WorldWideScience

Sample records for non-permissive brain disorder

  1. Genetic Brain Disorders

    Science.gov (United States)

    A genetic brain disorder is caused by a variation or a mutation in a gene. A variation is a different form ... mutation is a change in a gene. Genetic brain disorders affect the development and function of the ...

  2. Metallothionein in Brain Disorders

    Directory of Open Access Journals (Sweden)

    Daniel Juárez-Rebollar

    2017-01-01

    Full Text Available Metallothioneins are a family of proteins which are able to bind metals intracellularly, so their main function is to regulate the cellular metabolism of essential metals. There are 4 major isoforms of MTs (I–IV, three of which have been localized in the central nervous system. MT-I and MT-II have been localized in the spinal cord and brain, mainly in astrocytes, whereas MT-III has been found mainly in neurons. MT-I and MT-II have been considered polyvalent proteins whose main function is to maintain cellular homeostasis of essential metals such as zinc and copper, but other functions have also been considered: detoxification of heavy metals, regulation of gene expression, processes of inflammation, and protection against free radicals generated by oxidative stress. On the other hand, the MT-III has been related in events of pathogenesis of neurodegenerative diseases such as Parkinson and Alzheimer. Likewise, the participation of MTs in other neurological disorders has also been reported. This review shows recent evidence about the role of MT in the central nervous system and its possible role in neurodegenerative diseases as well as in brain disorders.

  3. Mental disorders are not brain disorders.

    Science.gov (United States)

    Banner, Natalie F

    2013-06-01

    As advances in neuroscience and genetics reveal complex associations between brain structures, functions and symptoms of mental disorders, there have been calls for psychiatric classifications to be reconfigured, to conceptualize mental disorders as disorders of the brain. In this paper, I argue that this view is mistaken, and that the level at which we identify mental disorders is, and should be, the person, not the brain. This is not to deny physicalism or argue that the mental realm is somehow distinct from the physical, but rather to suggest the things that are going 'wrong' in mental disorder are picked out at the person-level: they are characterized by breaches in epistemic, rational, evaluative, emotional, social and moral norms. However, as our scientific understanding of the brain becomes advanced, what makes an identified neurobiological difference in brain structure or functioning indicative of pathology is its association with these behaviours at the person-level. Instead of collapsing psychiatry into biomedicine, biomedicine may benefit from drawing closer to the expertise of psychiatry, as it is able to accommodate social, psychological and biological explanations while focusing on the person, within their environment.

  4. Traumatic brain injury-induced sleep disorders

    Directory of Open Access Journals (Sweden)

    Viola-Saltzman M

    2016-02-01

    Full Text Available Mari Viola-Saltzman, Camelia Musleh Department of Neurology, NorthShore University HealthSystem, Evanston, IL, USA Abstract: Sleep disturbances are frequently identified following traumatic brain injury, affecting 30%–70% of persons, and often occur after mild head injury. Insomnia, fatigue, and sleepiness are the most frequent sleep complaints after traumatic brain injury. Sleep apnea, narcolepsy, periodic limb movement disorder, and parasomnias may also occur after a head injury. In addition, depression, anxiety, and pain are common brain injury comorbidities with significant influence on sleep quality. Two types of traumatic brain injury that may negatively impact sleep are acceleration/deceleration injuries causing generalized brain damage and contact injuries causing focal brain damage. Polysomnography, multiple sleep latency testing, and/or actigraphy may be utilized to diagnose sleep disorders after a head injury. Depending on the disorder, treatment may include the use of medications, positive airway pressure, and/or behavioral modifications. Unfortunately, the treatment of sleep disorders associated with traumatic brain injury may not improve neuropsychological function or sleepiness. Keywords: traumatic brain injury, insomnia, hypersomnia, sleep apnea, periodic limb movement disorder, fatigue

  5. Brain Imaging in Gambling Disorder

    OpenAIRE

    Quester, Saskia; Romanczuk-Seiferth, Nina

    2015-01-01

    Gambling disorder recently was reclassified under the category “substance-related and addictive disorders.” With regard to the diagnostic criteria, it overlaps a great deal with substance use disorder, i.e., loss of control, craving/withdrawal, and neglect of other areas of life. However, the gambling disorder symptom “chasing one’s losses” is the only criterion absent from substance use disorder. Therefore, special forms of reward (i.e., gain/loss) processing, such as the processing of loss ...

  6. Brain CB₂ Receptors: Implications for Neuropsychiatric Disorders.

    Science.gov (United States)

    Roche, Michelle; Finn, David P

    2010-08-10

    Although previously thought of as the peripheral cannabinoid receptor, it is now accepted that the CB₂ receptor is expressed in the central nervous system on microglia, astrocytes and subpopulations of neurons. Expression of the CB₂ receptor in the brain is significantly lower than that of the CB₁ receptor. Conflicting findings have been reported on the neurological effects of pharmacological agents targeting the CB₂ receptor under normal conditions. Under inflammatory conditions, CB₂ receptor expression in the brain is enhanced and CB2 receptor agonists exhibit potent anti-inflammatory effects. These findings have prompted research into the CB₂ receptor as a possible target for the treatment of neuroinflammatory and neurodegenerative disorders. Neuroinflammatory alterations are also associated with neuropsychiatric disorders and polymorphisms in the CB₂ gene have been reported in depression, eating disorders and schizophrenia. This review will examine the evidence to date for a role of brain CB₂ receptors in neuropsychiatric disorders.

  7. Movement disorders induced by deep brain stimulation.

    Science.gov (United States)

    Baizabal-Carvallo, José Fidel; Jankovic, Joseph

    2016-04-01

    Deep brain stimulation represents a major advance in the treatment of several types of movement disorders. However, during stimulation new movement disorders may emerge, thus limiting the positive effects of this therapy. These movement disorders may be induced by: 1) stimulation of the targeted nucleus, 2) stimulation of surrounding tracts and nuclei, and 3) as a result of dose adjustment of accompanying medications, such as reduction of dopaminergic drugs in patients with Parkinson's disease. Various dyskinesias, blepharospasm, and apraxia of eyelid opening have been described mainly with subthalamic nucleus stimulation, whereas hypokinesia and freezing of gait have been observed with stimulation of the globus pallidus internus. Other deep brain stimulation-related movement disorders include dyskinesias associated with stimulation of the globus pallidus externus and ataxic gait as a side effect of chronic bilateral stimulation of the ventral intermediate nucleus of thalamus. These movement disorders are generally reversible and usually resolved once the stimulation is reduced or turned off. This, however, typically leads to loss of benefit of the underlying movement disorder which can be re-gained by using different contacts, changing targets or stimulation parameters, and adjusting pharmacological therapy. New and innovative emerging technologies and stimulation techniques may help to prevent or overcome the various deep brain stimulation-induced movement disorders. In this review we aim to describe the clinical features, frequency, pathophysiology, and strategies for treatment of these iatrogenic movement disorders.

  8. Deep Brain Stimulation for Movement Disorders.

    Science.gov (United States)

    Revell, Maria A

    2015-12-01

    Disruption in the interaction between the central nervous system, nerves, and muscles cause movement disorders. These disorders can negatively affect quality of life. Deep brain stimulation (DBS) has been identified as a therapy for Parkinson disease and essential tremor that has significant advantages compared with medicinal therapies. Surgical intervention for these disorders before DBS included ablative therapies such as thalamotomy and pallidotomy. These procedures were not reversible and did not allow for treatment adjustments. The advent of DBS progressed therapies for significant movement disorders into the realm of being reversible and adjustable based on patient symptoms.

  9. Movement disorders caused by brain tumours.

    Directory of Open Access Journals (Sweden)

    Bhatoe H

    1999-01-01

    Full Text Available Movement disorders are uncommon presenting features of brain tumours. Early recognition of such lesions is important to arrest further deficit. We treated seven patients with movement disorders secondary to brain tumours over a period of seven years. Only two of these were intrinsic thalamic tumours (astrocytomas while the rest were extrinsic tumours. The intrinsic tumours were accompanied by hemichorea. Among the extrinsic tumours, there was one pituitary macroadenoma with hemiballismus and four meningiomas with parkinsonism. Symptoms were unilateral in all patients except one with anterior third falcine meningioma who had bilateral rest tremors. There was relief in movement disorders observed after surgery. Imaging by computed tomography or magnetic resonance imaging is mandatory in the evaluation of movement disorders, especially if the presentation is atypical, unilateral and/or accompanied by long tract signs.

  10. [Roles of Aquaporins in Brain Disorders].

    Science.gov (United States)

    Yasui, Masato

    2015-06-01

    Aquaporin (AQP) is a water channel protein that is expressed in the cell membranes. AQPs are related to several kinds of human diseases such as cataract. In the mammalian central nervous system (CNS), AQP4 is specifically expressed in the astrocyte membranes lining the perivascular and periventricular structures. AQP4 plays a role in the development of brain edema associated with certain brain disorders. Neuromyelitis optica (NMO) is a demyelinating disorder, and patients with NMO develop autoimmune antibodies against AQP4 in their serum. Therefore, AQP4 is involved in NMO pathogenesis. A new concept referred to as "glymphatic pathway" has been recently proposed to explain the lymphatic system in the CNS. Dysfunction of the "glymphatic pathway" may cause several neurodegenerative diseases and mood disorders. Importantly, AQP4 may play a role in the "glymphatic pathway". Further investigation of AQP4 in CNS disorders is necessary, and a new drug against AQP4 is expected.

  11. Cannabis use disorders and brain morphology

    NARCIS (Netherlands)

    Lorenzetti, V.; Cousijn, J.; Preedy, V.R.

    2016-01-01

    Cannabis use disorders (CUDs) affect 13.1. million individuals worldwide and represent the most vulnerable portion of regular cannabis users. Neuroanatomical alterations in the brain may mediate the adverse outcomes of CUDs. We reviewed findings from 16 structural neuroimaging studies of gray matter

  12. Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

    Science.gov (United States)

    Kim, Woojun; Kim, Su-Hyun; Huh, So-Young; Kim, Ho Jin

    2012-01-01

    Neuromyelitis optica (NMO) is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON) and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD), and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced. PMID:23259063

  13. Brain Abnormalities in Neuromyelitis Optica Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Woojun Kim

    2012-01-01

    Full Text Available Neuromyelitis optica (NMO is an idiopathic inflammatory syndrome of the central nervous system that is characterized by severe attacks of optic neuritis (ON and myelitis. Until recently, NMO was considered a disease without brain involvement. However, since the discovery of NMO-IgG/antiaqaporin-4 antibody, the concept of NMO was broadened to NMO spectrum disorder (NMOSD, and brain lesions are commonly recognized. Furthermore, some patients present with brain symptoms as their first manifestation and develop recurrent brain symptoms without ON or myelitis. Brain lesions with characteristic locations and configurations can be helpful in the diagnosis of NMOSD. Due to the growing recognition of brain abnormalities in NMOSD, these have been included in the NMO and NMOSD diagnostic criteria or guidelines. Recent technical developments such as diffusion tensor imaging, MR spectroscopy, and voxel-based morphometry reveal new findings related to brain abnormalities in NMOSD that were not identified using conventional MRI. This paper focuses on the incidence and characteristics of the brain lesions found in NMOSD and the symptoms that they cause. Recent studies using advanced imaging techniques are also introduced.

  14. Brain stimulation in posttraumatic stress disorder.

    Science.gov (United States)

    Novakovic, Vladan; Sher, Leo; Lapidus, Kyle A B; Mindes, Janet; A Golier, Julia; Yehuda, Rachel

    2011-01-01

    Posttraumatic stress disorder (PTSD) is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT) and Cranial electrotherapy stimulation (CES) have both been in use for decades; transcranial magnetic stimulation (TMS), magnetic seizure therapy (MST), deep brain stimulation (DBS), transcranial Direct Current Stimulation (tDCS), and vagus nerve stimulation (VNS) have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES), depression (ECT, CES, rTMS, VNS, DBS), obsessive-compulsive disorder (OCD) (DBS), essential tremor, dystonia (DBS), epilepsy (DBS, VNS), Parkinson Disease (DBS), pain (CES), and insomnia (CES). To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

  15. [Deep brain stimulation for hyperkinetic movement disorders].

    Science.gov (United States)

    Reich, M M; Volkmann, J

    2014-02-01

    The term hyperkinetic movement disorder encompasses dystonia, tremor, chorea, myoclon and tics. These symptoms are all caused by dysfunctional neural networks including the basal ganglia loop and can be accompanied by other neurological or psychiatric symptoms. Deep brain stimulation (DBS) is an important extension of therapeutic options for this group of patients in whom drug therapy is limited. Permanent electrodes are implanted in various subcortical brain areas in order to achieve an improvement in motor symptoms by high frequency stimulation. Already established indications include primary generalized or segmental dystonia and essential tremor but an increasingly better understanding of systemic pathophysiology has allowed DBS to be explored as a treatment for other disorders of the hyperkinetic spectrum. This article provides an overview of common hyperkinetic movement disorders from the viewpoint of recent advances in neurostimulation therapy.

  16. Hemodynamic Disorders in Severe Brain Injury

    Directory of Open Access Journals (Sweden)

    Yu. A. Churlyaev

    2006-01-01

    Full Text Available This study was undertaken to determine the general regularities of hemodynamic disorders in relation to the severity of brain damage for the subsequent development of pathogenetically warranted methods for their correction in the complex of intensive care for severe brain injury. Studies were made in 67 victims, by using neurophysiological studies (electroencephalography, studies of acoustical stem-evoked potentials and somatosensory stem-evoked potentials, computed tomography and magnetic resonance imaging. Central hemodynamics was studied by a Sirecust 1260 monitoring system using Swan-Ganz catheters and thermodilution. The overall condition of the victims was regarded as very bad. Loss of consciousness was 8-4 scores by the Glasgow coma scale. The studies have indicated that the victims in whose clinical picture the signs of compression of the cerebral hemispheres dominate over those of the latter’s contusion develop a hemodynamic reaction by the normodynamic type. The hyperdynamic type of hemodynamic disorder develops in cerebral hemispheric and diencephalic lesions with a parallel increase in oxygen transport and uptake; and in severe brain injury, lower brain stem damages are accompanied by hemodynamic disorder by the hypodynamic type with a reduction in oxygen transport and uptake.

  17. Psychiatric disorders and traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Marcelo Schwarzbold

    2008-09-01

    Full Text Available Marcelo Schwarzbold1, Alexandre Diaz1, Evandro Tostes Martins2, Armanda Rufino1, Lúcia Nazareth Amante1,3, Maria Emília Thais1, João Quevedo4, Alexandre Hohl1, Marcelo Neves Linhares1,5,6, Roger Walz1,61Núcleo de Pesquisas em Neurologia Clínica e Experimental (NUPNEC, Departamento de Clínica Médica, Hospital Universitário, UFSC, Florianópolis, SC, Brazil; 2Unidade de Terapia Intensiva, Hospital Governador Celso Ramos, Florianópolis, SC, Brazil; 3Departamento de Enfermagem, UFSC, Florianópolis, SC, Brazil; 4Laboratório de Neurociências, UNESC, Criciúma, SC, Brazil; 5Departamento de Cirurgia, Hospital Universitário, UFSC, Florianópolis, SC, Brazil; 6Centro de Cirurgia de Epilepsia de Santa Catarina (CEPESC, Hospital Governador Celso Ramos, Florianópolis, SC, BrazilAbstract: Psychiatric disorders after traumatic brain injury (TBI are frequent. Researches in this area are important for the patients’ care and they may provide hints for the comprehension of primary psychiatric disorders. Here we approach epidemiology, diagnosis, associated factors and treatment of the main psychiatric disorders after TBI. Finally, the present situation of the knowledge in this field is discussed.Keywords: psychiatric disorders, traumatic brain injury, neuropsychiatry, diagnostic, epidemiology, pathophysiology

  18. Brain stimulation in posttraumatic stress disorder

    Directory of Open Access Journals (Sweden)

    Vladan Novakovic

    2011-10-01

    Full Text Available Posttraumatic stress disorder (PTSD is a complex, heterogeneous disorder that develops following trauma and often includes perceptual, cognitive, affective, physiological, and psychological features. PTSD is characterized by hyperarousal, intrusive thoughts, exaggerated startle response, flashbacks, nightmares, sleep disturbances, emotional numbness, and persistent avoidance of trauma-associated stimuli. The efficacy of available treatments for PTSD may result in part from relief of associated depressive and anxiety-related symptoms in addition to treatment of core symptoms that derive from reexperiencing, numbing, and hyperarousal. Diverse, heterogeneous mechanisms of action and the ability to act broadly or very locally may enable brain stimulation devices to address PTSD core symptoms in more targeted ways. To achieve this goal, specific theoretical bases derived from novel, well-designed research protocols will be necessary. Brain stimulation devices include both long-used and new electrical and magnetic devices. Electroconvulsive therapy (ECT and Cranial electrotherapy stimulation (CES have both been in use for decades; transcranial magnetic stimulation (TMS, magnetic seizure therapy (MST, deep brain stimulation (DBS, transcranial Direct Current Stimulation (tDCS, and vagus nerve stimulation (VNS have been developed recently, over approximately the past twenty years. The efficacy of brain stimulation has been demonstrated as a treatment for psychiatric and neurological disorders such as anxiety (CES, depression (ECT, CES, rTMS, VNS, DBS, obsessive-compulsive disorder (OCD (DBS, essential tremor, dystonia (DBS, epilepsy (DBS, VNS, Parkinson Disease (DBS, pain (CES, and insomnia (CES. To date, limited data on brain stimulation for PTSD offer only modest guidance. ECT has shown some efficacy in reducing comorbid depression in PTSD patients but has not been demonstrated to improve most core PTSD symptoms. CES and VNS have shown some efficacy in

  19. MRI of brain disease in veterinary patients part 1: Basic principles and congenital brain disorders.

    Science.gov (United States)

    Hecht, Silke; Adams, William H

    2010-01-01

    Magnetic resonance imaging (MRI) is increasingly being used in the diagnosis of central nervous system disorders in veterinary patients and is quickly becoming the imaging modality of choice in evaluation of brain and intracranial disease. This article provides an overview of the basic principles of MRI, a description of sequences and their applications in brain imaging, and an approach to interpretation of brain MRI. A detailed discussion of imaging findings in general intracranial disorders including hydrocephalus, vasogenic edema, brain herniation, and seizure-associated changes, and the MR diagnosis of congenital brain disorders is provided. MRI evaluation of acquired brain disorders is described in a second companion article.

  20. COST OF DISORDERS OF THE BRAIN IN SLOVENIA*

    Directory of Open Access Journals (Sweden)

    David B.Vodušek

    2008-05-01

    Full Text Available Whereas there are many publications on disorders of, for instance, heart or kidney function, there are few, if any, on brain disorders, which are traditionally viewed separately asmental, neurological or neurosurgical disorders. There are, however, marked similaritiesand shared interests between the fields and, most importantly, basic neuroscience is equally relevant for all clinical problems. The European Brain Council has analysed the burdenand the cost of brain disorders in Europe. The aim of the present text is to report data forSlovenia.Twelve different disorders (or groups of disorders of brain believed to have the highestcost (addiction, affective disorders, anxiety disorders, brain tumours, dementia, epilepsy,migraine and other headaches, multiple sclerosis, Parkinson’s disease, psychotic disorders,stroke, and trauma were analysed. Epidemiology data for Europe were collected as12-month prevalence data for disorders by country and stratified according to age,gender, and disorder severity. Because little original data were available for Slovenia,extrapolated data were used. Health economic data (representing direct medical costs,direct non-medical costs, and indirect costs being transformed into euros for the year2004 were entered into a health economic model.The total number of brain disorders in Slovenia amounted to 570,000 in 2004, and whencorrected for co-morbidity, 1/5 of the Slovenian population have a brain disorder. Inparticular, this is 39,000 alcohol dependents and illicit drug dependants, 105.000 affectivedisorders, 195,000 anxiety disorders, 178,000 migraine, etc. The total cost of all includedbrain disorders in Slovenia was estimated at 833 million euros, the most costly beingaffective disorders, dementia, and addiction. It should be mentioned that both the epidemiological data and the resulting cost are significantly underestimated for several disorders,particularly stroke. Direct health care cost mounted to 403 million

  1. The economic cost of brain disorders in Europe

    DEFF Research Database (Denmark)

    Olesen, J; Gustavsson, A; Svensson, M

    2012-01-01

    In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries.......In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries....

  2. Cost of disorders of the brain in Europe 2010.

    NARCIS (Netherlands)

    Gustavsson, A.; Svensson, M.; Jacobi, F.; Allgulander, C.; Alonso, J.; Beghi, E.; Dodel, R.; Ekman, M.; Faravelli, C.; Fratiglioni, L.; Gannon, B.; Jones, D.H.; Jennum, P.; Jordanova, A.; Jonsson, L.; Karampampa, K.; Knapp, M.; Kobelt, G.; Kurth, T.; Lieb, R.; Linde, M.; Ljungcrantz, C.; Maercker, A.; Melin, B.; Moscarelli, M.; Musayev, A.; Norwood, F.; Preisig, M.; Pugliatti, M.; Rehm, J.; Salvador-Carulla, L.; Schlehofer, B.; Simon, R.; Steinhausen, H.C.; Stovner, L.J.; Vallat, J.M.; Bergh, P.V. den; Os, J. van; Vos, P.E.; Xu, W.; Wittchen, H.U.; Jonsson, B.; Olesen, J.

    2011-01-01

    BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-ter

  3. Cost of disorders of the brain in Europe 2010.

    NARCIS (Netherlands)

    Gustavsson, A.; Svensson, M.; Jacobi, F.; Allgulander, C.; Alonso, J.; Beghi, E.; Dodel, R.; Ekman, M.; Faravelli, C.; Fratiglioni, L.; Gannon, B.; Jones, D.H.; Jennum, P.; Jordanova, A.; Jonsson, L.; Karampampa, K.; Knapp, M.; Kobelt, G.; Kurth, T.; Lieb, R.; Linde, M.; Ljungcrantz, C.; Maercker, A.; Melin, B.; Moscarelli, M.; Musayev, A.; Norwood, F.; Preisig, M.; Pugliatti, M.; Rehm, J.; Salvador-Carulla, L.; Schlehofer, B.; Simon, R.; Steinhausen, H.C.; Stovner, L.J.; Vallat, J.M.; Bergh, P.V. den; Os, J. van; Vos, P.E.; Xu, W.; Wittchen, H.U.; Jonsson, B.; Olesen, J.

    2011-01-01

    BACKGROUND: The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and

  4. Brain connectivity and sensory stimulation in disorders of consciousness

    OpenAIRE

    Heine, Lizette

    2016-01-01

    This thesis explores brain connectivity and sensory stimulation in patients with disorders of consciousness (DOC). These are serious conditions where massive brain damage can lead to a dissociation between arousal and awareness (e.g., UWS and MCS). Part I explores brain connectivity. We highlight that brain function and structure are intimately related to each other, and to consciousness. The decrease in brain function can be used to distinguish between the clinically indicated states of ...

  5. Establishment of hepatitis E virus infection-permissive and -non-permissive human hepatoma PLC/PRF/5 subclones.

    Science.gov (United States)

    Shiota, Tomoyuki; Li, Tian-Cheng; Yoshizaki, Sayaka; Kato, Takanobu; Wakita, Takaji; Ishii, Koji

    2015-02-01

    PLC/PRF/5 cells show limited permissiveness, meaning that almost all subclones are permissive; however, some subclones do not exhibit permissiveness for hepatitis E virus (HEV) infection. In this study, the single-cell cloning of PLC/PRF/5 was performed and heterogeneous subclones characterized. Notably, the efficiency of intracellular virus replication did not correlate with the permissiveness for HEV infection. However, as well as binding permissive subclones, virus-like particles bound non-permissive subclones on various levels, suggesting that these subclones have some deficiencies in the attachment and entry steps of infection. Our data would be useful for investigating the HEV life cycle. © 2014 The Societies and Wiley Publishing Asia Pty Ltd.

