of Normal Brain Development. This study followed a longitudinal design such that participants underwent MRI scanning and behavioral testing on up to 3 separate visits, occurring at 2-year intervals. MRI, IQ, and music training data were available for 232 youths (334 scans), ranging from 6 to 18 years of age. Cortical thickness was regressed against the number of years that each youth had played a musical instrument. Next, thickness was regressed against an "Age × Years of Playing" interaction term. Age, gender, total brain volume, and scanner were controlled for in analyses. Participant ID was entered as a random effect to account for within-person dependence. False discovery rate correction was applied (p ≤ .05). There was no association between thickness and years playing a musical instrument. The "Age × Years of Playing" interaction was associated with thickness in motor, premotor, and supplementary motor cortices, as well as prefrontal and parietal cortices. Follow-up analysis revealed that music training was associated with an increased rate of thickness maturation. Results were largely unchanged when IQ and handedness were included as covariates. Playing a musical instrument was associated with more rapid cortical thickness maturation within areas implicated in motor planning and coordination, visuospatial ability, and emotion and impulse regulation. However, given the quasi-experimental nature of this study, we cannot rule out the influence of confounding variables. Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  10. Aspartic acid-promoted highly selective and sensitive colorimetric sensing of cysteine in rat brain.

    Science.gov (United States)

    Qian, Qin; Deng, Jingjing; Wang, Dalei; Yang, Lifen; Yu, Ping; Mao, Lanqun

    2012-11-06

    Direct selective determination of cysteine in the cerebral system is of great importance because of the crucial roles of cysteine in physiological and pathological processes. In this study, we report a sensitive and selective colorimetric assay for cysteine in the rat brain with gold nanoparticles (Au-NPs) as the signal readout. Initially, Au-NPs synthesized with citrate as the stabilizer are red in color and exhibit absorption at 520 nm. The addition of an aqueous solution (20 μL) of cysteine or aspartic acid alone to a 200 μL Au-NP dispersion causes no aggregation, while the addition of an aqueous solution of cysteine into a Au-NP dispersion containing aspartic acid (1.8 mM) causes the aggregation of Au-NPs and thus results in the color change of the colloid from wine red to blue. These changes are ascribed to the ion pair interaction between aspartic acid and cysteine on the interface between Au-NPs and solution. The concentration of cysteine can be visualized with the naked eye and determined by UV-vis spectroscopy. The signal output shows a linear relationship for cysteine within the concentration range from 0.166 to 1.67 μM with a detection limit of 100 nM. The assay demonstrated here is highly selective and is free from the interference of other natural amino acids and other thiol-containing species as well as the species commonly existing in the brain such as lactate, ascorbic acid, and glucose. The basal dialysate level of cysteine in the microdialysate from the striatum of adult male Sprague-Dawley rats is determined to be around 9.6 ± 2.1 μM. The method demonstrated here is facile but reliable and durable and is envisaged to be applicable to understanding the chemical essence involved in physiological and pathological events associated with cysteine.

  11. Effective promotion of breastfeeding among Latin American women newly immigrated to the United States.

    Science.gov (United States)

    Denman-Vitale, S; Murillo, E K

    1999-07-01

    Across the United States, advance practice nurses (APNs) are increasingly encountering recently immigrated Latin American populations. This article provides an overview of the situation of Latin Americans in the United States and discusses aspects of Latin American culture such as, respeto (respect), confianza (confidence), the importance of family, and the value of a personal connection. Strategies that will assist practitioners to incorporate culturally holistic principles in the promotion of breastfeeding among Latin American women who are new arrivals in the United States are described. If practitioners are to respond to the increasing numbers of Latin American women who need health care services, and also provide thorough, holistic health care then health care activities must be integrated with cultural competence.

  12. Voluntary exercise promotes beneficial anti-aging mechanisms in SAMP8 female brain.

    Science.gov (United States)

    Bayod, Sergi; Guzmán-Brambila, Carolina; Sanchez-Roige, Sandra; Lalanza, Jaume F; Kaliman, Perla; Ortuño-Sahagun, Daniel; Escorihuela, Rosa M; Pallàs, Mercè

    2015-02-01

    Regular physical exercise mediates health and longevity promotion involving Sirtuin 1 (SIRT1)-regulated pathways. The anti-aging activity of SIRT1 is achieved, at least in part, by means of fine-tuning the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway by preventing the transition of an originally pro-survival program into a pro-aging mechanism. Additionally, SIRT1 promotes mitochondrial function and reduces the production of reactive oxygen species (ROS) through regulating peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), the master controller of mitochondrial biogenesis. Here, by using senescence-accelerated mice prone 8 (SAMP8) as a model for aging, we determined the effect of wheel-running as a paradigm for long-term voluntary exercise on SIRT1-AMPK pathway and mitochondrial functionality measured by oxidative phosphorylation (OXPHOS) complex content in the hippocampus and cortex. We found differential activation of SIRT1 in both tissues and hippocampal-specific activation of AMPK. These findings correlated well with significant changes in OXPHOS in the hippocampal, but not in the cerebral cortex, area. Collectively, the results revealed greater benefits of the exercise in the wheel-running intervention in a murine model of senescence, which was directly related with mitochondrial function and which was mediated through the modulation of SIRT1 and AMPK pathways.

  13. Towards Development of a 3-State Self-Paced Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Ali Bashashati

    2007-01-01

    the presence of a right- or a left-hand movement and the second classifies the detected movement as a right or a left one. In an offline analysis of the EEG data collected from four able-bodied individuals, the 3-state brain-computer interface shows a comparable performance with a 2-state system and significant performance improvement if used as a 2-state BCI, that is, in detecting the presence of a right- or a left-hand movement (regardless of the type of movement. It has an average true positive rate of 37.5% and 42.8% (at false positives rate of 1% in detecting right- and left-hand extensions, respectively, in the context of a 3-state self-paced BCI and average detection rate of 58.1% (at false positive rate of 1% in the context of a 2-state self-paced BCI.

  14. Ground State and Excited State Tuning in Ferric Dipyrrin Complexes Promoted by Ancillary Ligand Exchange

    Energy Technology Data Exchange (ETDEWEB)

    Kleinlein, Claudia; Zheng, Shao-Liang; Betley, Theodore A.

    2017-04-24

    Three ferric dipyrromethene complexes featuring different ancillary ligands were synthesized by one electron oxidation of ferrous precursors. Four-coordinate iron complexes of the type (ArL)FeX2 [ArL = 1,9-(2,4,6-Ph3C6H2)2-5-mesityldipyrromethene] with X = Cl or tBuO were prepared and found to be high-spin (S = 5/2), as determined by superconducting quantum interference device magnetometry, electron paramagnetic resonance, and 57Fe Mössbauer spectroscopy. The ancillary ligand substitution was found to affect both ground state and excited properties of the ferric complexes examined. While each ferric complex displays reversible reduction and oxidation events, each alkoxide for chloride substitution results in a nearly 600 mV cathodic shift of the FeIII/II couple. The oxidation event remains largely unaffected by the ancillary ligand substitution and is likely dipyrrin-centered. While the alkoxide substituted ferric species largely retain the color of their ferrous precursors, characteristic of dipyrrin-based ligand-to-ligand charge transfer (LLCT), the dichloride ferric complex loses the prominent dipyrrin chromophore, taking on a deep green color. Time-dependent density functional theory analyses indicate the weaker-field chloride ligands allow substantial configuration mixing of ligand-to-metal charge transfer into the LLCT bands, giving rise to the color changes observed. Furthermore, the higher degree of covalency between the alkoxide ferric centers is manifest in the observed reactivity. Delocalization of spin density onto the tert-butoxide ligand in (ArL)FeCl(OtBu) is evidenced by hydrogen atom abstraction to yield (ArL)FeCl and HOtBu in the presence of substrates containing weak C–H bonds, whereas the chloride (ArL)FeCl2 analogue does not react under these conditions.

  15. Possible promotion of neuronal differentiation in fetal rat brain neural progenitor cells after sustained exposure to static magnetism.

    Science.gov (United States)

    Nakamichi, Noritaka; Ishioka, Yukichi; Hirai, Takao; Ozawa, Shusuke; Tachibana, Masaki; Nakamura, Nobuhiro; Takarada, Takeshi; Yoneda, Yukio

    2009-08-15

    We have previously shown significant potentiation of Ca(2+) influx mediated by N-methyl-D-aspartate receptors, along with decreased microtubules-associated protein-2 (MAP2) expression, in hippocampal neurons cultured under static magnetism without cell death. In this study, we investigated the effects of static magnetism on the functionality of neural progenitor cells endowed to proliferate for self-replication and differentiate into neuronal, astroglial, and oligodendroglial lineages. Neural progenitor cells were isolated from embryonic rat neocortex and hippocampus, followed by culture under static magnetism at 100 mT and subsequent determination of the number of cells immunoreactive for a marker protein of particular progeny lineages. Static magnetism not only significantly decreased proliferation of neural progenitor cells without affecting cell viability, but also promoted differentiation into cells immunoreactive for MAP2 with a concomitant decrease in that for an astroglial marker, irrespective of the presence of differentiation inducers. In neural progenitors cultured under static magnetism, a significant increase was seen in mRNA expression of several activator-type proneural genes, such as Mash1, Math1, and Math3, together with decreased mRNA expression of the repressor type Hes5. These results suggest that sustained static magnetism could suppress proliferation for self-renewal and facilitate differentiation into neurons through promoted expression of activator-type proneural genes by progenitor cells in fetal rat brain.

  16. Toward determining the lifetime occurrence of metastatic brain tumors estimated from 2007 United States cancer incidence data

    Science.gov (United States)

    Davis, Faith G.; Dolecek, Therese A.; McCarthy, Bridget J.; Villano, John L.

    2012-01-01

    Few population estimates of brain metastasis in the United States are available, prompting this study. Our objective was to estimate the expected number of metastatic brain tumors that would subsequently develop among incident cancer cases for 1 diagnosis year in the United States. Incidence proportions for primary cancer sites known to develop brain metastasis were applied to United States cancer incidence data for 2007 that were retrieved from accessible data sets through Centers for Disease Control and Prevention (CDC Wonder) and Surveillance, Epidemiology, and End Results (SEER) Program Web sites. Incidence proportions were identified for cancer sites, reflecting 80% of all cancers. It was conservatively estimated that almost 70 000 new brain metastases would occur over the remaining lifetime of individuals who received a diagnosis in 2007 of primary invasive cancer in the United States. That is, 6% of newly diagnosed cases of cancer during 2007 would be expected to develop brain metastasis as a progression of their original cancer diagnosis; the most frequent sites for metastases being lung and bronchus and breast cancers. The estimated numbers of brain metastasis will be expected to be higher among white individuals, female individuals, and older age groups. Changing patterns in the occurrence of primary cancers, trends in populations at risk, effectiveness of treatments on survival, and access to those treatments will influence the extent of brain tumor metastasis at the population level. These findings provide insight on the patterns of brain tumor metastasis and the future burden of this condition in the United States. PMID:22898372

  17. Brain-state classification and a dual-state decoder dramatically improve the control of cursor movement through a brain-machine interface

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    Sachs, Nicholas A.; Ruiz-Torres, Ricardo; Perreault, Eric J.; Miller, Lee E.

    2017-01-01

    Objective It is quite remarkable that Brain Machine Interfaces (BMIs) can be used to control complex movements with fewer than 100 neurons. Success may be due in part to the limited range of dynamical conditions under which most BMIs are tested. Achieving high-quality control that spans these conditions with a single linear mapping will be more challenging. Even for simple reaching movements, existing BMIs must reduce the stochastic noise of neurons by averaging the control signals over time, instead of over the many neurons that normally control movement. This forces a compromise between a decoder with dynamics allowing rapid movement and one that allows postures to be maintained with little jitter. Our current work presents a method for addressing this compromise, which may also generalize to more highly varied dynamical situations, including movements with more greatly varying speed. Approach We have developed a system that uses two independent Weiner filters as individual components in a single decoder, one optimized for movement, and the other for postural control. We computed an LDA classifier using the same neural inputs. The classifier combined the outputs of the two filters in proportion to the likelihood assigned by the classifier to each state. Main results We have performed online experiments with two monkeys using this neural-classifier, dual-state decoder, comparing it to a standard, single-state decoder as well as to a dual-state decoder that switched states automatically based on the cursor’s proximity to a target. The performance of both monkeys using the classifier decoder was markedly better than that of the single-state decoder and comparable to the proximity decoder. Significance We have demonstrated a novel strategy for dealing with the need to make rapid movements while also maintaining precise cursor control when approaching and stabilizing within targets. Further gains can undoubtedly be realized by optimizing the performance of the

  18. Brain-state classification and a dual-state decoder dramatically improve the control of cursor movement through a brain-machine interface

    Science.gov (United States)

    Sachs, Nicholas A.; Ruiz-Torres, Ricardo; Perreault, Eric J.; Miller, Lee E.

    2016-02-01

    Objective. It is quite remarkable that brain machine interfaces (BMIs) can be used to control complex movements with fewer than 100 neurons. Success may be due in part to the limited range of dynamical conditions under which most BMIs are tested. Achieving high-quality control that spans these conditions with a single linear mapping will be more challenging. Even for simple reaching movements, existing BMIs must reduce the stochastic noise of neurons by averaging the control signals over time, instead of over the many neurons that normally control movement. This forces a compromise between a decoder with dynamics allowing rapid movement and one that allows postures to be maintained with little jitter. Our current work presents a method for addressing this compromise, which may also generalize to more highly varied dynamical situations, including movements with more greatly varying speed. Approach. We have developed a system that uses two independent Wiener filters as individual components in a single decoder, one optimized for movement, and the other for postural control. We computed an LDA classifier using the same neural inputs. The decoder combined the outputs of the two filters in proportion to the likelihood assigned by the classifier to each state. Main results. We have performed online experiments with two monkeys using this neural-classifier, dual-state decoder, comparing it to a standard, single-state decoder as well as to a dual-state decoder that switched states automatically based on the cursor’s proximity to a target. The performance of both monkeys using the classifier decoder was markedly better than that of the single-state decoder and comparable to the proximity decoder. Significance. We have demonstrated a novel strategy for dealing with the need to make rapid movements while also maintaining precise cursor control when approaching and stabilizing within targets. Further gains can undoubtedly be realized by optimizing the performance of the

  19. Breathing and brain state: urethane anesthesia as a model for natural sleep.

    Science.gov (United States)

    Pagliardini, Silvia; Funk, Gregory D; Dickson, Clayton T

    2013-09-15

    Respiratory control differs dramatically across sleep stages. Indeed, along with rapid eye movements (REM), respiration was one of the first physiological variables shown to be modulated across sleep stages. The study of sleep stages, their physiological correlates, and neurobiological underpinnings present a challenge because of the fragility and unpredictability of individual stages, not to mention sleep itself. Although anesthesia has often substituted as a model for a unitary stage of slow-wave (non-REM) sleep, it is only recently that urethane anesthesia has been proposed to model the full spectrum of sleep given the presence of spontaneous brain state alternations and concurrent physiological correlates that appear remarkably similar to natural sleep. We describe this model, its parallels with natural sleep, and its power for studying modulation of respiration. Specifically, we report data on the EEG characteristics across brain states under urethane anesthesia, the dependence of brain alternations on neurotransmitter systems, and the observations on state dependent modulation of respiration. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Brain-state dependent uncoupling of BOLD and local field potentials in laminar olfactory bulb.

    Science.gov (United States)

    Gong, Ling; Li, Bo; Wu, Ruiqi; Li, Anan; Xu, Fuqiang

    2014-09-19

    The neural activities of the olfactory bulb (OB) can be modulated significantly by internal brain states. While blood oxygenation level dependent functional MRI (BOLD-fMRI) has been extensively applied to study OB in small animals, the relationship between BOLD signals and electrophysiological signals remains to be elucidated. Our recent study has revealed a complex relationship between BOLD and local field potentials (LFP) signals in different OB layers during odor stimulation. However, no study has been performed to compare these two types of signals under global brain states. Here, the changes of BOLD and LFP signals in the glomerular, mitral cell, and granular cell layers of the OB under different brain states, which were induced by different concentrations of isoflurane, were sequentially acquired using electrode array and high-resolution MRI. It was found that under deeper anesthesia, the LFP powers in all layers were decreased but the BOLD signals were unexpectedly increased. Furthermore, the decreases of LFP powers were layer-independent, but the increases of BOLD signal were layer-specific, with the order of glomerular>mitral cell>granular cell layer. The results provide new evidence that the direct neural activity levels might not be correlated well with BOLD signals in some cases, and remind us that cautions should be taken to use BOLD signals as the index of neural activities. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Distinction in coherent neural network between resting and working brain states.

    Science.gov (United States)

    Liu, Xiao; Zhu, Xiao-Hong; Chen, Wei

    2011-01-01

    The resting brain is not silent; rather, it is characterized by organized resting-state networks showing spontaneous and coherent neuronal activities, which can be mapped using the spatiotemporal correlation of blood oxygenation level-dependent (BOLD) signal fluctuations measured by functional magnetic resonance imaging (fMRI). However, it remains elusive whether the similar fMRI approach is able to image the coherent network in a working brain, and if yes, whether there is a distinction between the resting- and working-state coherent networks. This study aimed to address these questions in the human visual cortex with a desired activation paradigm using continuous, sustained visual stimuli. It was found that the resting-state coherent network covering the human visual cortex was spatially reorganized during the stimulation into two coherent networks with distinct temporal characteristics of BOLD fluctuations: one covering the activated visual cortical region and the other covering the remaining (nonactivated) visual cortex. The stimulus-specific reorganization of the coherent network observed in the present fMRI study in human is consistent with previous electrophysiological findings from animal studies, and may suggest an essential mechanism for brain functioning. Finally, a similar fMRI experiment was also conducted under brief, short stimulation to examine how the stimulation paradigm can affect the observations.

  2. Extraversion and Neuroticism relate to topological properties of resting-state brain networks

    Directory of Open Access Journals (Sweden)

    Qing eGao

    2013-06-01

    Full Text Available With the advent and development of modern neuroimaging techniques, there is an increasing interest in linking extraversion and neuroticism to anatomical and functional brain markers. Here we aimed to test the theoretically derived biological personality model as proposed by Eysenck using graph theoretical analyses. Specifically, the association between the topological organization of whole-brain functional networks and extraversion/neuroticism was explored. To construct functional brain networks, functional connectivity among 90 brain regions was measured by temporal correlation using resting-state functional magnetic resonance imaging (fMRI data of 71 healthy subjects. Graph theoretical analysis revealed a positive association of extraversion scores and normalized clustering coefficient values. These results suggested a more clustered configuration in brain networks of individuals high in extraversion, which could imply a higher arousal threshold and higher levels of arousal tolerance in the cortex of extraverts. On a local network level, we observed that a specific nodal measure, i.e. betweenness centrality (BC, was positively associated with neuroticism scores in the right precentral gyrus, right caudate nucleus, right olfactory cortex and bilateral amygdala. For individuals high in neuroticism, these results suggested a more frequent participation of these specific regions in information transition within the brain network and, in turn, may partly explain greater regional activation levels and lower arousal thresholds in these regions. In contrast, extraversion scores were positively correlated with BC in the right insula, while negatively correlated with BC in the bilateral middle temporal gyrus, indicating that the relationship between extraversion and regional arousal is not as simple as proposed by Eysenck.

  3. Robust brain parcellation using sparse representation on resting-state fMRI.

    Science.gov (United States)

    Zhang, Yu; Caspers, Svenja; Fan, Lingzhong; Fan, Yong; Song, Ming; Liu, Cirong; Mo, Yin; Roski, Christian; Eickhoff, Simon; Amunts, Katrin; Jiang, Tianzi

    2015-11-01

    Resting-state fMRI (rs-fMRI) has been widely used to segregate the brain into individual modules based on the presence of distinct connectivity patterns. Many parcellation methods have been proposed for brain parcellation using rs-fMRI, but their results have been somewhat inconsistent, potentially due to various types of noise. In this study, we provide a robust parcellation method for rs-fMRI-based brain parcellation, which constructs a sparse similarity graph based on the sparse representation coefficients of each seed voxel and then uses spectral clustering to identify distinct modules. Both the local time-varying BOLD signals and whole-brain connectivity patterns may be used as features and yield similar parcellation results. The robustness of our method was tested on both simulated and real rs-fMRI datasets. In particular, on simulated rs-fMRI data, sparse representation achieved good performance across different noise levels, including high accuracy of parcellation and high robustness to noise. On real rs-fMRI data, stable parcellation of the medial frontal cortex (MFC) and parietal operculum (OP) were achieved on three different datasets, with high reproducibility within each dataset and high consistency across these results. Besides, the parcellation of MFC was little influenced by the degrees of spatial smoothing. Furthermore, the consistent parcellation of OP was also well corresponding to cytoarchitectonic subdivisions and known somatotopic organizations. Our results demonstrate a new promising approach to robust brain parcellation using resting-state fMRI by sparse representation.

  4. Resting state brain network function in major depression - Depression symptomatology, antidepressant treatment effects, future research.

    Science.gov (United States)

    Brakowski, Janis; Spinelli, Simona; Dörig, Nadja; Bosch, Oliver Gero; Manoliu, Andrei; Holtforth, Martin Grosse; Seifritz, Erich

    2017-09-01

    The alterations of functional connectivity brain networks in major depressive disorder (MDD) have been subject of a large number of studies. Using different methodologies and focusing on diverse aspects of the disease, research shows heterogeneous results lacking integration. Disrupted network connectivity has been found in core MDD networks like the default mode network (DMN), the central executive network (CEN), and the salience network, but also in cerebellar and thalamic circuitries. Here we review literature published on resting state brain network function in MDD focusing on methodology, and clinical characteristics including symptomatology and antidepressant treatment related findings. There are relatively few investigations concerning the qualitative aspects of symptomatology of MDD, whereas most studies associate quantitative aspects with distinct resting state functional connectivity alterations. Such depression severity associated alterations are found in the DMN, frontal, cerebellar and thalamic brain regions as well as the insula and the subgenual anterior cingulate cortex. Similarly, different therapeutical options in MDD and their effects on brain function showed patchy results. Herein, pharmaceutical treatments reveal functional connectivity alterations throughout multiple brain regions notably the DMN, fronto-limbic, and parieto-temporal regions. Psychotherapeutical interventions show significant functional connectivity alterations in fronto-limbic networks, whereas electroconvulsive therapy and repetitive transcranial magnetic stimulation result in alterations of the subgenual anterior cingulate cortex, the DMN, the CEN and the dorsal lateral prefrontal cortex. While it appears clear that functional connectivity alterations are associated with the pathophysiology and treatment of MDD, future research should also generate a common strategy for data acquisition and analysis, as a least common denominator, to set the basis for comparability across

  5. Brain functional network connectivity based on a visual task: visual information processing-related brain regions are significantly activated in the task state

    Directory of Open Access Journals (Sweden)

    Yan-li Yang

    2015-01-01

    Full Text Available It is not clear whether the method used in functional brain-network related research can be applied to explore the feature binding mechanism of visual perception. In this study, we investigated feature binding of color and shape in visual perception. Functional magnetic resonance imaging data were collected from 38 healthy volunteers at rest and while performing a visual perception task to construct brain networks active during resting and task states. Results showed that brain regions involved in visual information processing were obviously activated during the task. The components were partitioned using a greedy algorithm, indicating the visual network existed during the resting state. Z-values in the vision-related brain regions were calculated, confirming the dynamic balance of the brain network. Connectivity between brain regions was determined, and the result showed that occipital and lingual gyri were stable brain regions in the visual system network, the parietal lobe played a very important role in the binding process of color features and shape features, and the fusiform and inferior temporal gyri were crucial for processing color and shape information. Experimental findings indicate that understanding visual feature binding and cognitive processes will help establish computational models of vision, improve image recognition technology, and provide a new theoretical mechanism for feature binding in visual perception.

  6. Music making as a tool for promoting brain plasticity across the life span.

    Science.gov (United States)

    Wan, Catherine Y; Schlaug, Gottfried

    2010-10-01

    Playing a musical instrument is an intense, multisensory, and motor experience that usually commences at an early age and requires the acquisition and maintenance of a range of skills over the course of a musician's lifetime. Thus, musicians offer an excellent human model for studying the brain effects of acquiring specialized sensorimotor skills. For example, musicians learn and repeatedly practice the association of motor actions with specific sound and visual patterns (musical notation) while receiving continuous multisensory feedback. This association learning can strengthen connections between auditory and motor regions (e.g., arcuate fasciculus) while activating multimodal integration regions (e.g., around the intraparietal sulcus). We argue that training of this neural network may produce cross-modal effects on other behavioral or cognitive operations that draw on this network. Plasticity in this network may explain some of the sensorimotor and cognitive enhancements that have been associated with music training. These enhancements suggest the potential for music making as an interactive treatment or intervention for neurological and developmental disorders, as well as those associated with normal aging.

  7. Music Making as a Tool for Promoting Brain Plasticity across the Life Span

    Science.gov (United States)

    Wan, Catherine Y.; Schlaug, Gottfried

    2010-01-01

    Playing a musical instrument is an intense, multisensory, and motor experience that usually commences at an early age and requires the acquisition and maintenance of a range of skills over the course of a musician's lifetime. Thus, musicians offer an excellent human model for studying the brain effects of acquiring specialized sensorimotor skills. For example, musicians learn and repeatedly practice the association of motor actions with specific sound and visual patterns (musical notation) while receiving continuous multisensory feedback. This association learning can strengthen connections between auditory and motor regions (e.g., arcuate fasciculus) while activating multimodal integration regions (e.g., around the intraparietal sulcus). We argue that training of this neural network may produce cross-modal effects on other behavioral or cognitive operations that draw on this network. Plasticity in this network may explain some of the sensorimotor and cognitive enhancements that have been associated with music training. These enhancements suggest the potential for music making as an interactive treatment or intervention for neurological and developmental disorders, as well as those associated with normal aging. PMID:20889966

  8. mTOR and neuronal cell cycle reentry: How impaired brain insulin signaling promotes Alzheimer's disease.

    Science.gov (United States)

    Norambuena, Andrés; Wallrabe, Horst; McMahon, Lloyd; Silva, Antonia; Swanson, Eric; Khan, Shahzad S; Baerthlein, Daniel; Kodis, Erin; Oddo, Salvatore; Mandell, James W; Bloom, George S

    2017-02-01

    A major obstacle to presymptomatic diagnosis and disease-modifying therapy for Alzheimer's disease (AD) is inadequate understanding of molecular mechanisms of AD pathogenesis. For example, impaired brain insulin signaling is an AD hallmark, but whether and how it might contribute to the synaptic dysfunction and neuron death that underlie memory and cognitive impairment has been mysterious. Neuron death in AD is often caused by cell cycle reentry (CCR) mediated by amyloid-β oligomers (AβOs) and tau, the precursors of plaques and tangles. We now report that CCR results from AβO-induced activation of the protein kinase complex, mTORC1, at the plasma membrane and mTORC1-dependent tau phosphorylation, and that CCR can be prevented by insulin-stimulated activation of lysosomal mTORC1. AβOs were also shown previously to reduce neuronal insulin signaling. Our data therefore indicate that the decreased insulin signaling provoked by AβOs unleashes their toxic potential to cause neuronal CCR, and by extension, neuron death. Copyright © 2016 the Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  9. Transient brain activity explains the spectral content of steady-state visual evoked potentials.

    Science.gov (United States)

    Gaume, Antoine; Vialatte, François; Dreyfus, Gérard

    2014-01-01

    Steady-state visual evoked potentials (SSVEPs) are widely used in the design of brain-computer interfaces (BCIs). A lot of effort has therefore been devoted to find a fast and reliable way to detect SSVEPs. We study the link between transient and steady-state VEPs and show that it is possible to predict the spectral content of a subject's SSVEPs by simulating trains of transient VEPs. This could lead to a better understanding of evoked potentials as well as to better performances of SSVEP-based BCIs, by providing a tool to improve SSVEP detection algorithms.

  10. Cortical neurons and networks are dormant but fully responsive during isoelectric brain state.

    Science.gov (United States)

    Altwegg-Boussac, Tristan; Schramm, Adrien E; Ballestero, Jimena; Grosselin, Fanny; Chavez, Mario; Lecas, Sarah; Baulac, Michel; Naccache, Lionel; Demeret, Sophie; Navarro, Vincent; Mahon, Séverine; Charpier, Stéphane

    2017-09-01

    A continuous isoelectric electroencephalogram reflects an interruption of endogenously-generated activity in cortical networks and systematically results in a complete dissolution of conscious processes. This electro-cerebral inactivity occurs during various brain disorders, including hypothermia, drug intoxication, long-lasting anoxia and brain trauma. It can also be induced in a therapeutic context, following the administration of high doses of barbiturate-derived compounds, to interrupt a hyper-refractory status epilepticus. Although altered sensory responses can be occasionally observed on an isoelectric electroencephalogram, the electrical membrane properties and synaptic responses of individual neurons during this cerebral state remain largely unknown. The aim of the present study was to characterize the intracellular correlates of a barbiturate-induced isoelectric electroencephalogram and to analyse the sensory-evoked synaptic responses that can emerge from a brain deprived of spontaneous electrical activity. We first examined the sensory responsiveness from patients suffering from intractable status epilepticus and treated by administration of thiopental. Multimodal sensory responses could be evoked on the flat electroencephalogram, including visually-evoked potentials that were significantly amplified and delayed, with a high trial-to-trial reproducibility compared to awake healthy subjects. Using an analogous pharmacological procedure to induce prolonged electro-cerebral inactivity in the rat, we could describe its cortical and subcortical intracellular counterparts. Neocortical, hippocampal and thalamo-cortical neurons were all silent during the isoelectric state and displayed a flat membrane potential significantly hyperpolarized compared with spontaneously active control states. Nonetheless, all recorded neurons could fire action potentials in response to intracellularly injected depolarizing current pulses and their specific intrinsic

  11. Disrutpted resting-state functional architecture of the brain after 45-day simulated microgravity.

    Science.gov (United States)

    Zhou, Yuan; Wang, Yun; Rao, Li-Lin; Liang, Zhu-Yuan; Chen, Xiao-Ping; Zheng, Dang; Tan, Cheng; Tian, Zhi-Qiang; Wang, Chun-Hui; Bai, Yan-Qiang; Chen, Shan-Guang; Li, Shu

    2014-01-01

    Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI) to study whether the functional architecture of the brain is altered after 45 days of -6° head-down tilt (HDT) bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of -6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC), to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC) analysis. We found decreased DC in two regions, the left anterior insula (aINS) and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies), in the male volunteers after 45 days of -6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS-MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function, and central neural activity.

  12. Disrutpted resting-state functional architecture of the brain after 45-day simulated microgravity

    Directory of Open Access Journals (Sweden)

    Yuan eZhou

    2014-06-01

    Full Text Available Long-term spaceflight induces both physiological and psychological changes in astronauts. To understand the neural mechanisms underlying these physiological and psychological changes, it is critical to investigate the effects of microgravity on the functional architecture of the brain. In this study, we used resting-state functional MRI (rs-fMRI to study whether the functional architecture of the brain is altered after 45 days of -6° head-down tilt (HDT bed rest, which is a reliable model for the simulation of microgravity. Sixteen healthy male volunteers underwent rs-fMRI scans before and after 45 days of -6° HDT bed rest. Specifically, we used a commonly employed graph-based measure of network organization, i.e., degree centrality (DC, to perform a full-brain exploration of the regions that were influenced by simulated microgravity. We subsequently examined the functional connectivities of these regions using a seed-based resting-state functional connectivity (RSFC analysis. We found decreased DC in two regions, the left anterior insula (aINS and the anterior part of the middle cingulate cortex (MCC; also called the dorsal anterior cingulate cortex in many studies, in the male volunteers after 45 days of -6° HDT bed rest. Furthermore, seed-based RSFC analyses revealed that a functional network anchored in the aINS and MCC was particularly influenced by simulated microgravity. These results provide evidence that simulated microgravity alters the resting-state functional architecture of the brains of males and suggest that the processing of salience information, which is primarily subserved by the aINS–MCC functional network, is particularly influenced by spaceflight. The current findings provide a new perspective for understanding the relationships between microgravity, cognitive function, autonomic neural function and central neural activity.

  13. Brain connectivity analysis from EEG signals using stable phase-synchronized states during face perception tasks

    Science.gov (United States)

    Jamal, Wasifa; Das, Saptarshi; Maharatna, Koushik; Pan, Indranil; Kuyucu, Doga

    2015-09-01

    Degree of phase synchronization between different Electroencephalogram (EEG) channels is known to be the manifestation of the underlying mechanism of information coupling between different brain regions. In this paper, we apply a continuous wavelet transform (CWT) based analysis technique on EEG data, captured during face perception tasks, to explore the temporal evolution of phase synchronization, from the onset of a stimulus. Our explorations show that there exists a small set (typically 3-5) of unique synchronized patterns or synchrostates, each of which are stable of the order of milliseconds. Particularly, in the beta (β) band, which has been reported to be associated with visual processing task, the number of such stable states has been found to be three consistently. During processing of the stimulus, the switching between these states occurs abruptly but the switching characteristic follows a well-behaved and repeatable sequence. This is observed in a single subject analysis as well as a multiple-subject group-analysis in adults during face perception. We also show that although these patterns remain topographically similar for the general category of face perception task, the sequence of their occurrence and their temporal stability varies markedly between different face perception scenarios (stimuli) indicating toward different dynamical characteristics for information processing, which is stimulus-specific in nature. Subsequently, we translated these stable states into brain complex networks and derived informative network measures for characterizing the degree of segregated processing and information integration in those synchrostates, leading to a new methodology for characterizing information processing in human brain. The proposed methodology of modeling the functional brain connectivity through the synchrostates may be viewed as a new way of quantitative characterization of the cognitive ability of the subject, stimuli and information integration

  14. Brain-Computer Interfaces Using Sensorimotor Rhythms: Current State and Future Perspectives

    Science.gov (United States)

    Yuan, Han; He, Bin

    2014-01-01

    Many studies over the past two decades have shown that people can use brain signals to convey their intent to a computer using brain-computer interfaces (BCIs). BCI systems extract specific features of brain activity and translate them into control signals that drive an output. Recently, a category of BCIs that are built on the rhythmic activity recorded over the sensorimotor cortex, i.e. the sensorimotor rhythm (SMR), has attracted considerable attention among the BCIs that use noninvasive neural recordings, e.g. electroencephalography (EEG), and have demonstrated the capability of multi-dimensional prosthesis control. This article reviews the current state and future perspectives of SMR-based BCI and its clinical applications, in particular focusing on the EEG SMR. The characteristic features of SMR from the human brain are described and their underlying neural sources are discussed. The functional components of SMR-based BCI, together with its current clinical applications are reviewed. Lastly, limitations of SMR-BCIs and future outlooks are also discussed. PMID:24759276

  15. Regional homogeneity of the resting-state brain activity correlates with individual intelligence.

    Science.gov (United States)

    Wang, Leiqiong; Song, Ming; Jiang, Tianzi; Zhang, Yunting; Yu, Chunshui

    2011-01-25

    Resting-state functional magnetic resonance imaging has confirmed that the strengths of the long distance functional connectivity between different brain areas are correlated with individual differences in intelligence. However, the association between the local connectivity within a specific brain region and intelligence during rest remains largely unknown. The aim of this study is to investigate the relationship between local connectivity and intelligence. Fifty-nine right-handed healthy adults participated in the study. The regional homogeneity (ReHo) was used to assess the strength of local connectivity. The associations between ReHo and full-scale intelligence quotient (FSIQ) scores were studied in a voxel-wise manner using partial correlation analysis controlling for age and sex. We found that the FSIQ scores were positively correlated with the ReHo values of the bilateral inferior parietal lobules, middle frontal, parahippocampal and inferior temporal gyri, the right thalamus, superior frontal and fusiform gyri, and the left superior parietal lobule. The main findings are consistent with the parieto-frontal integration theory (P-FIT) of intelligence, supporting the view that general intelligence involves multiple brain regions throughout the brain. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  16. Whole Brain Functional Connectivity Using Phase Locking Measures Of Resting State Magnetoencephalography

    Directory of Open Access Journals (Sweden)

    Benjamin T Schmidt

    2014-06-01

    Full Text Available The analysis of spontaneous functional connectivity reveals the statistical connections between regions of the brain consistent with underlying functional communication networks within the brain. In this work, we describe the implementation of a complete all-to-all network analysis of resting state neuronal activity from magnetoencephalography (MEG. Using graph theory to define networks at the dipole level, we established functionally defined regions by k-means clustering cortical surface locations using Eigenvector centrality scores from the all-to-all adjacency model. Permutation testing was used to estimate regions with statistically significant connections compared to empty room data, which adjusts for spatial dependencies introduced by the MEG inverse problem. In order to test this model, we preformed a series of numerical simulations investigating the effects of the MEG reconstruction on connectivity estimates. We subsequently applied the approach to subject data to investigate the effectiveness of our method in obtaining whole brain networks. Our findings indicated that our model provides statistically robust estimates of functional region networks. Application of our phase locking network methodology to real data produced networks with similar connectivity to previously published findings, specifically, we found connections between contralateral areas of the arcuate fasciculus that have been previously investigated. The use of data-driven methods for neuroscientific investigations provides a new tool for researchers in identifying and characterizing whole brain functional connectivity networks.