  6. Genomic studies of mood disorders - the brain as a muscle?

    OpenAIRE

    Niculescu, Alexander B.

    2005-01-01

    Recent genomic studies showing abnormalities in the fibroblast growth factor system in the postmortem brains of people with major depressive disorder support previous indications of a role for growth factors in mood disorders. Similar molecular pathways, volumetric changes, and the effects of exercise on mood suggest a superficial analogy, and perhaps a deeper relationship, between muscle and brain functioning.

  7. Traumatic Brain Injury as a Cause of Behavior Disorders.

    Science.gov (United States)

    Nordlund, Marcia R.

    There is increasing evidence that many children and adolescents who display behavior disorders have sustained a traumatic brain injury. Traumatic brain injury can take the following forms: closed head trauma in which the brain usually suffers diffuse damage; open head injury which usually results in specific focal damage; or internal trauma (e.g.,…

  8. Devastating metabolic brain disorders of newborns and young infants.

    Science.gov (United States)

    Yoon, Hyun Jung; Kim, Ji Hye; Jeon, Tae Yeon; Yoo, So-Young; Eo, Hong

    2014-01-01

    Metabolic disorders of the brain that manifest in the neonatal or early infantile period are usually associated with acute and severe illness and are thus referred to as devastating metabolic disorders. Most of these disorders may be classified as organic acid disorders, amino acid metabolism disorders, primary lactic acidosis, or fatty acid oxidation disorders. Each disorder has distinctive clinical, biochemical, and radiologic features. Early diagnosis is important both for prompt treatment to prevent death or serious sequelae and for genetic counseling. However, diagnosis is often challenging because many findings overlap and may mimic those of more common neonatal conditions, such as hypoxic-ischemic encephalopathy and infection. Ultrasonography (US) may be an initial screening method for the neonatal brain, and magnetic resonance (MR) imaging is the modality of choice for evaluating metabolic brain disorders. Although nonspecific imaging findings are common in early-onset metabolic disorders, characteristic patterns of brain involvement have been described for several disorders. In addition, diffusion-weighted images may be used to characterize edema during an acute episode of encephalopathy, and MR spectroscopy depicts changes in metabolites that may help diagnose metabolic disorders and assess response to treatment. Imaging findings, including those of advanced MR imaging techniques, must be closely reviewed. If one of these rare disorders is suspected, the appropriate biochemical test or analysis of the specific gene should be performed to confirm the diagnosis.

  9. Fractionation of Social Brain Circuits in Autism Spectrum Disorders

    Science.gov (United States)

    Gotts, Stephen J.; Simmons, W. Kyle; Milbury, Lydia A.; Wallace, Gregory L.; Cox, Robert W.; Martin, Alex

    2012-01-01

    Autism spectrum disorders are developmental disorders characterized by impairments in social and communication abilities and repetitive behaviours. Converging neuroscientific evidence has suggested that the neuropathology of autism spectrum disorders is widely distributed, involving impaired connectivity throughout the brain. Here, we evaluate the…

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

    Science.gov (United States)

    Frank, Guido K W

    2013-10-01

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

  11. TOOL USE DISORDERS AFTER LEFT BRAIN DAMAGE

    Directory of Open Access Journals (Sweden)

    Josselin eBaumard

    2014-05-01

    Full Text Available In this paper we review studies that investigated tool use disorders in left-brain damaged (LBD patients over the last thirty years. Four tasks are classically used in the field of apraxia: Pantomime of tool use, single tool use, real tool use and mechanical problem solving. Our aim was to address two issues, namely, (1 the role of mechanical knowledge in real tool use and (2 the cognitive mechanisms underlying pantomime of tool use, a task widely employed by clinicians and researchers. To do so, we extracted data from 36 papers and computed the difference between healthy subjects and LBD patients. On the whole, pantomime of tool use is the most difficult task and real tool use is the easiest one. Moreover, associations seem to appear between pantomime of tool use, real tool use and mechanical problem solving. These results suggest that the loss of mechanical knowledge is critical in LBD patients, even if all of those tasks (and particularly pantomime of tool use might put differential demands on semantic memory and working memory.

  12. Cost of disorders of the brain in Denmark

    DEFF Research Database (Denmark)

    Olesen, J.; Sobocki, P.; Truelsen, T.

    2008-01-01

    scientific literature. The present study presents results for Denmark. There were an estimated 1.4 million Danish citizens who in 2004 had one of the selected 12 brain diseases, equivalent to one quarter of the total population. Anxiety disorders and migraine were the two most frequent diseases with 500......The cost of brain disorders in Denmark is unknown and such information is important to decision makers. The aims of the study were to estimate the total number of subjects with brain diseases, and the associated direct and indirect expenses in Denmark. This was part of a larger pan-European study......,000 and 340,000 patients, respectively. The total expenses for all selected brain diseases were 37.3 billion DKR. Affective disorders, dependency, dementia and stroke were the most costly diseases. An estimated 12% of all direct costs in the Danish health system were spent on brain diseases; 9% of the total...

  13. The gut-brain axis, BDNF, NMDA and CNS disorders

    OpenAIRE

    Maqsood, Raeesah; Stone, Trevor W.

    2016-01-01

    Gastro-intestinal (GI) microbiota and the ‘gut-brain axis’ are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-d-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of...

  14. Differential expression of microRNAs in the non-permissive schistosome host Microtus fortis under schistosome infection.

    Directory of Open Access Journals (Sweden)

    Hongxiao Han

    Full Text Available The reed vole Microtus fortis is the only mammal known in China in which the growth, development and maturation of schistosomes (Schistosoma japonicum is prevented. It might be that the anti-schistosomiasis mechanisms of M. fortis associate with microRNA-mediated gene expression, given that the latter has been found to be involved in gene regulation in eukaryotes. In the present study, the difference between pathological changes in tissues of M. fortis and of mice (Mus musculus post-schistosome infection were observed by using hematoxylin-eosin staining. In addition, microarray technique was applied to identify differentially expressed miRNAs in the same tissues before and post-infection to analyze the potential roles of miRNAs in schistosome infection in these two different types of host. Histological analyses showed that S. japonicum infection in M. fortis resulted in a more intensive inflammatory response and pathological change than in mice. The microarray analysis revealed that 162 miRNAs were expressed in both species, with 12 in liver, 32 in spleen and 34 in lung being differentially expressed in M. fortis. The functions of the differentially expressed miRNAs were mainly revolved in nutrient metabolism, immune regulation, etc. Further analysis revealed that important signaling pathways were triggered after infection by S. japonicum in M. fortis but not in the mice. These results provide new insights into the general mechanisms of regulation in the non-permissive schistosome host M. fortis that exploits potential miRNA regulatory networks. Such information will help improve current understanding of schistosome development and host-parasite interactions.

  15. Differential expression of microRNAs in the non-permissive schistosome host Microtus fortis under schistosome infection.

    Science.gov (United States)

    Han, Hongxiao; Peng, Jinbiao; Han, Yanhui; Zhang, Min; Hong, Yang; Fu, Zhiqiang; Yang, Jianmei; Tao, Jianping; Lin, Jiaojiao

    2013-01-01

    The reed vole Microtus fortis is the only mammal known in China in which the growth, development and maturation of schistosomes (Schistosoma japonicum) is prevented. It might be that the anti-schistosomiasis mechanisms of M. fortis associate with microRNA-mediated gene expression, given that the latter has been found to be involved in gene regulation in eukaryotes. In the present study, the difference between pathological changes in tissues of M. fortis and of mice (Mus musculus) post-schistosome infection were observed by using hematoxylin-eosin staining. In addition, microarray technique was applied to identify differentially expressed miRNAs in the same tissues before and post-infection to analyze the potential roles of miRNAs in schistosome infection in these two different types of host. Histological analyses showed that S. japonicum infection in M. fortis resulted in a more intensive inflammatory response and pathological change than in mice. The microarray analysis revealed that 162 miRNAs were expressed in both species, with 12 in liver, 32 in spleen and 34 in lung being differentially expressed in M. fortis. The functions of the differentially expressed miRNAs were mainly revolved in nutrient metabolism, immune regulation, etc. Further analysis revealed that important signaling pathways were triggered after infection by S. japonicum in M. fortis but not in the mice. These results provide new insights into the general mechanisms of regulation in the non-permissive schistosome host M. fortis that exploits potential miRNA regulatory networks. Such information will help improve current understanding of schistosome development and host-parasite interactions.

  16. Cost of disorders of the brain in Europe 2010

    DEFF Research Database (Denmark)

    Gustavsson, Anders; Svensson, Mikael; Jacobi, Frank

    2011-01-01

    The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long-term impairm......The spectrum of disorders of the brain is large, covering hundreds of disorders that are listed in either the mental or neurological disorder chapters of the established international diagnostic classification systems. These disorders have a high prevalence as well as short- and long......-term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate...... report we cover 19 major groups of disorders, 7 more than previously, of an increased range of age groups and more cost items. We therefore present much improved cost estimates. Our revised estimates also now include the new EU member states, and hence a population of 514 million people....

  17. The economic cost of brain disorders in Europe

    NARCIS (Netherlands)

    Olesen, J.; Gustavsson, A.; Svensson, M.; Wittchen, H.U.; Jonsson, B.; Vos, P.E.

    2012-01-01

    BACKGROUND AND PURPOSE: In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries. METHODS: One-year prevalenc

  18. Cost of disorders of the brain in Slovenia in 2010

    Directory of Open Access Journals (Sweden)

    Jurij Bon

    2013-02-01

    Conclusion: This EBC study is based on the best currently available data in Europe and the model enables extrapolation to countries where no data could be found. Still, the scarcity of data is an important source of uncertainty in estimates and may imply over- or underestimations in some disorders and countries, including Slovenia, where there are still no reliable epidemiological and health-economic data on brain disorders. Even though this review included many disorders, diagnoses, age groups and cost items that were omitted in 2004, there are still remaining disorders that could not be included due to limitations in the available data. The estimate of the total cost of brain disorders in Europe and Slovenia is therefore considered to be conservative. In terms of the health economic burden outlined in the EBC report and here, disorders of the brain likely constitute the number one economic challenge for health care in all European countries, now and in the future. The results are consistent with administrative data on the health care expenditure in Europe, and comparable to previous studies on the cost of specific disorders in Europe, while being lower than analogous estimates from the US. The reported results should be considered by all stakeholders, including policy makers, industry and patient advocacy groups, to reconsider the current science, research and public health agenda and shape a coordinated national action-plan to address the imminent challenges posed by disorders of the brain.

  19. The economic cost of brain disorders in Europe

    NARCIS (Netherlands)

    Olesen, J.; Gustavsson, A.; Svensson, M.; Wittchen, H.U.; Jonsson, B.; Vos, P.E.

    2012-01-01

    BACKGROUND AND PURPOSE: In 2005, we presented for the first time overall estimates of annual costs for brain disorders (mental and neurologic disorders) in Europe. This new report presents updated, more accurate, and comprehensive 2010 estimates for 30 European countries. METHODS: One-year

  20. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    Science.gov (United States)

    Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

    2013-01-01

    Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

  1. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    Science.gov (United States)

    Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

    2008-01-01

    Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

  2. Morphometric Brain Abnormalities in Boys with Conduct Disorder

    Science.gov (United States)

    Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

    2008-01-01

    Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

  3. Brain Structure Abnormalities in Adolescent Girls with Conduct Disorder

    Science.gov (United States)

    Fairchild, Graeme; Hagan, Cindy C.; Walsh, Nicholas D.; Passamonti, Luca; Calder, Andrew J.; Goodyer, Ian M.

    2013-01-01

    Background: Conduct disorder (CD) in female adolescents is associated with a range of negative outcomes, including teenage pregnancy and antisocial personality disorder. Although recent studies have documented changes in brain structure and function in male adolescents with CD, there have been no neuroimaging studies of female adolescents with CD.…

  4. Brain CB2 Receptors: Implications for Neuropsychiatric Disorders

    Science.gov (United States)

    Roche, Michelle; Finn, David P

    2010-01-01

    Although previously thought of as the peripheral cannabinoid receptor, it is now accepted that the CB2 receptor is expressed in the central nervous system on microglia, astrocytes and subpopulations of neurons. Expression of the CB2 receptor in the brain is significantly lower than that of the CB1 receptor. Conflicting findings have been reported on the neurological effects of pharmacological agents targeting the CB2 receptor under normal conditions. Under inflammatory conditions, CB2 receptor expression in the brain is enhanced and CB2 receptor agonists exhibit potent anti-inflammatory effects. These findings have prompted research into the CB2 receptor as a possible target for the treatment of neuroinflammatory and neurodegenerative disorders. Neuroinflammatory alterations are also associated with neuropsychiatric disorders and polymorphisms in the CB2 gene have been reported in depression, eating disorders and schizophrenia. This review will examine the evidence to date for a role of brain CB2 receptors in neuropsychiatric disorders. PMID:27713365

  5. Brain CB2 Receptors: Implications for Neuropsychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Michelle Roche

    2010-08-01

    Full Text Available Although previously thought of as the peripheral cannabinoid receptor, it is now accepted that the CB2 receptor is expressed in the central nervous system on microglia, astrocytes and subpopulations of neurons. Expression of the CB2 receptor in the brain is significantly lower than that of the CB1 receptor. Conflicting findings have been reported on the neurological effects of pharmacological agents targeting the CB2 receptor under normal conditions. Under inflammatory conditions, CB2 receptor expression in the brain is enhanced and CB2 receptor agonists exhibit potent anti-inflammatory effects. These findings have prompted research into the CB2 receptor as a possible target for the treatment of neuroinflammatory and neurodegenerative disorders. Neuroinflammatory alterations are also associated with neuropsychiatric disorders and polymorphisms in the CB2 gene have been reported in depression, eating disorders and schizophrenia. This review will examine the evidence to date for a role of brain CB2 receptors in neuropsychiatric disorders.

  6. Brain imaging of affective disorders and schizophrenia.

    Science.gov (United States)

    Kishimoto, H; Yamada, K; Iseki, E; Kosaka, K; Okoshi, T

    1998-12-01

    We review recent findings in human brain imaging, for example, which brain areas are used during perception of colors, moving objects, human faces, facial expressions, sadness and happiness etc. One study used fluorine-18-labeled deoxyglucose positron emission tomography (PET) in patients with unipolar depression and bipolar depression, and found hypometabolism in the left anterolateral prefrontal cortex. Another study reported increased regional cerebral blood flow in the amygdala in familial pure depressive disease. Using 11C-glucose PET, we reported that the glutamic acid pool was reduced in cortical areas of the brain in patients with major depression. We also found that the thalamic and cingulate areas were hyperactive in drug-naive (never medicated) acute schizophrenics, while the associative frontal, parietal, temporal gyri were hypoactive in drug-naive chronic schizophrenics. Brain biochemical disturbances of schizophrenic patients involved glutamic acid, N-acetyl aspartic acid, phosphatidylcholine and sphingomyelin which are important chemical substances in the working brain. The areas of the thalamus and the cingulate which become hyperactive in acute schizophrenic patients are important brain areas for perception and communication. The association areas of the cortex which become disturbed in chronic schizophrenia are essential brain areas in human creativity (language, concepts, formation of cultures and societies) and exist only in human beings.

  7. Shining light on the head: Photobiomodulation for brain disorders

    Directory of Open Access Journals (Sweden)

    Michael R. Hamblin

    2016-12-01

    Full Text Available Photobiomodulation (PBM describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia, degenerative diseases (dementia, Alzheimer's and Parkinson's, and psychiatric disorders (depression, anxiety, post traumatic stress disorder. There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM application, near-infrared (NIR light is often applied to the forehead because of the better penetration (no hair, longer wavelength. Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED arrays has allowed the development of light emitting helmets or “brain caps”. This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.

  8. Brain oscillations in bipolar disorder and lithium-induced changes.

    Science.gov (United States)

    Atagün, Murat İlhan

    2016-01-01

    Electroencephalography (EEG) studies in patients with bipolar disorder have revealed lower amplitudes in brain oscillations. The aim of this review is to describe lithium-induced EEG changes in bipolar disorder and to discuss potential underlying factors. A literature survey about lithium-induced EEG changes in bipolar disorder was performed. Lithium consistently enhances magnitudes of brain oscillations in slow frequencies (delta and theta) in both resting-state EEG studies as well as event-related oscillations studies. Enhancement of magnitudes of beta oscillations is specific to event-related oscillations. Correlation between serum lithium levels and brain oscillations has been reported. Lithium-induced changes in brain oscillations might correspond to lithium-induced alterations in neurotransmitters, signaling cascades, plasticity, brain structure, or biophysical properties of lithium. Therefore, lithium-induced changes in brain oscillations could be promising biomarkers to assess the molecular mechanisms leading to variability in efficacy. Since the variability of lithium response in bipolar disorder is due to the genetic differences in the mechanisms involving lithium, it would be highly promising to assess the lithium-induced EEG changes as biomarkers in genetic studies.

  9. Brain disorders and the biological role of music.

    Science.gov (United States)

    Clark, Camilla N; Downey, Laura E; Warren, Jason D

    2015-03-01

    Despite its evident universality and high social value, the ultimate biological role of music and its connection to brain disorders remain poorly understood. Recent findings from basic neuroscience have shed fresh light on these old problems. New insights provided by clinical neuroscience concerning the effects of brain disorders promise to be particularly valuable in uncovering the underlying cognitive and neural architecture of music and for assessing candidate accounts of the biological role of music. Here we advance a new model of the biological role of music in human evolution and the link to brain disorders, drawing on diverse lines of evidence derived from comparative ethology, cognitive neuropsychology and neuroimaging studies in the normal and the disordered brain. We propose that music evolved from the call signals of our hominid ancestors as a means mentally to rehearse and predict potentially costly, affectively laden social routines in surrogate, coded, low-cost form: essentially, a mechanism for transforming emotional mental states efficiently and adaptively into social signals. This biological role of music has its legacy today in the disordered processing of music and mental states that characterizes certain developmental and acquired clinical syndromes of brain network disintegration. © The Author (2014). Published by Oxford University Press.

  10. Urea cycle disorders: brain MRI and neurological outcome

    Energy Technology Data Exchange (ETDEWEB)

    Bireley, William R. [University of Colorado, Department of Radiology, Aurora, CO (United States); Van Hove, Johan L.K. [University of Colorado, Department of Genetics and Inherited Metabolic Diseases, Aurora, CO (United States); Gallagher, Renata C. [Children' s Hospital Colorado, Department of Genetics and Inherited Metabolic Diseases, Aurora, CO (United States); Fenton, Laura Z. [Children' s Hospital Colorado, Department of Pediatric Radiology, Aurora, CO (United States)

    2012-04-15

    Urea cycle disorders encompass several enzyme deficiencies that can result in cerebral damage, with a wide clinical spectrum from asymptomatic to severe. The goal of this study was to correlate brain MRI abnormalities in urea cycle disorders with clinical neurological sequelae to evaluate whether MRI abnormalities can assist in guiding difficult treatment decisions. We performed a retrospective chart review of patients with urea cycle disorders and symptomatic hyperammonemia. Brain MRI images were reviewed for abnormalities that correlated with severity of clinical neurological sequelae. Our case series comprises six urea cycle disorder patients, five with ornithine transcarbamylase deficiency and one with citrullinemia type 1. The observed trend in distribution of brain MRI abnormalities as the severity of neurological sequelae increased was the peri-insular region first, extending into the frontal, parietal, temporal and, finally, the occipital lobes. There was thalamic restricted diffusion in three children with prolonged hyperammonemia. Prior to death, this site is typically reported to be spared in urea cycle disorders. The pattern and extent of brain MRI abnormalities correlate with clinical neurological outcome in our case series. This suggests that brain MRI abnormalities may assist in determining prognosis and helping clinicians with subsequent treatment decisions. (orig.)

  11. Clinical features of depressive disorders in patients with brain tumors

    Directory of Open Access Journals (Sweden)

    Ogorenko V.V.

    2014-03-01

    Full Text Available The aim of the study was to examine the structure of psychopathology and clinical features of depressive disorders in patients with brain oncopathology. Polymorphic mental disorders of various clinical content and severity in most cases not only are comorbid to oncological pathology of the brain, but most often are the first clinical signs of early tumors. The study was conducted using the following methods: clinical psychiatric, questionnaire Simptom Check List- 90 -Revised-SCL- 90 -R, Luscher test and mathematical processing methods. Sample included 175 patients with brain tumors with non-psychotic level of mental disorders. The peculiarities of mental disorders and psychopathological structure of nonpsychotic depressive disorders have been a clinical option of cancer debut in patients with brain tumors. We found that nonpsychotic depression is characterized by polymorphism and syndromal incompletion; this causes ambiguity of diagnoses interpretation on stages of diagnostic period. Features of depressive symptoms depending on the signs of malignancy / nonmalignancy of brain tumor were defined.

  12. Subcortical brain alterations in major depressive disorder : findings from the ENIGMA Major Depressive Disorder working group

    NARCIS (Netherlands)

    Schmaal, L.; Veltman, D. J.; van Erp, T. G. M.; Saemann, P. G.; Frodl, T.; Jahanshad, N.; Loehrer, E.; Tiemeier, H.; Hofman, A.; Niessen, W. J.; Vernooij, M. W.; Ikram, M. A.; Wittfeld, K.; Grabe, H. J.; Block, A.; Hegenscheid, K.; Voelzke, H.; Hoehn, D.; Czisch, M.; Lagopoulos, J.; Hatton, S. N.; Hickie, I. B.; Goya-Maldonado, R.; Kraemer, B.; Gruber, O.; Couvy-Duchesne, B.; Renteria, M. E.; Strike, L. T.; Mills, N. T.; de Zubicaray, G. I.; McMahon, K. L.; Medland, S. E.; Martin, N. G.; Gillespie, N. A.; Wright, M. J.; Hall, G.B.; MacQueen, G. M.; Frey, E. M.; Carballedo, A.; van Velzen, L. S.; van Tol, M. J.; van der Wee, N. J.; Veer, I. M.; Walter, H.; Schnell, K.; Schramm, E.; Normann, C.; Schoepf, D.; Konrad, C.; Zurowski, B.; Nickson, T.; McIntosh, A. M.; Papmeyer, M.; Whalley, H. C.; Sussmann, J. E.; Godlewska, B. R.; Cowen, P. J.; Fischer, F. H.; Rose, M.; Penninx, B. W. J. H.; Thompson, P. M.; Hibar, D. P.

    2016-01-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristic

  13. [Neuroprotective mechanisms of cannabinoids in brain ischemia and neurodegenerative disorders].

    Science.gov (United States)

    Osuna-Zazuetal, Marcela Amparo; Ponce-Gómez, Juan Antonio; Pérez-Neri, Iván

    2015-06-01

    One of the most important causes of morbidity and mortality is neurologic dysfunction; its high incidence has led to an intense research of the mechanisms that protect the central nervous system from hypoxia and ischemia. The mayor challenge is to block the biochemical events leading to neuronal death. This may be achieved by neuroprotective mechanisms that avoid the metabolic and immunologic cascades that follow a neurological damage. When it occurs, several pathophysiological events develop including cytokine release, oxidative stress and excitotoxicity. Neuroprotective effects of cannabinoids to all those mechanisms have been reported in animal models of brain ischemia, excitotoxicity, brain trauma and neurodegenerative disorders. Some endocannabinoid analogs are being tested in clinical studies (I-III phase) for acute disorders involving neuronal death (brain trauma and ischemia). The study of the cannabinoid system may allow the discovery of effective neuroprotective drugs for the treatment of neurological disorders.