  17. Whole brain functional connectivity using phase locking measures of resting state magnetoencephalography.

    Science.gov (United States)

    Schmidt, Benjamin T; Ghuman, Avniel S; Huppert, Theodore J

    2014-01-01

    The analysis of spontaneous functional connectivity (sFC) reveals the statistical connections between regions of the brain consistent with underlying functional communication networks within the brain. In this work, we describe the implementation of a complete all-to-all network analysis of resting state neuronal activity from magnetoencephalography (MEG). Using graph theory to define networks at the dipole level, we established functionally defined regions by k-means clustering cortical surface locations using Eigenvector centrality (EVC) scores from the all-to-all adjacency model. Permutation testing was used to estimate regions with statistically significant connections compared to empty room data, which adjusts for spatial dependencies introduced by the MEG inverse problem. In order to test this model, we performed a series of numerical simulations investigating the effects of the MEG reconstruction on connectivity estimates. We subsequently applied the approach to subject data to investigate the effectiveness of our method in obtaining whole brain networks. Our findings indicated that our model provides statistically robust estimates of functional region networks. Application of our phase locking network methodology to real data produced networks with similar connectivity to previously published findings, specifically, we found connections between contralateral areas of the arcuate fasciculus that have been previously investigated. The use of data-driven methods for neuroscientific investigations provides a new tool for researchers in identifying and characterizing whole brain functional connectivity networks.

  18. NEUROREHABILITATION OF POST-TRAUMATIC STRESS AND DEPRESSIVE BEHAVIORS BY BRAIN STATE CONDITIONING

    Directory of Open Access Journals (Sweden)

    Vijendra K. SINGH

    2009-06-01

    Full Text Available Brain State Conditioning™ (BSC is an innovative technology that optimizes brainwaves in real-time to achieve balance and harmony of the human brain. Since the brain function is imbalanced in individuals with psychiatric disorders and neurological diseases, we explored the possibility of using this technology to help people with post-traumatic stress disorder (PTSD and depression. We conducted a pilot study of 8 adult subjects who had symptoms of PTSD, depression and anxiety problems. The severity of symptoms was evaluated by Objective survey and Beck’s inventory for depression and anxiety. After the initial assessment of brain maps, individuals were administered with highly personalized training sessions, for example 4-5 sessions over 4-5 days. After the administration of BSC, we found a consistent decline in Beck’s inventory scores, which implied alleviation of depressive and anxiety tendencies. All subjects in the study responded to BSC technology and showed noticeable improvement in the quality of their lives. Thus we suggest that BSC is a viable approach to brainwave optimization to help people overcome health problems due to PTSD and depression.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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.

  1. Active auditory experience in infancy promotes brain plasticity in Theta and Gamma oscillations

    Directory of Open Access Journals (Sweden)

    Gabriella Musacchia

    2017-08-01

    Full Text Available Language acquisition in infants is driven by on-going neural plasticity that is acutely sensitive to environmental acoustic cues. Recent studies showed that attention-based experience with non-linguistic, temporally-modulated auditory stimuli sharpens cortical responses. A previous ERP study from this laboratory showed that interactive auditory experience via behavior-based feedback (AEx, over a 6-week period from 4- to 7-months-of-age, confers a processing advantage, compared to passive auditory exposure (PEx or maturation alone (Naïve Control, NC. Here, we provide a follow-up investigation of the underlying neural oscillatory patterns in these three groups. In AEx infants, Standard stimuli with invariant frequency (STD elicited greater Theta-band (4–6 Hz activity in Right Auditory Cortex (RAC, as compared to NC infants, and Deviant stimuli with rapid frequency change (DEV elicited larger responses in Left Auditory Cortex (LAC. PEx and NC counterparts showed less-mature bilateral patterns. AEx infants also displayed stronger Gamma (33–37 Hz activity in the LAC during DEV discrimination, compared to NCs, while NC and PEx groups demonstrated bilateral activity in this band, if at all. This suggests that interactive acoustic experience with non-linguistic stimuli can promote a distinct, robust and precise cortical pattern during rapid auditory processing, perhaps reflecting mechanisms that support fine-tuning of early acoustic mapping.

  2. 78 FR 29779 - Labor Affairs Council of the United States-Colombia Trade Promotion Agreement; Notice of Public...

    Science.gov (United States)

    2013-05-21

    ... of the Secretary Labor Affairs Council of the United States-Colombia Trade Promotion Agreement; Notice of Public Session Meeting AGENCY: International Labor Affairs Bureau (ILAB), U.S. Department of... Article 17.5 of the U.S.-Colombia Trade Promotion Agreement (TPA), the International Labor Affairs Bureau...

  3. Central thalamic deep brain stimulation for support of forebrain arousal regulation in the minimally conscious state.

    Science.gov (United States)

    Schiff, Nicholas D

    2013-01-01

    This chapter considers the use of central thalamic deep brain stimulation (CT/DBS) to support arousal regulation mechanisms in the minimally conscious state (MCS). CT/DBS for selected patients in a MCS is first placed in the historical context of prior efforts to use thalamic electrical brain stimulation to treat the unconscious clinical conditions of coma and vegetative state. These previous studies and a proof of concept result from a single-subject study of a patient in a MCS are reviewed against the background of new population data providing benchmarks of the natural history of vegetative and MCSs. The conceptual foundations for CT/DBS in selected patients in a MCS are then presented with consideration of both circuit and cellular mechanisms underlying recovery of consciousness identified from empirical studies. Directions for developing future generalizable criteria for CT/DBS that focus on the integrity of necessary brain systems and behavioral profiles in patients in a MCS that may optimally response to support of arousal regulation mechanisms are proposed. © 2013 Elsevier B.V. All rights reserved.

  4. EEG Resting-State Brain Topological Reorganization as a Function of Age.

    Science.gov (United States)

    Petti, Manuela; Toppi, Jlenia; Babiloni, Fabio; Cincotti, Febo; Mattia, Donatella; Astolfi, Laura

    2016-01-01

    Resting state connectivity has been increasingly studied to investigate the effects of aging on the brain. A reduced organization in the communication between brain areas was demonstrated by combining a variety of different imaging technologies (fMRI, EEG, and MEG) and graph theory. In this paper, we propose a methodology to get new insights into resting state connectivity and its variations with age, by combining advanced techniques of effective connectivity estimation, graph theoretical approach, and classification by SVM method. We analyzed high density EEG signals recorded at rest from 71 healthy subjects (age: 20-63 years). Weighted and directed connectivity was computed by means of Partial Directed Coherence based on a General Linear Kalman filter approach. To keep the information collected by the estimator, weighted and directed graph indices were extracted from the resulting networks. A relation between brain network properties and age of the subject was found, indicating a tendency of the network to randomly organize increasing with age. This result is also confirmed dividing the whole population into two subgroups according to the age (young and middle-aged adults): significant differences exist in terms of network organization measures. Classification of the subjects by means of such indices returns an accuracy greater than 80%.

  5. EEG Resting-State Brain Topological Reorganization as a Function of Age

    Directory of Open Access Journals (Sweden)

    Manuela Petti

    2016-01-01

    Full Text Available Resting state connectivity has been increasingly studied to investigate the effects of aging on the brain. A reduced organization in the communication between brain areas was demonstrated by combining a variety of different imaging technologies (fMRI, EEG, and MEG and graph theory. In this paper, we propose a methodology to get new insights into resting state connectivity and its variations with age, by combining advanced techniques of effective connectivity estimation, graph theoretical approach, and classification by SVM method. We analyzed high density EEG signals recorded at rest from 71 healthy subjects (age: 20–63 years. Weighted and directed connectivity was computed by means of Partial Directed Coherence based on a General Linear Kalman filter approach. To keep the information collected by the estimator, weighted and directed graph indices were extracted from the resulting networks. A relation between brain network properties and age of the subject was found, indicating a tendency of the network to randomly organize increasing with age. This result is also confirmed dividing the whole population into two subgroups according to the age (young and middle-aged adults: significant differences exist in terms of network organization measures. Classification of the subjects by means of such indices returns an accuracy greater than 80%.

  6. Netrin-1 hyperexpression in mouse brain promotes angiogenesis and long-term neurological recovery after transient focal ischemia.

    Science.gov (United States)

    Lu, Haiyan; Wang, Yongting; He, Xiaosong; Yuan, Falei; Lin, Xiaojie; Xie, Bohua; Tang, Guanghui; Huang, Jun; Tang, Yaohui; Jin, Kunlin; Chen, Shengdi; Yang, Guo-Yuan

    2012-03-01

    Netrin-1 (NT-1) stimulates endothelial cell proliferation and migration in vitro and promotes focal neovascularization in the adult brain in vivo. This in vivo study in mice investigated the effect of NT-1 hyperexpression on focal angiogenesis and long-term functional outcome after transient middle cerebral artery occlusion (tMCAO). Adeno-associated viral vectors carrying either the NT-1 gene (AAV-NT-1) or GFP (AAV-GFP) were generated and injected into the brains of separate groups of 93 mice. Seven days later, tMCAO followed by 7-28 days of reperfusion were carried out. Histological outcomes and behavioral deficits were quantified 7-28 days after tMCAO. Small cerebral vessel network and angiogenesis were assessed 28 days after tMCAO, using synchrotron radiation microangiography and immunohistochemistry. Western blot and immunohistochemistry showed that on the day of tMCAO, NT-1 hyperexpression had been achieved in both normal and ischemic hemispheres. Immunofluorescence imaging showed that NT-1 expression was primarily in neurons and astrocytes. Ischemia-induced infarction in the NT-1 hyperexpression group was attenuated in comparison to saline or AAV-GFP-treated groups (PAAV-NT-1-treated mice compared with mice in saline or AAV-GFP-treated groups (PAAV-NT-1-treated mice compared with the other 2 groups (PAAV-NT-1-treated mice than in other groups. AAV-NT-1 induced NT-1 hyperexpression before tMCAO reduced infarct size, enhanced neovascularization, and improved long-term functional recovery.

  7. Brain-derived neurotrophic factor promotes adaptive plasticity within the spinal cord and mediates the beneficial effects of controllable stimulation.

    Science.gov (United States)

    Huie, J R; Garraway, S M; Baumbauer, K M; Hoy, K C; Beas, B S; Montgomery, K S; Bizon, J L; Grau, J W

    2012-01-03

    Brain-derived neurotrophic factor (BDNF) has been characterized as a potent modulator of neural plasticity in both the brain and spinal cord. The present experiments use an in vivo model system to demonstrate that training with controllable stimulation increases spinal BDNF expression and engages a BDNF-dependent process that promotes adaptive plasticity. Spinally transected rats administered legshock whenever one hind limb is extended (controllable stimulation) exhibit a progressive increase in flexion duration. This simple form of response-outcome (instrumental) learning is not observed when shock is given independent of leg position (uncontrollable stimulation). Uncontrollable electrical stimulation also induces a lasting effect that impairs learning for up to 48 h. Training with controllable shock can counter the adverse consequences of uncontrollable stimulation, to both prevent and reverse the learning deficit. Here it is shown that the protective and restorative effect of instrumental training depends on BDNF. Cellular assays showed that controllable stimulation increased BDNF mRNA expression and protein within the lumbar spinal cord. These changes were associated with an increase in the BDNF receptor TrkB protein within the dorsal horn. Evidence is then presented that these changes play a functional role in vivo. Application of a BDNF inhibitor (TrkB-IgG) blocked the protective effect of instrumental training. Direct (intrathecal) application of BDNF substituted for instrumental training to block both the induction and expression of the learning deficit. Uncontrollable stimulation also induced an increase in mechanical reactivity (allodynia), and this too was prevented by BDNF. TrkB-IgG blocked the restorative effect of instrumental training and intrathecal BDNF substituted for training to reverse the deficit. Taken together, these findings outline a critical role for BDNF in mediating the beneficial effects of controllable stimulation on spinal plasticity

  8. Detection of electroporation-induced membrane permeabilization states in the brain using diffusion-weighted MRI

    DEFF Research Database (Denmark)

    Mahmood, Faisal; Hansen, Rasmus H; Agerholm-Larsen, Birgit

    2015-01-01

    (DW-MRI) as a quantitative method for detecting EP-induced membrane permeabilization of brain tissue using a rat brain model. MATERIAL AND METHODS: Fifty-four anesthetized Sprague-Dawley male rats were electroporated in the right hemisphere, using different voltage levels to induce no permeabilization...... (NP), transient membrane permeabilization (TMP), and permanent membrane permeabilization (PMP), respectively. DW-MRI was acquired 5 minutes, 2 hours, 24 hours and 48 hours after EP. Histology was performed for validation of the permeabilization states. Tissue content of water, Na+, K+, Ca2......+, and extracellular volume were determined. The Kruskal-Wallis test was used to compare the DW-MRI parameters, apparent diffusion coefficient (ADC) and kurtosis, at different voltage levels. The two-sample Mann- Whitney test with Holm's Bonferroni correction was used to identify pairs of significantly different...

  9. Testing a dual-systems model of adolescent brain development using resting-state connectivity analyses.

    Science.gov (United States)

    van Duijvenvoorde, A C K; Achterberg, M; Braams, B R; Peters, S; Crone, E A

    2016-01-01

    The current study aimed to test a dual-systems model of adolescent brain development by studying changes in intrinsic functional connectivity within and across networks typically associated with cognitive-control and affective-motivational processes. To this end, resting-state and task-related fMRI data were collected of 269 participants (ages 8-25). Resting-state analyses focused on seeds derived from task-related neural activation in the same participants: the dorsal lateral prefrontal cortex (dlPFC) from a cognitive rule-learning paradigm and the nucleus accumbens (NAcc) from a reward-paradigm. Whole-brain seed-based resting-state analyses showed an age-related increase in dlPFC connectivity with the caudate and thalamus, and an age-related decrease in connectivity with the (pre)motor cortex. nAcc connectivity showed a strengthening of connectivity with the dorsal anterior cingulate cortex (ACC) and subcortical structures such as the hippocampus, and a specific age-related decrease in connectivity with the ventral medial PFC (vmPFC). Behavioral measures from both functional paradigms correlated with resting-state connectivity strength with their respective seed. That is, age-related change in learning performance was mediated by connectivity between the dlPFC and thalamus, and age-related change in winning pleasure was mediated by connectivity between the nAcc and vmPFC. These patterns indicate (i) strengthening of connectivity between regions that support control and learning, (ii) more independent functioning of regions that support motor and control networks, and (iii) more independent functioning of regions that support motivation and valuation networks with age. These results are interpreted vis-à-vis a dual-systems model of adolescent brain development. Copyright © 2015. Published by Elsevier Inc.

  10. Brain cancer incidence trends in relation to cellular telephone use in the United States

    Science.gov (United States)

    Inskip, Peter D.; Hoover, Robert N.; Devesa, Susan S.

    2010-01-01

    The use of cellular telephones has grown explosively during the past two decades, and there are now more than 279 million wireless subscribers in the United States. If cellular phone use causes brain cancer, as some suggest, the potential public health implications could be considerable. One might expect the effects of such a prevalent exposure to be reflected in general population incidence rates, unless the induction period is very long or confined to very long-term users. To address this issue, we examined temporal trends in brain cancer incidence rates in the United States, using data collected by the Surveillance, Epidemiology, and End Results (SEER) Program. Log-linear models were used to estimate the annual percent change in rates among whites. With the exception of the 20–29-year age group, the trends for 1992–2006 were downward or flat. Among those aged 20–29 years, there was a statistically significant increasing trend between 1992 and 2006 among females but not among males. The recent trend in 20–29-year-old women was driven by a rising incidence of frontal lobe cancers. No increases were apparent for temporal or parietal lobe cancers, or cancers of the cerebellum, which involve the parts of the brain that would be more highly exposed to radiofrequency radiation from cellular phones. Frontal lobe cancer rates also rose among 20–29-year-old males, but the increase began earlier than among females and before cell phone use was highly prevalent. Overall, these incidence data do not provide support to the view that cellular phone use causes brain cancer. PMID:20639214

  11. Real-time fMRI using brain-state classification.

    Science.gov (United States)

    LaConte, Stephen M; Peltier, Scott J; Hu, Xiaoping P

    2007-10-01

    We have implemented a real-time functional magnetic resonance imaging system based on multivariate classification. This approach is distinctly different from spatially localized real-time implementations, since it does not require prior assumptions about functional localization and individual performance strategies, and has the ability to provide feedback based on intuitive translations of brain state rather than localized fluctuations. Thus this approach provides the capability for a new class of experimental designs in which real-time feedback control of the stimulus is possible-rather than using a fixed paradigm, experiments can adaptively evolve as subjects receive brain-state feedback. In this report, we describe our implementation and characterize its performance capabilities. We observed approximately 80% classification accuracy using whole brain, block-design, motor data. Within both left and right motor task conditions, important differences exist between the initial transient period produced by task switching (changing between rapid left or right index finger button presses) and the subsequent stable period during sustained activity. Further analysis revealed that very high accuracy is achievable during stable task periods, and that the responsiveness of the classifier to changes in task condition can be much faster than signal time-to-peak rates. Finally, we demonstrate the versatility of this implementation with respect to behavioral task, suggesting that our results are applicable across a spectrum of cognitive domains. Beyond basic research, this technology can complement electroencephalography-based brain computer interface research, and has potential applications in the areas of biofeedback rehabilitation, lie detection, learning studies, virtual reality-based training, and enhanced conscious awareness. Wiley-Liss, Inc.

  12. The Brain Functional State of Music Creation: an fMRI Study of Composers.

    Science.gov (United States)

    Lu, Jing; Yang, Hua; Zhang, Xingxing; He, Hui; Luo, Cheng; Yao, Dezhong

    2015-07-23

    In this study, we used functional magnetic resonance imaging (fMRI) to explore the functional networks in professional composers during the creation of music. We compared the composing state and resting state imagery of 17 composers and found that the functional connectivity of primary networks in the bilateral occipital lobe and bilateral postcentral cortex decreased during the composing period. However, significantly stronger functional connectivity appeared between the anterior cingulate cortex (ACC), the right angular gyrus and the bilateral superior frontal gyrus during composition. These findings indicate that a specific brain state of musical creation is formed when professional composers are composing, in which the integration of the primary visual and motor areas is not necessary. Instead, the neurons of these areas are recruited to enhance the functional connectivity between the ACC and the default mode network (DMN) to plan the integration of musical notes with emotion.

  13. Effect of Resting-State fNIRS Scanning Duration on Functional Brain Connectivity and Graph Theory Metrics of Brain Network.

    Science.gov (United States)

    Geng, Shujie; Liu, Xiangyu; Biswal, Bharat B; Niu, Haijing

    2017-01-01

    As an emerging brain imaging technique, functional near infrared spectroscopy (fNIRS) has attracted widespread attention for advancing resting-state functional connectivity (FC) and graph theoretical analyses of brain networks. However, it remains largely unknown how the duration of the fNIRS signal scanning is related to stable and reproducible functional brain network features. To answer this question, we collected resting-state fNIRS signals (10-min duration, two runs) from 18 participants and then truncated the hemodynamic time series into 30-s time bins that ranged from 1 to 10 min. Measures of nodal efficiency, nodal betweenness, network local efficiency, global efficiency, and clustering coefficient were computed for each subject at each fNIRS signal acquisition duration. Analyses of the stability and between-run reproducibility were performed to identify optimal time length for each measure. We found that the FC, nodal efficiency and nodal betweenness stabilized and were reproducible after 1 min of fNIRS signal acquisition, whereas network clustering coefficient, local and global efficiencies stabilized after 1 min and were reproducible after 5 min of fNIRS signal acquisition for only local and global efficiencies. These quantitative results provide direct evidence regarding the choice of the resting-state fNIRS scanning duration for functional brain connectivity and topological metric stability of brain network connectivity.

  14. Effect of Resting-State fNIRS Scanning Duration on Functional Brain Connectivity and Graph Theory Metrics of Brain Network

    Directory of Open Access Journals (Sweden)

    Shujie Geng

    2017-07-01

    Full Text Available As an emerging brain imaging technique, functional near infrared spectroscopy (fNIRS has attracted widespread attention for advancing resting-state functional connectivity (FC and graph theoretical analyses of brain networks. However, it remains largely unknown how the duration of the fNIRS signal scanning is related to stable and reproducible functional brain network features. To answer this question, we collected resting-state fNIRS signals (10-min duration, two runs from 18 participants and then truncated the hemodynamic time series into 30-s time bins that ranged from 1 to 10 min. Measures of nodal efficiency, nodal betweenness, network local efficiency, global efficiency, and clustering coefficient were computed for each subject at each fNIRS signal acquisition duration. Analyses of the stability and between-run reproducibility were performed to identify optimal time length for each measure. We found that the FC, nodal efficiency and nodal betweenness stabilized and were reproducible after 1 min of fNIRS signal acquisition, whereas network clustering coefficient, local and global efficiencies stabilized after 1 min and were reproducible after 5 min of fNIRS signal acquisition for only local and global efficiencies. These quantitative results provide direct evidence regarding the choice of the resting-state fNIRS scanning duration for functional brain connectivity and topological metric stability of brain network connectivity.

  15. A soluble biocompatible guanidine-containing polyamidoamine as promoter of primary brain cell adhesion and in vitro cell culturing

    Science.gov (United States)

    Tonna, Noemi; Bianco, Fabio; Matteoli, Michela; Cagnoli, Cinzia; Antonucci, Flavia; Manfredi, Amedea; Mauro, Nicolò; Ranucci, Elisabetta; Ferruti, Paolo

    2014-08-01

    This paper reports on a novel application of an amphoteric water-soluble polyamidoamine named AGMA1 bearing 4-butylguanidine pendants. AGMA1 is an amphoteric, prevailingly cationic polyelectrolyte with isoelectric point of about 10. At pH 7.4 it is zwitterionic with an average of 0.55 excess positive charges per unit, notwithstanding it is highly biocompatible. In this work, it was found that AGMA1 surface-adsorbed on cell culturing coverslips exhibits excellent properties as adhesion and proliferation promoter of primary brain cells such as microglia, as well as of hippocampal neurons and astrocytes. Microglia cells cultured on AGMA1-coated coverslips substrate displayed the typical resting, ramified morphology of those cultured on poly-L-lysine and poly-L-ornithine, employed as reference substrates. Mixed cultures of primary astrocytes and neuronal cells grown on AGMA1- and poly-L-lysine coated coverslips were morphologically undistinguishable. On both substrates, neurons differentiated axon and dendrites and eventually established perfectly functional synaptic contacts. Quantitative immunocytochemical staining revealed no difference between AGMA1 and poly-L-lysine. Electrophysiological experiments allowed recording neuron spontaneous activity on AGMA1. In addition, cell cultures on both AGMA1 and PLL displayed comparable excitatory and inhibitory neurotransmission, demonstrating that the synaptic contacts formed were fully functional.

  16. β5 Integrin Up-Regulation in Brain-Derived Neurotrophic Factor Promotes Cell Motility in Human Chondrosarcoma

    Science.gov (United States)

    Li, Te-Mao; Fong, Yi-Chin; Liu, Shan-Chi; Chen, Po-Chun; Tang, Chih-Hsin

    2013-01-01

    Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF) is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis. PMID:23874483

  17. β5 integrin up-regulation in brain-derived neurotrophic factor promotes cell motility in human chondrosarcoma.

    Directory of Open Access Journals (Sweden)

    Chih-Yang Lin

    Full Text Available Chondrosarcoma is a primary malignant bone cancer, with a potent capacity to invade locally and cause distant metastasis; it has a poor prognosis and shows a predilection for metastasis to the lungs. Brain derived neurotrophic factor (BDNF is a small-molecule protein from the neurotrophin family of growth factors that is associated with the disease status and outcomes of cancers. However, the effect of BDNF on migration activity in human chondrosarcoma cells is mostly unknown. Here, we found that human chondrosarcoma tissues showed significant expression of BDNF, which was higher than that in normal cartilage and primary chondrocytes. We also found that BDNF increased the migration and expression of β5 integrin in human chondrosarcoma cells. In addition, knockdown of BDNF expression markedly inhibited migratory activity. BDNF-mediated migration and β5 integrin up-regulation were attenuated by antibody, inhibitor, or siRNA against the TrkB receptor. Pretreatment of chondrosarcoma cells with PI3K, Akt, and NF-κB inhibitors or mutants also abolished BDNF-promoted migration and integrin expression. The PI3K, Akt, and NF-κB signaling pathway was activated after BDNF treatment. Taken together, our results indicate that BDNF enhances the migration of chondrosarcoma by increasing β5 integrin expression through a signal transduction pathway that involves the TrkB receptor, PI3K, Akt, and NF-κB. BDNF thus represents a promising new target for treating chondrosarcoma metastasis.

  18. Human FGF1 promoter is active in ependymal cells and dopaminergic neurons in the brains of F1B-GFP transgenic mice.

    Science.gov (United States)

    Chen, Mei-Shu; Lin, Hua-Kuo; Chiu, Hsun; Lee, Don-Ching; Chung, Yu-Fen; Chiu, Ing-Ming

    2015-03-01

    FGF1 is involved in multiple biological functions and exhibits the importance in neuroprotective effects. Our previous studies indicated that, in human brain and retina, the FGF1B promoter controlled the expression of FGF1. However, the exact function and regulation of FGF1 in brain is still unclear. Here, we generated F1B-GFP transgenic mice that expressed the GFP reporter gene under the control of human FGF1B promoter (-540 to +31). Using the fresh brain sections of F1B-GFP transgenic mice, we found that the F1B-GFP cells expressed strong fluorescent signals in the ventricular system throughout the brain. The results of immunohistochemistry further showed that two distinct populations of F1B-GFP(+) cells existed in the brains of F1B-GFP transgenic mice. We demonstrated that one population of F1B-GFP(+) cells was ependymal cells, which distributed along the entire ventricles, and the second population of F1B-GFP(+) cells was neuronal cells that projected their long processes into multiple directions in specific areas of the brain. The double labeling of F1B-GFP(+) cells and tyrosine hydroxylase indicated that a subpopulation of F1B-GFP(+) -neuronal cells was dopaminergic neurons. Importantly, these F1B-GFP(+) /TH(+) cells were distributed in the main dopaminergic neuronal groups including hypothalamus, ventral tegmental area, and raphe nuclei. These results suggested that human FGF1B promoter was active in ependymal cells, neurons, and a portion of dopaminergic neurons. Thus, the F1B-GFP transgenic mice provide an animal model not only for studying FGF1 gene expression in vivo but also for understanding the role of FGF1 contribution in neurodegenerative disorders such as Parkinson's disease and Alzheimer's disease. © 2014 The Authors Developmental Neurobiology Published by Wiley Periodicals, Inc.

  19. [Music-Acoustic Signals Controlled by Subject's Brain Potentials in the Correction of Unfavorable Functional States].

    Science.gov (United States)

    Fedotchev, A I; Bondar, A T; Bakhchina, A V; Parin, S B; Polevaya, S A; Radchenko, G S

    2016-01-01

    Literature review and the results of own studies on the development and experimental testing of musical EEG neurofeedback technology are presented. The technology is based on exposure of subjects to music or music-like signals that are organized in strict accordance with the current values of brain potentials of the patient. The main attention is paid to the analysis of the effectiveness of several versions of the technology, using specific and meaningful for the individual narrow-frequency EEG oscillators during the correction of unfavorable changes of the functional state.

  20. Examination of corticothalamic fiber projections in United States service members with mild traumatic brain injury

    Science.gov (United States)

    Rashid, Faisal M.; Dennis, Emily L.; Villalon-Reina, Julio E.; Jin, Yan; Lewis, Jeffrey D.; York, Gerald E.; Thompson, Paul M.; Tate, David F.

    2017-11-01

    Mild traumatic brain injury (mTBI) is characterized clinically by a closed head injury involving differential or rotational movement of the brain inside the skull. Over 3 million mTBIs occur annually in the United States alone. Many of the individuals who sustain an mTBI go on to recover fully, but around 20% experience persistent symptoms. These symptoms often last for many weeks to several months. The thalamus, a structure known to serve as a global networking or relay system for the rest of the brain, may play a critical role in neurorehabiliation and its integrity and connectivity after injury may also affect cognitive outcomes. To examine the thalamus, conventional tractography methods to map corticothalamic pathways with diffusion-weighted MRI (DWI) lead to sparse reconstructions that may contain false positive fibers that are anatomically inaccurate. Using a specialized method to zero in on corticothalamic pathways with greater robustness, we noninvasively examined corticothalamic fiber projections using DWI, in 68 service members. We found significantly lower fractional anisotropy (FA), a measure of white matter microstructural integrity, in pathways projecting to the left pre- and postcentral gyri - consistent with sensorimotor deficits often found post-mTBI. Mapping of neural circuitry in mTBI may help to further our understanding of mechanisms underlying recovery post-TBI.

  1. BUILDING AN EU MEMBER STATE THROUGH DEMOCRACY PROMOTION: THE CASE OF CROATIA'S PUBLIC ADMINISTRATION REFORM

    Directory of Open Access Journals (Sweden)

    Sonja Grimm

    2013-01-01

    Full Text Available This contribution studies the process of building an EU member state through democracy promotion in the case of Croatia with a special focus on two reform initiatives in the field of Public Administration Reform (PAR. Croatia’s experience is representative of intense efforts of the international community to overcome the consequences of violent state dissolution and civil war. The EU in particular has assisted post-conflict democratization with diplomatic initiatives, the provision of aid, and political conditionality. The Croatian political elite showed great willingness to implement democratic reforms, while at the same time remaining critical of what they viewed as ‘too much’ external interference in domestic state affairs. Based on 30 interviews with Croatian officials, Croatian civil society actors, members of the EU delegation and other representatives of the International donor community, we empirically assess progress and setbacks in Croatia’s public administration reform and explain why some reform initiatives have been successfully implemented while others are still pending.

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

    Directory of Open Access Journals (Sweden)

    Lu D

    2014-02-01

    Full Text Available Dali Lu,1 Qing Jiao,2 Yuan Zhong,3,4 Weijia Gao,1 Qian Xiao,1 Xiaoqun Liu,1 Xiaoling Lin,5 Wentao Cheng,6 Lanzhu Luo,6 Chuanjian Xu,3 Guangming Lu,2 Linyan Su1 1Mental Health Institute of the Second Xiangya Hospital, Key Laboratory of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, People's Republic of China; 2Department of Radiology, Taishan Medical University, Taian, People's Republic of China; 3Department of Medical Imaging, Jinling Hospital, Nanjing University School of Medicine, Nanjing, People's Republic of China; 4School of Psychology, Nanjing Normal University, Nanjing, People's Republic of China; 5School of Nursing of Central South University, Changsha, People's Republic of China; 6Department of Pediatric and Geriatric Psychiatry, Fuzhou Neuropsychiatric Hospital, Fuzhou, People's Republic of China Background: Previous functional magnetic resonance imaging (fMRI studies have shown abnormal functional connectivity in regions involved in emotion processing and regulation in pediatric bipolar disorder (PBD. Recent studies indicate, however, that task-dependent neural changes only represent a small fraction of the brain's total activity. How the brain allocates the majority of its resources at resting state is still unknown. We used the amplitude of low-frequency fluctuation (ALFF method of fMRI to explore the spontaneous neuronal activity in resting state in PBD patients. Methods: Eighteen PBD patients during the mania phase and 18 sex-, age- and education-matched healthy subjects were enrolled in this study and all patients underwent fMRI scanning. The ALFF method was used to compare the resting-state spontaneous neuronal activity between groups. Correlation analysis was performed between the ALFF values and Young Mania Rating Scale scores. Results: Compared with healthy controls, PBD patients presented increased ALFF in bilateral caudate and left pallidum as well as decreased ALFF in left precuneus

  3. Association between number of cell phone contracts and brain tumor incidence in nineteen U.S. States.

    Science.gov (United States)

    Lehrer, Steven; Green, Sheryl; Stock, Richard G

    2011-02-01

    Some concern has arisen about adverse health effects of cell phones, especially the possibility that the low power microwave-frequency signal transmitted by the antennas on handsets might cause brain tumors or accelerate the growth of subclinical tumors. We analyzed data from the Statistical Report: Primary Brain Tumors in the United States, 2000-2004 and 2007 cell phone subscription data from the Governing State and Local Sourcebook. There was a significant correlation between number of cell phone subscriptions and brain tumors in nineteen US states (r = 0.950, P numbers of both cell phone subscriptions and brain tumors could be due solely to the fact that some states, such as New York, have much larger populations than other states, such as North Dakota, multiple linear regression was performed with number of brain tumors as the dependent variable, cell phone subscriptions, population, mean family income and mean age as independent variables. The effect of cell phone subscriptions was significant (P = 0.017), and independent of the effect of mean family income (P = 0.894), population (P = 0.003) and age (0.499). The very linear relationship between cell phone usage and brain tumor incidence is disturbing and certainly needs further epidemiological evaluation. In the meantime, it would be prudent to limit exposure to all sources of electro-magnetic radiation.

  4. Decreased Complexity in Alzheimer's Disease: Resting-State fMRI Evidence of Brain Entropy Mapping

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    Bin Wang

    2017-11-01

    Full Text Available Alzheimer's disease (AD is a frequently observed, irreversible brain function disorder among elderly individuals. Resting-state functional magnetic resonance imaging (rs-fMRI has been introduced as an alternative approach to assessing brain functional abnormalities in AD patients. However, alterations in the brain rs-fMRI signal complexities in mild cognitive impairment (MCI and AD patients remain unclear. Here, we described the novel application of permutation entropy (PE to investigate the abnormal complexity of rs-fMRI signals in MCI and AD patients. The rs-fMRI signals of 30 normal controls (NCs, 33 early MCI (EMCI, 32 late MCI (LMCI, and 29 AD patients were obtained from the Alzheimer's disease Neuroimaging Initiative (ADNI database. After preprocessing, whole-brain entropy maps of the four groups were extracted and subjected to Gaussian smoothing. We performed a one-way analysis of variance (ANOVA on the brain entropy maps of the four groups. The results after adjusting for age and sex differences together revealed that the patients with AD exhibited lower complexity than did the MCI and NC controls. We found five clusters that exhibited significant differences and were distributed primarily in the occipital, frontal, and temporal lobes. The average PE of the five clusters exhibited a decreasing trend from MCI to AD. The AD group exhibited the least complexity. Additionally, the average PE of the five clusters was significantly positively correlated with the Mini-Mental State Examination (MMSE scores and significantly negatively correlated with Functional Assessment Questionnaire (FAQ scores and global Clinical Dementia Rating (CDR scores in the patient groups. Significant correlations were also found between the PE and regional homogeneity (ReHo in the patient groups. These results indicated that declines in PE might be related to changes in regional functional homogeneity in AD. These findings suggested that complexity analyses using PE

  5. The menthol marketing mix: targeted promotions for focus communities in the United States.

    Science.gov (United States)

    Cruz, Tess Boley; Wright, La Tanisha; Crawford, George

    2010-12-01

    This study analyzes tobacco industry menthol marketing strategies aimed at urban predominantly Black populations. Data are drawn from an interview with a former Brown & Williamson Tobacco Company trade marketing manager, tobacco industry documents on Kool promotions in urban areas, and public health literature on tobacco marketing. Tobacco companies recognize the growth potential for the menthol segment in these urban communities. They have higher levels of price discounts and signage, exert tight controls over the retail environment, and use hip-hop lifestyle to associate menthol products with urban nightlife, music, fame, and cultural edginess among younger smokers. Tobacco companies regard the urban Black menthol segment as one of the few markets in which they can grow sales despite declines elsewhere in the United States. Consequently, this population is surrounded by intense and integrated levels of marketing. We need strong monitoring, regulation, and enforcement efforts that will counter the industry's use of menthol at multiple levels in urban environments.

  6. Relating dynamic brain states to dynamic machine states: Human and machine solutions to the speech recognition problem.

    Science.gov (United States)

    Wingfield, Cai; Su, Li; Liu, Xunying; Zhang, Chao; Woodland, Phil; Thwaites, Andrew; Fonteneau, Elisabeth; Marslen-Wilson, William D

    2017-09-01

    There is widespread interest in the relationship between the neurobiological systems supporting human cognition and emerging computational systems capable of emulating these capacities. Human speech comprehension, poorly understood as a neurobiological process, is an important case in point. Automatic Speech Recognition (ASR) systems with near-human levels of performance are now available, which provide a computationally explicit solution for the recognition of words in continuous speech. This research aims to bridge the gap between speech recognition processes in humans and machines, using novel multivariate techniques to compare incremental 'machine states', generated as the ASR analysis progresses over time, to the incremental 'brain states', measured using combined electro- and magneto-encephalography (EMEG), generated as the same inputs are heard by human listeners. This direct comparison of dynamic human and machine internal states, as they respond to the same incrementally delivered sensory input, revealed a significant correspondence between neural response patterns in human superior temporal cortex and the structural properties of ASR-derived phonetic models. Spatially coherent patches in human temporal cortex responded selectively to individual phonetic features defined on the basis of machine-extracted regularities in the speech to lexicon mapping process. These results demonstrate the feasibility of relating human and ASR solutions to the problem of speech recognition, and suggest the potential for further studies relating complex neural computations in human speech comprehension to the rapidly evolving ASR systems that address the same problem domain.

  7. Alcohol affects the brain's resting-state network in social drinkers.

    Directory of Open Access Journals (Sweden)

    Chrysa Lithari

    Full Text Available Acute alcohol intake is known to enhance inhibition through facilitation of GABA(A receptors, which are present in 40% of the synapses all over the brain. Evidence suggests that enhanced GABAergic transmission leads to increased large-scale brain connectivity. Our hypothesis is that acute alcohol intake would increase the functional connectivity of the human brain resting-state network (RSN. To test our hypothesis, electroencephalographic (EEG measurements were recorded from healthy social drinkers at rest, during eyes-open and eyes-closed sessions, after administering to them an alcoholic beverage or placebo respectively. Salivary alcohol and cortisol served to measure the inebriation and stress levels. By calculating Magnitude Square Coherence (MSC on standardized Low Resolution Electromagnetic Tomography (sLORETA solutions, we formed cortical networks over several frequency bands, which were then analyzed in the context of functional connectivity and graph theory. MSC was increased (p<0.05, corrected with False Discovery Rate, FDR corrected in alpha, beta (eyes-open and theta bands (eyes-closed following acute alcohol intake. Graph parameters were accordingly altered in these bands quantifying the effect of alcohol on the structure of brain networks; global efficiency and density were higher and path length was lower during alcohol (vs. placebo, p<0.05. Salivary alcohol concentration was positively correlated with the density of the network in beta band. The degree of specific nodes was elevated following alcohol (vs. placebo. Our findings support the hypothesis that short-term inebriation considerably increases large-scale connectivity in the RSN. The increased baseline functional connectivity can -at least partially- be attributed to the alcohol-induced disruption of the delicate balance between inhibitory and excitatory neurotransmission in favor of inhibitory influences. Thus, it is suggested that short-term inebriation is associated, as

  8. Specific and evolving resting-state network alterations in post-concussion syndrome following mild traumatic brain injury.

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    Arnaud Messé

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

  9. Brain-computer interfaces in the completely locked-in state and chronic stroke.

    Science.gov (United States)

    Chaudhary, U; Birbaumer, N; Ramos-Murguialday, A

    2016-01-01

    Brain-computer interfaces (BCIs) use brain activity to control external devices, facilitating paralyzed patients to interact with the environment. In this chapter, we discuss the historical perspective of development of BCIs and the current advances of noninvasive BCIs for communication in patients with amyotrophic lateral sclerosis and for restoration of motor impairment after severe stroke. Distinct techniques have been explored to control a BCI in patient population especially electroencephalography (EEG) and more recently near-infrared spectroscopy (NIRS) because of their noninvasive nature and low cost. Previous studies demonstrated successful communication of patients with locked-in state (LIS) using EEG- and invasive electrocorticography-BCI and intracortical recordings when patients still showed residual eye control, but not with patients with complete LIS (ie, complete paralysis). Recently, a NIRS-BCI and classical conditioning procedure was introduced, allowing communication in patients in the complete locked-in state (CLIS). In severe chronic stroke without residual hand function first results indicate a possible superior motor rehabilitation to available treatment using BCI training. Here we present an overview of the available studies and recent results, which open new doors for communication, in the completely paralyzed and rehabilitation in severely affected stroke patients. We also reflect on and describe possible neuronal and learning mechanisms responsible for BCI control and perspective for future BMI research for communication in CLIS and stroke motor recovery. © 2016 Elsevier B.V. All rights reserved.

  10. Combining Brain-Computer Interfaces and Assistive Technologies: State-of-the-Art and Challenges.

    Science.gov (United States)

    Millán, J D R; Rupp, R; Müller-Putz, G R; Murray-Smith, R; Giugliemma, C; Tangermann, M; Vidaurre, C; Cincotti, F; Kübler, A; Leeb, R; Neuper, C; Müller, K-R; Mattia, D

    2010-01-01

    In recent years, new research has brought the field of electroencephalogram (EEG)-based brain-computer interfacing (BCI) out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT). In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely, "Communication and Control", "Motor Substitution", "Entertainment", and "Motor Recovery". We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user-machine adaptation algorithms, the exploitation of users' mental states for BCI reliability and confidence measures, the incorporation of principles in human-computer interaction (HCI) to improve BCI usability, and the development of novel BCI technology including better EEG devices.

  11. Combining Brain-Computer Interfaces and Assistive Technologies: State-of-the-Art and Challenges

    Directory of Open Access Journals (Sweden)

    José del R. Millán

    2010-09-01

    Full Text Available In recent years, new research has brought the field of EEG-based Brain-Computer Interfacing (BCI out of its infancy and into a phase of relative maturity through many demonstrated prototypes such as brain-controlled wheelchairs, keyboards, and computer games. With this proof-of-concept phase in the past, the time is now ripe to focus on the development of practical BCI technologies that can be brought out of the lab and into real-world applications. In particular, we focus on the prospect of improving the lives of countless disabled individuals through a combination of BCI technology with existing assistive technologies (AT. In pursuit of more practical BCIs for use outside of the lab, in this paper, we identify four application areas where disabled individuals could greatly benefit from advancements in BCI technology, namely,“Communication & Control”, “Motor Substitution”, “Entertainment”, and “Motor Recovery”. We review the current state of the art and possible future developments, while discussing the main research issues in these four areas. In particular, we expect the most progress in the development of technologies such as hybrid BCI architectures, user-machine adaptation algorithms, the exploitation of users’ mental states for BCI reliability and confidence measures, the incorporation of principles in human-computer interaction (HCI to improve BCI usability, and the development of novel BCI technology including better EEG devices.

  12. Information-geometric measures estimate neural interactions during oscillatory brain states.

    Science.gov (United States)

    Nie, Yimin; Fellous, Jean-Marc; Tatsuno, Masami

    2014-01-01

    The characterization of functional network structures among multiple neurons is essential to understanding neural information processing. Information geometry (IG), a theory developed for investigating a space of probability distributions has recently been applied to spike-train analysis and has provided robust estimations of neural interactions. Although neural firing in the equilibrium state is often assumed in these studies, in reality, neural activity is non-stationary. The brain exhibits various oscillations depending on cognitive demands or when an animal is asleep. Therefore, the investigation of the IG measures during oscillatory network states is important for testing how the IG method can be applied to real neural data. Using model networks of binary neurons or more realistic spiking neurons, we studied how the single- and pairwise-IG measures were influenced by oscillatory neural activity. Two general oscillatory mechanisms, externally driven oscillations and internally induced oscillations, were considered. In both mechanisms, we found that the single-IG measure was linearly related to the magnitude of the external input, and that the pairwise-IG measure was linearly related to the sum of connection strengths between two neurons. We also observed that the pairwise-IG measure was not dependent on the oscillation frequency. These results are consistent with the previous findings that were obtained under the equilibrium conditions. Therefore, we demonstrate that the IG method provides useful insights into neural interactions under the oscillatory condition that can often be observed in the real brain.

  13. Information-geometric measures estimate neural interactions during oscillatory brain states

    Directory of Open Access Journals (Sweden)

    Yimin eNie

    2014-02-01

    Full Text Available The characterization of functional network structures among multiple neurons is essential to understanding neural information processing. Information geometry (IG, a theory developed for investigating a space of probability distributions has recently been applied to spike-train analysis and has provided robust estimations of neural interactions. Although neural firing in the equilibrium state is often assumed in these studies, in reality, neural activity is non-stationary. The brain exhibits various oscillations depending on cognitive demands or when an animal is asleep. Therefore, the investigation of the IG measures during oscillatory network states is important for testing how the IG method can be applied to real neural data. Using model networks of binary neurons or more realistic spiking neurons, we studied how the single- and pairwise-IG measures were influenced by oscillatory neural activity. Two general oscillatory mechanisms, externally driven oscillations and internally induced oscillations, were considered. In both mechanisms, we found that the single-IG measure was linearly related to the magnitude of the external input, and that the pairwise-IG measure was linearly related to the sum of connection strengths between two neurons. We also observed that the pairwise-IG measure was not dependent on the oscillation frequency. These results are consistent with the previous findings that were obtained under the equilibrium conditions. Therefore, we demonstrate that the IG method provides useful insights into neural interactions under the oscillatory condition that can often be observed in the real brain.

  14. A Comparison of Brain Death Criteria between China and the United States

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    Ze-Yu Ding

    2015-01-01

    Full Text Available Background: Criteria for determining brain death (BD vary between China and the United States. We reported the results of an investigation designed to compare procedures to determine BD in two countries. Methods: The latest criteria in the United states were published in 2010. The latest criteria in China were published in 2009. We used these two types of BD criteria to evaluate patients who were considered to be BD. The time, cost, and accuracy of the diagnosis were compared. Results: From January 1, 2012 to October 8, 2013, there were 37 patients which were applied for BD evaluation in the Neurological Intensive Care Unit of Beijing Tiantan Hospital. The cause of coma were known as subarachnoid hemorrhage (18 patients, 48.6%, intracerebral hemorrhage (8 patients, 21.6%, cerebral ischemia (9 patients, 24.3%, brain stem tumor (1 patient, 2.7%, and intracranial infection (1 patient, 2.7%. The clinical examinations were done for all of the patients except 1 patient who had low blood pressure. Three patients had brainstem reflexes that were excluded from BD. Twenty-five patients had apnea tests, and 20 tests were completed that were all positive. Confirmatory tests were completed differently: Transcranial Doppler (30 patients, positive rate 86.7%, electroencephalogram (25 patients, positive rate 100%, and somatosensory evoked potential (16 patients, positive rate 100%. Thirty-three patients were diagnosed BD by criteria of the United States. Only 9 patients were diagnosed BD by Chinese criteria. The use of time and money in the USA criteria was obviously fewer than those in Chinese criteria (P = 0.000. Conclusion: Compared with BD criteria of the United States, Chinese criteria were stricter, lower positive rate, more cost in money and time, and more reliable by families and doctors.

  15. Directionality of large-scale resting-state brain networks during eyes open and eyes closed conditions

    NARCIS (Netherlands)

    Zhang, Delong; Liang, Bishan; Wu, Xia; Wang, Zengjian; Xu, Pengfei; Chang, Song; Liu, Bo; Liu, Ming; Huang, Ruiwang

    2015-01-01

    The present study examined directional connections in the brain among resting-state networks (RSNs) when the participant had their eyes open (E0) or had their eyes closed (EC). The resting state fMRI data were collected from 20 healthy participants (9 males, 20.17 +/- 2.74 years) under the EO and EC

  16. Red-backed vole brain promotes highly efficient in vitro amplification of abnormal prion protein from macaque and human brains infected with variant Creutzfeldt-Jakob disease agent.

    Science.gov (United States)

    Nemecek, Julie; Nag, Nabanita; Carlson, Christina M.; Schneider, Jay R.; Heisey, Dennis M.; Johnson, Christopher J.; Asher, David M.; Gregori, Luisa

    2013-01-01

    Rapid antemortem tests to detect individuals with transmissible spongiform encephalopathies (TSE) would contribute to public health. We investigated a technique known as protein misfolding cyclic amplification (PMCA) to amplify abnormal prion protein (PrPTSE) from highly diluted variant Creutzfeldt-Jakob disease (vCJD)-infected human and macaque brain homogenates, seeking to improve the rapid detection of PrPTSE in tissues and blood. Macaque vCJD PrPTSE did not amplify using normal macaque brain homogenate as substrate (intraspecies PMCA). Next, we tested interspecies PMCA with normal brain homogenate of the southern red-backed vole (RBV), a close relative of the bank vole, seeded with macaque vCJD PrPTSE. The RBV has a natural polymorphism at residue 170 of the PrP-encoding gene (N/N, S/S, and S/N). We investigated the effect of this polymorphism on amplification of human and macaque vCJD PrPTSE. Meadow vole brain (170N/N PrP genotype) was also included in the panel of substrates tested. Both humans and macaques have the same 170S/S PrP genotype. Macaque PrPTSE was best amplified with RBV 170S/S brain, although 170N/N and 170S/N were also competent substrates, while meadow vole brain was a poor substrate. In contrast, human PrPTSE demonstrated a striking narrow selectivity for PMCA substrate and was successfully amplified only with RBV 170S/S brain. These observations suggest that macaque PrPTSE was more permissive than human PrPTSE in selecting the competent RBV substrate. RBV 170S/S brain was used to assess the sensitivity of PMCA with PrPTSE from brains of humans and macaques with vCJD. PrPTSE signals were reproducibly detected by Western blot in dilutions through 10-12 of vCJD-infected 10% brain homogenates. This is the first report showing PrPTSE from vCJD-infected human and macaque brains efficiently amplified with RBV brain as the substrate. Based on our estimates, PMCA showed a sensitivity that might be sufficient to detect PrPTSE in v

  17. Brain-derived neurotrophic factor signaling plays a role in resilience to stress promoted by isoquinoline in defeated mice.

    Science.gov (United States)

    Pesarico, Ana Paula; Rosa, Suzan G; Martini, Franciele; Goulart, Tales A; Zeni, Gilson; Nogueira, Cristina Wayne

    2017-11-01

    Certain stressful life events have been associated with the onset of depression. This study aims to investigate if 7-fluoro-1,3-diphenylisoquinoline-1-amine (FDPI) is effective against social avoidance induced by social defeat stress model in mice. Furthermore, it was investigated the effects of FDPI in the mouse prefrontal cortical plasticity-related proteins and some parameters of toxicity. Adult Swiss mice were subjected to social defeat stress for 10 days. Two protocols with FDPI were carried out: 1- FDPI (25 mg/kg, intragastric) was administered to mice 24 h after the last social defeat stress episode; 2- FDPI (1-25 mg/kg, intragastric) was administered to mice once a day for 10 days concomitant with the social defeat stress. The mice performed social avoidance and locomotor tests. The prefrontal cortical protein contents of kinase B (Akt), extracellular signal-regulated kinase (ERK), cAMP-response element binding protein (CREB), pro-brain-derived neurotrophic factor (proBDNF), p75NTR, neuronal nuclear protein (NeuN) and nuclear factor-κB (NF-κB) were determined in mice. A single administration of FDPI (25 mg/kg) partially protected against social avoidance induced by stress in mice. Repeated administration of FDPI (25 mg/kg) protected against social avoidance induced by stress in mice. Social defeat stress decreased the protein contents of p75NTR, NeuN and the pERK/ERK ratio but increased those of proBDNF and the pCREB/CREB ratio, without changing that of NF-κB. Repeated administration of FDPI modulated signaling pathways altered by social defeat stress in mice. The present findings demonstrate that FDPI promoted resilience to stress in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Transient Cerebral Ischemia Promotes Brain Mitochondrial Dysfunction and Exacerbates Cognitive Impairments in Young 5xFAD Mice

    Science.gov (United States)

    Lu, Lin; Guo, Lan; Gauba, Esha; Tian, Jing; Wang, Lu; Tandon, Neha; Shankar, Malini; Beck, Simon J.; Du, Yifeng; Du, Heng

    2015-01-01

    Alzheimer's disease (AD) is heterogeneous and multifactorial neurological disorder; and the risk factors of AD still remain elusive. Recent studies have highlighted the role of vascular factors in promoting the progression of AD and have suggested that ischemic events increase the incidence of AD. However, the detailed mechanisms linking ischemic insult to the progression of AD is still largely undetermined. In this study, we have established a transient cerebral ischemia model on young 5xFAD mice and their non-transgenic (nonTg) littermates by the transient occlusion of bilateral common carotid arteries. We have found that transient cerebral ischemia significantly exacerbates brain mitochondrial dysfunction including mitochondrial respiration deficits, oxidative stress as well as suppressed levels of mitochondrial fusion proteins including optic atrophy 1 (OPA1) and mitofusin 2 (MFN2) in young 5xFAD mice resulting in aggravated spatial learning and memory. Intriguingly, transient cerebral ischemia did not induce elevation in the levels of cortical or mitochondrial Amyloid beta (Aβ)1-40 or 1–42 levels in 5xFAD mice. In addition, the glucose- and oxygen-deprivation-induced apoptotic neuronal death in Aβ-treated neurons was significantly mitigated by mitochondria-targeted antioxidant mitotempo which suppresses mitochondrial superoxide levels. Therefore, the simplest interpretation of our results is that young 5xFAD mice with pre-existing AD-like mitochondrial dysfunction are more susceptible to the effects of transient cerebral ischemia; and ischemic events may exacerbate dementia and worsen the outcome of AD patients by exacerbating mitochondrial dysfunction. PMID:26632816

  19. Brain-derived neurotrophic factor promotes nerve regeneration by activating the JAK/STAT pathway in Schwann cells.

    Science.gov (United States)

    Lin, Guiting; Zhang, Haiyang; Sun, Fionna; Lu, Zhihua; Reed-Maldonado, Amanda; Lee, Yung-Chin; Wang, Guifang; Banie, Lia; Lue, Tom F

    2016-04-01

    Radical prostatectomy (RP) carries the risk of erectile dysfunction (ED) due to cavernous nerve (CN) injury. Schwann cells are essential for the maintenance of integrity and function of peripheral nerves such as the CNs. We hypothesize that brain-derived neurotrophic factor (BDNF) activates the Janus kinase (JAK)/(signal transducer and activator of transcription) STAT pathway in Schwann cells, not in neuronal axonal fibers, with the resultant secretion of cytokines from Schwann cells to facilitate nerve recovery. Using four different cell lines-human neuroblastoma BE(2)-C and SH-SY5Y, human Schwann cell (HSC), and rat Schwann cell (RSC) RT4-D6P2T-we assessed the effect of BDNF application on the activation of the JAK/STAT pathway. We also assessed the time response of JAK/STAT pathway activation in RSCs and HSCs after BDNF treatment. We then assayed cytokine release from HSCs as a response to BDNF treatment using oncostatin M and IL6 as markers. We showed extensive phosphorylation of STAT3/STAT1 by BDNF at high dose (100 pM) in RSCs, with no JAK/STAT pathway activation in human neuroblastoma cell lines. The time response of JAK/STAT pathway activation in RSCs and HSCs after BDNF treatment showed an initial peak at shortly after treatment and then a second higher peak at 24-48 hours. Cytokine release from HSCs increased progressively after BDNF application, reaching statistical significance for IL6. We demonstrated for the first time the indirect mechanism of BDNF enhancement of nerve regeneration through the activation of JAK/STAT pathway in Schwann cells, rather than directly on neurons. As a result of BDNF application, Schwann cells produce cytokines that promote nerve regeneration.

  20. Impact of asymptomatic nodavirus carrier state and intraperitoneal viral mimic injection on brain transcript expression in Atlantic cod (Gadus morhua).

    Science.gov (United States)

    Rise, Matthew L; Hall, Jennifer R; Rise, Marlies; Hori, Tiago S; Browne, Mitchell J; Gamperl, A Kurt; Hubert, Sophie; Kimball, Jennifer; Bowman, Sharen; Johnson, Stewart C

    2010-07-07

    Nodaviruses and other RNA viruses have a profoundly negative impact on the global aquaculture industry. Nodaviruses target nervous tissue causing viral nervous necrosis, a disease characterized by neurological damage, swimming abnormalities, and morbidity. This study used functional genomic techniques to study the Atlantic cod (Gadus morhua) brain transcript expression responses to asymptomatic high nodavirus carrier state and intraperitoneal injection of polyriboinosinic polyribocytidylic acid (pIC). Reciprocal suppression subtractive hybridization (SSH) cDNA libraries enriched for virus-responsive brain transcripts were constructed and characterized. We generated 1,938 expressed sequence tags (ESTs) from a forward brain SSH library (enriched for transcripts upregulated by nodavirus and/or pIC) and 1,980 ESTs from a reverse brain SSH library (enriched for transcripts downregulated by nodavirus and/or pIC). To examine the effect of nodavirus carrier state on individual brain gene expression in asymptomatic cod, 27 transcripts of interest were selected for quantitative reverse transcription-polymerase chain reaction (QPCR) studies. Transcripts found to be >10-fold upregulated in individuals with a high nodavirus carrier state relative to those in a no/low nodavirus carrier state were identified as ISG15, IL8, DHX58 (alias LGP2), ZNFX1, RSAD2 (alias viperin), and SACS (sacsin, alias spastic ataxia of Charlevoix-Saguenay). These and other SSH-identified transcripts were also found by QPCR to be significantly (P SSH library, including two putative ubiquitination pathway members (HERC4 and SUMO2), were found to be significantly (P < 0.05) downregulated in individuals with a high nodavirus carrier state. Our data shows that Atlantic cod brains have a strong interferon pathway response to asymptomatic high nodavirus carrier state and that many interferon pathway and other immune relevant transcripts are significantly induced in brain by both nodavirus and pIC.

  1. Effective brain network analysis with resting-state EEG data: a comparison between heroin abstinent and non-addicted subjects

    Science.gov (United States)

    Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang

    2017-08-01

    Objective. Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. Approach. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. Main results. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. Significance. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.

  2. Brain correlates of hypnotic paralysis-a resting-state fMRI study.

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    Pyka, M; Burgmer, M; Lenzen, T; Pioch, R; Dannlowski, U; Pfleiderer, B; Ewert, A W; Heuft, G; Arolt, V; Konrad, C

    2011-06-15

    Hypnotic paralysis has been used since the times of Charcot to study altered states of consciousness; however, the underlying neurobiological correlates are poorly understood. We investigated human brain function during hypnotic paralysis using resting-state functional magnetic resonance imaging (fMRI), focussing on two core regions of the default mode network and the representation of the paralysed hand in the primary motor cortex. Hypnotic suggestion induced an observable left-hand paralysis in 19 participants. Resting-state fMRI at 3T was performed in pseudo-randomised order awake and in the hypnotic condition. Functional connectivity analyses revealed increased connectivity of the precuneus with the right dorsolateral prefrontal cortex, angular gyrus, and a dorsal part of the precuneus. Functional connectivity of the medial frontal cortex and the primary motor cortex remained unchanged. Our results reveal that the precuneus plays a pivotal role during maintenance of an altered state of consciousness. The increased coupling of selective cortical areas with the precuneus supports the concept that hypnotic paralysis may be mediated by a modified representation of the self which impacts motor abilities. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Genotypic association of the DAOA gene with resting-state brain activity in major depression.

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    Chen, Jun; Xu, Yong; Zhang, Juan; Liu, Zhifen; Xu, Cheng; Zhang, Kerang; Shen, Yan; Xu, Qi

    2012-10-01

    Compelling evidence suggests that the glutamatergic system may contribute to the pathophysiology of major depression (MDD). While the D-amino acid oxidase activator (DAOA) gene can affect glutamatergic function, its genetic associations with MDD and abnormal resting-state brain activity have yet to be elucidated. A total of 488 patients with MDD and 480 controls were recruited to examine MDD association for the DAOA gene in a Chinese population, of whom 53 medication-free patients and 46 well-matched controls underwent resting-state functional magnetic resonance imaging for regional homogeneity (ReHo) analysis. The differences in ReHo between genotypes of interest were initially tested by the Student's t test, and the 2 × 2 (genotypes × disease status) ANOVA was then performed to identify the main effects of genotypes, disease status, and their interactions in MDD. Allelic association of the DAOA gene with MDD was observed for rs2391191, rs3918341, and rs778294 and haplotypic association for 2- and 3-SNP haplotypes. Six clusters in the cerebellum, right middle frontal gyrus and left middle temporal gyrus showed genotypic association between altered ReHo and rs2391191. The main effects of rs2391191 genotypes were found in the right culmen and right middle frontal gyrus. The left uvula and left middle temporal gyrus showed a genotypes × disease status interaction. Our results suggest that the DAOA gene may confer genetic risk of MDD. Genotypic effect of rs2391191 and its interaction with disease status may contribute to the altered ReHo in patients with MDD. Glutamatergic modulation may play an important role in alteration of the resting-state brain activities.

  4. Love-related changes in the brain: A resting-state functional magnetic resonance imaging study

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    Hongwen eSong

    2015-02-01

    Full Text Available Romantic love is a motivational state associated with a desire to enter or maintain a close relationship with a specific other person. Studies with functional magnetic resonance imaging (fMRI have found activation increases in brain regions involved in processing of reward, emotion, motivation when romantic lovers view photographs of their partners. However, not much is known on whether romantic love affects the brain’s functional architecture during rest. In the present study, resting state functional magnetic resonance imaging (rsfMRI data was collected to compare the regional homogeneity (ReHo and functional connectivity (FC across a lover group (LG, N=34, currently intensely in love, ended-love group (ELG, N=34, romantic relationship ended recently, and single group (SG, N=32, never fallen in love.The results showed that:1 ReHo of the left dorsal anterior cingulate cortex (dACC was significantly increased in the LG (in comparison to the ELG and the SG; 2 ReHo of the left dACC was positively correlated with length of time in love in the LG, and negatively correlated with the lovelorn duration since breakup in the ELG; 3 functional connectivity (FC within the reward, motivation, and emotion network (dACC, insula, caudate, amygdala and nucleus accumbens and the social cognition network (temporo-parietal junction (TPJ, posterior cingulate cortex (PCC, medial prefrontal cortex (MPFC, inferior parietal, precuneus and temporal lobe was significantly increased in the LG (in comparison to the ELG and SG; 4 in most regions within both networks FC was positively correlated with the love duration in the LG but negatively correlated with the lovelorn duration in the ELG. This study provides first empirical evidence of love-related alterations of brain functional architecture. The results shed light on the underlying neural mechanisms of romantic love, and demonstrate the possibility of applying a resting state approach for investigating romantic love.

  5. Meal Replacement: Calming the Hot-State Brain Network of Appetite

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    Brielle ePaolini

    2014-03-01

    Full Text Available There is a growing awareness in the field of neuroscience that the self-regulation of eating behavior is driven by complex networks within the brain. These networks may be vulnerable to hot states which people can move into and out of dynamically throughout the course of a day as a function of changes in affect or visceral cues. The goal of the current study was to identify and determine differences in the Hot-state Brain Network of Appetite (HBN-A that exists after a brief period of food restraint followed either by the consumption of a meal replacement (MR or water. Fourteen overweight/obese adults came to our laboratory on two different occasions. Both times they consumed a controlled breakfast meal and then were restricted from eating for 2.5 hours prior to an MRI scan. On one visit, they consumed a meal replacement (MR liquid meal after this period of food restriction; on the other visit they consumed an equal amount of water. After these manipulations, the participants underwent a resting fMRI scan. Our first study aim employed an exploratory, data-driven approach to identify hubs relevant to the HBN-A. Using data from the water condition, five regions were found to be the hubs or nodes of the HBN-A: insula, anterior cingulated cortex, the superior temporal pole, the amygdala, and the hippocampus. We then demonstrated that the consumption of a liquid MR dampened interconnectivity between the nodes of the HBN-A as compared to water. Importantly and consistent with these network data, the consumption of a MR beverage also lowered state cravings and hunger.

  6. Altered causal connectivity of resting state brain networks in amnesic MCI.

    Science.gov (United States)

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

    2014-01-01

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

  7. Altered causal connectivity of resting state brain networks in amnesic MCI.

    Directory of Open Access Journals (Sweden)

    Peipeng Liang

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

  8. Antipsychotic drugs attenuate aberrant DNA methylation of DTNBP1 (dysbindin) promoter in saliva and post-mortem brain of patients with schizophrenia and Psychotic bipolar disorder.

    Science.gov (United States)

    Abdolmaleky, Hamid M; Pajouhanfar, Sara; Faghankhani, Masoomeh; Joghataei, Mohammad Taghi; Mostafavi, Ashraf; Thiagalingam, Sam

    2015-12-01

    Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region. Quantitative methylation specific PCR (qMSP) was employed to assess methylation of DTNBP1 promoter CpGs flanking a SP1 binding site in the saliva of SCZ patients, their first-degree relatives and control subjects (30, 15, and 30/group, respectively) as well as in post-mortem brains of patients with SCZ and bipolar disorder (BD) versus controls (35/group). qRT-PCR was used to assess DTNBP1 expression. We found DNA hypermethylation of DTNBP1 promoter in the saliva of SCZ patients (∼12.5%, P = 0.036), particularly in drug-naïve patients (∼20%, P = 0.011), and a trend toward hypermethylation in their first-degree relatives (P = 0.085) versus controls. Analysis of post-mortem brain samples revealed an inverse correlation between DTNBP1 methylation and expression, and normalization of this epigenetic change by classic antipsychotic drugs. Additionally, BD patients with psychotic depression exhibited higher degree of methylation versus other BD patients (∼80%, P = 0.025). DTNBP1 promoter DNA methylation may become a key element in a panel of biomarkers for diagnosis, prevention, or therapy in SCZ and at risk individuals pending confirmatory studies with larger sample sizes to attain a higher degree of significance. © 2015 Wiley Periodicals, Inc.

  9. Resting-state EEG oscillatory dynamics in fragile X syndrome: abnormal functional connectivity and brain network organization.

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    Melle J W van der Molen

    Full Text Available Disruptions in functional connectivity and dysfunctional brain networks are considered to be a neurological hallmark of neurodevelopmental disorders. Despite the vast literature on functional brain connectivity in typical brain development, surprisingly few attempts have been made to characterize brain network integrity in neurodevelopmental disorders. Here we used resting-state EEG to characterize functional brain connectivity and brain network organization in eight males with fragile X syndrome (FXS and 12 healthy male controls. Functional connectivity was calculated based on the phase lag index (PLI, a non-linear synchronization index that is less sensitive to the effects of volume conduction. Brain network organization was assessed with graph theoretical analysis. A decrease in global functional connectivity was observed in FXS males for upper alpha and beta frequency bands. For theta oscillations, we found increased connectivity in long-range (fronto-posterior and short-range (frontal-frontal and posterior-posterior clusters. Graph theoretical analysis yielded evidence of increased path length in the theta band, suggesting that information transfer between brain regions is particularly impaired for theta oscillations in FXS. These findings are discussed in terms of aberrant maturation of neuronal oscillatory dynamics, resulting in an imbalance in excitatory and inhibitory neuronal circuit activity.

  10. Down-Regulation of Olfactory Receptors in Response to Traumatic Brain Injury Promotes Risk for Alzheimer’s Disease

    Science.gov (United States)

    2013-10-01

    self-assessment of mood (Fig. 4D). Ectopic expression of OR TBI biomarkers in multiple brain regions outside of the olfactory bulb The brain represents...observation that the three OR biomarkers were ectopically expressed in multiple brain regions outside of the olfactory bulb suggested potential function...AD_________________ Award Number: W81XWH-12-1-0582 TITLE: Down-Regulation of Olfactory Receptors in

  11. Cohort Effects in Promotions and Wages: Evidence from Sweden and the United States

    Science.gov (United States)

    Kwon, Illoong; Meyersson Milgrom, Eva; Hwang, Seiwoon

    2010-01-01

    This paper studies the long-term effects of the business cycle on workers' future promotions and wages. Using the Swedish employer-employee matched data, we find that a cohort of workers entering the labor market during a boom gets promoted faster and reaches higher ranks. This procyclical promotion cohort effect persists even after controlling…

  12. Association between resting-state brain network topological organization and creative ability: Evidence from a multiple linear regression model.

    Science.gov (United States)

    Jiao, Bingqing; Zhang, Delong; Liang, Aiying; Liang, Bishan; Wang, Zengjian; Li, Junchao; Cai, Yuxuan; Gao, Mengxia; Gao, Zhenni; Chang, Song; Huang, Ruiwang; Liu, Ming

    2017-10-01

    Previous studies have indicated a tight linkage between resting-state functional connectivity of the human brain and creative ability. This study aimed to further investigate the association between the topological organization of resting-state brain networks and creativity. Therefore, we acquired resting-state fMRI data from 22 high-creativity participants and 22 low-creativity participants (as determined by their Torrance Tests of Creative Thinking scores). We then constructed functional brain networks for each participant and assessed group differences in network topological properties before exploring the relationships between respective network topological properties and creative ability. We identified an optimized organization of intrinsic brain networks in both groups. However, compared with low-creativity participants, high-creativity participants exhibited increased global efficiency and substantially decreased path length, suggesting increased efficiency of information transmission across brain networks in creative individuals. Using a multiple linear regression model, we further demonstrated that regional functional integration properties (i.e., the betweenness centrality and global efficiency) of brain networks, particularly the default mode network (DMN) and sensorimotor network (SMN), significantly predicted the individual differences in creative ability. Furthermore, the associations between network regional properties and creative performance were creativity-level dependent, where the difference in the resource control component may be important in explaining individual difference in creative performance. These findings provide novel insights into the neural substrate of creativity and may facilitate objective identification of creative ability. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Love-related changes in the brain: a resting-state functional magnetic resonance imaging study.