  14. The microbiota-gut-brain axis in functional gastrointestinal disorders

    Science.gov (United States)

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients’ quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other’s expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis. PMID:24921926

  15. The microbiota-gut-brain axis in functional gastrointestinal disorders.

    Science.gov (United States)

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl

    2014-01-01

    Functional gastrointestinal disorders (FGIDs) are highly prevalent and pose a significant burden on health care and society, and impact patients' quality of life. FGIDs comprise a heterogeneous group of disorders, with unclear underlying pathophysiology. They are considered to result from the interaction of altered gut physiology and psychological factors via the gut-brain axis, where brain and gut symptoms are reciprocally influencing each other's expression. Intestinal microbiota, as a part of the gut-brain axis, plays a central role in FGIDs. Patients with Irritable Bowel Syndrome, a prototype of FGIDs, display altered composition of the gut microbiota compared with healthy controls and benefit, at the gastrointestinal and psychological levels, from the use of probiotics and antibiotics. This review aims to recapitulate the available literature on FGIDs and microbiota-gut-brain axis.

  16. Shining light on the head: Photobiomodulation for brain disorders

    OpenAIRE

    Hamblin, Michael R.

    2016-01-01

    Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, trauma...

  17. Brain-Derived Neurotrophic Factor and Neuropsychiatric Disorders

    OpenAIRE

    Anita E Autry; Monteggia, Lisa M.

    2012-01-01

    Brain derived neurotrophic factor (BDNF) is the most prevalent growth factor in the central nervous system (CNS). It is essential for the development of the CNS and for neuronal plasticity. Because BDNF plays a crucial role in development and plasticity of the brain, it is widely implicated in psychiatric diseases. This review provides a summary of clinical and preclinical evidence for the involvement of this ubiquitous growth factor in major depressive disorder, schizophrenia, addiction, Ret...

  18. A review of heterogeneous data mining for brain disorder identification.

    Science.gov (United States)

    Cao, Bokai; Kong, Xiangnan; Yu, Philip S

    2015-12-01

    With rapid advances in neuroimaging techniques, the research on brain disorder identification has become an emerging area in the data mining community. Brain disorder data poses many unique challenges for data mining research. For example, the raw data generated by neuroimaging experiments is in tensor representations, with typical characteristics of high dimensionality, structural complexity, and nonlinear separability. Furthermore, brain connectivity networks can be constructed from the tensor data, embedding subtle interactions between brain regions. Other clinical measures are usually available reflecting the disease status from different perspectives. It is expected that integrating complementary information in the tensor data and the brain network data, and incorporating other clinical parameters will be potentially transformative for investigating disease mechanisms and for informing therapeutic interventions. Many research efforts have been devoted to this area. They have achieved great success in various applications, such as tensor-based modeling, subgraph pattern mining, and multi-view feature analysis. In this paper, we review some recent data mining methods that are used for analyzing brain disorders.

  19. Brain vein disorders in newborn infants

    NARCIS (Netherlands)

    Raets, Marlou; Dudink, Jeroen; Raybaud, Charles; Ramenghi, Luca; Lequin, Maarten; Govaert, Paul

    2015-01-01

    The brain veins of infants are in a complex phase of remodelling in the perinatal period. Magnetic resonance venography and susceptibility-weighted imaging, together with high-resolution Doppler ultrasound, have provided new tools to aid study of venous developmental anatomy and disease. This review

  20. Genomic and Epigenomic Insights into Nutrition and Brain Disorders

    OpenAIRE

    Margaret Joy Dauncey

    2013-01-01

    Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer’s disease, schizophrenia, Parkinson’s disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype...

  1. Gene-Tailored Treatments for Brain Disorders: Challenges and Opportunities.

    Science.gov (United States)

    Esposito, Giovanni; Burgunder, Jean Marc; Dunlop, John; Gorwood, Philip; Inamdar, Amir; Pfister, Stefan M; Pochet, Roland; van den Bent, Martin J; Van Hoylandt, Nancy; Weller, Michael; Westphal, Manfred; Wick, Wolfgang; Nutt, David

    Brain disorders pose major challenges to medicine and treatment innovation. This is because their spectrum spans inflammatory, degenerative, traumatic/ischaemic, and neoplastic disease processes with a complex and often ill- understood aetiology. An improved genetic and genomic understanding of specific disease pathways offers new approaches to these challenges, but at present it is in its infancy. Here, we review different aspects of the challenges facing neuromedicine, give examples of where there are advances, and highlight challenges to be overcome. We see that some disorders such as Huntington's disease are the product of single gene mutations, whose discovery has been leading to the development of new targeted interventions. In the field of neurosurgery, the identification of a number of mutations allows an elaborated genetic analysis of brain tumours and opens the door to individualised therapies. Psychiatric disorders remain the area where progress is slow. Genetic analyses show that for major common disorders such as schizophrenia and depression there are no single gene alterations which offer options for targeted therapy development. However, new approaches are being developed to leverage genetic information to predict patients' responses to treatment. These recent developments hold promise for early diagnosis, follow-up with personalised treatments with adjusted therapeutic doses, predictable responses, reduced adverse drug reactions, and personal health planning. The scenario is promising but calls for increased support for curiosity-driven research into the mechanisms of normal brain functioning as well as challenging adaptations of health care and research infrastructures, encompassing legal frameworks for analysing large amounts of personal data, a flexible regulatory framework for correlating big data analyses in cooperative networks between academia and the drug development industry, and finally new strategies for brain banking in order to increase

  2. [Depressive Disorder and Gut-brain Interaction].

    Science.gov (United States)

    Kunugi, Hiroshi

    2016-06-01

    Depressive disorder is a stress-induced condition, which has been suggested to have bidirectional interactions with the gut microbiota. Probiotics such as Bifidobacterium and Lactobacillus have been suggested to mitigate stress response. Irritable bowel syndrome (IBS) is a typical phenotype of psychological distress manifested in the gastrointestinal system, and often develops in patients with depressive disorder. The altered gut microbiota and resultant inflammation in the gut play an important role in at least a portion of IBS. Animal models of depression have shown abnormalities in the gut such as increased gut permeability, and the probiotics ameliorate their chronic depression-like behaviors and altered stress responses. There have been only a few studies that have directly investigated the gut microbiota in patients with depression. We reported results suggesting that individuals with lower bacterial counts for Bifidobacterium and/or Lactobacillus are more common in patients with major depressive disorder than in healthy controls. the collectively use of gut microbiota in the diagnosis and treatment of depressive disorder seems to be a promising approach.

  3. Transdiagnostic brain responses to disorder-related threat across four psychiatric disorders.

    Science.gov (United States)

    Feldker, K; Heitmann, C Y; Neumeister, P; Tupak, S V; Schrammen, E; Moeck, R; Zwitserlood, P; Bruchmann, M; Straube, T

    2017-03-01

    There is an ongoing debate whether transdiagnostic neural mechanisms are shared by different anxiety-related disorders or whether different disorders show distinct neural correlates. To investigate this issue, studies controlling for design and stimuli across multiple anxiety-related disorders are needed. The present functional magnetic resonance imaging study investigated neural correlates of visual disorder-related threat processing across unmedicated patients suffering from panic disorder (n = 20), social anxiety disorder (n = 20), dental phobia (n = 16) and post-traumatic stress disorder (n = 11) relative to healthy controls (HC; n = 67). Each patient group and the corresponding HC group saw a tailor-made picture set with 50 disorder-related and 50 neutral scenes. Across all patients, increased activation to disorder-related v. neutral scenes was found in subregions of the bilateral amygdala. In addition, activation of the lateral amygdala to disorder-related v. neutral scenes correlated positively with subjective anxiety ratings of scenes across patients. Furthermore, whole-brain analysis revealed increased responses to disorder-related threat across the four disorders in middle, medial and superior frontal regions, (para-)limbic regions, such as the insula and thalamus, as well as in the brainstem and occipital lobe. We found no disorder-specific brain responses. The results suggest that pathologically heightened lateral amygdala activation is linked to experienced anxiety across anxiety disorders and trauma- and stressor-related disorders. Furthermore, the transdiagnostically shared activation network points to a common neural basis of abnormal responses to disorder-related threat stimuli across the four investigated disorders.

  4. Blood-brain barrier dysfunction in disorders of the developing brain

    Science.gov (United States)

    Moretti, Raffaella; Pansiot, Julien; Bettati, Donatella; Strazielle, Nathalie; Ghersi-Egea, Jean-François; Damante, Giuseppe; Fleiss, Bobbi; Titomanlio, Luigi; Gressens, Pierre

    2015-01-01

    Disorders of the developing brain represent a major health problem. The neurological manifestations of brain lesions can range from severe clinical deficits to more subtle neurological signs or behavioral problems and learning disabilities, which often become evident many years after the initial damage. These long-term sequelae are due at least in part to central nervous system immaturity at the time of the insult. The blood-brain barrier (BBB) protects the brain and maintains homeostasis. BBB alterations are observed during both acute and chronic brain insults. After an insult, excitatory amino acid neurotransmitters are released, causing reactive oxygen species (ROS)-dependent changes in BBB permeability that allow immune cells to enter and stimulate an inflammatory response. The cytokines, chemokines and other molecules released as well as peripheral and local immune cells can activate an inflammatory cascade in the brain, leading to secondary neurodegeneration that can continue for months or even years and finally contribute to post-insult neuronal deficits. The role of the BBB in perinatal disorders is poorly understood. The inflammatory response, which can be either acute (e.g., perinatal stroke, traumatic brain injury) or chronic (e.g., perinatal infectious diseases) actively modulates the pathophysiological processes underlying brain injury. We present an overview of current knowledge about BBB dysfunction in the developing brain during acute and chronic insults, along with clinical and experimental data. PMID:25741233

  5. Structural and functional brain changes in delusional disorder.

    Science.gov (United States)

    Vicens, Victor; Radua, Joaquim; Salvador, Raymond; Anguera-Camós, Maria; Canales-Rodríguez, Erick J; Sarró, Salvador; Maristany, Teresa; McKenna, Peter J; Pomarol-Clotet, Edith

    2016-02-01

    Delusional disorder has been the subject of very little investigation using brain imaging. To examine potential structural and/or functional brain abnormalities in this disorder. We used structural imaging (voxel-based morphometry, VBM) and functional imaging (during performance of the n-back task and whole-brain resting connectivity analysis) to examine 22 patients meeting DSM-IV criteria for delusional disorder and 44 matched healthy controls. The patients showed grey matter reductions in the medial frontal/anterior cingulate cortex and bilateral insula on unmodulated (but not on modulated) VBM analysis, failure of de-activation in the medial frontal/anterior cingulate cortex during performance of the n-back task, and decreased resting-state connectivity in the bilateral insula. The findings provide evidence of brain abnormality in the medial frontal/anterior cingulate cortex and insula in delusional disorder. A role for the former region in the pathogenesis of delusions is consistent with several other lines of evidence. © The Royal College of Psychiatrists 2016.

  6. Blood and Brain Glutamate Levels in Children with Autistic Disorder

    Science.gov (United States)

    Hassan, Tamer H.; Abdelrahman, Hadeel M.; Fattah, Nelly R. Abdel; El-Masry, Nagda M.; Hashim, Haitham M.; El-Gerby, Khaled M.; Fattah, Nermin R. Abdel

    2013-01-01

    Despite of the great efforts that move forward to clarify the pathophysiologic mechanisms in autism, the cause of this disorder, however, remains largely unknown. There is an increasing body of literature concerning neurochemical contributions to the pathophysiology of autism. We aimed to determine blood and brain levels of glutamate in children…

  7. Cost of disorders of the brain in Europe 2010

    DEFF Research Database (Denmark)

    Gustavsson, Anders; Svensson, Mikael; Jacobi, Frank

    2011-01-01

    -term impairments and disabilities. Therefore they are an emotional, financial and social burden to the patients, their families and their social network. In a 2005 landmark study, we estimated for the first time the annual cost of 12 major groups of disorders of the brain in Europe and gave a conservative estimate...

  8. The neurobiology of brain and cognitive reserve: mental and physical activity as modulators of brain disorders.

    Science.gov (United States)

    Nithianantharajah, Jess; Hannan, Anthony J

    2009-12-01

    The concept of 'cognitive reserve', and a broader theory of 'brain reserve', were originally proposed to help explain epidemiological data indicating that individuals who engaged in higher levels of mental and physical activity via education, occupation and recreation, were at lower risk of developing Alzheimer's disease and other forms of dementia. Subsequently, behavioral, cellular and molecular studies in animals (predominantly mice and rats) have revealed dramatic effects of environmental enrichment, which involves enhanced levels of sensory, cognitive and motor stimulation via housing in novel, complex environments. Furthermore, increasing levels of voluntary physical exercise, via ad libitum access to running wheels, can have significant effects on brain and behavior, thus informing the relative effects of mental and physical activity. More recently, animal models of brain disorders have been compared under environmentally stimulating and standard housing conditions, and this has provided new insights into environmental modulators and gene-environment interactions involved in pathogenesis. Here, we review animal studies that have investigated the effects of modifying mental and physical activity via experimental manipulations, and discuss their relevance to brain and cognitive reserve (BCR). Recent evidence suggests that the concept of BCR is not only relevant to brain aging, neurodegenerative diseases and dementia, but also to other neurological and psychiatric disorders. Understanding the cellular and molecular mechanisms mediating BCR may not only facilitate future strategies aimed at optimising healthy brain aging, but could also identify molecular targets for novel pharmacological approaches aimed at boosting BCR in 'at risk' and symptomatic individuals with various brain disorders.

  9. Molecular aging of the brain, neuroplasticity, and vulnerability to depression and other brain-related disorders.

    Science.gov (United States)

    Sibille, Etienne

    2013-03-01

    The increased risk for neurodegenerative and neuropsychiatric disorders associated with extended lifespan has long suggested mechanistic links between chronological age and brain-related disorders, including depression, Recent characterizations of age-dependent gene expression changes now show that aging of the human brain engages a specific set of biological pathways along a continuous lifelong trajectory, and that the same genes that are associated with normal brain aging are also frequently and similarly implicated in depression and other brain-related disorders. These correlative observations suggest a model of age-by-disease molecular interactions, in which brain aging promotes biological changes associated with diseases, and additional environmental factors and genetic variability contribute to defining disease risk or resiliency trajectories. Here we review the characteristic features of brain aging in terms of changes in gene function over time, and then focus on evidence supporting accelerated molecular aging in depression. This proposed age-by-disease biological interaction model addresses the current gap in research between "normal" brain aging and its connection to late-life diseases. The implications of this model are profound, as it provides an investigational framework for identifying critical moderating factors, outlines opportunities for early interventions or preventions, and may form the basis for a dimensional definition of diseases that goes beyond the current categorical system.

  10. Genomic and epigenomic insights into nutrition and brain disorders.

    Science.gov (United States)

    Dauncey, Margaret Joy

    2013-03-15

    Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer's disease, schizophrenia, Parkinson's disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1) recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2) the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3) novel approaches to nutrition, epigenetics and neuroscience; (4) gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders.

  11. Genomic and Epigenomic Insights into Nutrition and Brain Disorders

    Directory of Open Access Journals (Sweden)

    Margaret Joy Dauncey

    2013-03-01

    Full Text Available Considerable evidence links many neuropsychiatric, neurodevelopmental and neurodegenerative disorders with multiple complex interactions between genetics and environmental factors such as nutrition. Mental health problems, autism, eating disorders, Alzheimer’s disease, schizophrenia, Parkinson’s disease and brain tumours are related to individual variability in numerous protein-coding and non-coding regions of the genome. However, genotype does not necessarily determine neurological phenotype because the epigenome modulates gene expression in response to endogenous and exogenous regulators, throughout the life-cycle. Studies using both genome-wide analysis of multiple genes and comprehensive analysis of specific genes are providing new insights into genetic and epigenetic mechanisms underlying nutrition and neuroscience. This review provides a critical evaluation of the following related areas: (1 recent advances in genomic and epigenomic technologies, and their relevance to brain disorders; (2 the emerging role of non-coding RNAs as key regulators of transcription, epigenetic processes and gene silencing; (3 novel approaches to nutrition, epigenetics and neuroscience; (4 gene-environment interactions, especially in the serotonergic system, as a paradigm of the multiple signalling pathways affected in neuropsychiatric and neurological disorders. Current and future advances in these four areas should contribute significantly to the prevention, amelioration and treatment of multiple devastating brain disorders.

  12. New developments in brain research of internet and gaming disorder.

    Science.gov (United States)

    Weinstein, Aviv; Livny, Abigail; Weizman, Abraham

    2017-04-01

    There is evidence that the neural mechanisms underlying Internet Gaming Disorder (IGD) resemble those of drug addiction. Functional Magnetic Resonance Imaging (fMRI) studies of the resting state and measures of gray matter volume have shown that Internet game playing was associated with changes to brain regions responsible for attention and control, impulse control, motor function, emotional regulation, sensory-motor coordination. Furthermore, Internet game playing was associated with lower white matter density in brain regions that are involved in decision-making, behavioral inhibition and emotional regulation. Videogame playing involved changes in reward inhibitory mechanisms and loss of control. Structural brain imaging studies showed alterations in the volume of the ventral striatum that is an important part of the brain's reward mechanisms. Finally, videogame playing was associated with dopamine release similar in magnitude to those of drugs of abuse and lower dopamine transporter and dopamine receptor D2 occupancy indicating sub-sensitivity of dopamine reward mechanisms.

  13. Thyroid, brain and mood modulation in affective disorder: insights from molecular research and functional brain imaging.

    Science.gov (United States)

    Bauer, M; London, E D; Silverman, D H; Rasgon, N; Kirchheiner, J; Whybrow, P C

    2003-11-01

    The efficacy resulting from adjunctive use of supraphysiological doses of levothyroxine has emerged as a promising approach to therapy and prophylaxis for refractory mood disorders. Most patients with mood disorders who receive treatment with supraphysiological doses of levothyroxine have normal peripheral thyroid hormone levels, and also respond differently to the hormone and tolerate it better than healthy individuals and patients with primary thyroid diseases. Progress in molecular and functional brain imaging techniques has provided a new understanding of these phenomena, illuminating the relationship between thyroid function, mood modulation and behavior. Thyroid hormones are widely distributed in the brain and have a multitude of effects on the central nervous system. Notably many of the limbic system structures where thyroid hormone receptors are prevalent have been implicated in the pathogenesis of mood disorders. The influence of the thyroid system on neurotransmitters (particularly serotonin and norepinephrine), which putatively play a major role in the regulation of mood and behavior, may contribute to the mechanisms of mood modulation. Recent functional brain imaging studies using positron emission tomography (PET) with [ (18)F]-fluorodeoxyglucose demonstrated that thyroid hormone treatment with levothyroxine affects regional brain metabolism in patients with hypothyroidism and bipolar disorder. Theses studies confirm that thyroid hormones are active in modulating metabolic function in the mature adult brain, and provide intriging neuroanatomic clues that may guide future research.

  14. Combat posttraumatic stress disorder, substance use disorders, and traumatic brain injury.

    Science.gov (United States)

    Brady, Kathleen T; Tuerk, Peter; Back, Sudie E; Saladin, Michael E; Waldrop, Angela E; Myrick, Hugh

    2009-12-01

    Among both civilian and veteran populations, substance use disorders (SUDs) and anxiety disorders frequently co-occur. One of the most common comorbid anxiety disorder is posttraumatic stress disorder (PTSD), a condition which may develop after exposure to traumatic events, such as military combat. In comparison with the general population, rates of both SUDs and PTSD are elevated among veterans. Recent data show that soldiers returning from Iraq and Afghanistan demonstrate high rates of co-occurring SUDs, PTSD, and traumatic brain injury. Careful assessment of these conditions is critical and may be complicated by symptom overlap. More research targeting integrated interventions for these conditions is needed to establish optimal treatments.

  15. Molecular imaging of the brain. Using multi-quantum coherence and diagnostics of brain disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kaila, M.M. [New South Wales Univ., Sydney, NSW (Australia). School of Physics; Kaila, Rakhi [Univ. of New South Wales, Sydney (Australia). School of Medicine

    2013-11-01

    Explains the basics of the MRI and its use in the diagnostics and the treatment of the human brain disorders. Examines multi-quantum magnetic resonance imaging methods and the diagnostics of brain disorders. Covers how in a non-invasive manner one can diagnose diseases of the brain. This book examines multi-quantum magnetic resonance imaging methods and the diagnostics of brain disorders. It consists of two Parts. The part I is initially devoted towards the basic concepts of the conventional single quantum MRI techniques. It is supplemented by the basic knowledge required to understand multi-quantum MRI. Practical illustrations are included both on recent developments in conventional MRI and the MQ-MRI. This is to illustrate the connection between theoretical concepts and their scope in the clinical applications. The Part II initially sets out the basic details about quadrupole charge distribution present in certain nuclei and their importance about the functions they perform in our brain. Some simplified final mathematical expressions are included to illustrate facts about the basic concepts of the quantum level interactions between magnetic dipole and the electric quadrupole behavior of useful nuclei present in the brain. Selected practical illustrations, from research and clinical practices are included to illustrate the newly emerging ideas and techniques. The reader should note that the two parts of the book are written with no interdependence. One can read them quite independently.

  16. BLOOD-BRAIN BARRIER DYSFUNCTION IN DISORDERS OF THE DEVELOPING BRAIN

    Directory of Open Access Journals (Sweden)

    Raffaella eMoretti

    2015-02-01

    Full Text Available ABSTRACTDisorders of the developing brain represent a major health problem. The neurological manifestations of brain lesions can range from severe clinical deficits to more subtle neurological signs or behavioral problems and learning disabilities, which often become evident many years after the initial damage. These long-term sequelae are due at least in part to central nervous system immaturity at the time of the insult.The blood brain barrier (BBB protects the brain and maintains homeostasis. BBB alterations are observed during both acute and chronic brain insults. After an insult, excitatory amino acid neurotransmitters are released, causing reactive oxygen species (ROS-dependent changes in BBB permeability that allow immune cells to enter and stimulate an inflammatory response.The cytokines, chemokines and other molecules released as well as peripheral and local immune cells can activate an inflammatory cascade in the brain, leading to secondary neurodegeneration that can continue for months or even years and finally contribute to post-insult neuronal deficits. The role of the BBB in perinatal disorders is poorly understood. The inflammatory response, which can be either acute (e.g. perinatal stroke, traumatic brain injury or chronic (e.g. perinatal infectious diseases actively modulates the pathophysiological processes underlying brain injury. We present an overview of current knowledge about BBB dysfunction in the developing brain during acute and chronic insults, along with clinical and experimental data.

  17. Clinical Application of Neuroplastic Brain Research in Eating Disorder Treatment

    Directory of Open Access Journals (Sweden)

    Abigail H. Natenshon

    2016-12-01

    Neurophysiological and psychophysiological treatment interventions, by carving new neuronal pathways and creating connectivity that augments brain circuitry, carry the potential to remediate body image and self-image distortions, reintegrating the fragmented eating disordered core self. To date, intentional partnering between therapist, ED patient, and neuroplastic brain has been rarely applied in the clinical milieu and minimally referenced in the treatment literature. By bringing current neuroplasticity research into frontline practice, ED practitioners not only bridge the research/practice gap, but redefine new directions for future ED research.