    Science.gov (United States)

    Song, Hongwen; Zou, Zhiling; Kou, Juan; Liu, Yang; Yang, Lizhuang; Zilverstand, Anna; d'Oleire Uquillas, Federico; Zhang, Xiaochu

    2015-01-01

    Romantic love is a motivational state associated with a desire to enter or maintain a close relationship with a specific other person. Functional magnetic resonance imaging (fMRI) studies have found activation increases in brain regions involved in the processing of reward, motivation and emotion regulation, when romantic lovers view photographs of their partners. However, not much is known about whether romantic love affects the brain's functional architecture during rest. In the present study, resting state functional magnetic resonance imaging (rsfMRI) data was collected to compare the regional homogeneity (ReHo) and functional connectivity (FC) across an "in-love" group (LG, N = 34, currently intensely in love), an "ended-love" group (ELG, N = 34, ended romantic relationship recently), and a "single" group (SG, N = 32, never fallen in love). Results show that: (1) ReHo of the left dorsal anterior cingulate cortex (dACC) was significantly increased in the LG (in comparison to the ELG and the SG); (2) ReHo of the left dACC was positively correlated with length of time in love in the LG, and negatively correlated with the lovelorn duration since breakup in the ELG; (3) FC within the reward, motivation, and emotion regulation network (dACC, insula, caudate, amygdala, and nucleus accumbens) as well as FC in the social cognition network [temporo-parietal junction (TPJ), posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal, precuneus, and temporal lobe] was significantly increased in the LG (in comparison to the ELG and SG); (4) in most regions within both networks FC was positively correlated with the duration of love in the LG but negatively correlated with the lovelorn duration of time since breakup in the ELG. This study provides first empirical evidence of love-related alterations in brain functional architecture. Furthermore, the results shed light on the underlying neural mechanisms of romantic love, and demonstrate the

  14. Deep brain stimulation for the early treatment of the minimally conscious state and vegetative state: experience in 14 patients.

    Science.gov (United States)

    Chudy, Darko; Deletis, Vedran; Almahariq, Fadi; Marčinković, Petar; Škrlin, Jasenka; Paradžik, Veronika

    2017-06-16

    OBJECTIVE An effective treatment of patients in a minimally conscious state (MCS) or vegetative state (VS) caused by hypoxic encephalopathy or traumatic brain injury (TBI) is not yet available. Deep brain stimulation (DBS) of the thalamic reticular nuclei has been attempted as a therapeutic procedure mainly in patients with TBI. The purpose of this study was to investigate the therapeutic use of DBS for patients in VS or MCS. METHODS Fourteen of 49 patients in VS or MCS qualified for inclusion in this study and underwent DBS. Of these 14 patients, 4 were in MCS and 10 were in VS. The etiology of VS or MCS was TBI in 4 cases and hypoxic encephalopathy due to cardiac arrest in 10. The selection criteria for DBS, evaluating the status of the cerebral cortex and thalamocortical reticular formation, included: neurological evaluation, electrophysiological evaluation, and the results of positron emission tomography (PET) and MRI examinations. The target for DBS was the centromedian-parafascicular (CM-pf) complex. The duration of follow-up ranged from 38 to 60 months. RESULTS Two MCS patients regained consciousness and regained their ability to walk, speak fluently, and live independently. One MCS patient reached the level of consciousness, but was still in a wheelchair at the time the article was written. One VS patient (who had suffered a cerebral ischemic lesion) improved to the level of consciousness and currently responds to simple commands. Three VS patients died of respiratory infection, sepsis, or cerebrovascular insult (1 of each). The other 7 patients remained without substantial improvement of consciousness. CONCLUSIONS Spontaneous recovery from MCS/VS to the level of consciousness with no or minimal need for assistance in everyday life is very rare. Therefore, if a patient in VS or MCS fulfills the selection criteria (presence of somatosensory evoked potentials from upper extremities, motor and brainstem auditory evoked potentials, with cerebral glucose

  15. Neural correlates of envy: Regional homogeneity of resting-state brain activity predicts dispositional envy.

    Science.gov (United States)

    Xiang, Yanhui; Kong, Feng; Wen, Xue; Wu, Qihan; Mo, Lei

    2016-11-15

    Envy differs from common negative emotions across cultures. Although previous studies have explored the neural basis of episodic envy via functional magnetic resonance imaging (fMRI), little is known about the neural processes associated with dispositional envy. In the present study, we used regional homogeneity (ReHo) as an index in resting-state fMRI (rs-fMRI) to identify brain regions involved in individual differences in dispositional envy, as measured by the Dispositional Envy Scale (DES). Results showed that ReHo in the inferior/middle frontal gyrus (IFG/MFG) and dorsomedial prefrontal cortex (DMPFC) positively predicted dispositional envy. Moreover, of all the personality traits measured by the Revised NEO Personality Inventory (NEO-PI-R), only neuroticism was significantly associated with dispositional envy. Furthermore, neuroticism mediated the underlying association between the ReHo of the IFG/MFG and dispositional envy. Hence, to the best of our knowledge, this study provides the first evidence that spontaneous brain activity in multiple regions related to self-evaluation, social perception, and social emotion contributes to dispositional envy. In addition, our findings reveal that neuroticism may play an important role in the cognitive processing of dispositional envy. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Modular reorganization of brain resting state networks and its independent validation in Alzheimer's disease patients.

    Science.gov (United States)

    Chen, Guangyu; Zhang, Hong-Ying; Xie, Chunming; Chen, Gang; Zhang, Zhi-Jun; Teng, Gao-Jun; Li, Shi-Jiang

    2013-01-01

    Previous studies have demonstrated disruption in structural and functional connectivity occurring in the Alzheimer's Disease (AD). However, it is not known how these disruptions alter brain network reorganization. With the modular analysis method of graph theory, and datasets acquired by the resting-state functional connectivity MRI (R-fMRI) method, we investigated and compared the brain organization patterns between the AD group and the cognitively normal control (CN) group. Our main finding is that the largest homotopic module (defined as the insula module) in the CN group was broken down to the pieces in the AD group. Specifically, it was discovered that the eight pairs of the bilateral regions (the opercular part of inferior frontal gyrus, area triangularis, insula, putamen, globus pallidus, transverse temporal gyri, superior temporal gyrus, and superior temporal pole) of the insula module had lost symmetric functional connection properties, and the corresponding gray matter concentration (GMC) was significant lower in AD group. We further quantified the functional connectivity changes with an index (index A) and structural changes with the GMC index in the insula module to demonstrate their great potential as AD biomarkers. We further validated these results with six additional independent datasets (271 subjects in six groups). Our results demonstrated specific underlying structural and functional reorganization from young to old, and for diseased subjects. Further, it is suggested that by combining the structural GMC analysis and functional modular analysis in the insula module, a new biomarker can be developed at the single-subject level.

  17. Moral competence and brain connectivity: a resting-state fMRI study

    Science.gov (United States)

    Jung, Wi Hoon; Prehn, Kristin; Fang, Zhuo; Korczykowski, Marc; Kable, Joseph W.; Rao, Hengyi; Robertson, Diana C.

    2016-01-01

    Moral competence (MC) refers to the ability to apply certain moral orientations in a consistent and differentiated manner when judging moral issues. People greatly differ in terms of MC, however, little is known about how these differences are implemented in the brain. To investigate this question, we used functional magnetic resonance imaging and examined resting-state functional connectivity (RSFC) in n=31 individuals with MC scores in the highest 15% of the population and n=33 individuals with MC scores in the lowest 15%, selected from a large sample of 730 Master of Business Administration (MBA) students. Compared to individuals with lower MC, individuals with higher MC showed greater amygdala-ventromedial prefrontal connectivity, which may reflect better ability to cope with emotional conflicts elicited by moral dilemmas. Moreover, individuals with higher MC showed less inter-network connectivity between the amygdalar and fronto-parietal networks, suggesting a more independent operation of these networks. Our findings provide novel insights into how individual differences in moral judgment are associated with RSFC in brain circuits related to emotion processing and cognitive control. PMID:27456537

  18. The spectral diversity of resting-state fluctuations in the human brain.

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    Klaudius Kalcher

    Full Text Available In order to assess whole-brain resting-state fluctuations at a wide range of frequencies, resting-state fMRI data of 20 healthy subjects were acquired using a multiband EPI sequence with a low TR (354 ms and compared to 20 resting-state datasets from standard, high-TR (1800 ms EPI scans. The spatial distribution of fluctuations in various frequency ranges are analyzed along with the spectra of the time-series in voxels from different regions of interest. Functional connectivity specific to different frequency ranges (<0.1 Hz; 0.1-0.25 Hz; 0.25-0.75 Hz; 0.75-1.4 Hz was computed for both the low-TR and (for the two lower-frequency ranges the high-TR datasets using bandpass filters. In the low-TR data, cortical regions exhibited highest contribution of low-frequency fluctuations and the most marked low-frequency peak in the spectrum, while the time courses in subcortical grey matter regions as well as the insula were strongly contaminated by high-frequency signals. White matter and CSF regions had highest contribution of high-frequency fluctuations and a mostly flat power spectrum. In the high-TR data, the basic patterns of the low-TR data can be recognized, but the high-frequency proportions of the signal fluctuations are folded into the low frequency range, thus obfuscating the low-frequency dynamics. Regions with higher proportion of high-frequency oscillations in the low-TR data showed flatter power spectra in the high-TR data due to aliasing of the high-frequency signal components, leading to loss of specificity in the signal from these regions in high-TR data. Functional connectivity analyses showed that there are correlations between resting-state signal fluctuations of distant brain regions even at high frequencies, which can be measured using low-TR fMRI. On the other hand, in the high-TR data, loss of specificity of measured fluctuations leads to lower sensitivity in detecting functional connectivity. This underlines the advantages of low

  19. The Spectral Diversity of Resting-State Fluctuations in the Human Brain

    Science.gov (United States)

    Huf, Wolfgang; Bartova, Lucie; Kronnerwetter, Claudia; Derntl, Birgit; Pezawas, Lukas; Filzmoser, Peter; Nasel, Christian; Moser, Ewald

    2014-01-01

    In order to assess whole-brain resting-state fluctuations at a wide range of frequencies, resting-state fMRI data of 20 healthy subjects were acquired using a multiband EPI sequence with a low TR (354 ms) and compared to 20 resting-state datasets from standard, high-TR (1800 ms) EPI scans. The spatial distribution of fluctuations in various frequency ranges are analyzed along with the spectra of the time-series in voxels from different regions of interest. Functional connectivity specific to different frequency ranges (<0.1 Hz; 0.1–0.25 Hz; 0.25–0.75 Hz; 0.75–1.4 Hz) was computed for both the low-TR and (for the two lower-frequency ranges) the high-TR datasets using bandpass filters. In the low-TR data, cortical regions exhibited highest contribution of low-frequency fluctuations and the most marked low-frequency peak in the spectrum, while the time courses in subcortical grey matter regions as well as the insula were strongly contaminated by high-frequency signals. White matter and CSF regions had highest contribution of high-frequency fluctuations and a mostly flat power spectrum. In the high-TR data, the basic patterns of the low-TR data can be recognized, but the high-frequency proportions of the signal fluctuations are folded into the low frequency range, thus obfuscating the low-frequency dynamics. Regions with higher proportion of high-frequency oscillations in the low-TR data showed flatter power spectra in the high-TR data due to aliasing of the high-frequency signal components, leading to loss of specificity in the signal from these regions in high-TR data. Functional connectivity analyses showed that there are correlations between resting-state signal fluctuations of distant brain regions even at high frequencies, which can be measured using low-TR fMRI. On the other hand, in the high-TR data, loss of specificity of measured fluctuations leads to lower sensitivity in detecting functional connectivity. This underlines the advantages of low-TR EPI

  20. High spatial resolution brain functional MRI using submillimeter balanced steady-state free precession acquisition

    Energy Technology Data Exchange (ETDEWEB)

    Wu, Pei-Hsin; Chung, Hsiao-Wen [Department of Electrical Engineering, National Taiwan University, Taipei 10617, Taiwan (China); Tsai, Ping-Huei [Imaging Research Center, Taipei Medical University, Taipei 11031, Taiwan and Department of Medical Imaging, Taipei Medical University Hospital, Taipei Medical University, Taipei 11031, Taiwan (China); Wu, Ming-Long, E-mail: minglong.wu@csie.ncku.edu.tw [Institute of Medical Informatics, National Cheng-Kung University, Tainan 70101, Taiwan and Department of Computer Science and Information Engineering, National Cheng-Kung University, Tainan 70101, Taiwan (China); Chuang, Tzu-Chao [Department of Electrical Engineering, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan (China); Shih, Yi-Yu [Siemens Limited Healthcare Sector, Taipei 11503, Taiwan (China); Huang, Teng-Yi [Department of Electrical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan (China)

    2013-12-15

    Purpose: One of the technical advantages of functional magnetic resonance imaging (fMRI) is its precise localization of changes from neuronal activities. While current practice of fMRI acquisition at voxel size around 3 × 3 × 3 mm{sup 3} achieves satisfactory results in studies of basic brain functions, higher spatial resolution is required in order to resolve finer cortical structures. This study investigated spatial resolution effects on brain fMRI experiments using balanced steady-state free precession (bSSFP) imaging with 0.37 mm{sup 3} voxel volume at 3.0 T. Methods: In fMRI experiments, full and unilateral visual field 5 Hz flashing checkerboard stimulations were given to healthy subjects. The bSSFP imaging experiments were performed at three different frequency offsets to widen the coverage, with functional activations in the primary visual cortex analyzed using the general linear model. Variations of the spatial resolution were achieved by removing outerk-space data components. Results: Results show that a reduction in voxel volume from 3.44 × 3.44 × 2 mm{sup 3} to 0.43 × 0.43 × 2 mm{sup 3} has resulted in an increase of the functional activation signals from (7.7 ± 1.7)% to (20.9 ± 2.0)% at 3.0 T, despite of the threefold SNR decreases in the original images, leading to nearly invariant functional contrast-to-noise ratios (fCNR) even at high spatial resolution. Activation signals aligning nicely with gray matter sulci at high spatial resolution would, on the other hand, have possibly been mistaken as noise at low spatial resolution. Conclusions: It is concluded that the bSSFP sequence is a plausible technique for fMRI investigations at submillimeter voxel widths without compromising fCNR. The reduction of partial volume averaging with nonactivated brain tissues to retain fCNR is uniquely suitable for high spatial resolution applications such as the resolving of columnar organization in the brain.

  1. Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients

    DEFF Research Database (Denmark)

    Stender, Johan; Kupers, Ron; Rodell, Anders

    2015-01-01

    of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global...... cortical CMRglc in VS/UWS and MCS averaged 42% and 55% of normal, respectively. Differences between VS/UWS and MCS were most pronounced in the frontoparietal cortex, at 42% and 60% of normal. In brainstem and thalamus, metabolism declined equally in the two conditions. In EMCS, metabolic rates were...... indistinguishable from those of MCS. Ordinal logistic regression predicted that patients are likely to emerge into MCS at CMRglc above 45% of normal. Receiver-operating characteristics showed that patients in MCS and VS/UWS can be differentiated with 82% accuracy, based on cortical metabolism. Together...

  2. Steady State Visual Evoked Potential Based Brain-Computer Interface for Cognitive Assessment

    DEFF Research Database (Denmark)

    Westergren, Nicolai; Bendtsen, Rasmus L.; Kjær, Troels W.

    2016-01-01

    decline is important. Cognitive decline may be detected using fullyautomated computerized assessment. Such systems will provide inexpensive and widely available screenings of cognitive ability. The aim of this pilot study is to develop a real time steady state visual evoked potential (SSVEP) based brain-computer...... interface (BCI) for neurological cognitive assessment. It is intended for use by patients who suffer from diseases impairing their motor skills, but are still able to control their gaze. Results are based on 11 healthy test subjects. The system performance have an average accuracy of 100% ± 0%. The test...... subjects achieved an information transfer rate (ITR) of 14:64 bits/min ± 7:63 bits=min and a subject test performance of 47:22% ± 34:10%. This study suggests that BCI may be applicable in practice as a computerized cognitive assessment tool. However, many improvements are required for the system...

  3. Transfection of rat brain endothelium in a primary culture model of the blood-brain barrier at different states of barrier maturity

    DEFF Research Database (Denmark)

    Larsen, Annette Burkhart; Thomsen, Louiza Bohn; Lichota, Jacek

    approaches have been developed. Gene therapy could be a promising and novel approach to overcome the restricting properties of the BBB to polypeptides and proteins. Gene therapy is based on the delivery of genetic material into brain capillary endothelial cells (BCECs), which, theoretically, will result...... in expression and secretion of the recombinant protein from the BCECs and into the brain, thus turning BCECs into small recombinant protein factories. In this study, the possibility of using BCECs as small factories for recombinant protein production was investigated. To mimic the in-vivo situation as closely...... transfection is positively correlated with cell division, with dividing cells being more sensitive to gene transfection. Therefore, by using this model, the transfection efficiency of the rat endothelium was investigated in an immature state and mature state of the BBB. During the transfection period...

  4. Using community volunteers to promote exclusive breastfeeding in Sokoto State, Nigeria

    Directory of Open Access Journals (Sweden)

    Asma Misbah Qureshi

    2011-09-01

    Full Text Available for 6 months, were older (P=0.00 multi-parous (P=0.05 and more educated (P=0.00 compared to those who did not practice EBF. Among them, significantly increased proportion of women agreed that EBF should be continued during the night (P=0.03, infant should be fed on demand (P=0.05, sick child could be given medication (P=0.02, EBF offered protection against childhood diarrhea (P=0.01, and helped mothers with birth spacing (P=0.00. CONCLUSION: This study shows that there is a need for reaching women with reliable information about infant nutrition in Sokoto State. The results show decreased EBF practice among working mothers, young women, mothers with poor education and fewer than five children. Counseling is a useful strategy for promoting the duration of EBF for six months and for developing support systems for nursing mothers. Working mothers may need additional resources in this setting to enable them to practice EBF.

  5. Brain-Computer Interface-Based Communication in the Completely Locked-In State.

    Science.gov (United States)

    Chaudhary, Ujwal; Xia, Bin; Silvoni, Stefano; Cohen, Leonardo G; Birbaumer, Niels

    2017-01-01

    Despite partial success, communication has remained impossible for persons suffering from complete motor paralysis but intact cognitive and emotional processing, a state called complete locked-in state (CLIS). Based on a motor learning theoretical context and on the failure of neuroelectric brain-computer interface (BCI) communication attempts in CLIS, we here report BCI communication using functional near-infrared spectroscopy (fNIRS) and an implicit attentional processing procedure. Four patients suffering from advanced amyotrophic lateral sclerosis (ALS)-two of them in permanent CLIS and two entering the CLIS without reliable means of communication-learned to answer personal questions with known answers and open questions all requiring a "yes" or "no" thought using frontocentral oxygenation changes measured with fNIRS. Three patients completed more than 46 sessions spread over several weeks, and one patient (patient W) completed 20 sessions. Online fNIRS classification of personal questions with known answers and open questions using linear support vector machine (SVM) resulted in an above-chance-level correct response rate over 70%. Electroencephalographic oscillations and electrooculographic signals did not exceed the chance-level threshold for correct communication despite occasional differences between the physiological signals representing a "yes" or "no" response. However, electroencephalogram (EEG) changes in the theta-frequency band correlated with inferior communication performance, probably because of decreased vigilance and attention. If replicated with ALS patients in CLIS, these positive results could indicate the first step towards abolition of complete locked-in states, at least for ALS.

  6. The use of dopamine enhancing medications with children in low response states following brain injury.

    Science.gov (United States)

    Patrick, P D; Buck, M L; Conaway, M R; Blackman, J A

    2003-06-01

    The study examines the possible relationship between dopamine-enhancing medications and improvement of arousal and awareness in children during persistent low response states (Rancho Los Amigos Levels I, II and III). A retrospective review was conducted of 10 children enrolled in an existing clinical protocol. The Kluge Children's Rehabilitation Center (KCRC) low response protocol provides a double baseline serial measure (A, A, B, B, B) design. Scores on the Western NeuroSensory Stimulation Profile (WNSSP) are the dependent variable. Ten children, mean age of 13.7 years low response state (30 days or more) who were treated with dopamine agonists. Co-morbid or iatrogenic influences were addressed or ruled out. Seven children had traumatic brain injury, one cerebral vascular accident, one anoxia and one encephalitis. On average, dopamine medications were started 52.9 days post-event. Paired t-test of WNSSP scores before medications and on medications were significant at p = 0.03 (paired t-test). Also, the distributions of the slopes (rates of change of WNSSP scores over time) were significantly different in the pre-medication and medication phases (Paired T-test, p = 0.02). Random coefficient model comparison of individuals during pre- and medication phase response variability on WNSSP yielded F-test at p = 0.02. These results suggest a promising relationship between acceleration of recovery for some children in a low response state and administration of dopamine-enhancing medications.

  7. Idle state classification using spiking activity and local field potentials in a brain computer interface.

    Science.gov (United States)

    Williams, Jordan J; Tien, Rex N; Inoue, Yoh; Schwartz, Andrew B

    2016-08-01

    Previous studies of intracortical brain-computer interfaces (BCIs) have often focused on or compared the use of spiking activity and local field potentials (LFPs) for decoding kinematic movement parameters. Conversely, using these signals to detect the initial intention to use a neuroprosthetic device or not has remained a relatively understudied problem. In this study, we examined the relative performance of spiking activity and LFP signals in detecting discrete state changes in attention regarding a user's desire to actively control a BCI device. Preliminary offline results suggest that the beta and high gamma frequency bands of LFP activity demonstrated a capacity for discriminating idle/active BCI control states equal to or greater than firing rate activity on the same channel. Population classifier models using either signal modality demonstrated an indistinguishably high degree of accuracy in decoding rest periods from active BCI reach periods as well as other portions of active BCI task trials. These results suggest that either signal modality may be used to reliably detect discrete state changes on a fine time scale for the purpose of gating neural prosthetic movements.

  8. Altered spontaneous brain activity in patients with acute spinal cord injury revealed by resting-state functional MRI.

    Directory of Open Access Journals (Sweden)

    Ling Zhu

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

  9. Resting state brain connectivity patterns before eventual relapse into cocaine abuse.

    Science.gov (United States)

    Berlingeri, M; Losasso, D; Girolo, A; Cozzolino, E; Masullo, T; Scotto, M; Sberna, M; Bottini, G; Paulesu, E

    2017-06-01

    According to recent theories, drug addicted patients suffer of an impaired response inhibition and salience attribution (I-RISA) together with a perturbed connectivity between the nuclei accumbens (NAcs) and the orbito-prefrontal (oPFC) and dorsal prefrontal (dPFC) cortices, brain regions associated with motivation and cognitive control. To empirically test these assumptions, we evaluated the (neuro)psychological trait and the functional organization of the resting state brain networks associated with the NAcs in 18 former cocaine abusers (FCAs), while being in drug abstinence since 5 months. The psychological data were grouped into three empirical variables related with emotion regulation, emotion awareness and strategic and controlled behaviour. Comparison of the resting state patterns between the entire sample of FCAs and 19 controls revealed a reduction of functional connectivity between the NAcs and the dPFC and enhanced connectivity between the NAcs and the dorsal-striatum. In the 8 FCAs who relapsed into cocaine use after 3 months, the level of functional connectivity between the NAcs and dPFC was lower than the functional connectivity estimated in the group of patients that did not relapsed. Finally, in the entire sample of FCAs, the higher the connectivity between the NAc and the oPFC the lower was the level of strategic and controlled behaviour. Taken together, these results are compatible with models of the interactions between the NAcs, the dorsal striatum and frontal cortices in the I-RISA syndrome, showing that such interactions are particularly perturbed in patients at greater risk of relapse into cocaine abuse. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Advancing the detection of steady-state visual evoked potentials in brain-computer interfaces

    Science.gov (United States)

    Abu-Alqumsan, Mohammad; Peer, Angelika

    2016-06-01

    Objective. Spatial filtering has proved to be a powerful pre-processing step in detection of steady-state visual evoked potentials and boosted typical detection rates both in offline analysis and online SSVEP-based brain-computer interface applications. State-of-the-art detection methods and the spatial filters used thereby share many common foundations as they all build upon the second order statistics of the acquired Electroencephalographic (EEG) data, that is, its spatial autocovariance and cross-covariance with what is assumed to be a pure SSVEP response. The present study aims at highlighting the similarities and differences between these methods. Approach. We consider the canonical correlation analysis (CCA) method as a basis for the theoretical and empirical (with real EEG data) analysis of the state-of-the-art detection methods and the spatial filters used thereby. We build upon the findings of this analysis and prior research and propose a new detection method (CVARS) that combines the power of the canonical variates and that of the autoregressive spectral analysis in estimating the signal and noise power levels. Main results. We found that the multivariate synchronization index method and the maximum contrast combination method are variations of the CCA method. All three methods were found to provide relatively unreliable detections in low signal-to-noise ratio (SNR) regimes. CVARS and the minimum energy combination methods were found to provide better estimates for different SNR levels. Significance. Our theoretical and empirical results demonstrate that the proposed CVARS method outperforms other state-of-the-art detection methods when used in an unsupervised fashion. Furthermore, when used in a supervised fashion, a linear classifier learned from a short training session is able to estimate the hidden user intention, including the idle state (when the user is not attending to any stimulus), rapidly, accurately and reliably.

  11. Signalling through the Type 1 Insulin-Like Growth Factor Receptor (IGF1R Interacts with Canonical Wnt Signalling to Promote Neural Proliferation in Developing Brain

    Directory of Open Access Journals (Sweden)

    Qichen Hu

    2012-05-01

    Full Text Available Signalling through the IGF1R [type 1 IGF (insulin-like growth factor receptor] and canonical Wnt signalling are two signalling pathways that play critical roles in regulating neural cell generation and growth. To determine whether the signalling through the IGF1R can interact with the canonical Wnt signalling pathway in neural cells in vivo, we studied mutant mice with altered IGF signalling. We found that in mice with blunted IGF1R expression specifically in nestin-expressing neural cells (IGF1RNestin–KO mice the abundance of neural β-catenin was significantly reduced. Blunting IGF1R expression also markedly decreased: (i the activity of a LacZ (β-galactosidase reporter transgene that responds to Wnt nuclear signalling (LacZTCF reporter transgene and (ii the number of proliferating neural precursors. In contrast, overexpressing IGF-I (insulin-like growth factor I in brain markedly increased the activity of the LacZTCF reporter transgene. Consistently, IGF-I treatment also markedly increased the activity of the LacZTCF reporter transgene in embryonic neuron cultures that are derived from LacZTCF Tg (transgenic mice. Importantly, increasing the abundance of β-catenin in IGF1RNestin–KO embryonic brains by suppressing the activity of GSK3β (glycogen synthase kinase-3β significantly alleviated the phenotypic changes induced by IGF1R deficiency. These phenotypic changes includes: (i retarded brain growth, (ii reduced precursor proliferation and (iii decreased neuronal number. Our current data, consistent with our previous study of cultured oligodendrocytes, strongly support the concept that IGF signalling interacts with canonical Wnt signalling in the developing brain to promote neural proliferation. The interaction of IGF and canonical Wnt signalling plays an important role in normal brain development by promoting neural precursor proliferation.

  12. Complexity Analysis of Resting-State fMRI in Adult Patients with Attention Deficit Hyperactivity Disorder: Brain Entropy

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    Gülsüm Akdeniz

    2017-01-01

    Full Text Available Objective. Complexity analysis of functional brain structure data represents a new multidisciplinary approach to examining complex, living structures. I aimed to construct a connectivity map of visual brain activities using resting-state functional magnetic resonance imaging (fMRI data and to characterize the level of complexity of functional brain activity using these connectivity data. Methods. A total of 25 healthy controls and 20 patients with attention deficit hyperactivity disorder (ADHD participated. fMRI preprocessing analysis was performed that included head motion correction, temporal filtering, and spatial smoothing process. Brain entropy (BEN was calculated using the Shannon entropy equation. Results. My findings demonstrated that patients exhibited reduced brain complexity in visual brain areas compared to controls. The mean entropy value of the ADHD group was 0.56±0.14, compared to 0.64±0.11 in the control group. Conclusion. My study adds an important novel result to the growing literature pertaining to abnormal visual processing in ADHD that my ADHD patients had lower BEN values, indicating more-regular functional brain structure and abnormal visual information processing.

  13. The epidemiology of childhood brain injury in the state of Selangor and Federal Territory of Kuala Lumpur, Malaysia.

    Science.gov (United States)

    Tay, Ee Lin; Lee, Shaun Wen Huey; Jamaluddin, Sabariah Faizah; Tam, Cai Lian; Wong, Chee Piau

    2016-04-27

    There are limited studies describing the epidemiology of childhood brain injury, especially in developing countries. This study analyses data from the Malaysian National Trauma Database (NTrD) registry to estimate the incidence of childhood brain injury among various demographic groups within the state of Selangor and Federal Territory of Kuala Lumpur. This study analysed all traumatic brain injury cases for children ages 0-19 included in the 2010 NTrD report. A total of 5,836 paediatric patients were admitted to emergency departments (ED) of reporting hospitals for trauma. Of these, 742 patients (12.7 %) suffered from brain injuries. Among those with brain injuries, the mortality rate was 11.9 and 71.2 % were aged between 15 and 19. Traffic accidents were the most common mode of injury (95.4 %). Out of the total for traffic accidents, 80.2 % of brain injuries were incurred in motorcycle accidents. Severity of injury was higher among males and patients who were transferred or referred to the reporting centres from other clinics. Glasgow Coma Scale (GCS) total score and type of admission were found to be statistically significant, χ (2) (5, N = 178) = 66.53, p Malaysia. Most brain injuries occurred among older male children, with traffic, specifically motorcycle-related, accidents being the main mode of injury. These findings point to risk factors that could be targeted for future injury prevention programs.

  14. Induction of miR-155 after Brain Injury Promotes Type 1 Interferon and has a Neuroprotective Effect

    Directory of Open Access Journals (Sweden)

    Emily B. Harrison

    2017-07-01

    Full Text Available Traumatic brain injury (TBI produces profound and lasting neuroinflammation that has both beneficial and detrimental effects. Recent evidence has implicated microRNAs (miRNAs in the regulation of inflammation both in the periphery and the CNS. We examined the expression of inflammation associated miRNAs in the context of TBI using a mouse controlled cortical impact (CCI model and found increased levels of miR-21, miR-223 and miR-155 in the hippocampus after CCI. The expression of miR-155 was elevated 9-fold after CCI, an increase confirmed by in situ hybridization (ISH. Interestingly, expression of miR-155 was largely found in neuronal nuclei as evidenced by co-localization with DAPI in MAP2 positive neurons. In miR-155 knock out (KO mice expression of type I interferons IFNα and IFNβ, as well as IFN regulatory factor 1 and IFN-induced chemokine CXCL10 was decreased after TBI relative to wild type (WT mice. Unexpectedly, miR-155 KO mice had increased levels of microglial marker Iba1 and increased neuronal degeneration as measured by fluoro-jade C (FJC staining, suggesting a neuroprotective role for miR-155 in the context of TBI. This work demonstrates a role for miR-155 in regulation of the IFN response and neurodegeneration in the aftermath of TBI. While the presence of neuronal nuclear miRNAs has been described previously, their importance in disease states is relatively unknown. Here, we show evidence of dynamic regulation and pathological function of a nuclear miRNA in TBI.

  15. The Whole-Brain “Global” Signal from Resting State fMRI as a Potential Biomarker of Quantitative State Changes in Glucose Metabolism

    Science.gov (United States)

    Thompson, Garth J.; Grimmer, Timo; Drzezga, Alexander; Herman, Peter

    2016-01-01

    Abstract The evolution of functional magnetic resonance imaging to resting state (R-fMRI) allows measurement of changes in brain networks attributed to state changes, such as in neuropsychiatric diseases versus healthy controls. Since these networks are observed by comparing normalized R-fMRI signals, it is difficult to determine the metabolic basis of such group differences. To investigate the metabolic basis of R-fMRI network differences within a normal range, eyes open versus eyes closed in healthy human subjects was used. R-fMRI was recorded simultaneously with fluoro-deoxyglucose positron emission tomography (FDG-PET). Higher baseline FDG was observed in the eyes open state. Variance-based metrics calculated from R-fMRI did not match the baseline shift in FDG. Functional connectivity density (FCD)-based metrics showed a shift similar to the baseline shift of FDG, however, this was lost if R-fMRI “nuisance signals” were regressed before FCD calculation. Average correlation with the mean R-fMRI signal across the whole brain, generally regarded as a “nuisance signal,” also showed a shift similar to the baseline of FDG. Thus, despite lacking a baseline itself, changes in whole-brain correlation may reflect changes in baseline brain metabolism. Conversely, variance-based metrics may remain similar between states due to inherent region-to-region differences overwhelming the differences between normal physiological states. As most previous studies have excluded the spatial means of R-fMRI metrics from their analysis, this work presents the first evidence of a potential R-fMRI biomarker for baseline shifts in quantifiable metabolism between brain states. PMID:27029438

  16. Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4 in Neurons and Promotes ATF4-Dependent Induction of Sesn2

    Directory of Open Access Journals (Sweden)

    Jin Liu

    2018-03-01

    Full Text Available Activating transcription factor 4 (ATF4 plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.

  17. Microglial activation state exerts a biphasic influence on brain endothelial cell proliferation by regulating the balance of TNF and TGF-β1

    Directory of Open Access Journals (Sweden)

    Milner Richard

    2010-12-01

    Full Text Available Abstract Background Studies of cerebral ischemia and other neuroinflammatory states have demonstrated a strong association between new vessel formation and microglial recruitment and activation, raising the possibility that microglia may be involved in promoting angiogenesis. As endothelial cell proliferation is a fundamental early step in angiogenesis, the aim of this study was to test this hypothesis by examining the influence of microglial secreted factors on brain endothelial cell (BEC proliferation using BrdU incorporation. Methods Primary cultures of mouse BEC, microglia and astrocytes were used in this study. Proliferation of BEC was examined by BrdU incorporation. ELISA was used to quantify TNF and TGF-β1 levels within cell culture supernatants. Results Microglia regulated BEC proliferation in a biphasic manner; microglia conditioned medium (MG-CM from resting microglia inhibited, while that from activated microglia promoted BEC proliferation. A screen of microglial cytokines revealed that BEC proliferation was inhibited by TGF-β1, but promoted by TNF. ELISA showed that TNF and TGF-β1 were both present in MG-CM, and that while TGF-β1 dominated in resting MG-CM, TNF levels were massively increased in activated MG-CM, shifting the balance in favor of TNF. Antibody-blocking studies revealed that the influence of MG-CM to inhibit or promote BEC proliferation was largely attributable to the cytokines TGF-β1 and TNF, respectively. Conclusion This data suggests that microglial activation state might be an important determinant of cerebral angiogenesis; inhibiting BEC proliferation and neovascularization in the normal central nervous system (CNS, but stimulating the growth of new capillaries under neuroinflammatory conditions.