  18. PET imaging reveals brain functional changes in internet gaming disorder

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Mei; Zhang, Ying; Du, Fenglei; Hou, Haifeng; Chao, Fangfang; Zhang, Hong [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); Key Laboratory of Medical Molecular Imaging of Zhejiang Province, Hangzhou (China); Chen, Qiaozhen [The Second Hospital of Zhejiang University School of Medicine, Department of Nuclear Medicine, Hangzhou, Zhejiang (China); The Second Affiliated Hospital of Zhejiang University School of Medicine, Department of Psychiatry, Hangzhou (China)

    2014-07-15

    Internet gaming disorder is an increasing problem worldwide, resulting in critical academic, social, and occupational impairment. However, the neurobiological mechanism of internet gaming disorder remains unknown. The aim of this study is to assess brain dopamine D{sub 2} (D{sub 2})/Serotonin 2A (5-HT{sub 2A}) receptor function and glucose metabolism in the same subjects by positron emission tomography (PET) imaging approach, and investigate whether the correlation exists between D{sub 2} receptor and glucose metabolism. Twelve drug-naive adult males who met criteria for internet gaming disorder and 14 matched controls were studied with PET and {sup 11}C-N-methylspiperone ({sup 11}C-NMSP) to assess the availability of D{sub 2}/5-HT{sub 2A} receptors and with {sup 18}F-fluoro-D-glucose ({sup 18}F-FDG) to assess regional brain glucose metabolism, a marker of brain function. {sup 11}C-NMSP and {sup 18}F-FDG PET imaging data were acquired in the same individuals under both resting and internet gaming task states. In internet gaming disorder subjects, a significant decrease in glucose metabolism was observed in the prefrontal, temporal, and limbic systems. Dysregulation of D{sub 2} receptors was observed in the striatum, and was correlated to years of overuse. A low level of D{sub 2} receptors in the striatum was significantly associated with decreased glucose metabolism in the orbitofrontal cortex. For the first time, we report the evidence that D{sub 2} receptor level is significantly associated with glucose metabolism in the same individuals with internet gaming disorder, which indicates that D{sub 2}/5-HT{sub 2A} receptor-mediated dysregulation of the orbitofrontal cortex could underlie a mechanism for loss of control and compulsive behavior in internet gaming disorder subjects. (orig.)

  19. The size and burden of mental disorders and other disorders of the brain in Europe 2010.

    Science.gov (United States)

    Wittchen, H U; Jacobi, F; Rehm, J; Gustavsson, A; Svensson, M; Jönsson, B; Olesen, J; Allgulander, C; Alonso, J; Faravelli, C; Fratiglioni, L; Jennum, P; Lieb, R; Maercker, A; van Os, J; Preisig, M; Salvador-Carulla, L; Simon, R; Steinhausen, H-C

    2011-09-01

    , early retirement and treatment rates due to mental disorders, rates in the community have not increased with a few exceptions (i.e. dementia). There were also no consistent indications of improvements with regard to low treatment rates, delayed treatment provision and grossly inadequate treatment. Disability: Disorders of the brain and mental disorders in particular, contribute 26.6% of the total all cause burden, thus a greater proportion as compared to other regions of the world. The rank order of the most disabling diseases differs markedly by gender and age group; overall, the four most disabling single conditions were: depression, dementias, alcohol use disorders and stroke. In every year over a third of the total EU population suffers from mental disorders. The true size of "disorders of the brain" including neurological disorders is even considerably larger. Disorders of the brain are the largest contributor to the all cause morbidity burden as measured by DALY in the EU. No indications for increasing overall rates of mental disorders were found nor of improved care and treatment since 2005; less than one third of all cases receive any treatment, suggesting a considerable level of unmet needs. We conclude that the true size and burden of disorders of the brain in the EU was significantly underestimated in the past. Concerted priority action is needed at all levels, including substantially increased funding for basic, clinical and public health research in order to identify better strategies for improved prevention and treatment for disorders of the brain as the core health challenge of the 21st century. Copyright © 2011. Published by Elsevier B.V.

  20. Developmental origins of brain disorders: roles for dopamine

    Directory of Open Access Journals (Sweden)

    Kelli M Money

    2013-12-01

    Full Text Available Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.

  1. Gulf War Illness as a Brain Autoimmune Disorder

    Science.gov (United States)

    2016-10-01

    Suite 1204, Arlington, VA 22202- 4302. Respondents should be aware that notwithstanding any other provision of law , no person shall be subject to any...Autoimmune, neuroimaging, genetics , biomarkers 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF...comprehensively assess the association of GWI to autoimmune disorders using cutting-edge measures of brain structure and function, genetic analysis

  2. The Gut-Brain Axis, BDNF, NMDA and CNS Disorders.

    Science.gov (United States)

    Maqsood, Raeesah; Stone, Trevor W

    2016-11-01

    Gastro-intestinal (GI) microbiota and the 'gut-brain axis' are proving to be increasingly relevant to early brain development and the emergence of psychiatric disorders. This review focuses on the influence of the GI tract on Brain-Derived Neurotrophic Factor (BDNF) and its relationship with receptors for N-methyl-D-aspartate (NMDAR), as these are believed to be involved in synaptic plasticity and cognitive function. NMDAR may be associated with the development of schizophrenia and a range of other psychopathologies including neurodegenerative disorders, depression and dementias. An analysis of the routes and mechanisms by which the GI microbiota contribute to the pathophysiology of BDNF-induced NMDAR dysfunction could yield new insights relevant to developing novel therapeutics for schizophrenia and related disorders. In the absence of GI microbes, central BDNF levels are reduced and this inhibits the maintenance of NMDAR production. A reduction of NMDAR input onto GABA inhibitory interneurons causes disinhibition of glutamatergic output which disrupts the central signal-to-noise ratio and leads to aberrant synaptic behaviour and cognitive deficits. Gut microbiota can modulate BDNF function in the CNS, via changes in neurotransmitter function by affecting modulatory mechanisms such as the kynurenine pathway, or by changes in the availability and actions of short chain fatty acids (SCFAs) in the brain. Interrupting these cycles by inducing changes in the gut microbiota using probiotics, prebiotics or antimicrobial drugs has been found promising as a preventative or therapeutic measure to counteract behavioural deficits and these may be useful to supplement the actions of drugs in the treatment of CNS disorders.

  3. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

    Institute of Scientific and Technical Information of China (English)

    Natalie Kaminsky; Ofer Bihari; Sivan Kanner; Ari Barzilai

    2016-01-01

    The DNA damage response (DDR) is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to geno-mic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degener-ative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evi-dence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes). Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a‘‘hostile”environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  4. Connecting Malfunctioning Glial Cells and Brain Degenerative Disorders

    Directory of Open Access Journals (Sweden)

    Natalie Kaminsky

    2016-06-01

    Full Text Available The DNA damage response (DDR is a complex biological system activated by different types of DNA damage. Mutations in certain components of the DDR machinery can lead to genomic instability disorders that culminate in tissue degeneration, premature aging, and various types of cancers. Intriguingly, malfunctioning DDR plays a role in the etiology of late onset brain degenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. For many years, brain degenerative disorders were thought to result from aberrant neural death. Here we discuss the evidence that supports our novel hypothesis that brain degenerative diseases involve dysfunction of glial cells (astrocytes, microglia, and oligodendrocytes. Impairment in the functionality of glial cells results in pathological neuro-glial interactions that, in turn, generate a “hostile” environment that impairs the functionality of neuronal cells. These events can lead to systematic neural demise on a scale that appears to be proportional to the severity of the neurological deficit.

  5. Cognitive neuroscience and brain imaging in bipolar disorder.

    Science.gov (United States)

    Clark, Luke; Sahakian, Barbara J

    2008-01-01

    Bipolar disorder is characterized by a combination of state-related changes in psychological function that are restricted to illness episodes, coupled with trait-related changes that persist through periods of remission, irrespective of symptom status. This article reviews studies that have investigated the brain systems involved in these state- and trait-related changes, using two techniques: (i) indirect measures of neurocognitive function, and (ii) direct neuroimaging measures of brain function during performance of a cognitive task. Studies of neurocognitive function in bipolar disorder indicate deficits in three core domains: attention, executive function, and emotional processing. Functional imaging studies implicate pathophysiology in distributed neural circuitry that includes the prefrontal and anterior cingulate cortices, as well as subcortical limbic structures including the amygdala and the ventral striatum. Whilst there have been clear advances in our understanding of brain changes in bipolar disorder, there are limited data in bipolar depression, and there is limited understanding of the influence of clinical variables including medication status, illness severity, and specific symptom dimensions.

  6. On the Complexity of Brain Disorders: A symptom-based approach

    Directory of Open Access Journals (Sweden)

    Ahmed A. Moustafa

    2016-02-01

    Full Text Available Mounting evidence shows that brain disorders involve multiple and different neural dysfunctions, including regional brain damage, change to cell structure, chemical imbalance, and/or connectivity loss among different brain regions. Understanding the complexity of brain disorders can help us map these neural dysfunctions to different symptom clusters as well as understand subcategories of different brain disorders. Here, we discuss data on the mapping of symptom clusters to different neural dysfunctions using examples from brain disorders such as major depressive disorder, Parkinson’s disease, schizophrenia, PTSD and Alzheimer’s disease. In addition, we discuss data on the similarities of symptoms in different disorders. Importantly, computational modeling work may be able to shed light on plausible links between various symptoms and neural damage in brain disorders.

  7. Brain differences between persistent and remitted attention deficit hyperactivity disorder.

    Science.gov (United States)

    Mattfeld, Aaron T; Gabrieli, John D E; Biederman, Joseph; Spencer, Thomas; Brown, Ariel; Kotte, Amelia; Kagan, Elana; Whitfield-Gabrieli, Susan

    2014-09-01

    Previous resting state studies examining the brain basis of attention deficit hyperactivity disorder have not distinguished between patients who persist versus those who remit from the diagnosis as adults. To characterize the neurobiological differences and similarities of persistence and remittance, we performed resting state functional magnetic resonance imaging in individuals who had been longitudinally and uniformly characterized as having or not having attention deficit hyperactivity disorder in childhood and again in adulthood (16 years after baseline assessment). Intrinsic functional brain organization was measured in patients who had a persistent diagnosis in childhood and adulthood (n = 13), in patients who met diagnosis in childhood but not in adulthood (n = 22), and in control participants who never had attention deficit hyperactivity disorder (n = 17). A positive functional correlation between posterior cingulate and medial prefrontal cortices, major components of the default-mode network, was reduced only in patients whose diagnosis persisted into adulthood. A negative functional correlation between medial and dorsolateral prefrontal cortices was reduced in both persistent and remitted patients. The neurobiological dissociation between the persistence and remittance of attention deficit hyperactivity disorder may provide a framework for the relation between the clinical diagnosis, which indicates the need for treatment, and additional deficits that are common, such as executive dysfunctions.

  8. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders

    NARCIS (Netherlands)

    Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

    2016-01-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar

  9. Gender differences in brain serotonin transporter availability in panic disorder.

    Science.gov (United States)

    Maron, Eduard; Tõru, Innar; Hirvonen, Jussi; Tuominen, Lauri; Lumme, Ville; Vasar, Veiko; Shlik, Jakov; Nutt, David J; Helin, Semi; Någren, Kjell; Tiihonen, Jari; Hietala, Jarmo

    2011-07-01

    The role of the serotonin (5-HT) system in the neurobiology and treatment of panic disorder (PD) remains unproven. Previously we detected lower brain 5-HT transporter (SERT) availability in PD, but the findings were preliminary and mainly limited to female patients. The aim of this study was to assess non-displaceable brain SERT binding potential (BP (ND)) in male and female patients with PD. The SERT BP (ND) was measured in groups of patients with PD (five males and six females) and matched healthy control subjects (12 males and 12 females) using positron emission tomography (PET) and [¹¹C]MADAM tracer. SERT BP (ND) were significantly higher in 13 of 20 studied brain regions, including several cortical and raphe areas, but lower in the hippocampus in males with PD as compared with healthy males. No significant differences in SERT BP (ND) were observed between female patients and controls. The results suggest gender-dependent regional differences in brain SERT availability and converge with previous PET findings of reduced 5-HT(1A) receptor binding in similar brain areas in PD. Distinctive functioning of the 5-HT system in males and females may underlie certain gender-dependent differences in expressions of PD.

  10. Brain structural and functional correlates of resilience to Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Sophia eFrangou

    2012-01-01

    Full Text Available Background: Resilient adaptation can be construed in different ways, but as used here it refers to the adaptive brain changes associated with avoidance of psychopathology despite familiar risk for Bipolar Disorder (BD. Although family history of BD is associated with elevated risk of affective morbidity a significant proportion of first-degree relatives of BD patients remains free of psychopathology. Examination of brain structure and function in these individuals may inform on adaptive changes that may pre-empt disease expression. Methods: Data presented here are derived from the Vulnerability to Bipolar Disorders (VIBES study which includes patients with BD, asymptomatic relatives and healthy controls. Participants underwent extensive investigations including brain structural (sMRI and functional magnetic resonance imaging (fMRI. The data presented here focus on sMRI voxel-based-morphometry and on conventional and connectivity analyses of fMRI data obtained during the Stroop Colour Word Test (SCWT, a task of cognitive control during conflict resolution. All analyses were implemented in SPM (www.fil.ion.ucl.ac.uk/spm. Resilience in relatives was operationalized as the absence of clinical-range symptoms.Results: Resilient relatives of BD patients expressed structural, functional and connectivity changes reflecting the effect of genetic risk on the brain. These included increased insular volume, decreased activation within the posterior and inferior parietal regions involved in selective attention during the SCWT, and reduced fronto-insular and fronto-cingulate connectivity.Resilience was associated with increased cerebellar vermal volume and enhanced functional coupling between the dorsal and the ventral prefrontal cortex. Conclusions: Our findings suggests the presence of biological mechanisms associated with resilient adaptation of brain networks and pave the way for the identification of outcome-specific trajectories given a particular

  11. Postdeployment Symptom Changes and Traumatic Brain Injury and/or Posttraumatic Stress Disorder in Men

    Science.gov (United States)

    2012-01-01

    traumatic brain injury ( TBI ) and posttraumatic stress disorder...stress disorder, TBI = traumatic brain injury . *Address all correspondence to Hilary J. Aralis, MS; Naval Health Research Center, Warfighter...both diagnoses. See Figure 1 for sampling details. Figure 1. Flow diagram outlining selection of final blast traumatic brain injury ( TBI ) and no TBI

  12. Post-traumatic stress disorder and traumatic brain injury.

    Science.gov (United States)

    Motzkin, Julian C; Koenigs, Michael R

    2015-01-01

    Disentangling the effects of "organic" neurologic damage and psychological distress after a traumatic brain injury poses a significant challenge to researchers and clinicians. Establishing a link between traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) has been particularly contentious, reflecting difficulties in establishing a unique diagnosis for conditions with overlapping and sometimes contradictory symptom profiles. However, each disorder is linked to a variety of adverse health outcomes, underscoring the need to better understand how neurologic and psychiatric risk factors interact following trauma. Here, we present data showing that individuals with a TBI are more likely to develop PTSD, and that individuals with PTSD are more likely to develop persistent cognitive sequelae related to TBI. Further, we describe neurobiological models of PTSD, highlighting how patterns of neurologic damage typical in TBI may promote or protect against the development of PTSD in brain-injured populations. These data highlight the unique course of PTSD following a TBI and have important diagnostic, prognostic, and treatment implications for individuals with a dual diagnosis.

  13. Disorders of consciousness after severe brain injury: therapeutic options.

    Science.gov (United States)

    Schnakers, Caroline; Monti, Martin M

    2017-09-09

    Very few options exist for patients who survive severe traumatic brain injury but fail to fully recover and develop a disorder of consciousness (e.g. vegetative state, minimally conscious state). Among pharmacological approaches, Amantadine has shown the ability to accelerate functional recovery. Although with very low frequency, Zolpidem has shown the ability to improve the level of consciousness transiently and, possibly, also in a sustained fashion. Among neuromodulatory approaches, transcranial direct current stimulation has been shown to transiently improve behavioral responsiveness, but mostly in minimally conscious patients. New evidence for thalamic deep brain stimulation calls into question its cost/benefit trade-off. The growing understanding of the biology of disorders of consciousness has led to a renaissance in the development of therapeutic interventions for patients with disorders of consciousness. High-quality evidence is emerging for pharmacological (i.e. Amantadine) and neurostimulatory (i.e. transcranial direct current stimulation) interventions, although further studies are needed to delineate preconditions, optimal dosages, and timing of administration. Other exciting new approaches (e.g. low intensity focused ultrasound) still await systematic assessment. A crucial future direction should be the use of neuroimaging measures of functional and structural impairment as a means of tailoring patient-specific interventions.

  14. Brain-derived neurotrophic factor and neuropsychiatric disorders.

    Science.gov (United States)

    Autry, Anita E; Monteggia, Lisa M

    2012-04-01

    Brain derived neurotrophic factor (BDNF) is the most prevalent growth factor in the central nervous system (CNS). It is essential for the development of the CNS and for neuronal plasticity. Because BDNF plays a crucial role in development and plasticity of the brain, it is widely implicated in psychiatric diseases. This review provides a summary of clinical and preclinical evidence for the involvement of this ubiquitous growth factor in major depressive disorder, schizophrenia, addiction, Rett syndrome, as well as other psychiatric and neurodevelopmental diseases. In addition, the review includes a discussion of the role of BDNF in the mechanism of action of pharmacological therapies currently used to treat these diseases, such antidepressants and antipsychotics. The review also covers a critique of experimental therapies such as BDNF mimetics and discusses the value of BDNF as a target for future drug development.

  15. The thyroid-brain interaction in thyroid disorders and mood disorders.

    Science.gov (United States)

    Bauer, M; Goetz, T; Glenn, T; Whybrow, P C

    2008-10-01

    Thyroid hormones play a critical role in the metabolic activity of the adult brain, and neuropsychiatric manifestations of thyroid disease have long been recognised. However, it is only recently that methodology such as functional neuroimaging has been available to facilitate investigation of thyroid hormone metabolism. Although the role of thyroid hormones in the adult brain is not yet specified, it is clear that without optimal thyroid function, mood disturbance, cognitive impairment and other psychiatric symptoms can emerge. Additionally, laboratory measurements of peripheral thyroid function may not adequately characterise central thyroid metabolism. Here, we review the relationship between thyroid hormone and neuropsychiatric symptoms in patients with primary thyroid disease and primary mood disorders.

  16. Flowers for Algernon: steroid dysgenesis, epigenetics and brain disorders.

    Science.gov (United States)

    Sanders, Bryan K

    2012-01-01

    While a recent study has reported that early citalopram exposure alters cortical network function and produces autistic-like behaviors in male rats, when evaluating antidepressant animal models of autism spectrum disorder (ASD) it is important to note that some selective serotonin (5-HT) reuptake inhibitors alter 3α-hydroxysteroid dehydrogenase activity, and thus steroidogenesis. At least one study has examined the effect of repeated citalopram administration on the serum and brain concentration of testosterone (T) and its metabolites and shown that citalopram increases serum T. Several in vitro studies also suggest that sex steroid can alter 5-HT homeostasis. While research efforts have demonstrated that transgenic mice expressing the most common of multiple gain-of-function 5-HT reuptake transporter (SERT) coding variants, SERT Ala56, previously identified in children with ASD, exhibit autistic-like behaviors, elevated p38 MAPK-dependent transporter phosphorylation, enhanced 5-HT clearance rates and hyperserotonemia, a few studies provide some evidence that 5-HT may alter gonadal steroidogenesis. T, 17β-estradiol and synthetic estrogens are known inhibitors of AKR1C21 (BRENDA, E.C. 1.1.1.209), the epitestosterone (epiT) producing enzyme in rodents. EpiT is a naturally occurring steroid in mammals, including man. An analysis of the literature suggests that epiT may be the central mediator in the epigenetic regulation of gene expression. Over thirty years ago, it was shown that rat brain epiT production is higher in females than in males. A similar finding in humans could explain the sex differences in the incidence of autism and other brain disorders. Despite this, the role of epiT in brain development remains a long neglected area of research.

  17. Molecular Imaging of the Brain Using Multi-Quantum Coherence and Diagnostics of Brain Disorders

    CERN Document Server

    Kaila, M M

    2013-01-01

    This book examines multi-quantum magnetic resonance imaging methods and the diagnostics of brain disorders. It consists of two Parts. The part I is initially devoted towards the basic concepts of the conventional single quantum MRI techniques. It is supplemented by the basic knowledge required to understand multi-quantum MRI. Practical illustrations are included both on recent developments in conventional MRI and the MQ-MRI. This is to illustrate the connection between theoretical concepts and their scope in the clinical applications. The Part II initially sets out the basic details about quadrupole charge distribution present in certain nuclei and their importance about the functions they perform in our brain. Some simplified final mathematical expressions are included to illustrate facts about the basic concepts of the quantum level interactions between magnetic dipole and the electric quadrupole behavior of useful nuclei present in the brain. Selected practical illustrations, from research and clinical pra...

  18. Developing epigenetic diagnostics and therapeutics for brain disorders.

    Science.gov (United States)

    Qureshi, Irfan A; Mehler, Mark F

    2013-12-01

    Perturbations in epigenetic mechanisms have emerged as cardinal features in the molecular pathology of major classes of brain disorders. We therefore highlight evidence which suggests that specific epigenetic signatures measurable in central - and possibly even in peripheral tissues - have significant value as translatable biomarkers for screening, early diagnosis, and prognostication; developing molecularly targeted medicines; and monitoring disease progression and treatment responses. We also draw attention to existing and novel therapeutic approaches directed at epigenetic factors and mechanisms, including strategies for modulating enzymes that write and erase DNA methylation and histone/chromatin marks; protein-protein interactions responsible for reading epigenetic marks; and non-coding RNA pathways.

  19. Iron biomineralization of brain tissue and neurodegenerative disorders

    Science.gov (United States)

    Mikhaylova (Mikhailova), Albina

    The brain is an organ with a high concentration of iron in specific areas, particularly in the globus pallidus, the substantia nigra, and the red nucleus. In certain pathological states, such as iron overload disease and neurodegenerative disorders, a disturbed iron metabolism can lead to increased accumulation of iron not only in these areas, but also in the brain regions that are typically low in iron content. Recent studies of the physical and magnetic properties of metalloproteins, and in particular the discovery of biogenic magnetite in human brain tissue, have raised new questions about the role of biogenic iron formations in living organisms. Further investigations revealed the presence of magnetite-like crystalline structures in human ferritin, and indicated that released ferritin iron might act as promoter of oxidative damage to tissue, therefore contributing to pathogenesis of neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's diseases. The purpose of this work was to examine the elemental composition and structure of iron deposits in normal brain tissue as well as tissue affected by neurodegenerative disorders. Employing the methods of X-ray microfocus fluorescence mapping, X-ray Absorption Near Edge Structure (XANES), X-ray Absorption Fine Structure spectroscopy (XAFS), and light and electron microscopic examinations allows one to obtain qualitative as well as quantitative data with respect to the cellular distribution and chemical state of iron at levels not detected previously. The described tissue preparation technique allows not only satisfactory XAS iron elemental imaging in situ but also multimodal examination with light and electron microscopes of the same samples. The developed protocol has assured consistent and reproducible results on relatively large sections of flat-embedded tissue. The resulting tissue samples were adequate for XAS examination as well as sufficiently well-preserved for future microscopy studies

  20. Surgery insight: Deep brain stimulation for movement disorders.

    Science.gov (United States)

    Anderson, William S; Lenz, Frederick A

    2006-06-01

    Over the past two decades, deep brain stimulation (DBS) has supplanted lesioning techniques for the treatment of movement disorders, and has been shown to be safe and efficacious. The primary therapeutic indications for DBS are essential tremor, dystonia and Parkinson's disease. In the case of Parkinson's disease, DBS is effective for treating the primary symptoms--tremor, bradykinesia and rigidity--as well as the motor complications of drug treatment. Progress has been made in understanding the effects of stimulation at the neuronal level, and this knowledge should eventually improve the effectiveness of this therapy. Preliminary studies also indicate that DBS might be used to treat Tourette's syndrome, obsessive-compulsive disorder, depression and epilepsy. As we will discuss in this review, the success of DBS depends on an appropriate rationale for the procedure, and on collaborations between neurologists and neurosurgeons in defining outcomes.