  18. Resting state functional MRI in Parkinson’s disease: the impact of deep brain stimulation on ‘effective’ connectivity

    Science.gov (United States)

    Kahan, Joshua; Urner, Maren; Moran, Rosalyn; Flandin, Guillaume; Marreiros, Andre; Mancini, Laura; White, Mark; Thornton, John; Yousry, Tarek; Zrinzo, Ludvic; Hariz, Marwan; Limousin, Patricia; Friston, Karl

    2014-01-01

    Depleted of dopamine, the dynamics of the parkinsonian brain impact on both ‘action’ and ‘resting’ motor behaviour. Deep brain stimulation has become an established means of managing these symptoms, although its mechanisms of action remain unclear. Non-invasive characterizations of induced brain responses, and the effective connectivity underlying them, generally appeals to dynamic causal modelling of neuroimaging data. When the brain is at rest, however, this sort of characterization has been limited to correlations (functional connectivity). In this work, we model the ‘effective’ connectivity underlying low frequency blood oxygen level-dependent fluctuations in the resting Parkinsonian motor network—disclosing the distributed effects of deep brain stimulation on cortico-subcortical connections. Specifically, we show that subthalamic nucleus deep brain stimulation modulates all the major components of the motor cortico-striato-thalamo-cortical loop, including the cortico-striatal, thalamo-cortical, direct and indirect basal ganglia pathways, and the hyperdirect subthalamic nucleus projections. The strength of effective subthalamic nucleus afferents and efferents were reduced by stimulation, whereas cortico-striatal, thalamo-cortical and direct pathways were strengthened. Remarkably, regression analysis revealed that the hyperdirect, direct, and basal ganglia afferents to the subthalamic nucleus predicted clinical status and therapeutic response to deep brain stimulation; however, suppression of the sensitivity of the subthalamic nucleus to its hyperdirect afferents by deep brain stimulation may subvert the clinical efficacy of deep brain stimulation. Our findings highlight the distributed effects of stimulation on the resting motor network and provide a framework for analysing effective connectivity in resting state functional MRI with strong a priori hypotheses. PMID:24566670

  19. Love-related changes in the brain: a resting-state functional magnetic resonance imaging study

    Science.gov (United States)

    Song, Hongwen; Zou, Zhiling; Kou, Juan; Liu, Yang; Yang, Lizhuang; Zilverstand, Anna; d’Oleire Uquillas, Federico; Zhang, Xiaochu

    2015-01-01

    Romantic love is a motivational state associated with a desire to enter or maintain a close relationship with a specific other person. Functional magnetic resonance imaging (fMRI) studies have found activation increases in brain regions involved in the processing of reward, motivation and emotion regulation, when romantic lovers view photographs of their partners. However, not much is known about whether romantic love affects the brain’s functional architecture during rest. In the present study, resting state functional magnetic resonance imaging (rsfMRI) data was collected to compare the regional homogeneity (ReHo) and functional connectivity (FC) across an “in-love” group (LG, N = 34, currently intensely in love), an “ended-love” group (ELG, N = 34, ended romantic relationship recently), and a “single” group (SG, N = 32, never fallen in love). Results show that: (1) ReHo of the left dorsal anterior cingulate cortex (dACC) was significantly increased in the LG (in comparison to the ELG and the SG); (2) ReHo of the left dACC was positively correlated with length of time in love in the LG, and negatively correlated with the lovelorn duration since breakup in the ELG; (3) FC within the reward, motivation, and emotion regulation network (dACC, insula, caudate, amygdala, and nucleus accumbens) as well as FC in the social cognition network [temporo-parietal junction (TPJ), posterior cingulate cortex (PCC), medial prefrontal cortex (MPFC), inferior parietal, precuneus, and temporal lobe] was significantly increased in the LG (in comparison to the ELG and SG); (4) in most regions within both networks FC was positively correlated with the duration of love in the LG but negatively correlated with the lovelorn duration of time since breakup in the ELG. This study provides first empirical evidence of love-related alterations in brain functional architecture. Furthermore, the results shed light on the underlying neural mechanisms of romantic love, and demonstrate

  20. 75 FR 24373 - Cotton Research and Promotion Program: Designation of Cotton-Producing States

    Science.gov (United States)

    2010-05-05

    ... Service 7 CFR Part 1205 RIN 0581-AC84 Cotton Research and Promotion Program: Designation of Cotton... Marketing Service (AMS) is amending the Cotton Research and Promotion Order (Cotton Order) following a referendum held October 13 through November 10, 2009, in which Upland cotton producers and importers favored...

  1. Adult human dental pulp stem cells promote blood-brain barrier permeability through vascular endothelial growth factor-a expression.

    Science.gov (United States)

    Winderlich, Joshua N; Kremer, Karlea L; Koblar, Simon A

    2016-06-01

    Stem cell therapy is a promising new treatment option for stroke. Intravascular administration of stem cells is a valid approach as stem cells have been shown to transmigrate the blood-brain barrier. The mechanism that causes this effect has not yet been elucidated. We hypothesized that stem cells would mediate localized discontinuities in the blood-brain barrier, which would allow passage into the brain parenchyma. Here, we demonstrate that adult human dental pulp stem cells express a soluble factor that increases permeability across an in vitro model of the blood-brain barrier. This effect was shown to be the result of vascular endothelial growth factor-a. The effect could be amplified by exposing dental pulp stem cell to stromal-derived factor 1, which stimulates vascular endothelial growth factor-a expression. These findings support the use of dental pulp stem cell in therapy for stroke. © The Author(s) 2015.

  2. State of catecxolaminergine systems of the brain in forming of sydnocarb psychosis

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    Al Nasir Eiad

    2014-03-01

    Full Text Available Violations of mnestic reactions are one of substantial signs of disorders of nervous activity. On the basis of it, as a criterion of forming of experimental psychosis, in our supervisions, the state of processes of conditionally-reflex memory was studied in rats. To cover up mechanisms of derangements of conditionally reflex activity in the process of forming of psychotic symptomatic complex, maintenance of adrenalin, noradrenalinum and neurospecific albumen S - 100 in the brain structures, that take a direct part in the processes of memory was studied. Derangements of cognitive function, that are the result of neurotoxic action of sydnocarb, are related to reduction of maintenance of noradrenalinum in the frontal cortex, as well as adrenalin in the pons varolii. That is, sydnocarb psychosis is accompanied by reduction of activating role of the cortex and trunk structures, negatively affecting the state of mnestic reactions. In the hippocampus and striate body excitation causes violation of memory processes and on the contrary, concentration of noradrenalinum rose. Thus, the presented model of experimental psychosis, created by subacute introduction of sydnocarb, is an adequate and alternative methodology of psychotic disorders forming in animals resulted from direct participation of the catecholaminergetic systems of CNS.

  3. Determination of dominant frequency of resting-state brain interaction within one functional system.

    Science.gov (United States)

    Zhang, Yu-Jin; Duan, Lian; Zhang, Han; Biswal, Bharat B; Lu, Chun-Ming; Zhu, Chao-Zhe

    2012-01-01

    Accumulating evidence has revealed that the resting-state functional connectivity (RSFC) is frequency specific and functional system dependent. Determination of dominant frequency of RSFC (RSFC(df)) within a functional system, therefore, is of importance for further understanding the brain interaction and accurately assessing the RSFC within the system. Given the unique advantages over other imaging techniques, functional near-infrared spectroscopy (fNIRS) holds distinct merits for RSFC(df) determination. However, an obstacle that hinders fNIRS from potential RSFC(df) investigation is the interference of various global noises in fNIRS data which could bring spurious connectivity at the frequencies unrelated to spontaneous neural activity. In this study, we first quantitatively evaluated the interferences of multiple systemic physiological noises and the motion artifact by using simulated data. We then proposed a functional system dependent and frequency specific analysis method to solve the problem by introducing anatomical priori information on the functional system of interest. Both the simulated and real resting-state fNIRS experiments showed that the proposed method outperforms the traditional one by effectively eliminating the negative effects of the global noises and significantly improving the accuracy of the RSFC(df) estimation. The present study thus provides an effective approach to RSFC(df) determination for its further potential applications in basic and clinical neurosciences.

  4. Cytomegalovirus Infection of the Rat Developing Brain In Utero Prominently Targets Immune Cells and Promotes Early Microglial Activation.

    Science.gov (United States)

    Cloarec, Robin; Bauer, Sylvian; Luche, Hervé; Buhler, Emmanuelle; Pallesi-Pocachard, Emilie; Salmi, Manal; Courtens, Sandra; Massacrier, Annick; Grenot, Pierre; Teissier, Natacha; Watrin, Françoise; Schaller, Fabienne; Adle-Biassette, Homa; Gressens, Pierre; Malissen, Marie; Stamminger, Thomas; Streblow, Daniel N; Bruneau, Nadine; Szepetowski, Pierre

    2016-01-01

    Congenital cytomegalovirus infections are a leading cause of neurodevelopmental disorders in human and represent a major health care and socio-economical burden. In contrast with this medical importance, the pathophysiological events remain poorly known. Murine models of brain cytomegalovirus infection, mostly neonatal, have brought recent insights into the possible pathogenesis, with convergent evidence for the alteration and possible involvement of brain immune cells. In order to confirm and expand those findings, particularly concerning the early developmental stages following infection of the fetal brain, we have created a model of in utero cytomegalovirus infection in the developing rat brain. Rat cytomegalovirus was injected intraventricularly at embryonic day 15 (E15) and the brains analyzed at various stages until the first postnatal day, using a combination of gene expression analysis, immunohistochemistry and multicolor flow cytometry experiments. Rat cytomegalovirus infection was increasingly seen in various brain areas including the choroid plexi and the ventricular and subventricular areas and was prominently detected in CD45low/int, CD11b+ microglial cells, in CD45high, CD11b+ cells of the myeloid lineage including macrophages, and in CD45+, CD11b- lymphocytes and non-B non-T cells. In parallel, rat cytomegalovirus infection of the developing rat brain rapidly triggered a cascade of pathophysiological events comprising: chemokines upregulation, including CCL2-4, 7 and 12; infiltration by peripheral cells including B-cells and monocytes at E17 and P1, and T-cells at P1; and microglia activation at E17 and P1. In line with previous findings in neonatal murine models and in human specimen, our study further suggests that neuroimmune alterations might play critical roles in the early stages following cytomegalovirus infection of the brain in utero. Further studies are now needed to determine which role, whether favorable or detrimental, those putative

  5. Microparticles from stored red blood cells promote a hypercoagulable state in a murine model of transfusion.

    Science.gov (United States)

    Kim, Young; Xia, Brent T; Jung, Andrew D; Chang, Alex L; Abplanalp, William A; Caldwell, Charles C; Goodman, Michael D; Pritts, Timothy A

    2018-02-01

    Red blood cell-derived microparticles are biologically active, submicron vesicles shed by erythrocytes during storage. Recent clinical studies have linked the duration of red blood cell storage with thromboembolic events in critically ill transfusion recipients. In the present study, we hypothesized that microparticles from aged packed red blood cell units promote a hypercoagulable state in a murine model of transfusion. Microparticles were isolated from aged, murine packed red blood cell units via serial centrifugation. Healthy male C57BL/6 mice were transfused with microparticles or an equivalent volume of vehicle, and whole blood was harvested for analysis via rotational thromboelastometry. Serum was harvested from a separate set of mice after microparticles or saline injection, and analyzed for fibrinogen levels. Red blood cell-derived microparticles were analyzed for their ability to convert prothrombin to thrombin. Finally, mice were transfused with either red blood cell microparticles or saline vehicle, and a tail bleeding time assay was performed after an equilibration period of 2, 6, 12, or 24 hours. Mice injected with red blood cell-derived microparticles demonstrated an accelerated clot formation time (109.3 ± 26.9 vs 141.6 ± 28.2 sec) and increased α angle (68.8 ± 5.0 degrees vs 62.8 ± 4.7 degrees) compared with control (each P microparticles exhibited a hundredfold greater conversion of prothrombin substrate to its active thrombin form (66.60 ± 0.03 vs 0.70 ± 0.01 peak OD; Pmicroparticles-injected mice compared with saline vehicle, suggesting thrombin-mediated conversion to insoluble fibrin (14.0 vs 16.5 µg/mL, Pmicroparticles-injected mice as compared with saline vehicle (each Pmicroparticles induce a transient hypercoagulable state through accelerated activation of clotting factors. Copyright © 2017 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

    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

  7. Frequency-dependent brain regional homogeneity alterations in patients with mild cognitive impairment during working memory state relative to resting state

    Directory of Open Access Journals (Sweden)

    Pengyun eWang

    2016-03-01

    Full Text Available Several studies have reported working memory deficits in patients with mild cognitive impairment (MCI. However, previous studies investigating the neural mechanisms of MCI have primarily focused on brain activity alterations during working memory tasks. No study to date has compared brain network alterations in the working memory state between MCI patients and normal control subjects. Therefore, using the index of regional homogeneity (ReHo, we explored brain network impairments in MCI patients during a working memory task relative to the resting state, and identified frequency-dependent effects in separate frequency bands.Our results indicate that, in MCI patients, ReHo is altered in the posterior cingulate cortex in the slow-3 band (0.073–0.198 Hz, and in the bottom of the right occipital lobe and part of the right cerebellum, the right thalamus, a diffusing region in the bilateral prefrontal cortex, the left and right parietal-occipital regions, and the right angular gyrus in the slow-5 band (0.01–0.027 Hz. Furthermore, in normal controls, the value of ReHo in clusters belonging to the default mode network decreased, while the value of ReHo in clusters belonging to the attentional network increased during the task state. However, this pattern was reversed in MCI patients, and was associated with decreased working memory performance. In addition, we identified altered functional connectivity of the abovementioned regions with other parts of the brain in MCI patients.This is the first study to compare frequency-dependent alterations of ReHo in MCI patients between resting and working memory states. The results provide a new perspective regarding the neural mechanisms of working memory deficits in MCI patients, and extend our knowledge of altered brain patterns in resting and task-evoked states.

  8. Using auditory steady state responses to outline the functional connectivity in the tinnitus brain.

    Directory of Open Access Journals (Sweden)

    Winfried Schlee

    Full Text Available BACKGROUND: Tinnitus is an auditory phantom perception that is most likely generated in the central nervous system. Most of the tinnitus research has concentrated on the auditory system. However, it was suggested recently that also non-auditory structures are involved in a global network that encodes subjective tinnitus. We tested this assumption using auditory steady state responses to entrain the tinnitus network and investigated long-range functional connectivity across various non-auditory brain regions. METHODS AND FINDINGS: Using whole-head magnetoencephalography we investigated cortical connectivity by means of phase synchronization in tinnitus subjects and healthy controls. We found evidence for a deviating pattern of long-range functional connectivity in tinnitus that was strongly correlated with individual ratings of the tinnitus percept. Phase couplings between the anterior cingulum and the right frontal lobe and phase couplings between the anterior cingulum and the right parietal lobe showed significant condition x group interactions and were correlated with the individual tinnitus distress ratings only in the tinnitus condition and not in the control conditions. CONCLUSIONS: To the best of our knowledge this is the first study that demonstrates existence of a global tinnitus network of long-range cortical connections outside the central auditory system. This result extends the current knowledge of how tinnitus is generated in the brain. We propose that this global extend of the tinnitus network is crucial for the continuos perception of the tinnitus tone and a therapeutical intervention that is able to change this network should result in relief of tinnitus.

  9. Resting-state brain networks in patients with Parkinson's disease and impulse control disorders.

    Science.gov (United States)

    Tessitore, Alessandro; Santangelo, Gabriella; De Micco, Rosa; Giordano, Alfonso; Raimo, Simona; Amboni, Marianna; Esposito, Fabrizio; Barone, Paolo; Tedeschi, Gioacchino; Vitale, Carmine

    2017-09-01

    To investigate intrinsic neural networks connectivity changes in Parkinson's disease (PD) patients with and without impulse control disorders (ICD). Fifteen patients with PD with ICD (ICD+), 15 patients with PD without ICD (ICD-) and 24 age and sex-matched healthy controls (HC) were enrolled in the study. To identify patients with and without ICD and/or punding, we used the Minnesota Impulsive Disorders Interview (MIDI) and a clinical interview based on diagnostic criteria for each symptom. All patients underwent a detailed neuropsychological evaluation. Whole brain structural and functional imaging was performed on a 3T GE MR scanner. Statistical analysis of functional data was completed using BrainVoyager QX software. Voxel-based morphometry (VBM) was used to test whether between-group differences in resting-state connectivity were related to structural abnormalities. The presence of ICD symptoms was associated with an increased connectivity within the salience and default-mode networks, as well as with a decreased connectivity within the central executive network (p < .05 corrected). ICD severity was correlated with both salience and default mode networks connectivity changes only in the ICD+ group. VBM analysis did not reveal any statistically significant differences in local grey matter volume between ICD+ and ICD- patients and between all patients and HC (p < .05. FWE). The presence of a disrupted connectivity within the three core neurocognitive networks may be considered as a potential neural correlate of ICD presence in patients with PD. Our findings provide additional insights into the mechanisms underlying ICD in PD, confirming the crucial role of an abnormal prefrontal-limbic-striatal homeostasis in their development. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Resting-state functional MR imaging: a new window to the brain.

    Science.gov (United States)

    Barkhof, Frederik; Haller, Sven; Rombouts, Serge A R B

    2014-07-01

    Resting-state (RS) functional magnetic resonance (MR) imaging constitutes a novel paradigm that examines spontaneous brain function by using blood oxygen level-dependent contrast in the absence of a task. Spatially distributed networks of temporal synchronization can be detected that can characterize RS networks (RSNs). With a short acquisition time of less than 10 minutes, RS functional MR imaging can be applied in special populations such as children and patients with dementia. Some RSNs are already present in utero, while others mature in childhood. Around 10 major RSNs are consistently found in adults, but their exact spatial extent and strength of coherence are affected by physiologic parameters and drugs. Though the acquisition and analysis methods are still evolving, new disease insights are emerging in a variety of neurologic and psychiatric disorders. The default mode network is affected in Alzheimer disease and various other diseases of cognitive impairment. Alterations in RSNs have been identified in many diseases, in the absence of evident structural modifications, indicating a high sensitivity of the method. Moreover, there is evidence of correlation between RSN alterations and disease progression and severity. However, different diseases often affect the same RSN, illustrating the limited specificity of the findings. This suggests that neurologic and psychiatric diseases are characterized by altered interactions between RSNs and therefore the whole brain should be examined as an integral network (with subnetworks), for example, using graph analysis. A challenge for clinical applications of RS functional MR imaging is the potentially confounding effect of aging, concomitant vascular diseases, or medication on the neurovascular coupling and consequently the functional MR imaging response. Current investigation combines RS functional MR imaging and other methods such as electroencephalography or magnetoencephalography to better understand the vascular

  11. Altered Resting-State Brain Activity and Connectivity in Depressed Parkinson's Disease.

    Directory of Open Access Journals (Sweden)

    Xiao Hu

    Full Text Available Depressive symptoms are common in Parkinson's disease (PD, but the neurophysiological mechanisms of depression in PD are poorly understood. The current study attempted to examine disrupted spontaneous local brain activities and functional connectivities that underlie the depression in PD. We recruited a total of 20 depressed PD patients (DPD, 40 non-depressed PD patients (NDPD and 43 matched healthy controls (HC. All the subjects underwent neuropsychological tests and resting-state fMRI scanning. The between-group differences in the amplitude of low frequency fluctuations (ALFF of BOLD signals were examined using post-hoc tests after the analysis of covariance. Compared with the NDPD and HC, the DPD group showed significantly increased ALFF in the left median cingulated cortex (MCC. The functional connectivity (FC between left MCC and all the other voxels in the brain were then calculated. Compared with the HC and NDPD group, the DPD patients showed stronger FC between the left MCC and some of the major nodes of the default mode network (DMN, including the post cingulated cortex/precuneus, medial prefrontal cortex, inferior frontal gyrus, and cerebellum. Correlation analysis revealed that both the ALFF values in the left MCC and the FC between the left MCC and the nodes of DMN were significantly correlated with the Hamilton Depression Rating Scale score. Moreover, higher local activities in the left MCC were associated with increased functional connections between the MCC and the nodes of DMN in PD. These abnormal activities and connectivities of the limbic-cortical circuit may indicate impaired high-order cortical control or uncontrol of negative mood in DPD, which suggested a possible neural mechanism of the depression in PD.

  12. Abnormal baseline brain activity in patients with neuromyelitis optica: A resting-state fMRI study

    Energy Technology Data Exchange (ETDEWEB)

    Liu Yaou [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Liang Peipeng [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); International WIC institute, Beijing University of Technology, Beijing 100024 (China); Duan Yunyun; Jia Xiuqin; Wang Fei; Yu Chunshui; Qin Wen [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Dong Huiqing; Ye Jing [Department of Neurology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Li Kuncheng, E-mail: likuncheng1955@yahoo.com.cn [Department of Radiology, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China)

    2011-11-15

    Purpose: Recent immunopathologic and MRI findings suggest that tissue damage in neuromyelitis optica (NMO) is not limited to spinal cord and optic nerve, but also in brain. Baseline brain activity can reveal the brain functional changes to the tissue damages and give clues to the pathophysiology of NMO, however, it has never been explored by resting-state functional MRI (fMRI). We used regional amplitude of low frequency fluctuation (ALFF) as an index in resting-state fMRI to investigate how baseline brain activity changes in patients with NMO. Methods: Resting-state fMRIs collected from seventeen NMO patients and seventeen age- and sex-matched normal controls were compared to investigate the ALFF difference between the two groups. The relationships between ALFF in regions with significant group differences and the EDSS (Expanded Disability Status Scale), disease duration were further explored. Results: Our results showed that NMO patients had significantly decreased ALFF in precuneus, posterior cingulate cortex (PCC) and lingual gyrus; and increased ALFF in middle frontal gyrus, caudate nucleus and thalamus, compared to normal controls. Moderate negative correlations were found between the EDSS and ALFF in the left middle frontal gyrus (r = -0.436, p = 0.040) and the left caudate (r = -0.542, p = 0.012). Conclusion: The abnormal baseline brain activity shown by resting-state fMRI in NMO is relevant to cognition, visual and motor systems. It implicates a complex baseline brain status of both functional impairments and adaptations caused by tissue damages in these systems, which gives clues to the pathophysiology of NMO.

  13. A study of the brain's resting state based on alpha band power, heart rate and fMRI

    NARCIS (Netherlands)

    de Munck, J.C.; Goncalves, S.I.; Faes, T.J.C.; Kuijer, J.P.A.; Pouwels, P.J.W.; Heethaar, R.M.; Lopes da Silva, F.H.

    2008-01-01

    Considering that there are several theoretical reasons why fMRI data is correlated to variations in heart rate, these correlations are explored using experimental resting state data. In particular, the possibility is discussed that the "default network", being a brain area that deactivates during

  14. The use of social media by state tobacco control programs to promote smoking cessation: a cross-sectional study.

    Science.gov (United States)

    Duke, Jennifer C; Hansen, Heather; Kim, Annice E; Curry, Laurel; Allen, Jane

    2014-07-10

    The promotion of evidence-based cessation services through social media sites may increase their utilization by smokers. Data on social media adoption and use within tobacco control programs (TCPs) have not been reported. This study examines TCP use of and activity levels on social media, the reach of TCP sites, and the level of engagement with the content on sites. A cross-sectional descriptive study of state TCP social media sites and their content was conducted. In 2013, 60% (30/50) of TCPs were using social media. Approximately one-quarter (26%, 13/50) of all TCPs used 3 or more social media sites, 24% (12/50) used 2, and 10% (5/50) used 1 site. Overall, 60% (30/50) had a Facebook page, 36% (18/50) had a Twitter page, and 40% (20/50) had a YouTube channel. The reach of social media was different across each site and varied widely by state. Among TCPs with a Facebook page, 73% (22/30) had less than 100 likes per 100,000 adults in the state, and 13% (4/30) had more than 400 likes per 100,000 adults. Among TCPs with a Twitter page, 61% (11/18) had less than 10 followers per 100,000 adults, and just 1 state had more than 100 followers per 100,000 adults. Seven states (23%, 7/30) updated their social media sites daily. The most frequent social media activities focused on the dissemination of information rather than interaction with site users. Social media resources from a national cessation media campaign were promoted infrequently. The current reach of state TCP social media sites is low and most TCPs are not promoting existing cessation services or capitalizing on social media's interactive potential. TCPs should create an online environment that increases participation and 2-way communication with smokers to promote free cessation services.

  15. [Study on effect and mechanism of cinnabaris and realgar in promoting awake of endotoxin-induced brain injury rat applied with Angong Niuhuang Wan].

    Science.gov (United States)

    Zhu, Kun-Jie; Sun, Jian-Ning

    2014-10-01

    To explore the effect and mechanism of cinnabaris and realgar in promoting awake effect of endotoxin- induced brain injury rat applied with Angong Niuhuang Wan. Normal rats implanted cortical electrode in advance were divided into 6 groups: control, model, the Angong Niuhuang Wan (AGNH, 0.4, 0.2 g · kg(-1)), the Angong Niuhuang Wan without cinnabaris and realgar (QZX-AGNH, 0.32, 0.16 g · kg(-1)). Rats in the control and model groups were given distilled water. After three days of intragastric administration, the brain injury model was injected with endotoxin through tail vein. Then trace electro-corticogram (EcoG) 1-6 h after LPS injection, and compare the power and relative power of beta (β) and delta-waves (δ) at 6 h of these groups. The content of acetylcholine (Ach) and the affinity of M-receptor (M-R) in cortex and brainstem were detected by alkaline hydroxylamine colorimetric method and radioactive ligand binding assay, respectively. AGNH (0.4, 0.2 g · kg(-1)) could increase the power and relative power of β and AGNH (0.4 g · kg(-1)) showed better action on brain electrical activation. QZX-AGNH showed weak effect on it. AGNH (0.4 g · kg(-1)) could increase the affinity of M-R in cortex and the content of Ach in brainstem. The action of QZX-AGNH was not obvious. In endotoxin-induced brain injury rats, AGNH can raise the cholinergic system function of cortex, and strengthen the uplink of cortex activation of brainstem cholinergic system, improve the level of cortical activity and enhance the activation of EcoG to promote the body's awakening. QZX-AGNH show weak effect. Cinnabaris and realgar play an important role in promoting awake effect in endotoxin-induced brain injury applied with Angong Niuhuang Wan. The mechanism may be related to cortical and brainstem cholinergic system function.

  16. Voxel Scale Complex Networks of Functional Connectivity in the Rat Brain: Neurochemical State Dependence of Global and Local Topological Properties

    Directory of Open Access Journals (Sweden)

    Adam J. Schwarz

    2012-01-01

    Full Text Available Network analysis of functional imaging data reveals emergent features of the brain as a function of its topological properties. However, the brain is not a homogeneous network, and the dependence of functional connectivity parameters on neuroanatomical substrate and parcellation scale is a key issue. Moreover, the extent to which these topological properties depend on underlying neurochemical changes remains unclear. In the present study, we investigated both global statistical properties and the local, voxel-scale distribution of connectivity parameters of the rat brain. Different neurotransmitter systems were stimulated by pharmacological challenge (d-amphetamine, fluoxetine, and nicotine to discriminate between stimulus-specific functional connectivity and more general features of the rat brain architecture. Although global connectivity parameters were similar, mapping of local connectivity parameters at high spatial resolution revealed strong neuroanatomical dependence of functional connectivity in the rat brain, with clear differentiation between the neocortex and older brain regions. Localized foci of high functional connectivity independent of drug challenge were found in the sensorimotor cortices, consistent with the high neuronal connectivity in these regions. Conversely, the topological properties and node roles in subcortical regions varied with neurochemical state and were dependent on the specific dynamics of the different functional processes elicited.

  17. At risk of being risky: The relationship between “brain age” under emotional states and risk preference

    Directory of Open Access Journals (Sweden)

    Marc D. Rudolph

    2017-04-01

    Full Text Available Developmental differences regarding decision making are often reported in the absence of emotional stimuli and without context, failing to explain why some individuals are more likely to have a greater inclination toward risk. The current study (N = 212; 10–25y examined the influence of emotional context on underlying functional brain connectivity over development and its impact on risk preference. Using functional imaging data in a neutral brain-state we first identify the “brain age” of a given individual then validate it with an independent measure of cortical thickness. We then show, on average, that “brain age” across the group during the teen years has the propensity to look younger in emotional contexts. Further, we show this phenotype (i.e. a younger brain age in emotional contexts relates to a group mean difference in risk perception − a pattern exemplified greatest in young-adults (ages 18–21. The results are suggestive of a specified functional brain phenotype that relates to being at “risk to be risky.”

  18. State dependent properties of epileptic brain networks: comparative graph-theoretical analyses of simultaneously recorded EEG and MEG.

    Science.gov (United States)

    Horstmann, Marie-Therese; Bialonski, Stephan; Noennig, Nina; Mai, Heinke; Prusseit, Jens; Wellmer, Jörg; Hinrichs, Hermann; Lehnertz, Klaus

    2010-02-01

    To investigate whether functional brain networks of epilepsy patients treated with antiepileptic medication differ from networks of healthy controls even during the seizure-free interval. We applied different rules to construct binary and weighted networks from EEG and MEG data recorded under a resting-state eyes-open and eyes-closed condition from 21 epilepsy patients and 23 healthy controls. The average shortest path length and the clustering coefficient served as global statistical network characteristics. Independent on the behavioral condition, epileptic brains exhibited a more regular functional network structure. Similarly, the eyes-closed condition was characterized by a more regular functional network structure in both groups. The amount of network reorganization due to behavioral state changes was similar in both groups. Consistent findings could be achieved for networks derived from EEG but hardly from MEG recordings, and network construction rules had a rather strong impact on our findings. Despite the locality of the investigated processes epileptic brain networks differ in their global characteristics from non-epileptic brain networks. Further methodological developments are necessary to improve the characterization of disturbed and normal functional networks. An increased regularity and a diminished modulation capability appear characteristic of epileptic brain networks. Copyright (c) 2009 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Network Analysis of Functional Brain Connectivity Driven by Gamma-Band Auditory Steady-State Response in Auditory Hallucinations.

    Science.gov (United States)

    Ying, Jun; Zhou, Dan; Lin, Ke; Gao, Xiaorong

    The auditory steady-state response (ASSR) may reflect activity from different regions of the brain. Particularly, it was reported that the gamma-band ASSR plays an important role in working memory, speech understanding, and recognition. Traditionally, the ASSR has been determined by power spectral density analysis, which cannot detect the exact overall distributed properties of the ASSR. Functional network analysis has recently been applied in electroencephalography studies. Previous studies on resting or working state found a small-world organization of the brain network. Some researchers have studied dysfunctional networks caused by diseases. The present study investigates the brain connection networks of schizophrenia patients with auditory hallucinations during an ASSR task. A directed transfer function is utilized to estimate the brain connectivity patterns. Moreover, the structures of brain networks are analyzed by converting the connectivity matrices into graphs. It is found that for normal subjects, network connections are mainly distributed at the central and frontal-temporal regions. This indicates that the central regions act as transmission hubs of information under ASSR stimulation. For patients, network connections seem unordered. The finding that the path length was larger in patients compared to that in normal subjects under most thresholds provides insight into the structures of connectivity patterns. The results suggest that there are more synchronous oscillations that cover a long distance on the cortex but a less efficient network for patients with auditory hallucinations.

  20. Brain modifications after acute alcohol consumption analyzed by resting state fMRI.

    Science.gov (United States)

    Spagnolli, Federica; Cerini, Roberto; Cardobi, Nicolò; Barillari, Marco; Manganotti, Paolo; Storti, Silvia; Mucelli, Roberto Pozzi

    2013-10-01

    Resting-state functional magnetic resonance imaging (fMRI) is a recent breakthrough in neuroimaging research able to describe "in vivo" the spontaneous baseline neuronal activity characterized by blood oxygen level dependent (BOLD) signal fluctuations at slow frequency (0.01-0.1Hz) that, in the absence of any task, forms spatially distributed functional connectivity networks, called resting state networks (RSNs). The aim of this study was to investigate, in the young and healthy population, the changing of the RSNs after acute ingestion of an alcohol dose able to determine a blood concentration (0.5g/L) that barely exceeds the legal limits for driving in the majority of European Countries. Fifteen healthy volunteers underwent two fMRI sessions using a 1.5T MR scanner before and after alcohol oral consumption. The main sequence acquired was EPI 2D BOLD, one per each session. To prevent the excessive alcohol consumption the subjects underwent the estimation of blood rate by breath test and after the stabilization of blood alcohol level (BAL) at 0.5g/L the subjects underwent the second fMRI session. Functional data elaboration was carried out using the probabilistic independent component analysis (PICA). Spatial maps so obtained were further organized, with MELODIC multisession temporal concatenation FSL option, in a cluster representing the group of pre-alcohol sessions and the group of post-alcohol sessions, followed by the dual regression approach in order to evaluate the increase or decrease in terms of connectivity in the RSNs between the two sessions at group level. The results we obtained reveal that acute consumption of alcohol reduces in a significant way the BOLD signal fluctuations in the resting brain selectively in the sub-callosal cortex (SCC), in left temporal fusiform cortex (TFC) and left inferior temporal gyrus (ITG), which are cognitive regions known to be part of the reward brain network and the ventral visual system. Copyright © 2013 Elsevier Inc

  1. Probing of brain states in real-time: Introducing the ConSole environment

    Directory of Open Access Journals (Sweden)

    Thomas eHartmann

    2011-03-01

    Full Text Available Recent years have seen huge advancements in the methods available and used in neuroscience employing EEG or MEG. However, the standard approach is to average a large number of trials for experimentally defined conditions in order to reduce intertrial-variability, i.e. treating it as a source of "noise". Yet it is now more and more accepted that trial-to-trial fluctuations bear functional significance, reflecting fluctuations of "brain states" that predispose perception and action. Such effects are often revealed in a pre-stimulus period, when comparing response variability to an invariant stimulus. However such offline analyses are disadvantageous as they are correlational by drawing conclusions in a posthoc-manner and stimulus presentation is random with respect to the feature of interest. A more direct test is to trigger stimulus presentation when the relevant feature is present. The current paper introduces ConSole (CONstance System for OnLine Eeg, a software package capable of analyzing ongoing EEG / MEG in real-time and presenting auditory and visual stimuli via internal routines. Stimulation via external devices (e.g. TMS or third-party software (e.g. Psyscope X is possible by sending TTL-triggers. With ConSole it is thus possible to target the stimulation at specific brain-states. In contrast to many available applications, ConSole is open-source. Its modular design enhances the power of the software as it can be easily adapted to new challenges and writing new experiments is an easy task. ConSole is already pre-equipped with modules performing standard signal processing steps. The software is also independent from the EEG / MEG system, as long as a driver can be written (currently 2 EEG systems are supported. Besides a general introduction, we present benchmark data regarding performance and validity of the calculations used, as well as three example applications of ConSole in different settings. ConSole can be downloaded at: http://console-kn.sf.net.

  2. Interictal brain activity differs in migraine with and without aura: resting state fMRI study.

    Science.gov (United States)

    Faragó, Péter; Tuka, Bernadett; Tóth, Eszter; Szabó, Nikoletta; Király, András; Csete, Gergő; Szok, Délia; Tajti, János; Párdutz, Árpád; Vécsei, László; Kincses, Zsigmond Tamás

    2017-12-01

    Migraine is one of the most severe primary headache disorders. The nature of the headache and the associated symptoms during the attack suggest underlying functional alterations in the brain. In this study, we examined amplitude, the resting state fMRI fluctuation in migraineurs with and without aura (MWA, MWoA respectively) and healthy controls. Resting state functional MRI images and T1 high-resolution images were acquired from all participants. For data analysis we compared the groups (MWA-Control, MWA-MWoA, MWoA-Control). The resting state networks were identified by MELODIC. The mean time courses of the networks were identified for each participant for all networks. The time-courses were decomposed into five frequency bands by discrete wavelet decomposition. The amplitude of the frequency-specific activity was compared between groups. Furthermore, the preprocessed resting state images were decomposed by wavelet analysis into five specific frequency bands voxel-wise. The voxel-wise amplitudes were compared between groups by non-parametric permutation test. In the MWA-Control comparison the discrete wavelet decomposition found alterations in the lateral visual network. Higher activity was measured in the MWA group in the highest frequency band (0.16-0.08 Hz). In case of the MWA-MWoA comparison all networks showed higher activity in the 0.08-0.04 Hz frequency range in MWA, and the lateral visual network in in higher frequencies. In MWoA-Control comparison only the default mode network revealed decreased activity in MWoA group in the 0.08-0.04 Hz band. The voxel-wise frequency specific analysis of the amplitudes found higher amplitudes in MWA as compared to MWoA in the in fronto-parietal regions, anterior cingulate cortex and cerebellum. The amplitude of the resting state fMRI activity fluctuation is higher in MWA than in MWoA. These results are in concordance with former studies, which found cortical hyperexcitability in MWA.