  1. The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder

    NARCIS (Netherlands)

    Abramovic, Lucija|info:eu-repo/dai/nl/34549072X; Boks, Marco P M|info:eu-repo/dai/nl/286852071; Vreeker, Annabel; Bouter, Diandra C.; Kruiper, Caitlyn; Verkooijen, Sanne; van Bergen, Annet H.|info:eu-repo/dai/nl/345481240; Ophoff, Roel A.|info:eu-repo/dai/nl/16237299X; Kahn, René S.|info:eu-repo/dai/nl/073778532; van Haren, Neeltje E M|info:eu-repo/dai/nl/271562161

    2016-01-01

    There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain

  2. Brain proton magnetic resonance spectroscopy of alcohol use disorders.

    Science.gov (United States)

    Meyerhoff, Dieter J

    2014-01-01

    This chapter critically reviews brain proton magnetic resonance spectroscopy ((1)H MRS) studies performed since 1994 in individuals with alcohol use disorders (AUD). We describe the neurochemicals that can be measured in vivo at the most common magnetic field strengths, summarize our knowledge about their general brain functions, and briefly explain some basic human (1)H MRS methods. Both cross-sectional and longitudinal research of individuals in treatment and of treatment-naïve individuals with AUD are discussed and interpreted on the basis of reported neuropathology. As AUDs are highly comorbid with chronic cigarette smoking and illicit substance abuse, we also summarize reports on their respective influences on regional proton metabolite levels. After reviewing research on neurobiologic correlates of relapse and genetic influences on brain metabolite levels, we finish with suggestions on future directions for (1)H MRS studies in AUDs. The review demonstrates that brain metabolic alterations associated with AUDs as well as their cognitive correlates are not simply a consequence of chronic alcohol consumption. Future MR research of AUDs in general has to be better prepared - and supported - to study clinically complex relationships between personality characteristics, comorbidities, neurogenetics, lifestyle, and living environment, as all these factors critically affect an individual's neurometabolic profile. (1)H MRS is uniquely positioned to tackle these complexities by contributing to a comprehensive biopsychosocial profile of individuals with AUD: it can provide non-invasive biochemical information on select regions of the brain at comparatively low overall cost for the ultimate purpose of informing more efficient treatments of AUDs.

  3. Reduced predictable information in brain signals in autism spectrum disorder

    Science.gov (United States)

    Gómez, Carlos; Lizier, Joseph T.; Schaum, Michael; Wollstadt, Patricia; Grützner, Christine; Uhlhaas, Peter; Freitag, Christine M.; Schlitt, Sabine; Bölte, Sven; Hornero, Roberto; Wibral, Michael

    2014-01-01

    Autism spectrum disorder (ASD) is a common developmental disorder characterized by communication difficulties and impaired social interaction. Recent results suggest altered brain dynamics as a potential cause of symptoms in ASD. Here, we aim to describe potential information-processing consequences of these alterations by measuring active information storage (AIS)—a key quantity in the theory of distributed computation in biological networks. AIS is defined as the mutual information between the past state of a process and its next measurement. It measures the amount of stored information that is used for computation of the next time step of a process. AIS is high for rich but predictable dynamics. We recorded magnetoencephalography (MEG) signals in 10 ASD patients and 14 matched control subjects in a visual task. After a beamformer source analysis, 12 task-relevant sources were obtained. For these sources, stationary baseline activity was analyzed using AIS. Our results showed a decrease of AIS values in the hippocampus of ASD patients in comparison with controls, meaning that brain signals in ASD were either less predictable, reduced in their dynamic richness or both. Our study suggests the usefulness of AIS to detect an abnormal type of dynamics in ASD. The observed changes in AIS are compatible with Bayesian theories of reduced use or precision of priors in ASD. PMID:24592235

  4. Reduced Predictable Information in Brain Signals in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Carlos eGomez

    2014-02-01

    Full Text Available Autism spectrum disorder (ASD is a common developmental disorder characterized by communication difficulties and impaired social interaction. Recent results suggest altered brain dynamics as a potential cause of symptoms in ASD. Here, we aim to describe potential information-processing consequences of these alterations by measuring active information storage (AIS – a key quantity in the theory of distributed computation in biological networks. AIS is defined as the mutual information between the semi-infinite past of a process and its next state. It measures the amount of stored information that is used for computation of the next time step of a process. AIS is high for rich but predictable dynamics. We recorded magnetoencephalography (MEG signals in 13 ASD patients and 14 matched control subjects in a visual task. After a beamformer source analysis, twelve task-relevant sources were obtained. For these sources, stationary baseline activity was analyzed using AIS. Our results showed a decrease of AIS values in the hippocampus of ASD patients in comparison with controls, meaning that brain signals in ASD were either less predictable, reduced in their dynamic richness or both. Our study suggests the usefulness of AIS to detect an abnormal type of dynamics in ASD. The observed changes in AIS are compatible with Bayesian theories of reduced use or precision of priors in ASD.

  5. Face-brain asymmetry in autism spectrum disorders.

    Science.gov (United States)

    Hammond, P; Forster-Gibson, C; Chudley, A E; Allanson, J E; Hutton, T J; Farrell, S A; McKenzie, J; Holden, J J A; Lewis, M E S

    2008-06-01

    The heterogeneity of autism spectrum disorders (ASDs) confounds attempts to identify causes and pathogenesis. Identifiable endophenotypes and reliable biomarkers within ASDs would help to focus molecular research and uncover genetic causes and developmental mechanisms. We used dense surface-modelling techniques to compare the facial morphology of 72 boys with ASD and 128 first-degree relatives to that of 254 unrelated controls. Pattern-matching algorithms were able to discriminate between the faces of ASD boys and those of matched controls (AUC=0.82) and also discriminate between the faces of unaffected mothers of ASD children and matched female controls (AUC=0.76). We detected significant facial asymmetry in boys with ASD (Pbrain. Unaffected mothers of children with ASD display similar significant facial asymmetry, more exaggerated than that in matched controls (Pasymmetry of the periorbital region. Unaffected fathers of children with ASD did not show facial asymmetry to a significant degree compared to controls. Two thirds of unaffected male siblings tested were classified unseen as more facially similar to unrelated boys with ASD than to unrelated controls. These unaffected male siblings and two small groups of girls with ASD and female siblings, all show overall directional asymmetry, but without achieving statistical significance in two-tailed t-tests of individual asymmetry of ASD family and matched control groups. We conclude that previously identified right dominant asymmetry of the frontal poles of boys with ASD could explain their facial asymmetry through the direct effect of brain growth. The atypical facial asymmetry of unaffected mothers of children with ASD requires further brain studies before the same explanation can be proposed. An alternative explanation, not mutually exclusive, is a simultaneous and parallel action on face and brain growth by genetic factors. Both possibilities suggest the need for coordinated face and brain studies on ASD

  6. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders.

    Science.gov (United States)

    Meng, Qingying; Ying, Zhe; Noble, Emily; Zhao, Yuqi; Agrawal, Rahul; Mikhail, Andrew; Zhuang, Yumei; Tyagi, Ethika; Zhang, Qing; Lee, Jae-Hyung; Morselli, Marco; Orozco, Luz; Guo, Weilong; Kilts, Tina M; Zhu, Jun; Zhang, Bin; Pellegrini, Matteo; Xiao, Xinshu; Young, Marian F; Gomez-Pinilla, Fernando; Yang, Xia

    2016-05-01

    Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient-host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control) and hippocampus (cognitive processing) from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

  7. Systems Nutrigenomics Reveals Brain Gene Networks Linking Metabolic and Brain Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng

    2016-05-01

    Full Text Available Nutrition plays a significant role in the increasing prevalence of metabolic and brain disorders. Here we employ systems nutrigenomics to scrutinize the genomic bases of nutrient–host interaction underlying disease predisposition or therapeutic potential. We conducted transcriptome and epigenome sequencing of hypothalamus (metabolic control and hippocampus (cognitive processing from a rodent model of fructose consumption, and identified significant reprogramming of DNA methylation, transcript abundance, alternative splicing, and gene networks governing cell metabolism, cell communication, inflammation, and neuronal signaling. These signals converged with genetic causal risks of metabolic, neurological, and psychiatric disorders revealed in humans. Gene network modeling uncovered the extracellular matrix genes Bgn and Fmod as main orchestrators of the effects of fructose, as validated using two knockout mouse models. We further demonstrate that an omega-3 fatty acid, DHA, reverses the genomic and network perturbations elicited by fructose, providing molecular support for nutritional interventions to counteract diet-induced metabolic and brain disorders. Our integrative approach complementing rodent and human studies supports the applicability of nutrigenomics principles to predict disease susceptibility and to guide personalized medicine.

  8. Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

    Science.gov (United States)

    Schmaal, L; Veltman, D J; van Erp, T G M; Sämann, P G; Frodl, T; Jahanshad, N; Loehrer, E; Tiemeier, H; Hofman, A; Niessen, W J; Vernooij, M W; Ikram, M A; Wittfeld, K; Grabe, H J; Block, A; Hegenscheid, K; Völzke, H; Hoehn, D; Czisch, M; Lagopoulos, J; Hatton, S N; Hickie, I B; Goya-Maldonado, R; Krämer, B; Gruber, O; Couvy-Duchesne, B; Rentería, M E; Strike, L T; Mills, N T; de Zubicaray, G I; McMahon, K L; Medland, S E; Martin, N G; Gillespie, N A; Wright, M J; Hall, G B; MacQueen, G M; Frey, E M; Carballedo, A; van Velzen, L S; van Tol, M J; van der Wee, N J; Veer, I M; Walter, H; Schnell, K; Schramm, E; Normann, C; Schoepf, D; Konrad, C; Zurowski, B; Nickson, T; McIntosh, A M; Papmeyer, M; Whalley, H C; Sussmann, J E; Godlewska, B R; Cowen, P J; Fischer, F H; Rose, M; Penninx, B W J H; Thompson, P M; Hibar, D P

    2016-06-01

    The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

  9. The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both?

    Science.gov (United States)

    De Palma, Giada; Collins, Stephen M; Bercik, Premysl; Verdu, Elena F

    2014-07-15

    The gut-brain axis is the bidirectional communication between the gut and the brain, which occurs through multiple pathways that include hormonal, neural and immune mediators. The signals along this axis can originate in the gut, the brain or both, with the objective of maintaining normal gut function and appropriate behaviour. In recent years, the study of gut microbiota has become one of the most important areas in biomedical research. Attention has focused on the role of gut microbiota in determining normal gut physiology and immunity and, more recently, on its role as modulator of host behaviour ('microbiota-gut-brain axis'). We therefore review the literature on the role of gut microbiota in gut homeostasis and link it with mechanisms that could influence behaviour. We discuss the association of dysbiosis with disease, with particular focus on functional bowel disorders and their relationship to psychological stress. This is of particular interest because exposure to stressors has long been known to increase susceptibility to and severity of gastrointestinal diseases. © 2014 The Authors. The Journal of Physiology © 2014 The Physiological Society.

  10. Brain responses to disorder-related visual threat in panic disorder.

    Science.gov (United States)

    Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Bruchmann, Maximilian; Vibrans, Laura; Zwitserlood, Pienie; Straube, Thomas

    2016-12-01

    Panic disorder (PD) patients show aberrant neural responses to threatening stimuli in an extended fear network, but results are only partially comparable, and studies implementing disorder-related visual scenes are lacking as stimuli. The neural responses and functional connectivity to a newly developed set of disorder-related, ecologically valid scenes as compared with matched neutral visual scenes, using event-related functional magnetic resonance imaging (fMRI) in 26 PD patients and 26 healthy controls (HC) were investigated. PD patients versus HC showed hyperactivation in an extended fear network comprising brainstem, insula, thalamus, anterior, and mid-cingulate cortex and (dorso-)medial prefrontal cortex for disorder-related versus neutral scenes. Amygdala differences between groups failed significance. Subjective levels of anxiety significantly correlated with brainstem activation in PD patients. Analysis of functional connectivity by means of beta series correlation revealed no emotion-specific alterations in connectivity in PD patients versus HC. The results suggest that subjective anxiety evoked by external stimuli is directly related to altered activation in the homeostatic alarm system in PD. With novel disorder-related stimuli, the study sheds new light on the neural underpinnings of pathological threat processing in PD. Hum Brain Mapp 37:4439-4453, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Narratives reflecting the lived experiences of people with brain disorders: common psychosocial difficulties and determinants.

    Directory of Open Access Journals (Sweden)

    Sally Hartley

    Full Text Available BACKGROUND: People with brain disorders - defined as both, mental disorders and neurological disorders experience a wide range of psychosocial difficulties (PSDs (e.g., concentrating, maintaining energy levels, and maintaining relationships. Research evidence is required to show that these PSDs are common across brain disorders. OBJECTIVES: To explore and gain deeper understanding of the experiences of people with seven brain disorders (alcohol dependency, depression, epilepsy, multiple sclerosis, Parkinson's disease, schizophrenia, stroke. It examines the common PSDs and their influencing factors. METHODS: Seventy seven qualitative studies identified in a systematic literature review and qualitative data derived from six focus groups are used to generate first-person narratives representing seven brain disorders. A theory-driven thematic analysis of these narratives identifies the PSDs and their influencing factors for comparison between the seven disorders. RESULTS: First-person narratives illustrate realities for people with brain disorders facilitating a deeper understanding of their every-day life experiences. Thematic analysis serves to highlight the commonalities, both of PSDs, such as loneliness, anger, uncertainty about the future and problems with work activities, and their determinants, such as work opportunities, trusting relationships and access to self-help groups. CONCLUSIONS: The strength of the methodology and the narratives is that they provide the opportunity for the reader to empathise with people with brain disorders and facilitate deeper levels of understanding of the complexity of the relationship of PSDs, determinants and facilitators. The latter reflect positive aspects of the lives of people with brain disorders. The result that many PSDs and their influencing factors are common to people with different brain disorders opens up the door to the possibility of using cross-cutting interventions involving different sectors

  12. Differential Effects of Brain Disorders on Structural and Functional Connectivity

    Science.gov (United States)

    Vega-Pons, Sandro; Olivetti, Emanuele; Avesani, Paolo; Dodero, Luca; Gozzi, Alessandro; Bifone, Angelo

    2017-01-01

    Different measures of brain connectivity can be defined based on neuroimaging read-outs, including structural and functional connectivity. Neurological and psychiatric conditions are often associated with abnormal connectivity, but comparing the effects of the disease on different types of connectivity remains a challenge. In this paper, we address the problem of quantifying the relative effects of brain disease on structural and functional connectivity at a group level. Within the framework of a graph representation of connectivity, we introduce a kernel two-sample test as an effective method to assess the difference between the patients and control group. Moreover, we propose a common representation space for structural and functional connectivity networks, and a novel test statistics to quantitatively assess differential effects of the disease on different types of connectivity. We apply this approach to a dataset from BTBR mice, a murine model of Agenesis of the Corpus Callosum (ACC), a congenital disorder characterized by the absence of the main bundle of fibers connecting the two hemispheres. We used normo-callosal mice (B6) as a comparator. The application of the proposed methods to this data-set shows that the two types of connectivity can be successfully used to discriminate between BTBR and B6, meaning that both types of connectivity are affected by ACC. However, our novel test statistics shows that structural connectivity is significantly more affected than functional connectivity, consistent with the idea that functional connectivity has a robust topology that can tolerate substantial alterations in its structural connectivity substrate. PMID:28119556

  13. Cortical thickness and brain volumetric analysis in body dysmorphic disorder.

    Science.gov (United States)

    Madsen, Sarah K; Zai, Alex; Pirnia, Tara; Arienzo, Donatello; Zhan, Liang; Moody, Teena D; Thompson, Paul M; Feusner, Jamie D

    2015-04-30

    Individuals with body dysmorphic disorder (BDD) suffer from preoccupations with perceived defects in physical appearance, causing severe distress and disability. Although BDD affects 1-2% of the population, the neurobiology is not understood. Discrepant results in previous volumetric studies may be due to small sample sizes, and no study has investigated cortical thickness in BDD. The current study is the largest neuroimaging analysis of BDD. Participants included 49 medication-free, right-handed individuals with DSM-IV BDD and 44 healthy controls matched by age, sex, and education. Using high-resolution T1-weighted magnetic resonance imaging, we computed vertex-wise gray matter (GM) thickness on the cortical surface and GM volume using voxel-based morphometry. We also computed volumes in cortical and subcortical regions of interest. In addition to group comparisons, we investigated associations with symptom severity, insight, and anxiety within the BDD group. In BDD, greater anxiety was significantly associated with thinner GM in the left superior temporal cortex and greater GM volume in the right caudate nucleus. There were no significant differences in cortical thickness, GM volume, or volumes in regions of interest between BDD and control subjects. Subtle associations with clinical symptoms may characterize brain morphometric patterns in BDD, rather than large group differences in brain structure. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Insulin Resistance, Diabetes Mellitus, and Brain Structure in Bipolar Disorders

    Science.gov (United States)

    Hajek, Tomas; Calkin, Cynthia; Blagdon, Ryan; Slaney, Claire; Uher, Rudolf; Alda, Martin

    2014-01-01

    Type 2 diabetes mellitus (T2DM) damages the brain, especially the hippocampus, and frequently co-occurs with bipolar disorders (BD). Reduced hippocampal volumes are found only in some studies of BD subjects and may thus be secondary to the presence of certain clinical variables. Studying BD patients with abnormal glucose metabolism could help identify preventable risk factors for hippocampal atrophy in BD. We compared brain structure using optimized voxel-based morphometry of 1.5T MRI scans in 33 BD subjects with impaired glucose metabolism (19 with insulin resistance/glucose intolerance (IR/GI), 14 with T2DM), 15 euglycemic BD participants and 11 euglycemic, nonpsychiatric controls. The group of BD patients with IR, GI or T2DM had significantly smaller hippocampal volumes than the euglycemic BD participants (corrected p=0.02) or euglycemic, nonpsychiatric controls (corrected p=0.004). Already the BD subjects with IR/GI had smaller hippocampal volumes than euglycemic BD participants (t(32)=−3.15, p=0.004). Age was significantly more negatively associated with hippocampal volumes in BD subjects with IR/GI/T2DM than in the euglycemic BD participants (F(2, 44)=9.96, p=0.0003). The gray matter reductions in dysglycemic subjects extended to the cerebral cortex, including the insula. In conclusion, this is the first study demonstrating that T2DM or even prediabetes may be risk factors for smaller hippocampal and cortical volumes in BD. Abnormal glucose metabolism may accelerate the age-related decline in hippocampal volumes in BD. These findings raise the possibility that improving diabetes care among BD subjects and intervening already at the level of prediabetes could slow brain aging in BD. PMID:25074491

  15. Disorder-specific volumetric brain difference in adolescent major depressive disorder and bipolar depression.

    Science.gov (United States)

    MacMaster, Frank P; Carrey, Normand; Langevin, Lisa Marie; Jaworska, Natalia; Crawford, Susan

    2014-03-01

    Structural abnormalities in frontal, limbic and subcortical regions have been noted in adults with both major depressive disorder (MDD) and bipolar disorder (BD). In the current study, we examined regional brain morphology in youth with MDD and BD as compared to controls. Regional brain volumes were measured in 32 MDD subjects (15.7 ± 2.1 years), 14 BD subjects (16.0 ± 2.4 years) and 22 healthy controls (16.0 ± 2.8 years) using magnetic resonance imaging (MRI). Regions of interest included the hippocampus, dorsolateral prefrontal cortex (DLPFC), anterior cingulate cortex (ACC), caudate, putamen and thalamus. Volumetric differences between groups were significant (F26,80 = 1.80, p = 0.02). Post-hoc analyses indicated that individuals with MDD showed reduced left hippocampus volumes (p = 0.048) as well as right ACC white and gray matter volumes (p = 0.003; p = 0.01) compared to controls. BD participants also displayed reduced left hippocampal and right/left putamen volumes compared to controls (p < 0.001; p = 0.015; p = 0.046 respectively). Interestingly, right and left ACC white matter volumes were smaller in MDD than in BD participants (p = 0.019; p = 0.045 respectively). No volumetric group differences were observed for the DLPFC and thalamus. Discriminant analysis was able to correctly classify 81.0 % of subjects as having BD or as MDD based on imaging data. Confirmation and extension of our findings requires larger sample sizes. Our findings provide new evidence of distinct, specific regional brain volumetric differences between MDD and BD that may be used to distinguish the two disorders.

  16. The hubs of the human connectome are generally implicated in the anatomy of brain disorders.

    Science.gov (United States)

    Crossley, Nicolas A; Mechelli, Andrea; Scott, Jessica; Carletti, Francesco; Fox, Peter T; McGuire, Philip; Bullmore, Edward T

    2014-08-01

    Brain networks or 'connectomes' include a minority of highly connected hub nodes that are functionally valuable, because their topological centrality supports integrative processing and adaptive behaviours. Recent studies also suggest that hubs have higher metabolic demands and longer-distance connections than other brain regions, and therefore could be considered biologically costly. Assuming that hubs thus normally combine both high topological value and high biological cost, we predicted that pathological brain lesions would be concentrated in hub regions. To test this general hypothesis, we first identified the hubs of brain anatomical networks estimated from diffusion tensor imaging data on healthy volunteers (n = 56), and showed that computational attacks targeted on hubs disproportionally degraded the efficiency of brain networks compared to random attacks. We then prepared grey matter lesion maps, based on meta-analyses of published magnetic resonance imaging data on more than 20 000 subjects and 26 different brain disorders. Magnetic resonance imaging lesions that were common across all brain disorders were more likely to be located in hubs of the normal brain connectome (P brain disorders had lesions that were significantly more likely to be located in hubs (P human brain networks are more likely to be anatomically abnormal than non-hubs in many (if not all) brain disorders. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

  17. Brain network analysis reveals affected connectome structure in bipolar I disorder

    NARCIS (Netherlands)

    Collin, Guusje; van den Heuvel, Martijn P.; Abramovic, Lucija; Vreeker, Annabel; de Reus, Marcel A.; van Haren, Neeltje E M; Boks, Marco P M; Ophoff, Roel A.; Kahn, René S.