  3. Progesterone promotes neuronal differentiation of human umbilical cord mesenchymal stem cells in culture conditions that mimic the brain microenvironment★

    Science.gov (United States)

    Wang, Xianying; Wu, Honghai; Xue, Gai; Hou, Yanning

    2012-01-01

    In this study, human umbilical cord mesenchymal stem cells from full-term neonates born by vaginal delivery were cultured in medium containing 150 mg/mL of brain tissue extracts from Sprague-Dawley rats (to mimic the brain microenvironment). Immunocytochemical analysis demonstrated that the cells differentiated into neuron-like cells. To evaluate the effects of progesterone as a neurosteroid on the neuronal differentiation of human umbilical cord mesenchymal stem cells, we cultured the cells in medium containing progesterone (0.1, 1, 10 μM) in addition to brain tissue extracts. Reverse transcription-PCR and flow cytometric analysis of neuron specific enolase-positive cells revealed that the percentages of these cells increased significantly following progesterone treatment, with the optimal progesterone concentration for neuron-like differentiation being 1 μM. These results suggest that progesterone can enhance the neuronal differentiation of human umbilical cord mesenchymal stem cells in culture medium containing brain tissue extracts to mimic the brain microenvironment. PMID:25624820

  4. Assessing Opportunities to Enhance Comprehensive Health Promotion and Wellness Programming in a State Community College System.

    Science.gov (United States)

    Linnan, Laura A; Arandia, Gabriela; Naseer, Carolyn; Li, Jiang; Pomerantz, Meg; Diehl, Sandra J

    2017-01-01

    BACKGROUND North Carolina has the third largest community college system in the nation and reaches residents in all 100 counties. Few studies have focused on the health of employees who work at these institutions. We assessed the current status of and interest in supporting health promotion efforts among North Carolina Community College System members.METHODS North Carolina Community College System presidents completed a brief 15-item survey assessing support for and interest in offering health promotion programs. Wellness coordinators completed a 60-item questionnaire assessing current health promotion programming and organizational, environmental, and policy supports for health promotion efforts. Onsite interviews with a sub-sample of Wellness coordinators offered insights into important implementation considerations. We examined differences by campus size with Fisher's exact test.RESULTS All 58 presidents (100%) and 51 wellness coordinators (88%) completed surveys. Ten percent of colleges offered comprehensive employee health promotion programming. Most offered physical activity (70.6%), tobacco cessation (51.0%), weight loss/management (49.0%), and/or nutrition counseling (47.1%). Larger colleges were more likely to offer programming and environmental support. Nearly all presidents (89.7%) believed it is "very" or "extremely" important to offer health promotion programs to employees, and most (84%) were interested in promoting health through a university partnership.LIMITATIONS Despite very high survey response rates from presidents and wellness coordinators at each community college, onsite interviews were only done at select campuses, limiting the generalizability and scope of conclusions derived from interview data.CONCLUSION Community colleges in North Carolina are promising settings for promoting employee health. Findings identify resources, barriers, and technical assistance that could facilitate greater adoption and implementation of programs. ©2017 by

  5. Modulation of large-scale brain networks by transcranial direct current stimulation evidenced by resting-state functional MRI

    Science.gov (United States)

    Peña-Gómez, Cleofé; Sala-Lonch, Roser; Junqué, Carme; Clemente, Immaculada C.; Vidal, Dídac; Bargalló, Núria; Falcón, Carles; Valls-Solé, Josep; Pascual-Leone, Álvaro; Bartrés-Faz, David

    2013-01-01

    Background Brain areas interact mutually to perform particular complex brain functions such as memory or language. Furthermore, under resting-state conditions several spatial patterns have been identified that resemble functional systems involved in cognitive functions. Among these, the default-mode network (DMN), which is consistently deactivated during task periods and is related to a variety of cognitive functions, has attracted most attention. In addition, in resting-state conditions some brain areas engaged in focused attention (such as the anticorrelated network, AN) show a strong negative correlation with DMN; as task demand increases, AN activity rises, and DMN activity falls. Objective We combined transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) to investigate these brain network dynamics. Methods Ten healthy young volunteers underwent four blocks of resting-state fMRI (10-minutes), each of them immediately after 20 minutes of sham or active tDCS (2 mA), on two different days. On the first day the anodal electrode was placed over the left dorsolateral prefrontal cortex (DLPFC) (part of the AN) with the cathode over the contralateral supraorbital area, and on the second day, the electrode arrangement was reversed (anode right-DLPFC, cathode left-supraorbital). Results After active stimulation, functional network connectivity revealed increased synchrony within the AN components and reduced synchrony in the DMN components. Conclusions Our study reveals a reconfiguration of intrinsic brain activity networks after active tDCS. These effects may help to explain earlier reports of improvements in cognitive functions after anodal-tDCS, where increasing cortical excitability may have facilitated reconfiguration of functional brain networks to address upcoming cognitive demands. PMID:21962981

  6. Processing demands upon cognitive, linguistic, and articulatory functions promote grey matter plasticity in the adult multilingual brain: Insights from simultaneous interpreters.

    Science.gov (United States)

    Elmer, Stefan; Hänggi, Jürgen; Jäncke, Lutz

    2014-05-01

    Until now, considerable effort has been made to determine structural brain characteristics related to exceptional multilingual skills. However, at least one important question has not yet been satisfactorily addressed in the previous literature, namely whether and to which extent the processing demands upon cognitive, linguistic, and articulatory functions may promote grey matter plasticity in the adult multilingual brain. Based on the premise that simultaneous interpretation is a highly demanding linguistic task that places strong demands on executive and articulatory functions, here we compared grey matter volumes between professional simultaneous interpreters (SI) and multilingual control subjects. Thereby, we focused on a specific set of a-priori defined bilateral brain regions that have previously been shown to support neurocognitional aspects of language control and linguistic functions in the multilingual brain. These regions are the cingulate gyrus, caudate nucleus, frontal operculum (pars triangularis and opercularis), inferior parietal lobe (IPL) (supramarginal and angular gyrus), and the insula. As a main result, we found reduced grey matter volumes in professional SI, compared to multilingual controls, in the left middle-anterior cingulate gyrus, bilateral pars triangularis, left pars opercularis, bilateral middle part of the insula, and in the left supramarginal gyrus (SMG). Interestingly, grey matter volume in left pars triangularis, right pars opercularis, middle-anterior cingulate gyrus, and in the bilateral caudate nucleus was negatively correlated with the cumulative number of interpreting hours. Hence, we provide first evidence for an expertise-related grey matter architecture that may reflect a composite of brain characteristics that were still present before interpreting training and training-related changes. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. A Mechanism to Enhance Cellular Responsivity to Hormone Action: Krüppel-Like Factor 9 Promotes Thyroid Hormone Receptor-β Autoinduction During Postembryonic Brain Development.

    Science.gov (United States)

    Hu, Fang; Knoedler, Joseph R; Denver, Robert J

    2016-04-01

    Thyroid hormone (TH) receptor (TR)-β (trb) is induced by TH (autoinduced) in Xenopus tadpoles during metamorphosis. We previously showed that Krüppel-like factor 9 (Klf9) is rapidly induced by TH in the tadpole brain, associates in chromatin with the trb upstream region in a developmental stage and TH-dependent manner, and forced expression of Klf9 in the Xenopus laevis cell line XTC-2 accelerates and enhances trb autoinduction. Here we investigated whether Klf9 can promote trb autoinduction in tadpole brain in vivo. Using electroporation-mediated gene transfer, we transfected plasmids into premetamorphic tadpole brain to express wild-type or mutant forms of Klf9. Forced expression of Klf9 increased baseline trb mRNA levels in thyroid-intact but not in goitrogen-treated tadpoles, supporting that Klf9 enhances liganded TR action. As in XTC-2 cells, forced expression of Klf9 enhanced trb autoinduction in tadpole brain in vivo and also increased TH-dependent induction of the TR target genes klf9 and thbzip. Consistent with our previous mutagenesis experiments conducted in XTC-2 cells, the actions of Klf9 in vivo required an intact N-terminal region but not a functional DNA binding domain. Forced expression of TRβ in tadpole brain by electroporation-mediated gene transfer increased baseline and TH-induced TR target gene transcription, supporting a role for trb autoinduction during metamorphosis. Our findings support that Klf9 acts as an accessory transcription factor for TR at the trb locus during tadpole metamorphosis, enhancing trb autoinduction and transcription of other TR target genes, which increases cellular responsivity to further TH action on developmental gene regulation programs.

  8. Alcohol-induced one-carbon metabolism impairment promotes dysfunction of DNA base excision repair in adult brain.

    Science.gov (United States)

    Fowler, Anna-Kate; Hewetson, Aveline; Agrawal, Rajiv G; Dagda, Marisela; Dagda, Raul; Moaddel, Ruin; Balbo, Silvia; Sanghvi, Mitesh; Chen, Yukun; Hogue, Ryan J; Bergeson, Susan E; Henderson, George I; Kruman, Inna I

    2012-12-21

    The brain is one of the major targets of chronic alcohol abuse. Yet the fundamental mechanisms underlying alcohol-mediated brain damage remain unclear. The products of alcohol metabolism cause DNA damage, which in conditions of DNA repair dysfunction leads to genomic instability and neural death. We propose that one-carbon metabolism (OCM) impairment associated with long term chronic ethanol intake is a key factor in ethanol-induced neurotoxicity, because OCM provides cells with DNA precursors for DNA repair and methyl groups for DNA methylation, both critical for genomic stability. Using histological (immunohistochemistry and stereological counting) and biochemical assays, we show that 3-week chronic exposure of adult mice to 5% ethanol (Lieber-Decarli diet) results in increased DNA damage, reduced DNA repair, and neuronal death in the brain. These were concomitant with compromised OCM, as evidenced by elevated homocysteine, a marker of OCM dysfunction. We conclude that OCM dysfunction plays a causal role in alcohol-induced genomic instability in the brain because OCM status determines the alcohol effect on DNA damage/repair and genomic stability. Short ethanol exposure, which did not disturb OCM, also did not affect the response to DNA damage, whereas additional OCM disturbance induced by deficiency in a key OCM enzyme, methylenetetrahydrofolate reductase (MTHFR) in Mthfr(+/-) mice, exaggerated the ethanol effect on DNA repair. Thus, the impact of long term ethanol exposure on DNA repair and genomic stability in the brain results from OCM dysfunction, and MTHFR mutations such as Mthfr 677C→T, common in human population, may exaggerate the adverse effects of ethanol on the brain.

  9. Implications of the Dependence of Neuronal Activity on Neural Network States for the Design of Brain-Machine Interfaces.

    Science.gov (United States)

    Panzeri, Stefano; Safaai, Houman; De Feo, Vito; Vato, Alessandro

    2016-01-01

    Brain-machine interfaces (BMIs) can improve the quality of life of patients with sensory and motor disabilities by both decoding motor intentions expressed by neural activity, and by encoding artificially sensed information into patterns of neural activity elicited by causal interventions on the neural tissue. Yet, current BMIs can exchange relatively small amounts of information with the brain. This problem has proved difficult to overcome by simply increasing the number of recording or stimulating electrodes, because trial-to-trial variability of neural activity partly arises from intrinsic factors (collectively known as the network state) that include ongoing spontaneous activity and neuromodulation, and so is shared among neurons. Here we review recent progress in characterizing the state dependence of neural responses, and in particular of how neural responses depend on endogenous slow fluctuations of network excitability. We then elaborate on how this knowledge may be used to increase the amount of information that BMIs exchange with brain. Knowledge of network state can be used to fine-tune the stimulation pattern that should reliably elicit a target neural response used to encode information in the brain, and to discount part of the trial-by-trial variability of neural responses, so that they can be decoded more accurately.

  10. Implications of the dependence of neuronal activity on neural network states for the design of brain-machine interfaces

    Directory of Open Access Journals (Sweden)

    Stefano ePanzeri

    2016-04-01

    Full Text Available Brain-machine interfaces (BMIs can improve the quality of life of patients with sensory and motor disabilities by both decoding motor intentions expressed by neural activity, and by encoding artificially sensed information into patterns of neural activity elicited by causal interventions on the neural tissue. Yet, current BMIs can exchange relatively small amounts of information with the brain. This problem has proved difficult to overcome by simply increasing the number of recording or stimulating electrodes, because trial-to-trial variability of neural activity partly arises from intrinsic factors (collectively known as the network state that include ongoing spontaneous activity and neuromodulation, and so is shared among neurons. Here we review recent progress in characterizing the state dependence of neural responses, and in particular of how neural responses depend on endogenous slow fluctuations of network excitability. We then elaborate on how this knowledge may be used to increase the amount of information that BMIs exchange with brains. Knowledge of network state can be used to fine-tune the stimulation pattern that should reliably elicit a target neural response used to encode information in the brain, and to discount part of the trial-by-trial variability of neural responses, so that they can be decoded more accurately.

  11. Cell type-specific regulation of brain-derived neurotrophic factor in states of allergic inflammation.

    Science.gov (United States)

    Groneberg, D A; Fischer, T C; Peckenschneider, N; Noga, O; Dinh, Q T; Welte, T; Welker, P

    2007-09-01

    Brain-derived neurotrophic factor (BDNF) is a molecule influencing neuronal proliferation and differentiation. In states of allergy, it may orchestrate inflammatory changes by linking the immune system with the nervous system. Because the precise regulation of gene transcription in mast cells MCs is not clear, the present studies assessed the gene regulation of BDNF in this inflammatory cell type. Transcriptional expression of BDNF in human skin was studied in isolated cells using RT-PCR. In situ lesional MC BDNF protein expression was analysed by immunohistochemistry and related to the differential staining of MCs and functional effects of BDNF on HaCaT keratinocytes. BDNF mRNA expression was found in isolated human skin MCs, keratinocytes, and fibroblasts. Also, low levels were found in endothelial cells and melanocytes. BDNF protein expression was found in situ in lesional and non-lesional MCs. A significantly decreased expression of BDNF protein was found in atopic dermatitis lesional MCs when compared with control MC expression. Functional in vitro experiments demonstrated that a decrease in BDNF stimulation led to increased secretion rates for stem cell factor and IL-8 in HaCaT keratinocytes. The demonstration of a decreased level of BDNF gene transcription in lesional MCs points to a differential regulation of MC-released neutrotrophins in cutaneous allergic inflammation. Topically administered neurotrophin receptor-modulating compounds should be receptor target specific and not universally acting in diseases such as atopic dermatitis or allergic asthma.

  12. Abnormal baseline brain activity in bipolar depression: a resting state functional magnetic resonance imaging study.

    Science.gov (United States)

    Liu, Chun-Hong; Li, Feng; Li, Su-Fang; Wang, Yong-Jun; Tie, Chang-Le; Wu, Hai-Yan; Zhou, Zhen; Zhang, Dan; Dong, Jie; Yang, Zhi; Wang, Chuan-Yue

    2012-01-01

    We examined resting state brain activity in the depressive phase of bipolar disorder (BD) by measuring the amplitude of low-frequency fluctuations (ALFF) in the functional magnetic resonance imaging (fMRI) signal. Unlike functional connectivity, the ALFF approach reflects local properties in specific regions and provides direct information about impaired foci. Groups of 26 patients with BD depression and 26 gender-, age-, and education-matched healthy subjects participated in fMRI scans. We examined group differences in ALFF findings as well as correlations between clinical measurements and ALFF in the regions showing significant group differences. Our results showed that patients with BD depression had significantly increased ALFF in the left insula, the right caudate nucleus, the temporal gyrus, the bilateral inferior frontal gyrus, and the posterior lobe of the cerebellum. They also had decreased ALFF in the left postcentral gyrus, the left parahippocampal gyrus, and the cerebellum. Moderate negative correlations were found between the Hamilton Depression Rating Scale score and ALFF in the left insular cortex in the patient group. These results support a model of BD that involves dysfunction in the prefrontal-limbic networks and associated striatal systems. We also demonstrated the feasibility of ALFF as a technique to investigate persistent cerebral dysfunction in BD. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  13. Advancing brain-machine interfaces: Moving beyond linear state space models

    Directory of Open Access Journals (Sweden)

    Adam G Rouse

    2015-07-01

    Full Text Available Advances in recent years have dramatically improved output control by Brain-Machine Interfaces (BMIs. Such devices nevertheless remain robotic and limited in their movements compared to normal human motor performance. Most current BMIs rely on transforming recorded neural activity to a linear state space composed of a set number of fixed degrees of freedom. Here we consider a variety of ways in which BMI design might be advanced further by applying non-linear dynamics observed in normal motor behavior. We consider i the dynamic range and precision of natural movements, ii differences between cortical activity and actual body movement, iii kinematic and muscular synergies, and iv the implications of large neuronal populations. We advance the hypothesis that a given population of recorded neurons may transmit more useful information than can be captured by a single, linear model across all movement phases and contexts. We argue that incorporating these various non-linear characteristics will be an important next step in advancing BMIs to more closely match natural motor performance.

  14. The clinical use of drugs influencing neurotransmitters in the brain to promote motor recovery after stroke; A Cochrane systematic review.

    NARCIS (Netherlands)

    Berends, H.I.; Nijlant, J.M.M.; Movig, Kris L.L.; van Putten, Michel Johannes Antonius Maria; Jannink, M.J.A.; IJzerman, Maarten Joost

    2009-01-01

    The objective of this review was to compare and to discuss the results of studies that investigated the ability of drugs to improve motor recovery after stroke by influencing dopamine, norepinephrine, or serotonin concentrations in the brain. A systematic literature search up to January 2009 was

  15. Beyond neural cubism: promoting a multidimensional view of brain disorders by enhancing the integration of neurology and psychiatry in education.

    Science.gov (United States)

    Taylor, Joseph J; Williams, Nolan R; George, Mark S

    2015-05-01

    Cubism was an influential early-20th-century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stemmed from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood, or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders.

  16. Beyond Neural Cubism: Promoting a Multidimensional View of Brain Disorders by Enhancing the Integration of Neurology and Psychiatry in Education

    Science.gov (United States)

    Taylor, Joseph J.; Williams, Nolan R.; George, Mark S.

    2014-01-01

    Cubism was an influential early 20th century art movement characterized by angular, disjointed imagery. The two-dimensional appearance of Cubist figures and objects is created through juxtaposition of angles. The authors posit that the constrained perspectives found in Cubism may also be found in the clinical classification of brain disorders. Neurological disorders are often separated from psychiatric disorders as if they stem from different organ systems. Maintaining two isolated clinical disciplines fractionalizes the brain in the same way that Pablo Picasso fractionalized figures and objects in his Cubist art. This Neural Cubism perpetuates a clinical divide that does not reflect the scope and depth of neuroscience. All brain disorders are complex and multidimensional, with aberrant circuitry and resultant psychopharmacology manifesting as altered behavior, affect, mood or cognition. Trainees should receive a multidimensional education based on modern neuroscience, not a partial education based on clinical precedent. The authors briefly outline the rationale for increasing the integration of neurology and psychiatry and discuss a nested model with which clinical neuroscientists (neurologists and psychiatrists) can approach and treat brain disorders. PMID:25340364

  17. Adult sports-related traumatic brain injury in United States trauma centers.

    Science.gov (United States)

    Winkler, Ethan A; Yue, John K; Burke, John F; Chan, Andrew K; Dhall, Sanjay S; Berger, Mitchel S; Manley, Geoffrey T; Tarapore, Phiroz E

    2016-04-01

    OBJECTIVE Sports-related traumatic brain injury (TBI) is an important public health concern estimated to affect 300,000 to 3.8 million people annually in the United States. Although injuries to professional athletes dominate the media, this group represents only a small proportion of the overall population. Here, the authors characterize the demographics of sports-related TBI in adults from a community-based trauma population and identify predictors of prolonged hospitalization and increased morbidity and mortality rates. METHODS Utilizing the National Sample Program of the National Trauma Data Bank (NTDB), the authors retrospectively analyzed sports-related TBI data from adults (age ≥ 18 years) across 5 sporting categories-fall or interpersonal contact (FIC), roller sports, skiing/snowboarding, equestrian sports, and aquatic sports. Multivariable regression analysis was used to identify predictors of prolonged hospital length of stay (LOS), medical complications, inpatient mortality rates, and hospital discharge disposition. Statistical significance was assessed at α sports-related TBIs were documented in the NTDB, which represented 18,310 incidents nationally. Equestrian sports were the greatest contributors to sports-related TBI (45.2%). Mild TBI represented nearly 86% of injuries overall. Mean (± SEM) LOSs in the hospital or intensive care unit (ICU) were 4.25 ± 0.09 days and 1.60 ± 0.06 days, respectively. The mortality rate was 3.0% across all patients, but was statistically higher in TBI from roller sports (4.1%) and aquatic sports (7.7%). Age, hypotension on admission to the emergency department (ED), and the severity of head and extracranial injuries were statistically significant predictors of prolonged hospital and ICU LOSs, medical complications, failure to discharge to home, and death. Traumatic brain injury during aquatic sports was similarly associated with prolonged ICU and hospital LOSs, medical complications, and failure to be discharged to

  18. DNA Topoisomerases Maintain Promoters in a State Competent for Transcriptional Activation in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Pedersen, Jakob Madsen; Fredsøe, Jacob Christian; Rødgaard, Morten Terpager

    2012-01-01

    To investigate the role of DNA topoisomerases in transcription, we have studied global gene expression in Saccharomyces cerevisiae cells deficient for topoisomerases I and II and performed single-gene analyses to support our findings. The genome-wide studies show a general transcriptional down......-depth analysis of the inducible PHO5 gene reveals that topoisomerases are essential for binding of the Pho4p transcription factor to the PHO5 promoter, which is required for promoter nucleosome removal during activation. In contrast, topoisomerases are dispensable for constitutive transcription initiation...

  19. CHANGES IN REGIONAL BRAIN ACTIVATION RELATED TO DEPRESSIVE STATE : A 2-YEAR LONGITUDINAL FUNCTIONAL MRI STUDY

    NARCIS (Netherlands)

    Opmeer, Esther M.; Kortekaas, Rudie; van Tol, Marie-Jose; Renken, Remco J.; Demenescu, Liliana R.; Woudstra, Saskia; Horst, ter Gert J.; van Buchem, Mark A.; van der Wee, Nic J. A.; Veltman, Dick J.; Aleman, Andre

    BackgroundAbnormal brain activations during processing of emotional facial expressions in depressed patients have been demonstrated. We investigated the natural course of brain activation in response to emotional faces in depression, indexed by functional magnetic resonance imaging (fMRI) scans

  20. Steady-state properties of sodium channels from healthy and tumorous human brain

    NARCIS (Netherlands)

    Frenkel, C.; Wartenberg, H. C.; Duch, D. S.; Urban, B. W.

    1998-01-01

    This extensive bilayer study of unpurified human brain channels from non-diseased and tumorous human brain involves more than 300 lipid bilayer experiments. Single channel conductances and subconductances, single channel fractional open times, the voltage-dependence of tetrodotoxin (TTX) block and

  1. Aberrant spontaneous brain activity in chronic tinnitus patients revealed by resting-state functional MRI

    Directory of Open Access Journals (Sweden)

    Yu-Chen Chen

    2014-01-01

    Conclusions: The present study confirms that chronic tinnitus patients have aberrant ALFF in many brain regions, which is associated with specific clinical tinnitus characteristics. ALFF disturbance in specific brain regions might be used to identify the neuro-pathophysiological mechanisms in chronic tinnitus patients.

  2. Brain-computer interfaces using capacitive measurement of visual or auditory steady-state responses.

    Science.gov (United States)

    Baek, Hyun Jae; Kim, Hyun Seok; Heo, Jeong; Lim, Yong Gyu; Park, Kwang Suk

    2013-04-01

    Brain-computer interface (BCI) technologies have been intensely studied to provide alternative communication tools entirely independent of neuromuscular activities. Current BCI technologies use electroencephalogram (EEG) acquisition methods that require unpleasant gel injections, impractical preparations and clean-up procedures. The next generation of BCI technologies requires practical, user-friendly, nonintrusive EEG platforms in order to facilitate the application of laboratory work in real-world settings. A capacitive electrode that does not require an electrolytic gel or direct electrode-scalp contact is a potential alternative to the conventional wet electrode in future BCI systems. We have proposed a new capacitive EEG electrode that contains a conductive polymer-sensing surface, which enhances electrode performance. This paper presents results from five subjects who exhibited visual or auditory steady-state responses according to BCI using these new capacitive electrodes. The steady-state visual evoked potential (SSVEP) spelling system and the auditory steady-state response (ASSR) binary decision system were employed. Offline tests demonstrated BCI performance high enough to be used in a BCI system (accuracy: 95.2%, ITR: 19.91 bpm for SSVEP BCI (6 s), accuracy: 82.6%, ITR: 1.48 bpm for ASSR BCI (14 s)) with the analysis time being slightly longer than that when wet electrodes were employed with the same BCI system (accuracy: 91.2%, ITR: 25.79 bpm for SSVEP BCI (4 s), accuracy: 81.3%, ITR: 1.57 bpm for ASSR BCI (12 s)). Subjects performed online BCI under the SSVEP paradigm in copy spelling mode and under the ASSR paradigm in selective attention mode with a mean information transfer rate (ITR) of 17.78 ± 2.08 and 0.7 ± 0.24 bpm, respectively. The results of these experiments demonstrate the feasibility of using our capacitive EEG electrode in BCI systems. This capacitive electrode may become a flexible and non-intrusive tool fit for various applications in

  3. Abnormal Spontaneous Brain Activity in Patients With Anisometropic Amblyopia Using Resting-State Functional Magnetic Resonance Imaging.

    Science.gov (United States)

    Tang, Angcang; Chen, Taolin; Zhang, Junran; Gong, Qiyong; Liu, Longqian

    2017-09-01

    To explore the abnormality of spontaneous activity in patients with anisometropic amblyopia under resting-state functional magnetic resonance imaging (Rs-fMRI). Twenty-four participants were split into two groups. The anisometropic amblyopia group had 10 patients, all of whom had anisometropic amblyopia of the right eye, and the control group had 14 healthy subjects. All participants underwent Rs-fMRI scanning. Measurement of amplitude of low frequency fluctuations of the brain, which is a measure of the amplitudes of spontaneous brain activity, was used to investigate brain changes between the anisometropic amblyopia and control groups. Compared with an age- and gender-matched control group, the anisometropic amblyopia group showed increased amplitude of low frequency fluctuations of spontaneous brain activity in the left superior temporal gyrus, the left inferior parietal lobe, the left pons, and the right inferior semi-lunar lobe. The anisometropic amblyopia group also showed decreased amplitude of low frequency fluctuations in the bilateral medial frontal gyrus. This study demonstrated abnormal spontaneous brain activities in patients with anisometropic amblyopia under Rs-fMRI, and these abnormalities might contribute to the neuropathological mechanisms of anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus. 2017;54(5):303-310.]. Copyright 2017, SLACK Incorporated.

  4. Structural and Functional Brain Remodeling during Pregnancy with Diffusion Tensor MRI and Resting-State Functional MRI

    Science.gov (United States)

    Chan, Russell W.; Ho, Leon C.; Zhou, Iris Y.; Gao, Patrick P.; Chan, Kevin C.; Wu, Ed X.

    2015-01-01

    Although pregnancy-induced hormonal changes have been shown to alter the brain at the neuronal level, the exact effects of pregnancy on brain at the tissue level remain unclear. In this study, diffusion tensor imaging (DTI) and resting-state functional MRI (rsfMRI) were employed to investigate and document the effects of pregnancy on the structure and function of the brain tissues. Fifteen Sprague-Dawley female rats were longitudinally studied at three days before mating (baseline) and seventeen days after mating (G17). G17 is equivalent to the early stage of the third trimester in humans. Seven age-matched nulliparous female rats served as non-pregnant controls and were scanned at the same time-points. For DTI, diffusivity was found to generally increase in the whole brain during pregnancy, indicating structural changes at microscopic levels that facilitated water molecular movement. Regionally, mean diffusivity increased more pronouncedly in the dorsal hippocampus while fractional anisotropy in the dorsal dentate gyrus increased significantly during pregnancy. For rsfMRI, bilateral functional connectivity in the hippocampus increased significantly during pregnancy. Moreover, fractional anisotropy increase in the dentate gyrus appeared to correlate with the bilateral functional connectivity increase in the hippocampus. These findings revealed tissue structural modifications in the whole brain during pregnancy, and that the hippocampus was structurally and functionally remodeled in a more marked manner. PMID:26658306

  5. Structural and Functional Brain Remodeling during Pregnancy with Diffusion Tensor MRI and Resting-State Functional MRI.

    Directory of Open Access Journals (Sweden)

    Russell W Chan

    Full Text Available Although pregnancy-induced hormonal changes have been shown to alter the brain at the neuronal level, the exact effects of pregnancy on brain at the tissue level remain unclear. In this study, diffusion tensor imaging (DTI and resting-state functional MRI (rsfMRI were employed to investigate and document the effects of pregnancy on the structure and function of the brain tissues. Fifteen Sprague-Dawley female rats were longitudinally studied at three days before mating (baseline and seventeen days after mating (G17. G17 is equivalent to the early stage of the third trimester in humans. Seven age-matched nulliparous female rats served as non-pregnant controls and were scanned at the same time-points. For DTI, diffusivity was found to generally increase in the whole brain during pregnancy, indicating structural changes at microscopic levels that facilitated water molecular movement. Regionally, mean diffusivity increased more pronouncedly in the dorsal hippocampus while fractional anisotropy in the dorsal dentate gyrus increased significantly during pregnancy. For rsfMRI, bilateral functional connectivity in the hippocampus increased significantly during pregnancy. Moreover, fractional anisotropy increase in the dentate gyrus appeared to correlate with the bilateral functional connectivity increase in the hippocampus. These findings revealed tissue structural modifications in the whole brain during pregnancy, and that the hippocampus was structurally and functionally remodeled in a more marked manner.

  6. Adolescent Brain Development and Underage Drinking in the United States: Identifying Risks of Alcohol Use in College Populations

    Science.gov (United States)

    Silveri, Marisa M.

    2015-01-01

    Alcohol use typically is initiated during adolescence, an age period that overlaps with critical structural and functional maturation of the brain. Brain maturation and associated improvements in decision-making continue into the second decade of life, reaching plateaus within the period referred to as “emerging adulthood” (18–24 years). Emerging adulthood is the typical age span of the traditionally aged college student, which includes the age (21 years) when alcohol consumption becomes legal in the United States. This review highlights neurobiological evidence indicating the vulnerabilities of the emerging adult brain to alcohol effects. This review also identifies that reduced sensitivity to alcohol sedation and increased sensitivity to alcohol-related disruptions in memory, positive family history of alcoholism effects on brain structure and function, and emerging co-morbid psychiatric conditions serve as unique vulnerabilities that increase the risks associated with underage alcohol use. These vulnerabilities likely contribute to excessive and unsupervised drinking in college students. Discouraging alcohol consumption until neurobiological adulthood is reached is important for minimizing alcohol-related disruptions in brain development and decision-making capacity, and reducing the negative behavioral consequences associated with underage alcohol use. PMID:22894728

  7. Adolescent brain development and underage drinking in the United States: identifying risks of alcohol use in college populations.

    Science.gov (United States)

    Silveri, Marisa M

    2012-01-01

    Alcohol use typically is initiated during adolescence, a period that coincides with critical structural and functional maturation of the brain. Brain maturation and associated improvements in decision making continue into the third decade of life, reaching a plateau within the period referred to as emerging adulthood (18-24 years). This particular period covers that of traditionally aged college students, and includes the age (21 years) when alcohol consumption becomes legal in the United States. This review highlights neurobiological evidence indicating the vulnerabilities of the emerging-adult brain to the effects of alcohol. Factors increasing the risks associated with underage alcohol use include the age group's reduced sensitivity to alcohol sedation and increased sensitivity to alcohol-related disruptions in memory. On the individual level, factors increasing those risks are a positive family history of alcoholism, which has a demonstrated effect on brain structure and function, and emerging comorbid psychiatric conditions. These vulnerabilities-of the age group, in general, as well as of particular individuals-likely contribute to excessive and unsupervised drinking in college students. Discouraging alcohol consumption until neurobiological adulthood is reached is important for minimizing alcohol-related disruptions in brain development and decision-making capacity, and for reducing the negative behavioral consequences associated with underage alcohol use.

  8. Opposite brain emotion-regulation patterns in identity states of dissociative identity disorder: a PET study and neurobiological model.

    Science.gov (United States)

    Reinders, Antje A T S; Willemsen, Antoon T M; den Boer, Johan A; Vos, Herry P J; Veltman, Dick J; Loewenstein, Richard J

    2014-09-30

    Imaging studies in posttraumatic stress disorder (PTSD) have shown differing neural network patterns between hypo-aroused/dissociative and hyper-aroused subtypes. Since dissociative identity disorder (DID) involves different emotional states, this study tests whether DID fits aspects of the differing brain-activation patterns in PTSD. While brain activation was monitored using positron emission tomography, DID individuals (n=11) and matched DID-simulating healthy controls (n=16) underwent an autobiographic script-driven imagery paradigm in a hypo-aroused and a hyper-aroused identity state. Results were consistent with those previously found in the two PTSD subtypes for the rostral/dorsal anterior cingulate, the prefrontal cortex, and the amygdala and insula, respectively. Furthermore, the dissociative identity state uniquely activated the posterior association areas and the parahippocampal gyri, whereas the hyper-aroused identity state uniquely activated the caudate nucleus. Therefore, we proposed an extended PTSD-based neurobiological model for emotion modulation in DID: the hypo-aroused identity state activates the prefrontal cortex, cingulate, posterior association areas and parahippocampal gyri, thereby overmodulating emotion regulation; the hyper-aroused identity state activates the amygdala and insula as well as the dorsal striatum, thereby undermodulating emotion regulation. This confirms the notion that DID is related to PTSD as hypo-aroused and hyper-arousal states in DID and PTSD are similar. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  9. An emergency call system for patients in locked-in state using an SSVEP-based brain switch.

    Science.gov (United States)

    Lim, Jeong-Hwan; Kim, Yong-Wook; Lee, Jun-Hak; An, Kwang-Ok; Hwang, Han-Jeong; Cha, Ho-Seung; Han, Chang-Hee; Im, Chang-Hwan

    2017-11-01

    Patients in a locked-in state (LIS) due to severe neurological disorders such as amyotrophic lateral sclerosis (ALS) require seamless emergency care by their caregivers or guardians. However, it is a difficult job for the guardians to continuously monitor the patients' state, especially when direct communication is not possible. In the present study, we developed an emergency call system for such patients using a steady-state visual evoked potential (SSVEP)-based brain switch. Although there have been previous studies to implement SSVEP-based brain switch system, they have not been applied to patients in LIS, and thus their clinical value has not been validated. In this study, we verified whether the SSVEP-based brain switch system can be practically used as an emergency call system for patients in LIS. The brain switch used for our system adopted a chromatic visual stimulus, which proved to be visually less stimulating than conventional checkerboard-type stimuli but could generate SSVEP responses strong enough to be used for brain-computer interface (BCI) applications. To verify the feasibility of our emergency call system, 14 healthy participants and 3 patients with severe ALS took part in online experiments. All three ALS patients successfully called their guardians to their bedsides in about 6.56 seconds. Furthermore, additional experiments with one of these patients demonstrated that our emergency call system maintains fairly good performance even up to 4 weeks after the first experiment without renewing initial calibration data. Our results suggest that our SSVEP-based emergency call system might be successfully used in practical scenarios. © 2017 Society for Psychophysiological Research.

  10. State-of-the-art for food taxes to promote public health.

    Science.gov (United States)

    Jensen, J D; Smed, S

    2017-11-23

    The use of taxes to promote healthy nutritional behaviour has gained ground in the past decade. The present paper reviews existing applications of fiscal instruments in nutrition policy and derives some perspectives and recommendations from the experiences gained with these instruments. Many countries in different parts of the world have experiences with the taxation of sugar-sweetened beverages, in some cases in combination with taxes on unhealthy food commodities such as confectionery or high-fat foods. These tax schemes have many similarities, but also differ in their definitions of tax objects and in the applied tax rates. Denmark has been the only country in the world to operate a tax on saturated fat content in foods, from 2011 to 2012. Most of the existing food tax schemes have been introduced from fiscal motivations, with health promotion as a secondary objective, but a few have been introduced with health promotion as the primary objective. The diversity in experiences from existing tax schemes can provide valuable insights for future use of fiscal instruments to promote healthy nutrition, in terms of designing effective and efficient tax or subsidy instruments, and in terms of smooth and politically viable implementation of the instruments.