    The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections-i.e., the connectome-suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in

  18. Juvenile myoclonic epilepsy: A system disorder of the brain.

    Science.gov (United States)

    Wolf, Peter; Yacubian, Elza Márcia Targas; Avanzini, Giuliano; Sander, Thomas; Schmitz, Bettina; Wandschneider, Britta; Koepp, Matthias

    2015-08-01

    The prevailing understanding of generalized epilepsy is shaped by the traditional definition that "the responsible neuronal discharge takes place, if not throughout the entire grey matter, then at least in the greater part of it and simultaneously on both sides". This view is no longer tenable since concurrent findings using multiple methods have accumulated to reveal the role of bilateral networks of distributed and selective cortical and subcortical structures in so-called generalized ictogenesis. Most of this research has been focused on juvenile myoclonic epilepsy (JME), which today is commonly considered the archetypical syndrome of the idiopathic generalized epilepsies. Based upon recent research in the fields of clinical epileptology, neuropsychology and psychiatry, clinical neurophysiology, neuroimaging and epilepsy genetics this article, for the first time, unites these new findings into a comprehensive nosological view. Genetically determined dysfunctions of important cognitive systems like visuomotor coordination and linguistic communication appear now as key mechanisms of seizure generation in JME. This review suggests a new paradigm to consider JME as a system disorder of the brain analogous to other neurological system disorders.

  19. Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation

    DEFF Research Database (Denmark)

    Thrane, Jens F; Sunde, Niels A; Bergholt, Bo

    2014-01-01

    Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation......Increasing infection rate in multiple implanted pulse generator changes in movement disorder patients treated with deep brain stimulation...

  20. In Vivo NMR Studies of the Brain with Hereditary or Acquired Metabolic Disorders.

    Science.gov (United States)

    Sherry, Erica B; Lee, Phil; Choi, In-Young

    2015-12-01

    Metabolic disorders, whether hereditary or acquired, affect the brain, and abnormalities of the brain are related to cellular integrity; particularly in regard to neurons and astrocytes as well as interactions between them. Metabolic disturbances lead to alterations in cellular function as well as microscopic and macroscopic structural changes in the brain with diabetes, the most typical example of metabolic disorders, and a number of hereditary metabolic disorders. Alternatively, cellular dysfunction and degeneration of the brain lead to metabolic disturbances in hereditary neurological disorders with neurodegeneration. Nuclear magnetic resonance (NMR) techniques allow us to assess a range of pathophysiological changes of the brain in vivo. For example, magnetic resonance spectroscopy detects alterations in brain metabolism and energetics. Physiological magnetic resonance imaging (MRI) detects accompanying changes in cerebral blood flow related to neurovascular coupling. Diffusion and T1/T2-weighted MRI detect microscopic and macroscopic changes of the brain structure. This review summarizes current NMR findings of functional, physiological and biochemical alterations within a number of hereditary and acquired metabolic disorders in both animal models and humans. The global view of the impact of these metabolic disorders on the brain may be useful in identifying the unique and/or general patterns of abnormalities in the living brain related to the pathophysiology of the diseases, and identifying future fields of inquiry.

  1. Connecting combat-related mild traumatic brain injury with posttraumatic stress disorder symptoms through brain imaging.

    Science.gov (United States)

    Costanzo, Michelle E; Chou, Yi-Yu; Leaman, Suzanne; Pham, Dzung L; Keyser, David; Nathan, Dominic E; Coughlin, Mary; Rapp, Paul; Roy, Michael J

    2014-08-01

    Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may share common symptom and neuropsychological profiles in military service members (SMs) following deployment; while a connection between the two conditions is plausible, the relationship between them has been difficult to discern. The intent of this report is to enhance our understanding of the relationship between findings on structural and functional brain imaging and symptoms of PTSD. Within a cohort of SMs who did not meet criteria for PTSD but were willing to complete a comprehensive assessment within 2 months of their return from combat deployment, we conducted a nested case-control analysis comparing those with combat-related mTBI to age/gender-matched controls with diffusion tensor imaging, resting state functional magnetic resonance imaging and a range of psychological measures. We report degraded white matter integrity in those with a history of combat mTBI, and a positive correlation between the white matter microstructure and default mode network (DMN) connectivity. Higher clinician-administered and self-reported subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings offer a potential mechanism through which mTBI may alter brain function, and in turn, contribute to PTSD symptoms.

  2. Understanding the Impact of Brain Disorders: Towards a 'Horizontal Epidemiology' of Psychosocial Difficulties and Their Determinants.

    Directory of Open Access Journals (Sweden)

    Alarcos Cieza

    Full Text Available To test the hypothesis of 'horizontal epidemiology', i.e. that psychosocial difficulties (PSDs, such as sleep disturbances, emotional instability and difficulties in personal interactions, and their environmental determinants are experienced in common across neurological and psychiatric disorders, together called brain disorders.A multi-method study involving systematic literature reviews, content analysis of patient-reported outcomes and outcome instruments, clinical input and a qualitative study was carried out to generate a pool of PSD and environmental determinants relevant for nine different brain disorders, namely epilepsy, migraine, multiple sclerosis, Parkinson's disease, stroke, dementia, depression, schizophrenia and substance dependency. Information from these sources was harmonized and compiled, and after feedback from external experts, a data collection protocol including PSD and determinants common across these nine disorders was developed. This protocol was implemented as an interview in a cross-sectional study including a convenience sample of persons with one of the nine brain disorders. PSDs endorsed by at least 25% of patients with a brain disorder were considered associated with the disorder. PSD were considered common across disorders if associated to 5 out of the 9 brain disorders and if among the 5 both neurological and psychiatric conditions were represented.The data collection protocol with 64 PSDs and 20 determinants was used to collect data from a convenience sample of 722 persons in four specialized health care facilities in Europe.57 of the PSDs and 16 of the determinants included in the protocol were found to be experienced across brain disorders.This is the first evidence that supports the hypothesis of horizontal epidemiology in brain disorders. This result challenges the brain disorder-specific or vertical approach in which clinical and epidemiological research about psychosocial difficulties experienced in daily

  3. Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

    2017-01-18

    This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

  4. Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.

    Science.gov (United States)

    Butterfield, D A; Kanski, J

    2001-07-15

    Protein oxidation, one of a number of brain biomarkers of oxidative stress, is increased in several age-related neurodegenerative disorders or animal models thereof, including Alzheimer's disease, Huntington's disease, prion disorders, such as Creutzfeld-Jakob disease, and alpha-synuclein disorders, such as Parkinson's disease and frontotemporal dementia. Each of these neurodegenerative disorders is associated with aggregated proteins in brain. However, the relationship among protein oxidation, protein aggregation, and neurodegeneration remain unclear. The current rapid progress in elucidation of mechanisms of protein oxidation in neuronal loss should provide further insight into the importance of free radical oxidative stress in these neurodegenerative disorders.

  5. Neuroethics of deep brain stimulation for mental disorders: brain stimulation reward in humans.

    Science.gov (United States)

    Oshima, Hideki; Katayama, Yoichi

    2010-01-01

    The theoretical basis of some deep brain stimulation (DBS) trials undertaken in the early years was the phenomenon of "brain stimulation reward (BSR)," which was first identified in rats. The animals appeared to be rewarded by pleasure caused by the stimulation of certain brain regions (reward system), such as the septal area. "Self-stimulation" experiments, in which rats were allowed to stimulate their own brain by pressing a freely accessible lever, they quickly learned lever pressing and sometimes continued to stimulate until they exhausted themselves. BSR was also observed with DBS of the septal area in humans. DBS trials in later years were undertaken on other theoretical bases, but unexpected BSR was sometimes induced by stimulation of some areas, such as the locus coeruleus complex. When BSR was induced, the subjects experienced feelings that were described as "cheerful," "alert," "good," "well-being," "comfort," "relaxation," "joy," or "satisfaction." Since the DBS procedure is equivalent to a "self-stimulation" experiment, they could become "addicted to the stimulation itself" or "compulsive about the stimulation," and stimulate themselves "for the entire day," "at maximum amplitude" and, in some instances, "into convulsions." DBS of the reward system has recently been applied to alleviate anhedonia in patients with refractory major depression. Although this approach appears promising, there remains a difficult problem: who can adjust their feelings and reward-oriented behavior within the normal range? With a self-stimulation procedure, the BSR may become uncontrollable. To develop DBS to the level of a standard therapy for mental disorders, we need to discuss "Who has the right to control the mental condition?" and "Who makes decisions" on "How much control is appropriate?" in daily life.

  6. Neural correlates of apathy in patients with neurodegenerative disorders, acquired brain injury, and psychiatric disorders.

    Science.gov (United States)

    Kos, Claire; van Tol, Marie-José; Marsman, Jan-Bernard C; Knegtering, Henderikus; Aleman, André

    2016-10-01

    Apathy can be described as a loss of goal-directed purposeful behavior and is common in a variety of neurological and psychiatric disorders. Although previous studies investigated associations between abnormal brain functioning and apathy, it is unclear whether the neural basis of apathy is similar across different pathological conditions. The purpose of this systematic review was to provide an extensive overview of the neuroimaging literature on apathy including studies of various patient populations, and evaluate whether the current state of affairs suggest disorder specific or shared neural correlates of apathy. Results suggest that abnormalities within fronto-striatal circuits are most consistently associated with apathy across the different pathological conditions. Of note, abnormalities within the inferior parietal cortex were also linked to apathy, a region previously not included in neuroanatomical models of apathy. The variance in brain regions implicated in apathy may suggest that different routes towards apathy are possible. Future research should investigate possible alterations in different processes underlying goal-directed behavior, ranging from intention and goal-selection to action planning and execution.

  7. Anatomical and functional brain abnormalities in unmedicated major depressive disorder

    Directory of Open Access Journals (Sweden)

    Yang X

    2015-09-01

    Full Text Available Xiao Yang,1,2,* Xiaojuan Ma,3,* Mingli Li,1,2 Ye Liu,1 Jian Zhang,1 Bin Huang,4 Liansheng Zhao,1,2 Wei Deng,1,2 Tao Li,1,2 Xiaohong Ma1,2 1Psychiatric Laboratory and Department of Psychiatry, 2National Key Laboratory of Biotherapy, West China Hospital, Sichuan University, 3Chengdu First People’s Hospital, Chengdu, 4Dong Feng Mao Jian Hospital, Shiyan, People’s Republic of China *These authors contributed equally to this work Background: Using magnetic resonance imaging (MRI and resting-state functional magnetic resonance imaging (rsfMRI to explore the mechanism of brain structure and function in unmedicated patients with major depressive disorder (MDD. Patients and methods: Fifty patients with MDD and 50 matched healthy control participants free of psychotropic medication underwent high-resolution structural and rsfMRI scanning. Optimized diffeomorphic anatomical registration through exponentiated lie algebra and the Data Processing Assistant for rsfMRI were used to find potential differences in gray-matter volume (GMV and regional homogeneity (ReHo between the two groups. A Pearson correlation model was used to analyze associations of morphometric and functional changes with clinical symptoms. Results: Compared to healthy controls, patients with MDD showed significant GMV increase in the left posterior cingulate gyrus and GMV decrease in the left lingual gyrus (P<0.001, uncorrected. In ReHo analysis, values were significantly increased in the left precuneus and decreased in the left putamen (P<0.001, uncorrected in patients with MDD compared to healthy controls. There was no overlap between anatomical and functional changes. Linear correlation suggested no significant correlation between mean GMV values within regions with anatomical abnormality and ReHo values in regions with functional abnormality in the patient group. These changes were not significantly correlated with symptom severity. Conclusion: Our study suggests a dissociation

  8. Brain network analysis reveals affected connectome structure in bipolar I disorder.

    Science.gov (United States)

    Collin, Guusje; van den Heuvel, Martijn P; Abramovic, Lucija; Vreeker, Annabel; de Reus, Marcel A; van Haren, Neeltje E M; Boks, Marco P M; Ophoff, Roel A; Kahn, René S

    2016-01-01

    The notion that healthy brain function emerges from coordinated neural activity constrained by the brain's network of anatomical connections--i.e., the connectome--suggests that alterations in the connectome's wiring pattern may underlie brain disorders. Corroborating this hypothesis, studies in schizophrenia are indicative of altered connectome architecture including reduced communication efficiency, disruptions of central brain hubs, and affected "rich club" organization. Whether similar deficits are present in bipolar disorder is currently unknown. This study examines structural connectome topology in 216 bipolar I disorder patients as compared to 144 healthy controls, focusing in particular on central regions (i.e., brain hubs) and connections (i.e., rich club connections, interhemispheric connections) of the brain's network. We find that bipolar I disorder patients exhibit reduced global efficiency (-4.4%, P =0.002) and that this deficit relates (r = 0.56, P brain hub connections in general, or of connections spanning brain hubs (i.e., "rich club" connections) in particular (all P > 0.1). These findings highlight a role for aberrant brain network architecture in bipolar I disorder with reduced global efficiency in association with disruptions in interhemispheric connectivity, while the central "rich club" system appears not to be particularly affected.

  9. Non-human Primate Models for Brain Disorders - Towards Genetic Manipulations via Innovative Technology.

    Science.gov (United States)

    Qiu, Zilong; Li, Xiao

    2017-04-01

    Modeling brain disorders has always been one of the key tasks in neurobiological studies. A wide range of organisms including worms, fruit flies, zebrafish, and rodents have been used for modeling brain disorders. However, whether complicated neurological and psychiatric symptoms can be faithfully mimicked in animals is still debatable. In this review, we discuss key findings using non-human primates to address the neural mechanisms underlying stress and anxiety behaviors, as well as technical advances for establishing genetically-engineered non-human primate models of autism spectrum disorders and other disorders. Considering the close evolutionary connections and similarity of brain structures between non-human primates and humans, together with the rapid progress in genome-editing technology, non-human primates will be indispensable for pathophysiological studies and exploring potential therapeutic methods for treating brain disorders.

  10. 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.

  11. Great expectations: using whole-brain computational connectomics for understanding neuropsychiatric disorders.

    Science.gov (United States)

    Deco, Gustavo; Kringelbach, Morten L

    2014-12-01

    The study of human brain networks with in vivo neuroimaging has given rise to the field of connectomics, furthered by advances in network science and graph theory informing our understanding of the topology and function of the healthy brain. Here our focus is on the disruption in neuropsychiatric disorders (pathoconnectomics) and how whole-brain computational models can help generate and predict the dynamical interactions and consequences of brain networks over many timescales. We review methods and emerging results that exhibit remarkable accuracy in mapping and predicting both spontaneous and task-based healthy network dynamics. This raises great expectations that whole-brain modeling and computational connectomics may provide an entry point for understanding brain disorders at a causal mechanistic level, and that computational neuropsychiatry can ultimately be leveraged to provide novel, more effective therapeutic interventions, e.g., through drug discovery and new targets for deep brain stimulation.

  12. Weight change following deep brain stimulation for movement disorders.

    Science.gov (United States)

    Strowd, Roy E; Cartwright, Michael S; Passmore, Leah V; Ellis, Thomas L; Tatter, Stephen B; Siddiqui, Mustafa S

    2010-08-01

    Patients with Parkinson's disease (PD) and essential tremor (ET) tend to lose weight progressively over years. Weight gain following deep brain stimulation (DBS) of the subthalamic nucleus (STN) for treatment of PD has been documented in several studies that were limited by small sample size and exclusive focus on PD patients with STN stimulation. The current study was undertaken to examine weight change in a large sample of movement disorder patients following DBS. A retrospective review was undertaken of 182 patient charts following DBS of the STN, ventralis intermedius nucleus of the thalamus (VIM), and globus pallidus internus (GPi). Weight was collected preoperatively and postoperatively up to 24 months following surgery. Data were adjusted for baseline weight and multivariate linear regression was performed with repeated measures to assess weight change. Statistically significant mean weight gain of 1.8 kg (2.8% increase from baseline, p = 0.0113) was observed at a rate of approximately 1 kg per year up to 24 months following surgery. This gain was not predicted by age, gender, diagnosis, or stimulation target in a multivariate model. Significant mean weight gain of 2.3 kg (p = 0.0124) or 4.2% was observed in our PD patients. Most patients with PD and ET gain weight following DBS, and this gain is not predicted by age, gender, diagnosis, or stimulation target.

  13. Guanosine: a Neuromodulator with Therapeutic Potential in Brain Disorders

    Science.gov (United States)

    Lanznaster, Débora; Dal-Cim, Tharine; Piermartiri, Tetsadê C. B.; Tasca, Carla I.

    2016-01-01

    Guanosine is a purine nucleoside with important functions in cell metabolism and a protective role in response to degenerative diseases or injury. The past decade has seen major advances in identifying the modulatory role of extracellular action of guanosine in the central nervous system (CNS). Evidence from rodent and cell models show a number of neurotrophic and neuroprotective effects of guanosine preventing deleterious consequences of seizures, spinal cord injury, pain, mood disorders and aging-related diseases, such as ischemia, Parkinson’s and Alzheimer’s diseases. The present review describes the findings of in vivo and in vitro studies and offers an update of guanosine effects in the CNS. We address the protein targets for guanosine action and its interaction with glutamatergic and adenosinergic systems and with calcium-activated potassium channels. We also discuss the intracellular mechanisms modulated by guanosine preventing oxidative damage, mitochondrial dysfunction, inflammatory burden and modulation of glutamate transport. New and exciting avenues for future investigation into the protective effects of guanosine include characterization of a selective guanosine receptor. A better understanding of the neuromodulatory action of guanosine will allow the development of therapeutic approach to brain diseases. PMID:27699087

  14. Low-frequency deep brain stimulation for movement disorders.

    Science.gov (United States)

    Baizabal-Carvallo, José Fidel; Alonso-Juarez, Marlene

    2016-10-01

    Traditionally, deep brain stimulation (DBS) for movement disorders (MDs) is provided using stimulation frequencies equal to or above 100 Hz. However, recent evidence suggests that relatively low-frequency stimulation (LFS) below 100 Hz is an option to treat some patients with MDs. We aimed to review the clinical and pathophysiological evidence supporting the use of stimulation frequencies below 100 Hz in different MDs. Stimulation of the subthalamic nucleus at 60 Hz has provided benefit in gait and other axial symptoms such as swallowing and speech. Stimulation of the pedunculopontine nucleus between 20 and 45 Hz can provide benefit in freezing of gait, cognition, and sleep quality in select patients with Parkinson's disease. Stimulation of the globus pallidus internus below 100 Hz in patients with dystonia has provided benefit at the beginning of the therapy, although progressively higher stimulation frequencies seem to be necessary to maintain the clinical benefit. Relative LFS can lower energy requirements and reduce battery usage-a useful feature, particularly in patients treated with high current energy. DBS at frequencies below 100 Hz is a therapeutic option in select cases of Parkinson's disease with freezing of gait and other axial symptoms, and in select patients with dystonia and other hyperkinetic movements, particularly those requiring an energy-saving strategy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Discovering relations between mind, brain, and mental disorders using topic mapping.

    Directory of Open Access Journals (Sweden)

    Russell A Poldrack

    Full Text Available Neuroimaging research has largely focused on the identification of associations between brain activation and specific mental functions. Here we show that data mining techniques applied to a large database of neuroimaging results can be used to identify the conceptual structure of mental functions and their mapping to brain systems. This analysis confirms many current ideas regarding the neural organization of cognition, but also provides some new insights into the roles of particular brain systems in mental function. We further show that the same methods can be used to identify the relations between mental disorders. Finally, we show that these two approaches can be combined to empirically identify novel relations between mental disorders and mental functions via their common involvement of particular brain networks. This approach has the potential to discover novel endophenotypes for neuropsychiatric disorders and to better characterize the structure of these disorders and the relations between them.

  16. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults

    DEFF Research Database (Denmark)

    Hoogman, Martine; Bralten, Janita; Hibar, Derrek P

    2017-01-01

    BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies...

  17. Neuroimaging and genetic risk for Alzheimer's disease and addiction-related degenerative brain disorders.

    Science.gov (United States)

    Roussotte, Florence F; Daianu, Madelaine; Jahanshad, Neda; Leonardo, Cassandra D; Thompson, Paul M

    2014-06-01

    Neuroimaging offers a powerful means to assess the trajectory of brain degeneration in a variety of disorders, including Alzheimer's disease (AD). Here we describe how multi-modal imaging can be used to study the changing brain during the different stages of AD. We integrate findings from a range of studies using magnetic resonance imaging (MRI), positron emission tomography (PET), functional MRI (fMRI) and diffusion weighted imaging (DWI). Neuroimaging reveals how risk genes for degenerative disorders affect the brain, including several recently discovered genetic variants that may disrupt brain connectivity. We review some recent neuroimaging studies of genetic polymorphisms associated with increased risk for late-onset Alzheimer's disease (LOAD). Some genetic variants that increase risk for drug addiction may overlap with those associated with degenerative brain disorders. These common associations offer new insight into mechanisms underlying neurodegeneration and addictive behaviors, and may offer new leads for treating them before severe and irreversible neurological symptoms appear.

  18. The establishment and initial application of emotional disorder database in brain tumor patients

    Directory of Open Access Journals (Sweden)

    Hong-bo ZHANG

    2015-09-01

    Full Text Available  Objective To establish database for brain tumor patients with mood disorders and to explore the status and epidemiological characteristics of emotional function. Methods By using computer software, establish database of brain tumor with affective disorder based on clinical requirements. Record the data of 140 cases of brain tumors undergoing operation treatment, so as to found perfect public data platform and realize resource sharing. Results The clinical data of 140 brain tumor patients were successfully filled in the registration query system. The database provides simple and complex mood data queries for users to browse. Conclusions The mood disorder database for patients with brain tumors can provide related data samples and resources for basic and clinical research. Besides, it can effectively share clinical research data and reduce research costs. DOI: 10.3969/j.issn.1672-6731.2015.09.010

  19. Social competence in children with brain disorders: a meta-analytic review.

    Science.gov (United States)

    Kok, Tessa B; Post, Wendy J; Tucha, Oliver; de Bont, Eveline S J M; Kamps, Willem A; Kingma, Annette

    2014-06-01

    Social competence, i.e. appropriate or effective social functioning, is an important determinant of quality of life. Social competence consists of social skills, social performance and social adjustment. The current paper reviews social skills, in particular emotion recognition performance and its relationship with social adjustment in children with brain disorders. In this review, normal development and the neuro-anatomical correlates of emotion recognition in both healthy children and adults and in various groups of children with brain disorders, will be discussed. A systematic literature search conducted on PubMed, yielded nine papers. Emotion recognition tasks were categorized on the basis of task design and emotional categories to ensure optimal comparison across studies before an explorative meta-analysis was conducted. This meta-analytic review suggests that children with brain disorders show impaired emotion recognition, with the recognition of sad and fearful expressions being most impaired. Performance did not seem to be related to derivative measures of social adjustment. Despite the limited number of studies on a variety of brain disorders and control groups, outcomes were quite consistent across analyses and corresponded largely with the existing literature on development of emotion recognition in typically developing children. More longitudinal prospective studies on emotion recognition are needed to gain insight into recovery and subsequent development of children with distinct brain disorders. This will aid development, selection and implementation of interventions for improvement of social competence and quality of life in children with a brain disorder.

  20. Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders

    NARCIS (Netherlands)

    Koenders, L.; Machielsen, M.W.; van der Meer, F.J.; van Gasselt, A.C.; Meijer, C.J.; van den Brink, W.; Koeter, M.W.; Caan, M.W.; Cousijn, J.; den Braber, A.; van 't Ent, D.; Rive, M.M.; Schene, A.H.; van de Giessen, E.; Huyser, C.; de Kwaasteniet, B.P.; Veltman, D.J.; de Haan, L.

    2014-01-01

    BACKGROUND: Schizophrenia is highly comorbid with cannabis use disorders (CUDs), and this comorbidity is associated with an unfavourable course. Early onset or frequent cannabis use may influence brain structure. A key question is whether comorbid CUDs modulate brain morphology alterations associate

  1. Brain volume in male patients with recent onset schizophrenia with and without cannabis use disorders

    NARCIS (Netherlands)

    Koenders, L.; Machielsen, M.W.; Meer, F.J. van der; Gasselt, A.C. van; Meijer, C.J.W.; Brink, W. van den; Koeter, M.W.; Caan, M.W.; Cousijn, J.; Braber, A.; Ent, D. van 't; Rive, M.M.; Schene, A.H.; Giessen, E. van de; Huyser, C.; Kwaasteniet, B.P. de; Veltman, D.J.; Haan, L. de

    2015-01-01

    BACKGROUND: Schizophrenia is highly comorbid with cannabis use disorders (CUDs), and this comorbidity is associated with an unfavourable course. Early onset or frequent cannabis use may influence brain structure. A key question is whether comorbid CUDs modulate brain morphology alterations associate

  2. Annual Research Review: Progress in Using Brain Morphometry as a Clinical Tool for Diagnosing Psychiatric Disorders

    Science.gov (United States)

    Haubold, Alexander; Peterson, Bradley S.; Bansal, Ravi

    2012-01-01

    Brain morphometry in recent decades has increased our understanding of the neural bases of psychiatric disorders by localizing anatomical disturbances to specific nuclei and subnuclei of the brain. At least some of these disturbances precede the overt expression of clinical symptoms and possibly are endophenotypes that could be used to diagnose an…

  3. Association between flashbacks and structural brain abnormalities in posttraumatic stress disorder

    NARCIS (Netherlands)

    Kroes, M.C.W.; Whalley, M.G.; Rugg, M.D.; Brewin, C.R.

    2011-01-01

    OBJECTIVE: Posttraumatic stress disorder (PTSD) is reliably associated with reduced brain volume relative to healthy controls, in areas similar to those found in depression. We investigated whether in a PTSD sample brain volumes in these areas were related to reporting specific symptoms of PTSD or t

  4. Genetic and environmental influences on focal brain density in bipolar disorder

    NARCIS (Netherlands)

    van der Schot, Astrid C.; Vonk, Ronald; Brouwer, Rachel M.; van Baal, G. Caroline M.; Brans, Rachel G. H.; van Haren, Neeltje E. M.; Schnack, Hugo G.; Boomsma, Dorret I.; Nolen, Willem A.; Pol, Hilleke E. Hulshoff; Kahn, Rene S.

    2010-01-01

    Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. To investigate the contribution of genetic and environmental factors on grey

  5. 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…

  6. Multimodal Brain Imaging in Autism Spectrum Disorder and the Promise of Twin Research

    Science.gov (United States)

    Mevel, Katell; Fransson, Peter; Bölte, Sven

    2015-01-01

    Current evidence suggests the phenotype of autism spectrum disorder to be driven by a complex interaction of genetic and environmental factors impacting onto brain maturation, synaptic function, and cortical networks. However, findings are heterogeneous, and the exact neurobiological pathways of autism spectrum disorder still remain poorly…

  7. Deep brain stimulation for obsessive-compulsive disorders : long-term analysis of quality of life

    NARCIS (Netherlands)

    Ooms, Pieter; Mantione, Mariska; Figee, Martijn; Schuurman, P Richard; van den Munckhof, Pepijn; Denys, D.

    2014-01-01

    OBJECTIVE: To evaluate the long-term effects of deep brain stimulation (DBS) on quality of life (QOL) in therapy-refractory obsessive-compulsive disorder (OCD) patients. DESIGN: 16 patients who met Diagnostic and Statistical Manual of Mental Disorders (4th ed) (DSM-IV) criteria for OCD and were cons

  8. Cross-sensory gating in schizophrenia and autism spectrum disorder: EEG evidence for impaired brain connectivity?

    DEFF Research Database (Denmark)

    Magnée, Maurice J C M; Oranje, Bob; van Engeland, Herman

    2009-01-01

    Autism spectrum disorders (ASD) and schizophrenia are both neurodevelopmental disorders that have extensively been associated with impairments in functional brain connectivity. Using a cross-sensory P50 suppression paradigm, this study investigated low-level audiovisual interactions on cortical EEG...

  9. Brain Basics

    Medline Plus

    Full Text Available ... Brain Research Glossary Brain Basics (PDF, 10 pages) Introduction Watch the Brain Basics video Welcome. Brain Basics ... brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD) . Glutamate —the ...

  10. Role of histaminergic system in blood-brain barrier dysfunction associated with neurological disorders.

    Science.gov (United States)

    Bañuelos-Cabrera, Ivette; Valle-Dorado, María Guadalupe; Aldana, Blanca Irene; Orozco-Suárez, Sandra Adela; Rocha, Luisa

    2014-11-01

    Blood-brain barrier (BBB) disruption has been associated with several acute and chronic brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy. This represents a critical situation because damaged integrity of the BBB is related to the influx of immune mediators, plasma proteins and other outside elements from blood to the central nervous system (CNS) that may trigger a cascade of events that leads to neuroinflammation. In this review, evidence that mast cells and the release of factors such as histamine play an important role in the neuroinflammatory process associated with brain disorders such as Alzheimer's disease, Parkinson's disease and epilepsy is presented.

  11. ‘Liking’ and ‘wanting’ food rewards: Brain substrates and roles in eating disorders

    Science.gov (United States)

    Berridge, Kent C.

    2009-01-01

    What brain reward systems mediate motivational ‘wanting’ and hedonic ‘liking’ for food rewards? And what roles do those systems play in eating disorders? This article surveys recent findings regarding brain mechanisms of hedonic ‘liking’, such as the existence of cubic-millimeter hedonic hotspots in nucleus accumbens and ventral pallidum for opioid amplification of sensory pleasure. It also considers brain ‘wanting’ or incentive salience systems important to appetite, such as mesolimbic dopamine systems and opioid motivation circuits that extend beyond the hedonic hotspots. Finally, it considers some potential ways in which ‘wanting’ and ‘liking’ might relate to eating disorders. PMID:19336238

  12. Targeting Neuronal Networks with Combined Drug and Stimulation Paradigms Guided by Neuroimaging to Treat Brain Disorders.

    Science.gov (United States)

    Faingold, Carl L; Blumenfeld, Hal

    2015-10-01

    Improved therapy of brain disorders can be achieved by focusing on neuronal networks, utilizing combined pharmacological and stimulation paradigms guided by neuroimaging. Neuronal networks that mediate normal brain functions, such as hearing, interact with other networks, which is important but commonly neglected. Network interaction changes often underlie brain disorders, including epilepsy. "Conditional multireceptive" (CMR) brain areas (e.g., brainstem reticular formation and amygdala) are critical in mediating neuroplastic changes that facilitate network interactions. CMR neurons receive multiple inputs but exhibit extensive response variability due to milieu and behavioral state changes and are exquisitely sensitive to agents that increase or inhibit GABA-mediated inhibition. Enhanced CMR neuronal responsiveness leads to expression of emergent properties--nonlinear events--resulting from network self-organization. Determining brain disorder mechanisms requires animals that model behaviors and neuroanatomical substrates of human disorders identified by neuroimaging. However, not all sites activated during network operation are requisite for that operation. Other active sites are ancillary, because their blockade does not alter network function. Requisite network sites exhibit emergent properties that are critical targets for pharmacological and stimulation therapies. Improved treatment of brain disorders should involve combined pharmacological and stimulation therapies, guided by neuroimaging, to correct network malfunctions by targeting specific network neurons.

  13. Social Outcomes in Childhood Brain Disorder: A Heuristic Integration of Social Neuroscience and Developmental Psychology

    Science.gov (United States)

    Yeates, Keith Owen; Bigler, Erin D.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn

    2010-01-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer interactions and relationships, social problem solving and communication, social-affective and cognitive-executive processes, and their neural substrates. The model is illustrated by research on a specific form of childhood brain disorder, traumatic brain injury. The heuristic model may promote research regarding the neural and cognitive-affective substrates of children’s social development. It also may engender more precise methods of measuring impairments and disabilities in children with brain disorder and suggest ways to promote their social adaptation. PMID:17469991

  14. Social outcomes in childhood brain disorder: a heuristic integration of social neuroscience and developmental psychology.

    Science.gov (United States)

    Yeates, Keith Owen; Bigler, Erin D; Dennis, Maureen; Gerhardt, Cynthia A; Rubin, Kenneth H; Stancin, Terry; Taylor, H Gerry; Vannatta, Kathryn

    2007-05-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer interactions and relationships, social problem solving and communication, social-affective and cognitive-executive processes, and their neural substrates. The model is illustrated by research on a specific form of childhood brain disorder, traumatic brain injury. The heuristic model may promote research regarding the neural and cognitive-affective substrates of children's social development. It also may engender more precise methods of measuring impairments and disabilities in children with brain disorder and suggest ways to promote their social adaptation.

  15. Brain-specific transcriptional regulator T-brain-1 controls brain wiring and neuronal activity in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Tzyy-Nan eHuang

    2015-11-01

    Full Text Available T-brain-1 (TBR1 is a brain-specific T-box transcription factor. In 1995, Tbr1 was first identified from a subtractive hybridization that compared mouse embryonic and adult telencephalons. Previous studies of Tbr1–/– mice have indicated critical roles for TBR1 in the development of the cerebral cortex, amygdala and olfactory bulb. Neuronal migration and axonal projection are two important developmental features controlled by TBR1. Recently, recurrent de novo disruptive mutations in the TBR1 gene have been found in patients with autism spectrum disorders (ASDs. Human genetic studies have identified TBR1 as a high-confidence risk factor for ASDs. Because only one allele of the TBR1 gene is mutated in these patients, Tbr1+/– mice serve as a good genetic mouse model to explore the mechanism by which de novo TBR1 mutation leads to ASDs. Although neuronal migration and axonal projection defects of cerebral cortex are the most prominent phenotypes in Tbr1–/– mice, these features are not found in Tbr1+/– mice. Instead, inter- and intra-amygdalar axonal projections and NMDAR expression and activity in amygdala are particularly susceptible to Tbr1 haploinsufficiency. The studies indicated that both abnormal brain wiring (abnormal amygdalar connections and excitation/inhibition imbalance (NMDAR hypoactivity, two prominent models for ASD etiology, are present in Tbr1+/– mice. Moreover, calcium/calmodulin-dependent serine protein kinase (CASK was found to interact with TBR1. The CASK-TBR1 complex had been shown to directly bind the promoter of the Grin2b gene, which is also known as Nmdar2b, and upregulate Grin2b expression. This molecular function of TBR1 provides an explanation for NMDAR hypoactivity in Tbr1+/– mice. In addition to Grin2b, cell adhesion molecules-including Ntng1, Cdh8 and Cntn2-are also regulated by TBR1 to control axonal projections of amygdala. Taken together, the studies of Tbr1 provide an integrated picture of ASD

  16. PARADISE 24: A Measure to Assess the Impact of Brain Disorders on People’s Lives

    Science.gov (United States)

    Cieza, Alarcos; Sabariego, Carla; Anczewska, Marta; Ballert, Carolina; Bickenbach, Jerome; Cabello, Maria; Giovannetti, Ambra; Kaskela, Teemu; Mellor, Blanca; Pitkänen, Tuuli; Quintas, Rui; Raggi, Alberto; Świtaj, Piotr; Chatterji, Somnath

    2015-01-01

    Objective To construct a metric of the impact of brain disorders on people’s lives, based on the psychosocial difficulties (PSDs) that are experienced in common across brain disorders. Study Design Psychometric study using data from a cross-sectional study with a convenience sample of 722 persons with 9 different brain disorders interviewed in four European countries: Italy, Poland, Spain and Finland. Questions addressing 64 PSDs were first reduced based on statistical considerations, patient’s perspective and clinical expertise. Rasch analyses for polytomous data were also applied. Setting In and outpatient settings. Results A valid and reliable metric with 24 items was created. The infit of all questions ranged between 0.7 and 1.3. There were no disordered thresholds. The targeting between item thresholds and persons’ abilities was good and the person-separation index was 0.92. Persons’ abilities were linearly transformed into a more intuitive scale ranging from zero (no PSDs) to 100 (extreme PSDs). Conclusion The metric, called PARADISE 24, is based on the hypothesis of horizontal epidemiology, which affirms that people with brain disorders commonly experience PSDs. This metric is a useful tool to carry out cardinal comparisons over time of the magnitude of the psychosocial impact of brain disorders and between persons and groups in clinical practice and research. PMID:26147343

  17. PARADISE 24: A Measure to Assess the Impact of Brain Disorders on People's Lives.

    Science.gov (United States)

    Cieza, Alarcos; Sabariego, Carla; Anczewska, Marta; Ballert, Carolina; Bickenbach, Jerome; Cabello, Maria; Giovannetti, Ambra; Kaskela, Teemu; Mellor, Blanca; Pitkänen, Tuuli; Quintas, Rui; Raggi, Alberto; Świtaj, Piotr; Chatterji, Somnath

    2015-01-01

    To construct a metric of the impact of brain disorders on people's lives, based on the psychosocial difficulties (PSDs) that are experienced in common across brain disorders. Psychometric study using data from a cross-sectional study with a convenience sample of 722 persons with 9 different brain disorders interviewed in four European countries: Italy, Poland, Spain and Finland. Questions addressing 64 PSDs were first reduced based on statistical considerations, patient's perspective and clinical expertise. Rasch analyses for polytomous data were also applied. In and outpatient settings. A valid and reliable metric with 24 items was created. The infit of all questions ranged between 0.7 and 1.3. There were no disordered thresholds. The targeting between item thresholds and persons' abilities was good and the person-separation index was 0.92. Persons' abilities were linearly transformed into a more intuitive scale ranging from zero (no PSDs) to 100 (extreme PSDs). The metric, called PARADISE 24, is based on the hypothesis of horizontal epidemiology, which affirms that people with brain disorders commonly experience PSDs. This metric is a useful tool to carry out cardinal comparisons over time of the magnitude of the psychosocial impact of brain disorders and between persons and groups in clinical practice and research.

  18. Histaminergic system in brain disorders: lessons from the translational approach and future perspectives.

    Science.gov (United States)

    Baronio, Diego; Gonchoroski, Taylor; Castro, Kamila; Zanatta, Geancarlo; Gottfried, Carmem; Riesgo, Rudimar

    2014-01-01

    Histamine and its receptors were first described as part of immune and gastrointestinal systems, but their presence in the central nervous system and importance in behavior are gaining more attention. The histaminergic system modulates different processes including wakefulness, feeding, and learning and memory consolidation. Histamine receptors (H1R, H2R, H3R, and H4R) belong to the rhodopsin-like family of G protein-coupled receptors, present constitutive activity, and are subjected to inverse agonist action. The involvement of the histaminergic system in brain disorders, such as Alzheimer's disease, schizophrenia, sleep disorders, drug dependence, and Parkinson's disease, is largely studied. Data obtained from preclinical studies point antagonists of histamine receptors as promising alternatives to treat brain disorders. Thus, clinical trials are currently ongoing to assess the effects of these drugs on humans. This review summarizes the role of histaminergic system in brain disorders, as well as the effects of different histamine antagonists on animal models and humans.

  19. Cognitive remediation: potential novel brain-based treatment for bipolar disorder in children and adolescents.

    Science.gov (United States)

    Dickstein, Daniel P; Cushman, Grace K; Kim, Kerri L; Weissman, Alexandra B; Wegbreit, Ezra

    2015-08-01

    Bipolar disorder (BD) is among the most impairing psychiatric disorders affecting children and adolescents, despite our best psychopharmacological and psychotherapeutic treatments. Cognitive remediation, defined as a behavioral intervention designed to improve cognitive functions so as to reduce psychiatric illness, is an emerging brain-based treatment approach that has thus far not been studied in pediatric BD. The present article reviews the basic principles of cognitive remediation, describes what is known about cognitive remediation in psychiatric disorders, and delineates potential brain/behavior alterations implicated in pediatric BD that might be targets for cognitive remediation. Emerging data show that cognitive remediation may be useful in children and adults with schizophrenia, ADHD, and anxiety disorders, and in adults with BD. Potential targets for cognitive remediation in pediatric BD include face processing, response inhibition, frustration, and cognitive flexibility. Further study is warranted to determine if cognitive remediation for these targets, or others, may serve as a novel, brain-based treatment for pediatric BD.

  20. Evaluation of hyperbaric oxygen treatment of neuropsychiatric disorders following traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    SHI Xiao-yan; TANG Zhong-quan; SUN Da; HE Xiao-jun

    2006-01-01

    Background Improvement of clinical symptoms following hyperbaric oxygen (HBO) treatment of neuropsychiatric disorders arising from traumatic brain injury was proved by our previous study. This study was aim to obtain the evidence of other changes.Methods Three hundred and ten patients with neuropsychiatric disorders arising from traumatic brain injury were treated twice with hyperbaric oxygen. Cerebral single photon emissions computed tomography (SPECT)images and computed tomography scans (CT) before and after hyperbaric oxygen treatment, were compared.Results Before treatment, the proportion of abnormal cerebral changes detected by SPECT was 81.3% but only 15.2% by CT. After HBO treatment, 70.3% of SPECT scans showed no abnormalities and these patients were clinically improved. Treatment improved regional cerebral blood flow.Conclusion SPECT was much more sensitive than CT in the diagnosis of neuropsychiatric disorders following hyperbaric oxygen treatment of neuropsychiatric disorders arising from traumatic brain injury.

  1. Are Mental Disorders Brain Diseases, and What Does This Mean? A Clinical-Neuropsychological Perspective.

    Science.gov (United States)

    Frisch, Stefan

    Neuroscientific research has substantially increased our knowledge about mental disorders in recent years. Along with these benefits, radical postulates have been articulated according to which understanding and treatment of mental disorders should generally be based on biological terms, such as neurons/brain areas, transmitters, genes etc. Proponents of such a 'biological psychiatry' claim that mental disorders are analogous to neurological disorders and refer to neurology and neuropsychology to corroborate their claims. The present article argues that, from a clinical-neuropsychological perspective, 'biological psychiatry' is based on a mechanistic, 'cerebrocentric' framework of brain (dys-)function which has its roots in experimental neuroscience but runs up against narrow limits in clinical neurology and neuropsychology. In fact, understanding and treating neurological disorders generally demands a systems perspective including brain, organism and environment as intrinsically entangled. In this way, 'biological' characterizes a 'holistic', nonreductionist level of explanation, according to which the significance of particular mechanisms can only be estimated in the context of the organism (or person). This is evident in the common observation that local brain damage does not just lead to an isolated loss of function, but to multiple attempts of reorganization and readaptation; it initiates new developments. Furthermore, treating brain disorders necessarily includes aspects of individuality and subjectivity, a conclusion that contradicts the purely 'objectivist', third-person stance put forward by some proponents of biological psychiatry. In sum, understanding and treating brain damage sequelae in the clinical neurosciences demands a biopsychosocial perspective, for both conceptual and historical reasons. The same may hold for psychiatry when adopting a brain-based view on mental disorders. In such a perspective, biological psychiatry seems an interesting

  2. Current perspectives on deep brain stimulation for severe neurological and psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Kocabicak E

    2015-04-01

    Full Text Available Ersoy Kocabicak,1–3 Yasin Temel,1,2 Anke Höllig,4 Björn Falkenburger,5 Sonny KH Tan2,4 1Department of Neurosurgery, Maastricht University Medical Centre, 2Department of Neuroscience, Maastricht University, Maastricht, the Netherlands; 3Department of Neurosurgery, Ondokuz Mayis University, Samsun, Turkey; 4Department of Neurosurgery, 5Department of Neurology, RWTH Aachen University, Aachen, Germany Abstract: Deep brain stimulation (DBS has become a well-accepted therapy to treat movement disorders, including Parkinson’s disease, essential tremor, and dystonia. Long-term follow-up studies have demonstrated sustained improvement in motor symptoms and quality of life. DBS offers the opportunity to selectively modulate the targeted brain regions and related networks. Moreover, stimulation can be adjusted according to individual patients’ demands, and stimulation is reversible. This has led to the introduction of DBS as a treatment for further neurological and psychiatric disorders and many clinical studies investigating the efficacy of stimulating various brain regions in order to alleviate severe neurological or psychiatric disorders including epilepsy, major depression, and obsessive–compulsive disorder. In this review, we provide an overview of accepted and experimental indications for DBS therapy and the corresponding anatomical targets. Keywords: deep brain stimulation, movement disorders, neurological disorders, psychiatric disorders, Parkinson’s disease

  3. Brain structure abnormalities in early-onset and adolescent-onset conduct disorder.

    Science.gov (United States)

    Fairchild, Graeme; Passamonti, Luca; Hurford, Georgina; Hagan, Cindy C; von dem Hagen, Elisabeth A H; van Goozen, Stephanie H M; Goodyer, Ian M; Calder, Andrew J

    2011-06-01

    The developmental taxonomic theory proposes that neurodevelopmental factors play a critical role in the etiology of early-onset conduct disorder, whereas adolescent-onset conduct disorder arises as a result of social mimicry of deviant peers. Recent studies have challenged this theory by demonstrating that adolescents with both early- and adolescent-onset forms of conduct disorder show impaired emotional learning and abnormal neural activation during facial expression processing. The present study extends this work by investigating brain structure in both subtypes of conduct disorder. Voxel-based morphometry was used to compare gray matter volumes in four regions of interest (amygdala, insula, anterior cingulate, and orbitofrontal cortex) in male adolescents with early-onset (N=36) or adolescent-onset (N=27) conduct disorder and in healthy comparison subjects (N=27). Whole-brain structural analyses were also performed. The combined conduct disorder group displayed gray matter volume reductions in the bilateral amygdala, extending into the insula, relative to healthy comparison subjects. Separate comparisons between healthy subjects and each conduct disorder subgroup revealed lower amygdala volume in both subgroups and reduced right insula volume in the adolescent-onset subgroup. Regression analyses within the conduct disorder subjects alone demonstrated a negative correlation between conduct disorder symptoms and right insula volume. The results demonstrate that gray matter volume reductions in brain regions involved in processing socioemotional stimuli are associated with conduct disorder, regardless of age of onset. Brain structural abnormalities may contribute to the emergence of adolescent-onset as well as early-onset conduct disorder.

  4. Bipolar Disorder: not only in the Brain - immunological aspects

    NARCIS (Netherlands)

    E.M. Knijff (Esther)

    2006-01-01

    textabstractThe main objective of this thesis was to obtain more insight in the role of the immune system in the pathogenesis of bipolar disorder by investigating various aberrancies in the immune system of patients with bipolar disorder. In Chapter 1 some general concepts, important for the

  5. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders

    Directory of Open Access Journals (Sweden)

    Qingying Meng

    2017-02-01

    Full Text Available The complexity of the traumatic brain injury (TBI pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing, and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.

  6. Traumatic Brain Injury Induces Genome-Wide Transcriptomic, Methylomic, and Network Perturbations in Brain and Blood Predicting Neurological Disorders.