  11. Resting state cortical oscillations of patients with Parkinson disease and with and without subthalamic deep brain stimulation: a magnetoencephalography study.

    Science.gov (United States)

    Cao, Chunyan; Li, Dianyou; Jiang, Tianxiao; Ince, Nuri Firat; Zhan, Shikun; Zhang, Jing; Sha, Zhiyi; Sun, Bomin

    2015-04-01

    In this study, we investigate the modification to cortical oscillations of patients with Parkinson disease (PD) by subthalamic deep brain stimulation (STN-DBS). Spontaneous cortical oscillations of patients with PD were recorded with magnetoencephalography during on and off subthalamic nucleus deep brain stimulation states. Several features such as average frequency, average power, and relative subband power in regions of interest were extracted in the frequency domain, and these features were correlated with Unified Parkinson Disease Rating Scale III evaluation. The same features were also investigated in patients with PD without surgery and healthy controls. Patients with Parkinson disease without surgery compared with healthy controls had a significantly lower average frequency and an increased average power in 1 to 48 Hz range in whole cortex. Higher relative power in theta and simultaneous decrease in beta and gamma over temporal and occipital were also observed in patients with PD. The Unified Parkinson Disease Rating Scale III rigidity score correlated with the average frequency and with the relative power of beta and gamma in frontal areas. During subthalamic nucleus deep brain stimulation, the average frequency increased significantly when stimulation was on compared with off state. In addition, the relative power dropped in delta, whereas it rose in beta over the whole cortex. Through the course of stimulation, the Unified Parkinson Disease Rating Scale III rigidity and tremor scores correlated with the relative power of alpha over left parietal. Subthalamic nucleus deep brain stimulation improves the symptoms of PD by suppressing the synchronization of alpha rhythm in somatomotor region.

  12. Effect of deafferentation from spinal anesthesia on pain sensitivity and resting-state functional brain connectivity in healthy male volunteers.

    Science.gov (United States)

    Niesters, Marieke; Sitsen, Elske; Oudejans, Linda; Vuyk, Jaap; Aarts, Leon P H J; Rombouts, Serge A R B; de Rover, Mischa; Khalili-Mahani, Najmeh; Dahan, Albert

    2014-08-01

    Patients may perceive paradoxical heat sensation during spinal anesthesia. This could be due to deafferentation-related functional changes at cortical, subcortical, or spinal levels. In the current study, the effect of spinal deafferentation on sensory (pain) sensitivity was studied and linked to whole-brain functional connectivity as assessed by resting-state functional magnetic resonance imaging (RS-fMRI) imaging. Deafferentation was induced by sham or spinal anesthesia (15 mg bupivacaine injected at L3-4) in 12 male volunteers. RS-fMRI brain connectivity was determined in relation to eight predefined and seven thalamic resting-state networks (RSNs) and measured before, and 1 and 2 h after spinal/sham injection. To measure the effect of deafferentation on pain sensitivity, responses to heat pain were measured at 15-min intervals on nondeafferented skin and correlated to RS-fMRI connectivity data. Spinal anesthesia altered functional brain connectivity within brain regions involved in the sensory discriminative (i.e., pain intensity related) and affective dimensions of pain perception in relation to somatosensory and thalamic RSNs. A significant enhancement of pain sensitivity on nondeafferented skin was observed after spinal anesthesia compared to sham (area-under-the-curve [mean (SEM)]: 190.4 [33.8] versus 13.7 [7.2]; pbrain regions involved in affective and sensory pain processing and areas involved in descending control of pain.

  13. Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway.

    Science.gov (United States)

    Liu, Xin-yu; Zhou, Xin-yu; Hou, Jin-cai; Zhu, Hua; Wang, Zhong; Liu, Jian-xun; Zheng, Yong-qiu

    2015-04-01

    To investigate the effects of ginsenoside Rd (Rd) on neurogenesis in rat brain after ischemia/reperfusion injury (IRI). Male SD rats were subjected to transient middle cerebral artery occlusion (MCAO) followed by reperfusion. The rats were injected with Rd (1, 2.5, and 5 mg·kg(-1)·d(-1), ip) from d 1 to d 3 after MCAO, and with BrdU (50 mg·kg(-1)·d(-1), ip) from d 3 to d 6, then sacrificed on 7 d. The infarct size and neurological scores were assessed. Neurogenesis in the brains was detected by BrdU, DCX, Nestin, and GFAP immunohistochemistry staining. PC12 cells subjected to OGD/reperfusion were used as an in vitro model of brain ischemia. VEGF and BDNF levels were assessed with ELISA, and Akt and ERK phosphorylation was measured using Western blotting. Rd administration dose-dependently decreased the infarct size and neurological scores in the rats with IRI. The high dose of Rd 5 (mg·kg(-1)·d(-1)) significantly increased Akt phosphorylation in ipsilateral hemisphere, and markedly increased the number of BrdU/DCX and Nestin/GFAP double-positive cells in ischemic area, which was partially blocked by co-administration of the PI3 kinase inhibitor LY294002. Treatment with Rd (25, 50, and 100 μmol/L) during reperfusion significantly increased the expression of VEGF and BDNF in PC12 cells with IRI. Furthermore, treatment with Rd dose-dependently increased the phosphorylation of Akt and ERK, and significantly decreased PC12 cell apoptosis, which were blocked by co-application of LY294002. Rd not only attenuates ischemia/reperfusion injury in rat brain, but also promotes neurogenesis via increasing VEGF and BDNF expression and activating the PI3K/Akt and ERK1/2 pathways.

  14. Steady state visual evoked potential (SSVEP) based brain-computer interface (BCI) performance under different perturbations.

    Science.gov (United States)

    İşcan, Zafer; Nikulin, Vadim V

    2018-01-01

    Brain-computer interface (BCI) paradigms are usually tested when environmental and biological artifacts are intentionally avoided. In this study, we deliberately introduced different perturbations in order to test the robustness of a steady state visual evoked potential (SSVEP) based BCI. Specifically we investigated to what extent a drop in performance is related to the degraded quality of EEG signals or rather due to increased cognitive load. In the online tasks, subjects focused on one of the four circles and gave feedback on the correctness of the classification under four conditions randomized across subjects: Control (no perturbation), Speaking (counting loudly and repeatedly from one to ten), Thinking (mentally counting repeatedly from one to ten), and Listening (listening to verbal counting from one to ten). Decision tree, Naïve Bayes and K-Nearest Neighbor classifiers were used to evaluate the classification performance using features generated by canonical correlation analysis. During the online condition, Speaking and Thinking decreased moderately the mean classification accuracy compared to Control condition whereas there was no significant difference between Listening and Control conditions across subjects. The performances were sensitive to the classification method and to the perturbation conditions. We have not observed significant artifacts in EEG during perturbations in the frequency range of interest except in theta band. Therefore we concluded that the drop in the performance is likely to have a cognitive origin. During the Listening condition relative alpha power in a broad area including central and temporal regions primarily over the left hemisphere correlated negatively with the performance thus most likely indicating active suppression of the distracting presentation of the playback. This is the first study that systematically evaluates the effects of natural artifacts (i.e. mental, verbal and audio perturbations) on SSVEP-based BCIs. The

  15. Enhancing Brain Pregnenolone May Protect Cannabis Intoxication but Should Not Be Considered as an Anti-addiction Therapeutic: Hypothesizing Dopaminergic Blockade and Promoting Anti-Reward.

    Science.gov (United States)

    Blum, Kenneth; Oscar-Berman, Marlene; Braverman, Eric R; Febo, Marcelo; Li, Mona; Gold, Mark S

    Many US states now embrace the medical and recreational use of Cannabis. Changes in the laws have heightened interest and encouraged research into both cannabinoid products and the potential harms of Cannabis use, addiction, and intoxication. Some research into those harms will be reviewed here and misgivings about the use of Pregnenolone, to treat cannabis addiction and intoxication explained. Pregnenolone considered the inactive precursor of all steroid hormones, has recently been shown to protect the brain from Cannabis intoxication. The major active ingredient of Cannabis sativa (marijuana), Δ(9)-tetrahydrocannabinol (THC) enhances Pregnenolone synthesis in the brain via stimulation of the type-1 cannabinoid (CB1) receptor. This steroid has been shown to inhibit the activity of the CB1 receptor thereby reducing many of the effects of THC. While this mechanism seems correct, in our opinion, Vallee et al., incorrectly suggest that blocking CB1 receptors could open unforeseen approaches to the treatment of cannabis intoxication and addiction. In this hypothesis, we caution the scientific community that, other CB1 receptor blockers, such as, Rimonabant (SR141718) have been pulled off the market in Europe. In addition, CB1 receptor blockers were rejected by the FDA due to mood changes including suicide ideation. Blocking CB1 receptors would result in reduced neuronal release of Dopamine by disinhibition of GABA signaling. Long-term blockade of cannabinoid receptors could occur with raising Pregnenolone brain levels, may induce a hypodopaminergic state, and lead to aberrant substance and non-substance (behavioral) addictions.

  16. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect.

    Science.gov (United States)

    Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin

    2016-01-01

    The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

  17. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect

    Science.gov (United States)

    Yang, Chuan-Chih; Barrós-Loscertales, Alfonso; Pinazo, Daniel; Ventura-Campos, Noelia; Borchardt, Viola; Bustamante, Juan-Carlos; Rodríguez-Pujadas, Aina; Fuentes-Claramonte, Paola; Balaguer, Raúl; Ávila, César; Walter, Martin

    2016-01-01

    The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation) and between time points (before versus after training) were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression. PMID:26998365

  18. State and Training Effects of Mindfulness Meditation on Brain Networks Reflect Neuronal Mechanisms of Its Antidepressant Effect

    Directory of Open Access Journals (Sweden)

    Chuan-Chih Yang

    2016-01-01

    Full Text Available The topic of investigating how mindfulness meditation training can have antidepressant effects via plastic changes in both resting state and meditation state brain activity is important in the rapidly emerging field of neuroplasticity. In the present study, we used a longitudinal design investigating resting state fMRI both before and after 40 days of meditation training in 13 novices. After training, we compared differences in network connectivity between rest and meditation using common resting state functional connectivity methods. Interregional methods were paired with local measures such as Regional Homogeneity. As expected, significant differences in functional connectivity both between states (rest versus meditation and between time points (before versus after training were observed. During meditation, the internal consistency in the precuneus and the temporoparietal junction increased, while the internal consistency of frontal brain regions decreased. A follow-up analysis of regional connectivity of the dorsal anterior cingulate cortex further revealed reduced connectivity with anterior insula during meditation. After meditation training, reduced resting state functional connectivity between the pregenual anterior cingulate and dorsal medical prefrontal cortex was observed. Most importantly, significantly reduced depression/anxiety scores were observed after training. Hence, these findings suggest that mindfulness meditation might be of therapeutic use by inducing plasticity related network changes altering the neuronal basis of affective disorders such as depression.

  19. Putting the Mind in the Brain: Promoting an Appreciation of the Biological Basis to Understanding Human Behavior

    Science.gov (United States)

    Neumann, David L.

    2010-01-01

    A surprising number of students in psychology, behavioral science, and related social science classes fail to appreciate the importance of biological mechanisms to understanding behavior. To help teachers promote this understanding, this paper outlines six sources of evidence. These are (a) phylogenetic, (b) genetic/developmental, (c) clinical,…

  20. Riding the Hype: The Role of State-Owned Enterprise Elite Actors in the Promotion of Jatropha in Indonesia

    Directory of Open Access Journals (Sweden)

    Deasy Simandjuntak

    2014-06-01

    Full Text Available Within a few years following its ambitious promotion in 2006, the development of jatropha in Indonesia came to a halt. Claimed as a potential solution to problems in energy and poverty, the introduction of jatropha in Indonesia’s energy policy had been triggered by the high oil prices in 2005. While studies by biofuel scholars have generally focused on what brought the end of the “miracle crop” hype by underlining various technical problems and the absence of market structure as the cause of its failure, few have examined jatropha as part of a policy-making trajectory, which began with, and was influenced by, the development narratives disseminated by individual actors. This article sheds light on the role of elite actors in the making of biofuel energy policy in Indonesia. Taking the case of the promotion of jatropha in 2005–2007, the article illustrates the role of the director of Indonesia’s leading sugar state-owned enterprise (SOE, Rajawali Nusantara Indonesia (RNI, whose decision in promoting jatropha became influential in forwarding its narratives into the national energy and development policy in 2006. In order to discover why a specific elite actor decided to promote jatropha, the article relies on data, including the SOE’s documents and interviews with key actor(s. The analysis is conducted using an actor-oriented approach, which underlines the discrepancy between the ideals and the operational practice of developmental goals.

  1. Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson’s disease

    Science.gov (United States)

    Oswal, Ashwini; Beudel, Martijn; Zrinzo, Ludvic; Limousin, Patricia; Hariz, Marwan; Foltynie, Tom; Litvak, Vladimir

    2016-01-01

    Chronic dopamine depletion in Parkinson’s disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an effective treatment for Parkinson’s disease, but its influence on synchronous activity in cortico-basal-ganglia loops remains to be fully characterized. Here, we demonstrate that deep brain stimulation selectively suppresses certain spatially and spectrally segregated resting state subthalamic nucleus–cortical networks. To this end we used a validated and novel approach for performing simultaneous recordings of the subthalamic nucleus and cortex using magnetoencephalography (during concurrent subthalamic nucleus deep brain stimulation). Our results highlight that clinically effective subthalamic nucleus deep brain stimulation suppresses synchrony locally within the subthalamic nucleus in the low beta oscillatory range and furthermore that the degree of this suppression correlates with clinical motor improvement. Moreover, deep brain stimulation relatively selectively suppressed synchronization of activity between the subthalamic nucleus and mesial premotor regions, including the supplementary motor areas. These mesial premotor regions were predominantly coupled to the subthalamic nucleus in the high beta frequency range, but the degree of deep brain stimulation-associated suppression in their coupling to the subthalamic nucleus was not found to correlate with motor improvement. Beta band coupling between the subthalamic nucleus and lateral motor areas was not influenced by deep brain stimulation. Motor cortical coupling with subthalamic nucleus predominantly involved driving of the subthalamic nucleus, with those drives in the higher beta frequency band having much shorter net delays to subthalamic nucleus than those in the lower beta band. These observations raise

  2. Heart rate variability: an index of brain processing in vegetative state? An artificial intelligence, data mining study.

    Science.gov (United States)

    Riganello, F; Candelieri, A; Quintieri, M; Conforti, D; Dolce, G

    2010-12-01

    Brain processing at varying levels of functional complexity has been documented in vegetative state. In this study, data mining procedures are applied to identify significant changes in heart rate variability (an emerging objective descriptor of autonomic correlates of brain activation) in response to complex auditory stimuli with emotional value (music). The heart rate of subjects in vegetative state from brain damage (n=6) or spontaneous hemorrhage (n=3) and 16 healthy controls was recorded while they passively listened to four pre-selected music samples by different authors (mean recording time: 3m and 36s±24s). The parametric and non-parametric frequency spectra were computed on the heart rate, spectra were compared within/across subjects and music authors, and the spectra descriptors were entered into a 1-R rules data mining procedure (WEKA software Leave One Out and Ten Fold Cross validation). The procedure independently classified the heart rate spectral patterns of both patients and controls and the emotions reported by healthy subjects as "positive" or "negative". In both healthy controls and vegetative state subjects, the power spectra while passively listening to music differed from baseline when compared irrespective of the music authorship and from each other when compared across music samples. Data mining sorted the nu_LF (normalized parameter unit of the spectrum low frequency range) as the significant descriptor of heart rate variability in the conditions of the study. The nu_LF classification of the healthy controls' HRV changes in response to music replicated that based on subjective reports with 75-93.7% accuracy. Although preliminary, these findings suggest that autonomic changes with possible emotional value can be induced by complex stimuli also in vegetative state, with implications on the residual responsiveness of these subjects. Heart rate variability descriptors and data mining methods appear applicable to investigate brain function in

  3. Directionality of large-scale resting-state brain networks during eyes open and eyes closed conditions

    Directory of Open Access Journals (Sweden)

    Delong eZhang

    2015-02-01

    Full Text Available The present study examined directional connections in the brain among resting-state networks (RSNs when the participant had their eyes open (EO or had their eyes closed (EC. The resting-state fMRI data were collected from 20 healthy participants (11 males, 20.17 ± 2.74 years under the EO and EC states. Independent component analysis (ICA was applied to identify the separated RSNs (i.e., the primary/high-level visual, primary sensory-motor, ventral motor, salience/dorsal attention, and anterior/posterior default-mode networks, and the Gaussian Bayesian network (BN learning approach was then used to explore the conditional dependencies among these RSNs. The network-to-network directional connections related to EO and EC were depicted, and a support vector machine (SVM was further employed to identify the directional connection patterns that could effectively discriminate between the two states. The results indicated that the connections among RSNs are directionally connected within a BN during the EO and EC states. The directional connections from the salient attention network to the anterior/posterior default-mode networks and the high-level to primary-level visual network were the obvious characteristics of both the EO and EC resting-state BNs. Of the directional connections in BN, the attention (salient and dorsal-related directional connections were observed to be discriminative between the EO and EC states. In particular, we noted that the properties of the salient and dorsal attention networks were in opposite directions. Overall, the present study described the directional connections of RSNs using a BN learning approach during the EO and EC states, and the results suggested that the attention system (the salient and the dorsal attention network might have important roles in resting-state brain networks and the neural substrate underpinning of switching between the EO and EC states.

  4. Auditing Access to Outpatient Rehabilitation Services for Children With Traumatic Brain Injury and Public Insurance in Washington State.

    Science.gov (United States)

    Fuentes, Molly M; Thompson, Leah; Quistberg, D Alex; Haaland, Wren L; Rhodes, Karin; Kartin, Deborah; Kerfeld, Cheryl; Apkon, Susan; Rowhani-Rahbar, Ali; Rivara, Frederick P

    2017-09-01

    To identify insurance-based disparities in access to outpatient pediatric neurorehabilitation services. Audit study with paired calls, where callers posed as a mother seeking services for a simulated child with history of severe traumatic brain injury and public or private insurance. Outpatient rehabilitation clinics. Sample of rehabilitation clinics (N=287): 195 physical therapy (PT) clinics, 109 occupational therapy (OT) clinics, 102 speech therapy (ST) clinics, and 11 rehabilitation medicine clinics. Not applicable. Acceptance of public insurance and the number of business days until the next available appointment. Therapy clinics were more likely to accept private insurance than public insurance (relative risk [RR] for PT clinics, 1.33; 95% confidence interval [CI], 1.22-1.44; RR for OT clinics, 1.40; 95% CI, 1.24-1.57; and RR for ST clinics, 1.42; 95% CI, 1.25-1.62), with no significant difference for rehabilitation medicine clinics (RR, 1.10; 95% CI, 0.90-1.34). The difference in median wait time between clinics that accepted public insurance and those accepting only private insurance was 4 business days for PT clinics and 15 days for ST clinics (P≤.001), but the median wait time was not significantly different for OT clinics or rehabilitation medicine clinics. When adjusting for urban and multidisciplinary clinic statuses, the wait time at clinics accepting public insurance was 59% longer for PT (95% CI, 39%-81%), 18% longer for OT (95% CI, 7%-30%), and 107% longer for ST (95% CI, 87%-130%) than that at clinics accepting only private insurance. Distance to clinics varied by discipline and area within the state. Therapy clinics were less likely to accept public insurance than private insurance. Therapy clinics accepting public insurance had longer wait times than did clinics that accepted only private insurance. Rehabilitation professionals should attempt to implement policy and practice changes to promote equitable access to care. Copyright © 2017

  5. State-of-the-art for food taxes to promote public health

    DEFF Research Database (Denmark)

    Jensen, Jørgen Dejgård; Smed, Sinne

    2017-01-01

    countries in different parts of the world have experiences with the taxation of sugar-sweetened beverages, in some cases in combination with taxes on unhealthy food commodities such as confectionery or high-fat foods. These tax schemes have many similarities, but also differ in their definitions of tax......The use of taxes to promote healthy nutritional behaviour has gained ground in the past decade. The present paper reviews existing applications of fiscal instruments in nutrition policy and derives some perspectives and recommendations from the experiences gained with these instruments. Many...... objects and in the applied tax rates. Denmark has been the only country in the world to operate a tax on saturated fat content in foods, from 2011 to 2012. Most of the existing food tax schemes have been introduced from fiscal motivations, with health promotion as a secondary objective, but a few have...

  6. Regional Homogeneity of Resting-State Brain Activity Suppresses the Effect of Dopamine-Related Genes on Sensory Processing Sensitivity.

    Directory of Open Access Journals (Sweden)

    Chunhui Chen

    Full Text Available Sensory processing sensitivity (SPS is an intrinsic personality trait whose genetic and neural bases have recently been studied. The current study used a neural mediation model to explore whether resting-state brain functions mediated the effects of dopamine-related genes on SPS. 298 healthy Chinese college students (96 males, mean age = 20.42 years, SD = 0.89 were scanned with magnetic resonance imaging during resting state, genotyped for 98 loci within the dopamine system, and administered the Highly Sensitive Person Scale. We extracted a "gene score" that summarized the genetic variations representing the 10 loci that were significantly linked to SPS, and then used path analysis to search for brain regions whose resting-state data would help explain the gene-behavior association. Mediation analysis revealed that temporal homogeneity of regional spontaneous activity (ReHo in the precuneus actually suppressed the effect of dopamine-related genes on SPS. The path model explained 16% of the variance of SPS. This study represents the first attempt at using a multi-gene voxel-based neural mediation model to explore the complex relations among genes, brain, and personality.

  7. Effectiveness of cognitive-coping therapy and alteration of resting-state brain function in obsessive-compulsive disorder.

    Science.gov (United States)

    Zhao, Hong-Zeng; Wang, Chang-Hong; Gao, Zhong-Zhan; Ma, Jian-Dong; Huang, Ping; Li, Heng-Fen; Sang, De-En; Shan, Xiao-Wen; Kou, Shao-Jie; Li, Zhi-Rong; Ma, Li; Zhang, Zhao-Hui; Zhang, Jian-Hong; Ouyang, Hua; Lian, Hong-Kai; Zang, Yu-Feng; Hu, Xian-Zhang

    2017-01-15

    Cognitive-coping therapy (CCT), integrating cognitive theory with stress-coping theory, is an efficacious therapy for obsessive-compulsive disorder (OCD). However, the potential brain mediation for the effectiveness remains unclear. We sought to investigate differences of resting-state brain function between OCD and healthy controls and if such differences would be changed by a four-week CCT. Thirty-one OCD patients were recruited and randomized into CCT (n=15) and pharmacotherapy plus CCT (pCCT, n=16) groups, together with 25 age-, gender- and education-matched healthy controls. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was scored to evaluate the severity in symptoms. Resting-state functional magnetic resonance imaging was scanned pre- and post-treatment. For patients, Y-BOCS scores were reduced during four-week treatment for CCT and pCCT (POCD patients was higher in the left hippocampus, parahippocampus, and temporal lobes, but lower in the right orbitofrontal cortex, rectus, bilateral calcarine, cuneus, lingual, occipital, left parietal, postcentral, precentral, and parietal (corrected POCD symptoms. After a 4-week treatment, the ALFF differences between OCD patients and controls disappeared. The pharmacotherapy group was not included since OCD patients generally do not respond to pharmacotherapy in four weeks. Our data indicated that resting-state brain function was different between OCD and controls; such differences disappeared after OCD symptoms were relieved. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Clinical application of brain imaging for the diagnosis of mood disorders: the current state of play.

    Science.gov (United States)

    Savitz, J B; Rauch, S L; Drevets, W C

    2013-05-01

    In response to queries about whether brain imaging technology has reached the point where it is useful for making a clinical diagnosis and for helping to guide treatment selection, the American Psychiatric Association (APA) has recently written a position paper on the Clinical Application of Brain Imaging in Psychiatry. The following perspective piece is based on our contribution to this APA position paper, which specifically emphasized the application of neuroimaging in mood disorders. We present an introductory overview of the challenges faced by researchers in developing valid and reliable biomarkers for psychiatric disorders, followed by a synopsis of the extant neuroimaging findings in mood disorders, and an evidence-based review of the current research on brain imaging biomarkers in adult mood disorders. Although there are a number of promising results, by the standards proposed below, we argue that there are currently no brain imaging biomarkers that are clinically useful for establishing diagnosis or predicting treatment outcome in mood disorders.

  9. EU Rural Development Policy in the New Member States: Promoting Multifunctionality?

    Science.gov (United States)

    Ramniceanu, Irina; Ackrill, Robert

    2007-01-01

    European Union (EU) enlargement has seen 10 new member states (NMS) adopt the full range of EU policies. Within this, the rural development arm of the Common Agricultural Policy offers particular points of interest. Member states chose from an extensive list of policy measures developed within the EU15 and intended, in particular, to…

  10. State Legislative Recommendations to Promote Fair and Effective School Discipline. NEPC Discipline Resource Sheet

    Science.gov (United States)

    Losen, Daniel J.

    2011-01-01

    This document presents a summary of the larger report "Discipline Policies, Successful Schools, and Racial Justice." State legislation is an important lever for improving the equity of student discipline policies. However, states vary tremendously, and only some provide accurate public reports on school discipline, support effective…

  11. [Music therapy and "brain music": state of the art, problems and perspectives].

    Science.gov (United States)

    2013-01-01

    Recent literature on the problem of interaction between music and the brain is reviewed and summarized. Mechanisms and effects of two most popular music therapy applications are picked out, including music listening and music making. Special attention is paid to relatively new line of investigations that is called "music of the brain" and deals with transformation of bioelectric processes of human organism into music. Unresolved questions of music therapy are identified and some promising lines of future investigations are delineated.

  12. Alteration of Brain Functional Networks in Early-Stage Parkinson's Disease: A Resting-State fMRI Study.

    Science.gov (United States)

    Sang, Linqiong; Zhang, Jiuquan; Wang, Li; Zhang, Jingna; Zhang, Ye; Li, Pengyue; Wang, Jian; Qiu, Mingguo

    2015-01-01

    Although alterations of topological organization have previously been reported in the brain functional network of Parkinson's disease (PD) patients, the topological properties of the brain network in early-stage PD patients who received antiparkinson treatment are largely unknown. This study sought to determine the topological characteristics of the large-scale functional network in early-stage PD patients. First, 26early-stage PD patients (Hoehn and Yahr stage:1-2) and 30 age-matched normal controls were scanned using resting-state functional MRI. Subsequently, graph theoretical analysis was employed to investigate the abnormal topological configuration of the brain network in early-stage PD patients. We found that both the PD patient and control groups showed small-world properties in their functional brain networks. However, compared with the controls, the early-stage PD patients exhibited abnormal global properties, characterized by lower global efficiency. Moreover, the modular structure and the hub distribution were markedly altered in early-stage PD patients. Furthermore, PD patients exhibited increased nodal centrality, primarily in the bilateral pallidum, the inferior parietal lobule, and the medial superior frontal gyrus, and decreased nodal centrality in the caudate nucleus, the supplementary motor areas, the precentral gyrus, and the middle frontal gyrus. There were significant negative correlations between the Unified Parkinson Disease Rating Scale motor scores and nodal centralities of superior parietal gyrus. These results suggest that the topological organization of the brain functional network was altered in early-stage PD patients who received antiparkinson treatment, and we speculated that the antiparkinson treatment may affect the efficiency of the brain network to effectively relieve clinical symptoms of PD.

  13. Alteration of Brain Functional Networks in Early-Stage Parkinson's Disease: A Resting-State fMRI Study.

    Directory of Open Access Journals (Sweden)

    Linqiong Sang

    Full Text Available Although alterations of topological organization have previously been reported in the brain functional network of Parkinson's disease (PD patients, the topological properties of the brain network in early-stage PD patients who received antiparkinson treatment are largely unknown. This study sought to determine the topological characteristics of the large-scale functional network in early-stage PD patients. First, 26early-stage PD patients (Hoehn and Yahr stage:1-2 and 30 age-matched normal controls were scanned using resting-state functional MRI. Subsequently, graph theoretical analysis was employed to investigate the abnormal topological configuration of the brain network in early-stage PD patients. We found that both the PD patient and control groups showed small-world properties in their functional brain networks. However, compared with the controls, the early-stage PD patients exhibited abnormal global properties, characterized by lower global efficiency. Moreover, the modular structure and the hub distribution were markedly altered in early-stage PD patients. Furthermore, PD patients exhibited increased nodal centrality, primarily in the bilateral pallidum, the inferior parietal lobule, and the medial superior frontal gyrus, and decreased nodal centrality in the caudate nucleus, the supplementary motor areas, the precentral gyrus, and the middle frontal gyrus. There were significant negative correlations between the Unified Parkinson Disease Rating Scale motor scores and nodal centralities of superior parietal gyrus. These results suggest that the topological organization of the brain functional network was altered in early-stage PD patients who received antiparkinson treatment, and we speculated that the antiparkinson treatment may affect the efficiency of the brain network to effectively relieve clinical symptoms of PD.

  14. Deciphering the spatio-temporal expression and stress regulation of Fam107B, the paralog of the resilience-promoting protein DRR1 in the mouse brain.

    Science.gov (United States)

    Masana, M; Jukic, M M; Kretzschmar, A; Wagner, K V; Westerholz, S; Schmidt, M V; Rein, T; Brodski, C; Müller, M B

    2015-04-02

    Understanding the molecular mechanisms that promote stress resilience might open up new therapeutic avenues to prevent stress-related disorders. We recently characterized a stress and glucocorticoid-regulated gene, down-regulated in renal cell carcinoma - DRR1 (Fam107A). DRR1 is expressed in the mouse brain; it is up-regulated by stress and glucocorticoids and modulates neuronal actin dynamics. In the adult mouse, DRR1 was shown to facilitate specific behaviors which might be protective against some of the deleterious consequences of stress exposure: in the hippocampal CA3 region, DRR1 improved cognitive performance whereas in the septum, it specifically increased social behavior. Therefore DRR1 was suggested as a candidate protein promoting stress-resilience. Fam107B (family with sequence similarity 107, member B) is the unique paralog of DRR1, and both share high sequence similarities, predicted glucocorticoid response elements, heat-shock induction and tumor suppressor properties. So far, the role of Fam107B in the central nervous system was not studied. The aim of the present investigation, therefore, was to analyze whether Fam107B and DRR1 display comparable mRNA expression patterns in the brain and whether both are modulated by stress and glucocorticoids. Spatio-temporal mapping of Fam107B mRNA expression in the embryonic and adult mouse brain, by means of in situ hybridization, showed that Fam107B was expressed during embryogenesis and in the adulthood, with particularly high and specific expression in the forming telencephalon suggestive of an involvement in corticogenesis. In the adult mouse, expression was restricted to neurogenic niches, like the dentate gyrus. In contrast to DRR1, Fam107B mRNA expression failed to be modulated by glucocorticoids and social stress in the adult mouse. In summary, Fam107B and DRR1 show different spatio-temporal expression patterns in the central nervous system, suggesting at least partially different functional roles in

  15. Altered brain function in new onset childhood acute lymphoblastic leukemia before chemotherapy: A resting-state fMRI study.

    Science.gov (United States)

    Hu, Zhanqi; Zou, Dongfang; Mai, Huirong; Yuan, Xiuli; Wang, Lihong; Li, Yue; Liao, Jianxiang; Liu, Liwei; Liu, Guosheng; Zeng, Hongwu; Wen, Feiqiu

    2017-10-01

    Cognitive impairments had been reported in childhood acute lymphoblastic leukemia, what caused the impairments needed to be demonstrated, chemotherapy-related or the disease itself. The primary aim of this exploratory investigation was to determine if there were changes in brain function of children with acute lymphoblastic leukemia before chemotherapy. In this study, we advanced a measure named regional homogeneity to evaluate the resting-state brain activities, intelligence quotient test was performed at same time. Using regional homogeneity, we first investigated the resting state brain function in patients with new onset childhood acute lymphoblastic leukemia before chemotherapy, healthy children as control. The decreased ReHo values were mainly founded in the default mode network and left frontal lobe, bilateral inferior parietal lobule, bilateral temporal lobe, bilateral occipital lobe, precentral gyrus, bilateral cerebellum in the newly diagnosed acute lymphoblastic leukemia patients compared with the healthy control. While in contrast, increased ReHo values were mainly shown in the right frontal lobe (language area), superior frontal gyrus-R, middle frontal gyrus-R and inferior parietal lobule-R for acute lymphoblastic leukemia patients group. There were no significant differences for intelligence quotient measurements between the acute lymphoblastic leukemia patient group and the healthy control in performance intelligence quotient, verbal intelligence quotient, total intelligence quotient. The altered brain functions are associated with cognitive change and language, it is suggested that there may be cognition impairment before the chemotherapy. Regional homogeneity by functional magnetic resonance image is a sensitive way for early detection on brain damage in childhood acute lymphoblastic leukemia. Copyright © 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  16. Disrupted small-world brain networks in moderate Alzheimer's disease: a resting-state FMRI study.

    Directory of Open Access Journals (Sweden)

    Xiaohu Zhao

    Full Text Available The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD. However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI of carefully selected moderate AD patients and normal controls (NCs. Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients.

  17. Exploring Cortical Plasticity and Oscillatory Brain Dynamics via Transcranial Magnetic Stimulation and Resting-State Electroencephalogram.

    Science.gov (United States)

    Noh, Nor Azila

    2016-07-01

    Transcranial magnetic stimulation (TMS) is a non-invasive, non-pharmacological technique that is able to modulate cortical activity beyond the stimulation period. The residual aftereffects are akin to the plasticity mechanism of the brain and suggest the potential use of TMS for therapy. For years, TMS has been shown to transiently improve symptoms of neuropsychiatric disorders, but the underlying neural correlates remain elusive. Recently, there is evidence that altered connectivity of brain network dynamics is the mechanism underlying symptoms of various neuropsychiatric illnesses. By combining TMS and electroencephalography (EEG), the functional connectivity patterns among brain regions, and the causal link between function or behaviour and a specific brain region can be determined. Nonetheless, the brain network connectivity are highly complex and involve the dynamics interplay among multitude of brain regions. In this review article, we present previous TMS-EEG co-registration studies, which explore the functional connectivity patterns of human cerebral cortex. We argue the possibilities of neural correlates of long-term potentiation/depression (LTP-/LTD)-like mechanisms of synaptic plasticity that drive the TMS aftereffects as shown by the dissociation between EEG and motor evoked potentials (MEP) cortical output. Here, we also explore alternative explanations that drive the EEG oscillatory modulations post TMS. The precise knowledge of the neurophysiological mechanisms underlying TMS will help characterise disturbances in oscillatory patterns, and the altered functional connectivity in neuropsychiatric illnesses.

  18. State Public Health Actions to Prevent and Control Diabetes, Heart Disease, Obesity and Associated Risk Factors, and Promote School Health.

    Science.gov (United States)

    Park, Barbara Z; Cantrell, Letitia; Hunt, Holly; Farris, Rosanne P; Schumacher, Patricia; Bauer, Ursula E

    2017-12-07

    The National Center for Chronic Disease Prevention and Health Promotion at the Centers for Disease Control and Prevention funds a program to boost progress in reducing the prevalence and incidence of multiple chronic diseases and their associated risk factors. This article describes the program, State Public Health Actions to Prevent and Control Diabetes, Heart Disease, Obesity and Associated Risk Factors, and Promote School Health, and the program's action model, design, and administration and management structure. This program is based on 4 domains of public health action: 1) epidemiology and surveillance, 2) environmental approaches, 3) health care system interventions, and 4) community programs linked to clinical services. The 4 domains of public health action leverage data to inform action, support healthy choices and behaviors, strengthen delivery of clinical preventive services, and help Americans better manage their health.

  19. Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf.

    Science.gov (United States)

    Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; Nguyen, Thien An; Alfano, Robert R

    2014-06-01

    Two-photon (2P) excitation of the second singlet (S₂) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S₂ state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S₂ state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

  20. Deep two-photon microscopic imaging through brain tissue using the second singlet state from fluorescent agent chlorophyll α in spinach leaf

    Science.gov (United States)

    Shi, Lingyan; Rodríguez-Contreras, Adrián; Budansky, Yury; Pu, Yang; An Nguyen, Thien; Alfano, Robert R.

    2014-06-01

    Two-photon (2P) excitation of the second singlet (S) state was studied to achieve deep optical microscopic imaging in brain tissue when both the excitation (800 nm) and emission (685 nm) wavelengths lie in the "tissue optical window" (650 to 950 nm). S2 state technique was used to investigate chlorophyll α (Chl α) fluorescence inside a spinach leaf under a thick layer of freshly sliced rat brain tissue in combination with 2P microscopic imaging. Strong emission at the peak wavelength of 685 nm under the 2P S state of Chl α enabled the imaging depth up to 450 μm through rat brain tissue.

  1. Surface functionalizing of a lipid nanosystem to promote brain targeting: step-by-step design and physico-chemical characterization.

    Science.gov (United States)

    Cózar-Bernal, M J; García-Esteban, E; Sánchez-Soto, P J; Rabasco, A M; González-Rodríguez, M L

    2016-11-01

    The use of lipid nanosystems as drug delivery to the central nervous system may be advantageous over the current strategies. The aim of this study was to develop and characterize functionalized liposomes for treatment of brain diseases. The covalent method of coupling IgG to liposomes via the derivatized lipid 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine-N-[4-(p-maleimidophenyl)butyramide](MPB-PE) was investigated. Optimized coupling conditions are shown to result in the efficient conjugation of IgG to liposomes containing low concentrations of MPB-PE (3/1 SH:IgG). The qualitative analysis has shown that after the extrusion process, more homogeneous populations of vesicles have been obtained with a nanometric size suitable to be effective to further anchor the protein. Negative values of zeta potential demonstrate that they are stable systems. Lyophilization was used to maintain the stability of the formulation. These very interesting results encourage further investigations to formulate peptide- and protein-loaded immunoliposomes, making targeting of liposomes as an attractive approach for brain drug delivery.

  2. Assessing and Promoting the Wellness of United States Ophthalmology Residents: A Survey of Program Directors.

    Science.gov (United States)

    Tran, Elaine M; Scott, Ingrid U; Clark, Melissa A; Greenberg, Paul B

    To report on the status of residency-based wellness initiatives in ophthalmic graduate medical education and identify strategies for promoting ophthalmology resident wellness by surveying US ophthalmology program directors (PDs). The PDs were each sent an e-mail containing a link to an anonymous online 15-question survey. The PDs also received a letter with the survey link and a $1 incentive. After 2 weeks, nonresponders received 2 weekly reminder e-mails and phone calls. Descriptive statistics were used to analyze the multiple choice responses and categorize the free response answers. National survey. All 111 US ophthalmology PDs were invited to participate. Of 111 PDs, 56 (50%) responded; 14 (26%) of 53 respondents reported that their programs faced an issue involving resident depression, burnout, or suicide within the last year; 25 (45%) of 56 reported that their department had a resident wellness program. Respondents without wellness programs reported a shortage of time (19/30; 63%) and lack of training and resources (19/30; 63%) as barriers to instituting these programs. Respondents reported that the Accreditation Council for Graduate Medical Education could better promote resident wellness by providing training resources for burnout and depression screening (35/53; 66%), resilience skills building (38/53; 72%), and wellness program development (36/53; 68%). This survey suggests that there is a substantial burden of burnout and depression among residents in ophthalmic graduate medical education and that this burden can be addressed by promoting the training of educators to recognize the signs of burnout and depression, and providing resources to develop and expand formal wellness programs. Published by Elsevier Inc.

  3. CogState computerized memory tests in patients with brain metastases: secondary endpoint results of NRG Oncology RTOG 0933.

    Science.gov (United States)

    Caine, Chip; Deshmukh, Snehal; Gondi, Vinai; Mehta, Minesh; Tomé, Wolfgang; Corn, Benjamin W; Kanner, Andrew; Rowley, Howard; Kundapur, Vijayananda; DeNittis, Albert; Greenspoon, Jeffrey Noah; Konski, Andre A; Bauman, Glenn S; Raben, Adam; Shi, Wenyin; Wendland, Merideth; Kachnic, Lisa

    2016-01-01

    Whole brain radiotherapy (WBRT) is associated with memory dysfunction. As part of NRG Oncology RTOG 0933, a phase II study of WBRT for brain metastases that conformally avoided the hippocampal stem cell compartment (HA-WBRT), memory was assessed pre- and post-HA-WBRT using both traditional and computerized memory tests. We examined whether the computerized tests yielded similar findings and might serve as possible alternatives for assessment of memory in multi-institution clinical trials. Adult patients with brain metastases received HA-WBRT to 30 Gy in ten fractions and completed Hopkins Verbal Learning Test-Revised (HVLT-R), CogState International Shopping List Test (ISLT) and One Card Learning Test (OCLT), at baseline, 2 and 4 months. Tests' completion rates were 52-53 % at 2 months and 34-42 % at 4 months. All baseline correlations between HVLT-R and CogState tests were significant (p ≤ 0.003). At baseline, both CogState tests and one component of HVLT-R differentiated those who were alive at 6 months and those who had died (p ≤ 0.01). At 4 months, mean relative decline was 7.0 % for HVLT-R Delayed Recall and 18.0 % for ISLT Delayed Recall. OCLT showed an 8.0 % increase. A reliable change index found no significant changes from baseline to 2 and 4 months for ISLT Delayed Recall (z = -0.40, p = 0.34; z = -0.68, p = 0.25) or OCLT (z = 0.15, p = 0.56; z = 0.41, p = 0.66). Study findings support the possibility that hippocampal avoidance may be associated with preservation of memory test performance, and that these computerized tests also may be useful and valid memory assessments in multi-institution adult brain tumor trials.

  4. Breastfeeding protection, promotion, and support in the United States: a time to nudge, a time to measure.

    Science.gov (United States)

    Pérez-Escamilla, Rafael; Chapman, Donna J

    2012-05-01

    Strong evidence-based advocacy efforts have now translated into high level political support and concrete goals for improving breastfeeding outcomes among women in the United States. In spite of this, major challenge remain for promoting, supporting and especially for protecting breastfeeding in the country. The goals of this commentary are to argue in favor of: A) Changes in the default social and environmental systems, that would allow women to implement their right to breastfeed their infants, B) A multi-level and comprehensive monitoring system to measure process and outcomes indicators in the country. Evidence-based commentary. Breastfeeding rates in the United States can improve based on a well coordinated social marketing framework. This approach calls for innovative promotion through mass media, appropriate facility based and community based support (e.g., Baby Friendly Hospital Initiative, WIC-coordinated community based peer counseling), and adequate protection for working women (e.g., longer paid maternity leave, breastfeeding or breast milk extraction breaks during the working day) and women at large by adhering and enforcing the WHO ethics Code for the Marketing of Breast Milk Substitutes. Sound infant feeding practices monitoring systems, which include WIC administrative food package data, are needed. Given the current high level of political support to improve breastfeeding in the United States, a window of opportunity has been opened. Establishing breastfeeding as the social norm in the USA will take time, but the global experience indicates that it can be done.

  5. Simultaneous detection of P300 and steady-state visually evoked potentials for hybrid brain-computer interface.

    Science.gov (United States)

    Combaz, Adrien; Van Hulle, Marc M

    2015-01-01

    We study the feasibility of a hybrid Brain-Computer Interface (BCI) combining simultaneous visual oddball and Steady-State Visually Evoked Potential (SSVEP) paradigms, where both types of stimuli are superimposed on a computer screen. Potentially, such a combination could result in a system being able to operate faster than a purely P300-based BCI and encode more targets than a purely SSVEP-based BCI. We analyse the interactions between the brain responses of the two paradigms, and assess the possibility to detect simultaneously the brain activity evoked by both paradigms, in a series of 3 experiments where EEG data are analysed offline. Despite differences in the shape of the P300 response between pure oddball and hybrid condition, we observe that the classification accuracy of this P300 response is not affected by the SSVEP stimulation. We do not observe either any effect of the oddball stimulation on the power of the SSVEP response in the frequency of stimulation. Finally results from the last experiment show the possibility of detecting both types of brain responses simultaneously and suggest not only the feasibility of such hybrid BCI but also a gain over pure oddball- and pure SSVEP-based BCIs in terms of communication rate.

  6. Resting-state functional magnetic resonance imaging shows altered brain network topology in Type 2 diabetic patients without cognitive impairment.

    Science.gov (United States)

    Chen, Guan-Qun; Zhang, Xin; Xing, Yue; Wen, Dong; Cui, Guang-Bin; Han, Ying

    2017-11-28

    We analyzed topology of brain functional networks in type 2 diabetes mellitus (T2DM) patients without mild cognitive impairment. We recruited T2DM patients without mild cognitive impairment (4 males and 8 females) and healthy control subjects (8 males and 16 females) to undergo cognitive testing and resting-state functional magnetic resonance imaging. Graph theoretical analysis of functional brain networks revealed abnormal small-world architecture in T2DM patients as compared to control subjects. The functional brain networks of T2DM patients showed increased path length, decreased global efficiency and disrupted long-distance connections. Moreover, reduced nodal characteristics were distributed in the frontal, parietal and temporal lobes, while increased nodal characteristics were distributed in the frontal, occipital lobes, and basal ganglia in the T2DM patients. The disrupted topological properties correlated with cognitive performance of T2DM patients. These findings demonstrate altered topological organization of functional brain networks in T2DM patients without mild cognitive impairment.

  7. Abnormal Baseline Brain Activity in Patients with Pulsatile Tinnitus: A Resting-State fMRI Study

    Directory of Open Access Journals (Sweden)

    Lv Han

    2014-01-01

    Full Text Available Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI technique. The present study used unilateral PT patients (n=42 and age-, sex-, and education-matched normal control subjects (n=42 to investigate the changes in structural and amplitude of low-frequency (ALFF of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients.

  8. Glucose metabolism during resting state reveals abnormal brain networks organization in the Alzheimer's disease and mild cognitive impairment.

    Directory of Open Access Journals (Sweden)

    Gretel Sanabria-Diaz

    Full Text Available This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD and Mild Cognitive Impairment (MCI patients compared to Normal healthy controls (NC using the Alzheimer Disease Neuroimaging Initiative (ADNI database. The local cerebral metabolic rate for glucose (CMRgl in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others. MCI network's attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI.

  9. [Resting-state functional magnetic resonance study of brain function changes after TIPS operation in patients with liver cirrhosis].

    Science.gov (United States)

    Liu, C; Wang, H B; Yu, Y Q; Wang, M Q; Zhang, G B; Xu, L Y; Wu, J M

    2016-12-20

    Objective: To investigate the brain function changes in cirrhosis patients after transjugular intrahepatic portosystemic shunt (TIPS), resting-state functional MRI (rs-fMRI) performed and fractional amplitude of low frequency fluctuation (fALFF) was analyzed. Methods: From January 2014 to February 2016, a total of 96 cirrhotic patients from invasive technology department and infection department in the First Affiliated Hospital of Anhui Medical University were selected , the blood ammonia data of 96 cirrhotic patients with TIPS operation in four groups were collected after 1, 3, 6 and 12 month, and all subjects performed rs-fMRI scans. The rs-fMRI data processed with DPARSF and SPM12 softwares, whole-brain fALFF values were calculated, and One-Way analysis of variance , multiple comparison analysis and correlation analysis were performed. Results: There were brain regions with significant function changes in four groups patients with TIPS operation after 1, 3, 6 and 12 month, including bilateral superior temporal gyrus, right middle temportal gyrus , right hippocampus, right island of inferior frontal gyrus, left fusiform gyrus, left olfactory cortex, left orbital superior frontal gyrus (all Pbrain function areas increased in left olfactory cortex, left inferior temporal gyrus, left fusiform gyrus, left orbital middle frontal gyrus, left putamen, left cerebelum, and decreased in left lingual gyrus; patients in the 6-month follow-up showed that brain function areas increased in left middle temportal gyrus, right supramarginal gyrus, right temporal pole, right central operculum, and decreased in left top edge of angular gyrus, left postcentral gyrus; patients in the 12-month follow-up showed that brain function areas increased in right hippocampus, right middle cingulate gyrus, and decreased in right middle temportal gyrus.Compared with patients in the 3-month follow-up, patients in the 6-month follow-up showed that brain function areas increased in left superior

  10. Pediatric sports-related traumatic brain injury in United States trauma centers.

    Science.gov (United States)

    Yue, John K; Winkler, Ethan A; Burke, John F; Chan, Andrew K; Dhall, Sanjay S; Berger, Mitchel S; Manley, Geoffrey T; Tarapore, Phiroz E

    2016-04-01

    OBJECTIVE Traumatic brain injury (TBI) in children is a significant public health concern estimated to result in over 500,000 emergency department (ED) visits and more than 60,000 hospitalizations in the United States annually. Sports activities are one important mechanism leading to pediatric TBI. In this study, the authors characterize the demographics of sports-related TBI in the pediatric population and identify predictors of prolonged hospitalization and of increased morbidity and mortality rates. METHODS Utilizing the National Sample Program of the National Trauma Data Bank (NTDB), the authors retrospectively analyzed sports-related TBI data from children (age 0-17 years) across 5 sports categories: fall or interpersonal contact (FIC), roller sports, skiing/snowboarding, equestrian sports, and aquatic sports. Multivariable regression analysis was used to identify predictors of prolonged length of stay (LOS) in the hospital or intensive care unit (ICU), medical complications, inpatient mortality rates, and hospital discharge disposition. Statistical significance was assessed at α sports-related TBIs were recorded in the NTDB, and these injuries represented 11,614 incidents nationally after sample weighting. Fall or interpersonal contact events were the greatest contributors to sports-related TBI (47.4%). Mild TBI represented 87.1% of the injuries overall. Mean (± SEM) LOSs in the hospital and ICU were 2.68 ± 0.07 days and 2.73 ± 0.12 days, respectively. The overall mortality rate was 0.8%, and the prevalence of medical complications was 2.1% across all patients. Severities of head and extracranial injuries were significant predictors of prolonged hospital and ICU LOSs, medical complications, failure to discharge to home, and death. Hypotension on admission to the ED was a significant predictor of failure to discharge to home (OR 0.05, 95% CI 0.03-0.07, p injury incurred during roller sports was independently associated with prolonged hospital LOS compared

  11. Neurosurgery and brain shift: review of the state of the art and main contributions of robotics

    Directory of Open Access Journals (Sweden)

    Karin Correa-Arana

    2017-09-01

    Full Text Available This paper presents a review about neurosurgery, robotic assistants in this type of procedure, and the approach to the problem of brain tissue displacement, including techniques for obtaining medical images. It is especially focused on the phenomenon of brain displacement, commonly known as brain shift, which causes a loss of reference between the preoperative images and the volumes to be treated during image-guided surgery. Hypothetically, with brain shift prediction and correction for the neuronavigation system, minimal invasion trajectories could be planned and shortened. This would reduce damage to functional tissues and possibly lower the morbidity and mortality in delicate and demanding medical procedures such as the removal of a brain tumor. This paper also mentions other issues associated with neurosurgery and shows the way robotized systems have helped solve these problems. Finally, it highlights the future perspectives of neurosurgery, a branch of medicine that seeks to treat the ailments of the main organ of the human body from the perspective of many disciplines.

  12. Porcine brain extract promotes osteogenic differentiation of bone marrow derived mesenchymal stem cells and bone consolidation in a rat distraction osteogenesis model.

    Directory of Open Access Journals (Sweden)

    Jia Xu

    Full Text Available Distraction osteogenesis (DO is the gold standard to treat large bone defects, but long consolidation period is a major limitation. Innovative efforts to promote osteogenesis are needed. Porcine brain extract (PBE was reported to enhance the proliferation and differentiation of multiple primary cells. In this study, we aimed to develop a method for collecting PBE and investigate its effects on osteogenic differentiation of rat bone marrow derived mesenchymal stem cells (rBMSCs and bone consolidation in a rat DO model. The PBE was collected from neonatal brain tissues of porcine fetus and was used to treat rBMSCs. Following PBE treatment (700 ng/ml, osteogenic differentiation was assessed. Further, we locally injected PBE (7 μg/ml, 100μl or PBS (100μl into the gap in a Sprague-Dawley (SD male rat DO model every three days till termination. X-rays, micro-computed tomography, mechanical testing, histology and immunohischemistry examinations were used to exam the quality of the regenerates. The alkaline phosphatase, calcium deposits, and steogenic markers in the PBE treated rBMSCs were significantly increased. In the rat model, new bone properties of bone volume/total tissue volume and mechanical strength were higher in the PBE treated group. Histological analysis also confirmed more mineralized bone after PBE treatment. The current study reports a standard protocol for PBE collection and demonstrated its positive effects on osteogenic differentiation and bone consolidation in DO. Since the PBE is readily available and very cost effective, PBE may be a potential new bio-source to promote bone formation in patients undergo DO treatment.

  13. Promoting cross-sector partnerships in child welfare: qualitative results from a five-state strategic planning process.

    Science.gov (United States)

    Collins-Camargo, Crystal; Armstrong, Mary I; McBeath, Bowen; Chuang, Emmeline

    2013-01-01

    Little is known about effective strategic planning for public and private child welfare agencies working together to serve families. During a professionally facilitated, strategic planning event, public and private child welfare administrators from five states explored partnership challenges and strengths with a goal of improving collaborative interactions in order to improve outcomes for children and families. Summarizing thematic results of session notes from the planning event, this article describes effective strategies for facilitation of such processes as well as factors that challenge or promote group processes. Implications for conducting strategic planning in jurisdictions seeking to improve public/private partnerships are discussed.

  14. Melatonin Promotes Brain-Derived Neurotrophic Factor (BDNF) Expression and Anti-Apoptotic Effects in Neonatal Hemolytic Hyperbilirubinemia via a Phospholipase (PLC)-Mediated Mechanism.

    Science.gov (United States)

    Luo, Yong; Peng, Mei; Wei, Hong

    2017-12-16

    BACKGROUND Melatonin therapy shows positive effects on neuroprotective factor brain-derived neurotrophic factor (BDNF) expression and neuronal apoptosis in neonatal hemolytic hyperbilirubinemia. We hypothesized that melatonin promotes BDNF expression and anti-apoptotic effects in neonatal hemolytic hyperbilirubinemia through a phospholipase (PLC)-mediated mechanism. MATERIAL AND METHODS A phenylhydrazine hydrochloride (PHZ)-induced neonatal hemolytic hyperbilirubinemia model was constructed in neonatal rats. Four experimental groups - a control group (n=30), a PHZ group (n=30), a PHZ + melatonin group (n=30), and a PHZ + melatonin+U73122 (a PLC inhibitor) group (n=30) - were constructed. Trunk blood was assayed for serum hemoglobin, hematocrit, total and direct bilirubin, BDNF, S100B, and tau protein levels. Brain tissue levels of neuronal apoptosis, BDNF expression, PLC activity, IP3 content, phospho- and total Ca2+/calmodulin-dependent protein kinase type IV (CaMKIV) expression, and phospho- and total cAMP response element binding protein (CREB) expression were also assayed. RESULTS PHZ-induced hemolytic hyperbilirubinemia was validated by significantly decreased serum hemoglobin and hematocrit as well as significantly increased total and direct serum bilirubin (pPLC/IP3/Ca2+ pathway activation while increasing neuronal apoptosis levels (pPLC inhibitor U73122 largely abolished the positive effects of melatonin on PLC/IP3/Ca2+ pathway activation, downstream BDNF levels, and neuronal apoptosis (pPLC-mediated mechanism.

  15. Differences in brain functional connectivity at resting state in neonates born to healthy obese or normal-weight mothers.

    Science.gov (United States)

    Li, X; Andres, A; Shankar, K; Pivik, R T; Glasier, C M; Ramakrishnaiah, R H; Zhang, Y; Badger, T M; Ou, X

    2016-12-01

    Recent studies have shown associations between maternal obesity at pre- or early pregnancy and long-term neurodevelopment in children, suggesting in utero effects of maternal obesity on offspring brain development. In this study, we examined whether brain functional connectivity to the prefrontal lobe network is different in newborns from normal-weight or obese mothers. Thirty-four full-term healthy infants from uncomplicated pregnancies were included, with 18 born to normal-weight and 16 born to obese mothers. Two weeks after delivery, the infants underwent an magnetic resonance imaging (MRI) examination during natural sleep, which included structural imaging and resting-state functional MRI (fMRI) scans. Independent component analysis was used to identify the prefrontal lobe network, and dual regression was used to compare functional connectivity between groups. Infants born to normal-weight mothers had higher recruiting (Pweight gain and infant postmenstrual age, gender, birth weight/length, head circumference and neonatal diet. The functional connectivity strength in dorsal anterior cingulate cortex negatively correlated (P<0.05) with maternal fat mass percentage measured at early pregnancy. This preliminary study indicates that exposure to maternal obesity in utero may be associated with changes in resting-state functional connectivity in the newborn offspring's brain.

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

    Directory of Open Access Journals (Sweden)

    Cui-Ping Xu

    2013-01-01

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

  17. A Resting-State Brain Functional Network Study in MDD Based on Minimum Spanning Tree Analysis and the Hierarchical Clustering

    Directory of Open Access Journals (Sweden)

    Xiaowei Li

    2017-01-01

    Full Text Available A large number of studies demonstrated that major depressive disorder (MDD is characterized by the alterations in brain functional connections which is also identifiable during the brain’s “resting-state.” But, in the present study, the approach of constructing functional connectivity is often biased by the choice of the threshold. Besides, more attention was paid to the number and length of links in brain networks, and the clustering partitioning of nodes was unclear. Therefore, minimum spanning tree (MST analysis and the hierarchical clustering were first used for the depression disease in this study. Resting-state electroencephalogram (EEG sources were assessed from 15 healthy and 23 major depressive subjects. Then the coherence, MST, and the hierarchical clustering were obtained. In the theta band, coherence analysis showed that the EEG coherence of the MDD patients was significantly higher than that of the healthy controls especially in the left temporal region. The MST results indicated the higher leaf fraction in the depressed group. Compared with the normal group, the major depressive patients lost clustering in frontal regions. Our findings suggested that there was a stronger brain interaction in the MDD group and a left-right functional imbalance in the frontal regions for MDD controls.

  18. Using architecture and technology to promote improved quality of life for military service members with traumatic brain injury.

    Science.gov (United States)

    Pasquina, Paul F; Pasquina, Lavinia Fici; Anderson-Barnes, Victoria C; Giuggio, Jeffrey S; Cooper, Rory A

    2010-02-01

    Today, injured service members are surviving wounds that would have been fatal in previous wars. A recent RAND report estimates that approximately 320,000 service members may have experienced a traumatic brain injury (TBI) during deployment, and it is not uncommon for a soldier to sustain multiple associated injuries such as limb loss, paralysis, sensory loss, and psychological damage. As a result, many military service members and their families face significant challenges returning to a high quality of independent life. The architectural concepts of universal design (UD) and evidence-based design (EBD) are gaining interest as an integral part of the rehabilitation process of veterans with TBI. This article examines the possibilities presented by UD and EBD in accordance with the Americans with Disabilities Act of 1990, in terms of high-end building and interior design quality, and possible technological options for individuals with disabilities.

  19. Hericium erinaceus Extract Reduces Anxiety and Depressive Behaviors by Promoting Hippocampal Neurogenesis in the Adult Mouse Brain.

    Science.gov (United States)

    Ryu, Sun; Kim, Hyoun Geun; Kim, Joo Youn; Kim, Seong Yun; Cho, Kyung-Ok

    2018-02-01

    Versatile biological activities of Hericium erinaceus (HE) have been reported in many brain diseases. However, roles of HE in major psychiatric disorders such as depression and anxiety remain to be investigated. Therefore, we evaluated whether HE could reduce anxiety and depressive behaviors in the adult mouse and its underlying mechanisms. Male C57BL/6 mice were administered HE (20 or 60 mg/kg, p.o.) or saline once a day for 4 weeks. Open field and tail suspension tests were performed 30 min after the last administration of HE, followed by forced swim test 2 days later. We found that chronic administration of HE showed anxiolytic and antidepressant-like effects. To elucidate possible mechanisms, proliferative activity of the hippocampal progenitor cells was assessed by immunohistochemistry of proliferating cell nuclear antigen (PCNA) and Ki67. Moreover, to evaluate neuronal survival in the dentate gyrus, 5-bromo-2'-deoxyuridine (BrdU) (120 mg/kg, i.p.) was given at the first day of HE administration, followed by isolation of the brains 4 weeks later. HE (60 mg/kg) increased the number of PCNA- and Ki67-positive cells in the subgranular zone of the hippocampus, indicating increased proliferation of hippocampal progenitors. In addition, BrdU- and BrdU/NeuN-positive cells in the dentate gyrus were significantly increased when treated with HE (60 mg/kg) compared with the saline-treated group, demonstrating enhanced neurogenesis by HE treatment. Taken together, the results indicate that chronic HE administration can exert anxiolytic and antidepressant-like effects, possibly by enhancing adult hippocampal neurogenesis.

  20. Serum levels of brain-derived neurotrophic factor in major depressive disorder : state-trait issues, clinical features and pharmacological treatment

    NARCIS (Netherlands)

    Molendijk, M. L.; Bus, B. A. A.; Spinhoven, Ph; Penninx, B. W. J. H.; Kenis, G.; Prickaerts, J.; Voshaar, R. C. Oude; Elzinga, B. M.

    2011-01-01

    Recent evidence supports 'the neurotrophin hypothesis of depression' in its prediction that brain-derived neurotrophic factor (BDNF) is involved in depression. However, some key questions remain unanswered, including whether abnormalities in BDNF persist beyond the clinical state of depression,

  1. E-cigarette availability and promotion among retail outlets near college campuses in two southeastern states.

    Science.gov (United States)

    Wagoner, Kimberly G; Song, Eunyoung Y; Egan, Kathleen L; Sutfin, Erin L; Reboussin, Beth A; Spangler, John; Wolfson, Mark

    2014-08-01

    E-cigarettes are relatively new products that simulate the smoking experience. This descriptive study assessed changes in e-cigarette availability and promotions among retailers in 11 college communities in North Carolina and Virginia during a 1-year period. During the spring of 2012 and 2013, observers completed assessments in 320 tobacco-selling retailers, including grocery and convenience stores, pharmacies, and tobacco shops. Assessors collected e-cigarette availability, advertising, price, and promotions. E-cigarette availability increased among retailers from 24.7% in 2012 to 59.9% in 2013. They were available in the form of disposables and reusable kits and were most frequently available in tobacco shops, convenience stores, and pharmacies. The average price for disposables was $9.70 (SD = 1.07) in 2012 and $9.61 (SD = 2.10) in 2013; the average price for kits was $39.58 (SD = 15.79) in 2012 and $32.59 (SD = 18.65) in 2013. The presence of interior advertising increased from 12.7% to 50.6% (p cigarettes, including rechargeable kits and disposables, more than doubled during the study. The presence of interior and exterior advertising also significantly increased. Results underscore the need for further surveillance to understand how these environmental characteristics impact individual exposure and use of e-cigarettes. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Disrupted resting-state brain network properties in obesity: decreased global and putaminal cortico-striatal network efficiency.

    Science.gov (United States)

    Baek, K; Morris, L S; Kundu, P; Voon, V

    2017-03-01

    The efficient organization and communication of brain networks underlie cognitive processing and their disruption can lead to pathological behaviours. Few studies have focused on whole-brain networks in obesity and binge eating disorder (BED). Here we used multi-echo resting-state functional magnetic resonance imaging (rsfMRI) along with a data-driven graph theory approach to assess brain network characteristics in obesity and BED. Multi-echo rsfMRI scans were collected from 40 obese subjects (including 20 BED patients) and 40 healthy controls and denoised using multi-echo independent component analysis (ME-ICA). We constructed a whole-brain functional connectivity matrix with normalized correlation coefficients between regional mean blood oxygenation level-dependent (BOLD) signals from 90 brain regions in the Automated Anatomical Labeling atlas. We computed global and regional network properties in the binarized connectivity matrices with an edge density of 5%-25%. We also verified our findings using a separate parcellation, the Harvard-Oxford atlas parcellated into 470 regions. Obese subjects exhibited significantly reduced global and local network efficiency as well as decreased modularity compared with healthy controls, showing disruption in small-world and modular network structures. In regional metrics, the putamen, pallidum and thalamus exhibited significantly decreased nodal degree and efficiency in obese subjects. Obese subjects also showed decreased connectivity of cortico-striatal/cortico-thalamic networks associated with putaminal and cortical motor regions. These findings were significant with ME-ICA with limited group differences observed with conventional denoising or single-echo analysis. Using this data-driven analysis of multi-echo rsfMRI data, we found disruption in global network properties and motor cortico-striatal networks in obesity consistent with habit formation theories. Our findings highlight the role of network properties in

  3. Investigating Focal Connectivity Deficits in Alzheimer's Disease Using Directional Brain Networks Derived from Resting-State fMRI

    Directory of Open Access Journals (Sweden)

    Sinan Zhao

    2017-07-01

    Full Text Available Connectivity analysis of resting-state fMRI has been widely used to identify biomarkers of Alzheimer's disease (AD based on brain network aberrations. However, it is not straightforward to interpret such connectivity results since our understanding of brain functioning relies on regional properties (activations and morphometric changes more than connections. Further, from an interventional standpoint, it is easier to modulate the activity of regions (using brain stimulation, neurofeedback, etc. rather than connections. Therefore, we employed a novel approach for identifying focal directed connectivity deficits in AD compared to healthy controls. In brief, we present a model of directed connectivity (using Granger causality that characterizes the coupling among different regions in healthy controls and Alzheimer's disease. We then characterized group differences using a (between-subject generative model of pathology, which generates latent connectivity variables that best explain the (within-subject directed connectivity. Crucially, our generative model at the second (between-subject level explains connectivity in terms of local or regionally specific abnormalities. This allows one to explain disconnections among multiple regions in terms of regionally specific pathology; thereby offering a target for therapeutic intervention. Two foci were identified, locus coeruleus in the brain stem and right orbitofrontal cortex. Corresponding disrupted connectivity network associated with the foci showed that the brainstem is the critical focus of disruption in AD. We further partitioned the aberrant connectomic network into four unique sub-networks, which likely leads to symptoms commonly observed in AD. Our findings suggest that fMRI studies of AD, which have been largely cortico-centric, could in future investigate the role of brain stem in AD.

  4. Combining brain stimulation and video game to promote long-term transfer of learning and cognitive enhancement.

    Science.gov (United States)

    Looi, Chung Yen; Duta, Mihaela; Brem, Anna-Katharine; Huber, Stefan; Nuerk, Hans-Christoph; Cohen Kadosh, Roi

    2016-02-23

    Cognitive training offers the potential for individualised learning, prevention of cognitive decline, and rehabilitation. However, key research challenges include ecological validity (training design), transfer of learning and long-term effects. Given that cognitive training and neuromodulation affect neuroplasticity, their combination could promote greater, synergistic effects. We investigated whether combining transcranial direct current stimulation (tDCS) with cognitive training could further enhance cognitive performance compared to training alone, and promote transfer within a short period of time. Healthy adults received real or sham tDCS over their dorsolateral prefrontal cortices during two 30-minute mathematics training sessions involving body movements. To examine the role of training, an active control group received tDCS during a non-mathematical task. Those who received real tDCS performed significantly better in the game than the sham group, and showed transfer effects to working memory, a related but non-numerical cognitive domain. This transfer effect was absent in active and sham control groups. Furthermore, training gains were more pronounced amongst those with lower baseline cognitive abilities, suggesting the potential for reducing cognitive inequalities. All effects associated with real tDCS remained 2 months post-training. Our study demonstrates the potential benefit of this approach for long-term enhancement of human learning and cognition.

  5. Testing promotes long-term learning via stabilizing activation patterns in a large network of brain areas.

    Science.gov (United States)

    Keresztes, Attila; Kaiser, Daniel; Kovács, Gyula; Racsmány, Mihály

    2014-11-01

    The testing effect refers to the phenomenon that repeated retrieval of memories promotes better long-term retention than repeated study. To investigate the neural correlates of the testing effect, we used event-related functional magnetic resonance imaging methods while participants performed a cued recall task. Prior to the neuroimaging experiment, participants learned Swahili-German word pairs, then half of the word pairs were repeatedly studied, whereas the other half were repeatedly tested. For half of the participants, the neuroimaging experiment was performed immediately after the learning phase; a 1-week retention interval was inserted for the other half of the participants. We found that a large network of areas identified in a separate 2-back functional localizer scan were active during the final recall of the word pair associations. Importantly, the learning strategy (retest or restudy) of the word pairs determined the manner in which the retention interval affected the activations within this network. Recall of previously restudied memories was accompanied by reduced activation within this network at long retention intervals, but no reduction was observed for previously retested memories. We suggest that retrieval promotes learning via stabilizing cue-related activation patterns in a network of areas usually associated with cognitive and attentional control functions. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  6. Left Brain. Right Brain. Whole Brain

    Science.gov (United States)

    Farmer, Lesley S. J.

    2004-01-01

    As the United States student population is becoming more diverse, library media specialists need to find ways to address these distinctive needs. However, some of these differences transcend culture, touching on variations in the brain itself. Most people have a dominant side of the brain, which can affect their personality and learning style.…

  7. Honoring Work in Wisconsin: State Policies To Promote Self-Sufficiency for Working Families.

    Science.gov (United States)

    Wisconsin Univ., Madison. Center on Wisconsin Strategy.

    Many of Wisconsin's working families face economic distress, living from paycheck to paycheck and being forced to choose between paying their rent or buying food for their children. Parents under stress often cannot support their children with time, energy or resources. In order to affirm the importance of children in the state, and to help build…

  8. 78 FR 77368 - Peanut Promotion, Research, and Information Order; Amendment to Primary Peanut-Producing States...

    Science.gov (United States)

    2013-12-23

    ... reviewed under Executive Order 12988, Civil Justice Reform. It is not intended to have retroactive effect..., by the Commodity Credit Corporation. ] The Order distinguishes between the terms ``minor peanut... defined as minor peanut-producing States, pursuant to section 1217.15. As specified in section 1216.40(a...

  9. The Role of the State School Psychology Organizations in the Promotion of Professional Ethics.

    Science.gov (United States)

    Pryzwansky, Walter B.; Wenger, Ralph D.

    1979-01-01

    A survey was conducted to examine the role of state school psychology organizations in advocating for and monitoring the ethical practice of their members. Results revealed that 76 percent of the responding organizations had adopted a code of ethics, while only 43 percent had instituted due process procedures. (Author)

  10. USBF recognized President Ilves for promoting relations between the Baltic countries and the United States

    Index Scriptorium Estoniae

    2008-01-01

    President Toomas Hendrik Ilves pälvis Balti riikide ja Ameerika Ühendriikide suhete edendamise eest Ameerika-Balti Fondi (USBF - The United States-Baltic Foundation) autasu - Baltic Statesmanship Award'i. Vabariigi President töövisiidil Ameerika Ühendriikides 17.-23.04.2008

  11. Learning by Dispossession: Democracy Promotion and Civic Engagement in Iraq and the United States