    Science.gov (United States)

    Meng, Qingying; Zhuang, Yumei; Ying, Zhe; Agrawal, Rahul; Yang, Xia; Gomez-Pinilla, Fernando

    2017-02-01

    The complexity of the traumatic brain injury (TBI) pathology, particularly concussive injury, is a serious obstacle for diagnosis, treatment, and long-term prognosis. Here we utilize modern systems biology in a rodent model of concussive injury to gain a thorough view of the impact of TBI on fundamental aspects of gene regulation, which have the potential to drive or alter the course of the TBI pathology. TBI perturbed epigenomic programming, transcriptional activities (expression level and alternative splicing), and the organization of genes in networks centered around genes such as Anax2, Ogn, and Fmod. Transcriptomic signatures in the hippocampus are involved in neuronal signaling, metabolism, inflammation, and blood function, and they overlap with those in leukocytes from peripheral blood. The homology between genomic signatures from blood and brain elicited by TBI provides proof of concept information for development of biomarkers of TBI based on composite genomic patterns. By intersecting with human genome-wide association studies, many TBI signature genes and network regulators identified in our rodent model were causally associated with brain disorders with relevant link to TBI. The overall results show that concussive brain injury reprograms genes which could lead to predisposition to neurological and psychiatric disorders, and that genomic information from peripheral leukocytes has the potential to predict TBI pathogenesis in the brain.

  7. Dermatoglyphics in relation to brain volumes in twins concordant and discordant for bipolar disorder.

    Science.gov (United States)

    Vonk, R; van der Schot, A C; van Baal, G C M; van Oel, C J; Nolen, W A; Kahn, R S

    2014-12-01

    Palmar and finger dermatoglyphics are formed between the 10th and the 17th weeks of gestation and their morphology can be influenced by genetic or environmental factors, interfering with normal intrauterine development. As both the skin and the brain develop from the same embryonal ectoderm, dermatoglyphic alterations may be informative for early abnormal neurodevelopmental processes in the brain. We investigated whether dermatoglyphic alterations are related to structural brain abnormalities in bipolar disorder and to what extent they are of a genetic and of an environmental origin. Dermatoglyphics and volumetric data from structural MRI were obtained in 53 twin pairs concordant or discordant for bipolar disorder and 51 healthy matched control twin pairs. Structural equation modeling was used. Bipolar disorder was significantly positively associated with palmar a-b ridge count (ABRC), indicating higher ABRC in bipolar patients (rph=.17 (CI .04-.30)). Common genes appear to be involved because the genetic correlation with ABRC was significant (rph-A=.21 (CI .05-.36). Irrespective of disease, ABRC showed a genetically mediated association with brain volume, indicated by a significant genetic correlation rph-A of respectively -.36 (CI -.52 to -.22) for total brain, -.34 (CI -.51 to -.16) total cortical volume, -.27 (CI -.43 to -.08) cortical gray matter and -.23 (CI -.41 to -.04) cortical white matter. In conclusion, a genetically determined abnormal development of the foetal ectoderm between the 10th and 15th week of gestation appears related to smaller brain volumes in (subjects at risk for) bipolar disorder.

  8. Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia.

    Science.gov (United States)

    Nakagawa, Yutaka; Chiba, Kenji

    2016-09-01

    Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Head circumference and brain size in autism spectrum disorder: A systematic review and meta-analysis.

    Science.gov (United States)

    Sacco, Roberto; Gabriele, Stefano; Persico, Antonio M

    2015-11-30

    Macrocephaly and brain overgrowth have been associated with autism spectrum disorder. We performed a systematic review and meta-analysis to provide an overall estimate of effect size and statistical significance for both head circumference and total brain volume in autism. Our literature search strategy identified 261 and 391 records, respectively; 27 studies defining percentages of macrocephalic patients and 44 structural brain imaging studies providing total brain volumes for patients and controls were included in our meta-analyses. Head circumference was significantly larger in autistic compared to control individuals, with 822/5225 (15.7%) autistic individuals displaying macrocephaly. Structural brain imaging studies measuring brain volume estimated effect size. The effect size is higher in low functioning autistics compared to high functioning and ASD individuals. Brain overgrowth was recorded in 142/1558 (9.1%) autistic patients. Finally, we found a significant interaction between age and total brain volume, resulting in larger head circumference and brain size during early childhood. Our results provide conclusive effect sizes and prevalence rates for macrocephaly and brain overgrowth in autism, confirm the variation of abnormal brain growth with age, and support the inclusion of this endophenotype in multi-biomarker diagnostic panels for clinical use.

  10. Brain tumors in children and adolescents: cognitive and psychological disorders at different ages.

    Science.gov (United States)

    Poggi, Geraldina; Liscio, Mariarosaria; Galbiati, Susanna; Adduci, Annarita; Massimino, Maura; Gandola, Lorenza; Spreafico, Filippo; Clerici, Carlo Alfredo; Fossati-Bellani, Franca; Sommovigo, Michela; Castelli, Enrico

    2005-05-01

    Cognitive and psychological disorders are among the most frequently observed sequelae in brain tumor survivors. The goal of this work was to verify the presence of these disorders in a group of children and adolescents diagnosed with brain tumor before age 18 years, differentiate these disorders according to age of assessment, identify correlations between the two types of impairments and define possible associations between these impairments and clinical variables. The study involved 76 patients diagnosed with brain tumor before age 18 years. Three age groups were formed, and all the patients received a standardized battery of age-matched cognitive and psychological tests. According to our findings, all three groups present with cognitive and psychological-behavioral disorders. Their frequency varies according to age of onset and is strongly associated to time since diagnosis. The performance intelligence quotient (PIQ) was more impaired than the verbal intelligence quotient (VIQ). Internalizing problems, withdrawal and social problems were the most frequent psychological disorders. Correlations were found between cognitive impairment and the onset of the main psychological and behavioral disorders. These findings are relevant as they point out the long-term outcome of brain tumor survivors. Hence, the recommendation to diversify psychological interventions and rehabilitation plans according to the patients' age.

  11. The Developmental Brain Disorders Database (DBDB): a curated neurogenetics knowledge base with clinical and research applications.

    Science.gov (United States)

    Mirzaa, Ghayda M; Millen, Kathleen J; Barkovich, A James; Dobyns, William B; Paciorkowski, Alex R

    2014-06-01

    The number of single genes associated with neurodevelopmental disorders has increased dramatically over the past decade. The identification of causative genes for these disorders is important to clinical outcome as it allows for accurate assessment of prognosis, genetic counseling, delineation of natural history, inclusion in clinical trials, and in some cases determines therapy. Clinicians face the challenge of correctly identifying neurodevelopmental phenotypes, recognizing syndromes, and prioritizing the best candidate genes for testing. However, there is no central repository of definitions for many phenotypes, leading to errors of diagnosis. Additionally, there is no system of levels of evidence linking genes to phenotypes, making it difficult for clinicians to know which genes are most strongly associated with a given condition. We have developed the Developmental Brain Disorders Database (DBDB: https://www.dbdb.urmc.rochester.edu/home), a publicly available, online-curated repository of genes, phenotypes, and syndromes associated with neurodevelopmental disorders. DBDB contains the first referenced ontology of developmental brain phenotypes, and uses a novel system of levels of evidence for gene-phenotype associations. It is intended to assist clinicians in arriving at the correct diagnosis, select the most appropriate genetic test for that phenotype, and improve the care of patients with developmental brain disorders. For researchers interested in the discovery of novel genes for developmental brain disorders, DBDB provides a well-curated source of important genes against which research sequencing results can be compared. Finally, DBDB allows novel observations about the landscape of the neurogenetics knowledge base.

  12. Early brain enlargement and elevated extra-axial fluid in infants who develop autism spectrum disorder.

    Science.gov (United States)

    Shen, Mark D; Nordahl, Christine W; Young, Gregory S; Wootton-Gorges, Sandra L; Lee, Aaron; Liston, Sarah E; Harrington, Kayla R; Ozonoff, Sally; Amaral, David G

    2013-09-01

    Prospective studies of infants at risk for autism spectrum disorder have provided important clues about the early behavioural symptoms of autism spectrum disorder. Diagnosis of autism spectrum disorder, however, is not currently made until at least 18 months of age. There is substantially less research on potential brain-based differences in the period between 6 and 12 months of age. Our objective in the current study was to use magnetic resonance imaging to identify any consistently observable brain anomalies in 6-9 month old infants who would later develop autism spectrum disorder. We conducted a prospective infant sibling study with longitudinal magnetic resonance imaging scans at three time points (6-9, 12-15, and 18-24 months of age), in conjunction with intensive behavioural assessments. Fifty-five infants (33 'high-risk' infants having an older sibling with autism spectrum disorder and 22 'low-risk' infants having no relatives with autism spectrum disorder) were imaged at 6-9 months; 43 of these (27 high-risk and 16 low-risk) were imaged at 12-15 months; and 42 (26 high-risk and 16 low-risk) were imaged again at 18-24 months. Infants were classified as meeting criteria for autism spectrum disorder, other developmental delays, or typical development at 24 months or later (mean age at outcome: 32.5 months). Compared with the other two groups, infants who developed autism spectrum disorder (n = 10) had significantly greater extra-axial fluid at 6-9 months, which persisted and remained elevated at 12-15 and 18-24 months. Extra-axial fluid is characterized by excessive cerebrospinal fluid in the subarachnoid space, particularly over the frontal lobes. The amount of extra-axial fluid detected as early as 6 months was predictive of more severe autism spectrum disorder symptoms at the time of outcome. Infants who developed autism spectrum disorder also had significantly larger total cerebral volumes at both 12-15 and 18-24 months of age. This is the first magnetic

  13. Single subject prediction of brain disorders in neuroimaging: Promises and pitfalls.

    Science.gov (United States)

    Arbabshirani, Mohammad R; Plis, Sergey; Sui, Jing; Calhoun, Vince D

    2017-01-15

    Neuroimaging-based single subject prediction of brain disorders has gained increasing attention in recent years. Using a variety of neuroimaging modalities such as structural, functional and diffusion MRI, along with machine learning techniques, hundreds of studies have been carried out for accurate classification of patients with heterogeneous mental and neurodegenerative disorders such as schizophrenia and Alzheimer's disease. More than 500 studies have been published during the past quarter century on single subject prediction focused on a multiple brain disorders. In the first part of this study, we provide a survey of more than 200 reports in this field with a focus on schizophrenia, mild cognitive impairment (MCI), Alzheimer's disease (AD), depressive disorders, autism spectrum disease (ASD) and attention-deficit hyperactivity disorder (ADHD). Detailed information about those studies such as sample size, type and number of extracted features and reported accuracy are summarized and discussed. To our knowledge, this is by far the most comprehensive review of neuroimaging-based single subject prediction of brain disorders. In the second part, we present our opinion on major pitfalls of those studies from a machine learning point of view. Common biases are discussed and suggestions are provided. Moreover, emerging trends such as decentralized data sharing, multimodal brain imaging, differential diagnosis, disease subtype classification and deep learning are also discussed. Based on this survey, there is extensive evidence showing the great potential of neuroimaging data for single subject prediction of various disorders. However, the main bottleneck of this exciting field is still the limited sample size, which could be potentially addressed by modern data sharing models such as the ones discussed in this paper. Emerging big data technologies and advanced data-intensive machine learning methodologies such as deep learning have coincided with an increasing need

  14. Dysregulated Translational Control: From Brain Disorders to Psychoactive Drugs

    Directory of Open Access Journals (Sweden)

    Emanuela eSantini

    2011-11-01

    Full Text Available In the last decade, a plethora of studies utilizing pharmacological, biochemical, and genetic approaches have shown that precise translational control is required for long-lasting synaptic plasticity and the formation of long-term memory. Moreover, more recent studies indicate that alterations in translational control are a common pathophysiological feature of human neurological disorders, including developmental disorders, neuropsychiatric disorders, and neurodegenerative diseases. Finally, translational control mechanisms are susceptible to modification by psychoactive drugs. Taken together, these findings point to a central role for translational control in the regulation of synaptic function and behavior.

  15. Neuronal cell adhesion genes: Key players in risk for schizophrenia, bipolar disorder and other neurodevelopmental brain disorders?

    Science.gov (United States)

    Corvin, Aiden P

    2010-01-01

    The major mental disorders, schizophrenia and bipolar disorder are substantially heritable. Recent genomic studies have identified a small number of common and rare risk genes contributing to both disorders and support epidemiological evidence that genetic susceptibility overlaps between them. Prompted by the question of whether risk genes cluster in specific molecular pathways or implicate discrete mechanisms we and others have developed hypothesis-free methods of investigating genome-wide association datasets at a pathway-level. The application of our method to the 212 experimentally-derived pathways in the Kyoto Encycolpaedia of Genes and Genomes (KEGG) database identified significant association between the cell adhesion molecule (CAM) pathway and both schizophrenia and bipolar disorder susceptibility across three GWAS datasets. Interestingly, a similar approach applied to an autistic spectrum disorders (ASDs) sample identified a similar pathway and involved many of the same genes. Disruption of a number of these genes (including NRXN1, CNTNAP2 and CASK) are known to cause diverse neurodevelopmental brain disorder phenotypes including schizophenia, autism, learning disability and specific language disorder. Taken together these studies bring the CAM pathway sharply into focus for more comprehensive DNA sequencing to identify the critical genes, and investigate their relationships and interaction with environmental risk factors in the expression of many seemingly different neurodevelopmental disorders.

  16. Brain Imaging in Pediatric Obsessive-Compulsive Disorder

    Science.gov (United States)

    MacMaster, Frank P.; O'Neill, Joseph; Rosenberg, David R.

    2008-01-01

    Neuroimaging findings support the frontal-striatal-thalamic model of pediatric obsessive-compulsive disorder. Glutamate is also implicated in the pathological finding of the disease. Implications for pediatric OCD treatments are discussed.

  17. Brain Imaging in Pediatric Obsessive-Compulsive Disorder

    Science.gov (United States)

    MacMaster, Frank P.; O'Neill, Joseph; Rosenberg, David R.

    2008-01-01

    Neuroimaging findings support the frontal-striatal-thalamic model of pediatric obsessive-compulsive disorder. Glutamate is also implicated in the pathological finding of the disease. Implications for pediatric OCD treatments are discussed.

  18. Electroconvulsive therapy-induced brain plasticity determines therapeutic outcome in mood disorders

    Science.gov (United States)

    Dukart, Juergen; Regen, Francesca; Kherif, Ferath; Colla, Michael; Bajbouj, Malek; Heuser, Isabella; Frackowiak, Richard S.; Draganski, Bogdan

    2014-01-01

    There remains much scientific, clinical, and ethical controversy concerning the use of electroconvulsive therapy (ECT) for psychiatric disorders stemming from a lack of information and knowledge about how such treatment might work, given its nonspecific and spatially unfocused nature. The mode of action of ECT has even been ascribed to a “barbaric” form of placebo effect. Here we show differential, highly specific, spatially distributed effects of ECT on regional brain structure in two populations: patients with unipolar or bipolar disorder. Unipolar and bipolar disorders respond differentially to ECT and the associated local brain-volume changes, which occur in areas previously associated with these diseases, correlate with symptom severity and the therapeutic effect. Our unique evidence shows that electrophysical therapeutic effects, although applied generally, take on regional significance through interactions with brain pathophysiology. PMID:24379394

  19. Gut-Brain Axis: The Role of Gut Microbiota in Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Alper Evrensel

    2015-12-01

    Full Text Available Gut microbiota is essential to human health, playing a major and important role in the bidirectional communication between the gut and the brain. There is significant evidence linking gut microbiota and metabolic disorders such as obesity, diabetes and neuropsychiatric disorders such as schizophrenia, autism, anxiety, depression. New studies show microbiota can activate immune system, neural pathways and central nervous system signaling systems, including commensal, probiotic and pathogenic microorganisms in the gastrointestinal tract. This microorganisms are capable of producing and delivering neuroactive substances such as gamma-aminobutyric acid and serotonin, which act on the gut-brain axis. Preclinical evaluation in rodents suggests that certain probiotics possess antidepressant or anxiolytic activity. Effects may be mediated via the vagus nerve, spinal cord, immune system or neuroendocrine systems. Here we review recent literature that examines the impact of gut microbiota on the brain, behavior and psychiatric disorders.

  20. Brain Regions and Neuropsychological Deficits in Obsessive-Compulsive Disorder

    Directory of Open Access Journals (Sweden)

    Murat Erdem

    2013-09-01

    Full Text Available Neurobiological factors had been shown to play an important role in the emergence of obsessive-compulsive disorder by the information obtained from the methods developed over the years. According to the neuropsychological perspective, the defects had been detected mainly in executive functions, in attention, memory, visual-spatial functions; and abnormalities had been described in the frontal lobe, cingulate cortex, basal ganglia, and thalamus regions of the patients with obsessive-compulsive disorder. The main and the most repeated abnormalities in patients with obsessive-compulsive disorder are dysfunctions in executive function and visual memory. Dysfunctions of the inhibitory processes associated with the dominant frontal area lead to an insufficiency on the inhibition of verbal functions. Excessive activation of the orbitofrontal cortex that mediate the behavioral response suppression function in obsessive-compulsive disorder demonstrated by functional imaging techniques. Repeated-resistant behaviors (eg: compulsions are composed by the deteriorations of the inhibitions of motor or cognitive programs in basal ganglions provided through cycles of frontal lobe. The findings of clinical observations in patients with obsessive-compulsive disorder could be considered as a reflection of excessive work in 'error detection system' which is the cause of the thoughts that something goes wrong and efforts to achieve perfection. As neurobiological, this finding is observed as excessive activity in orbitofrontal cortex and anterior cingulate cortex representing the ability of humans to provide and detect errors. It is is expected to develop the vehicles that are more sensitive to the characteristics of cognitive deficits in obsessive-compulsive disorder. In addition to the neuropsychological tests, using electrophysiological and advanced functional imaging techniques will put forward a better underlying the physiopathology of this disorder in order to

  1. Brain activation to task-irrelevant disorder-related threat in social anxiety disorder: The impact of symptom severity

    Directory of Open Access Journals (Sweden)

    Carina Yvonne Heitmann

    2017-01-01

    Full Text Available Unintentional and uncontrollable processing of threat has been suggested to contribute to the pathology of social anxiety disorder (SAD. The present study investigated the neural correlates of processing task-irrelevant, highly ecologically valid, disorder-related stimuli as a function of symptom severity in SAD. Twenty-four SAD patients and 24 healthy controls (HC performed a feature-based comparison task during functional magnetic resonance imaging, while task-irrelevant, disorder-related or neutral scenes were presented simultaneously at a different spatial position. SAD patients showed greater activity than HC in response to disorder-related versus neutral scenes in brain regions associated with self-referential processing (e.g. insula, precuneus, dorsomedial prefrontal cortex and emotion regulation (e.g. dorsolateral prefrontal cortex (dlPFC, inferior frontal gyrus. Symptom severity was positively associated with amygdala activity, and negatively with activation in dorsal anterior cingulate cortex and dlPFC in SAD patients. Additional correlation analysis revealed that amygdala-prefrontal coupling was positively associated with symptom severity. A network of brain regions is thus involved in SAD patients' processing of task-irrelevant, complex, ecologically valid, disorder-related scenes. Furthermore, increasing symptom severity in SAD patients seems to reflect a growing imbalance between neural mechanisms related to stimulus-driven bottom-up and regulatory top-down processes resulting in dysfunctional regulation strategies.

  2. Brain activation to task-irrelevant disorder-related threat in social anxiety disorder: The impact of symptom severity.

    Science.gov (United States)

    Heitmann, Carina Yvonne; Feldker, Katharina; Neumeister, Paula; Brinkmann, Leonie; Schrammen, Elisabeth; Zwitserlood, Pienie; Straube, Thomas

    2017-01-01

    Unintentional and uncontrollable processing of threat has been suggested to contribute to the pathology of social anxiety disorder (SAD). The present study investigated the neural correlates of processing task-irrelevant, highly ecologically valid, disorder-related stimuli as a function of symptom severity in SAD. Twenty-four SAD patients and 24 healthy controls (HC) performed a feature-based comparison task during functional magnetic resonance imaging, while task-irrelevant, disorder-related or neutral scenes were presented simultaneously at a different spatial position. SAD patients showed greater activity than HC in response to disorder-related versus neutral scenes in brain regions associated with self-referential processing (e.g. insula, precuneus, dorsomedial prefrontal cortex) and emotion regulation (e.g. dorsolateral prefrontal cortex (dlPFC), inferior frontal gyrus). Symptom severity was positively associated with amygdala activity, and negatively with activation in dorsal anterior cingulate cortex and dlPFC in SAD patients. Additional correlation analysis revealed that amygdala-prefrontal coupling was positively associated with symptom severity. A network of brain regions is thus involved in SAD patients' processing of task-irrelevant, complex, ecologically valid, disorder-related scenes. Furthermore, increasing symptom severity in SAD patients seems to reflect a growing imbalance between neural mechanisms related to stimulus-driven bottom-up and regulatory top-down processes resulting in dysfunctional regulation strategies.

  3. Brain "fog," inflammation and obesity : key aspects of neuropsychiatric disorders improved by luteolin

    Directory of Open Access Journals (Sweden)

    Theoharis Constantin Theoharides

    2015-07-01

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

  4. Neurological disorders and therapeutics targeted to surmount the blood–brain barrier

    Directory of Open Access Journals (Sweden)

    Kanwar JR

    2012-07-01

    Full Text Available Jagat R Kanwar, Bhasker Sriramoju, Rupinder K KanwarNanomedicine Laboratory of Immunology and Molecular Biomedical Research, Centre for Biotechnology and Interdisciplinary Biosciences, Institute for Frontier Materials (IFM, Deakin University, Waurn Ponds, Victoria, AustraliaAbstract: We are now in an aging population, so neurological disorders, particularly the neurodegenerative diseases, are becoming more prevalent in society. As per the epidemiological studies, Europe alone suffers 35% of the burden, indicating an alarming rate of disease progression. Further, treatment for these disorders is a challenging area due to the presence of the tightly regulated blood–brain barrier and its unique ability to protect the brain from xenobiotics. Conventional therapeutics, although effective, remain critically below levels of optimum therapeutic efficacy. Hence, methods to overcome the blood–brain barrier are currently a focus of research. Nanotechnological applications are gaining paramount importance in addressing this question, and yielding some promising results. This review addresses the pathophysiology of the more common neurological disorders and novel drug candidates, along with targeted nanoparticle applications for brain delivery.Keywords: blood–brain barrier, neurological diseases, brain delivery, targeted nanoparticles

  5. Data on overlapping brain disorders and emerging drug targets in human Dopamine Receptors Interaction Network

    Directory of Open Access Journals (Sweden)

    Avijit Podder

    2017-06-01

    Full Text Available Intercommunication of Dopamine Receptors (DRs with their associate protein partners is crucial to maintain regular brain function in human. Majority of the brain disorders arise due to malfunctioning of such communication process. Hence, contributions of genetic factors, as well as phenotypic indications for various neurological and psychiatric disorders are often attributed as sharing in nature. In our earlier research article entitled “Human Dopamine Receptors Interaction Network (DRIN: a systems biology perspective on topology, stability and functionality of the network” (Podder et al., 2014 [1], we had depicted a holistic interaction map of human Dopamine Receptors. Given emphasis on the topological parameters, we had characterized the functionality along with the vulnerable properties of the network. In support of this, we hereby provide an additional data highlighting the genetic overlapping of various brain disorders in the network. The data indicates the sharing nature of disease genes for various neurological and psychiatric disorders in dopamine receptors connecting protein-protein interactions network. The data also indicates toward an alternative approach to prioritize proteins for overlapping brain disorders as valuable drug targets in the network.

  6. The association of antipsychotic medication and lithium with brain measures in patients with bipolar disorder.

    Science.gov (United States)

    Abramovic, Lucija; Boks, Marco P M; Vreeker, Annabel; Bouter, Diandra C; Kruiper, Caitlyn; Verkooijen, Sanne; van Bergen, Annet H; Ophoff, Roel A; Kahn, René S; van Haren, Neeltje E M

    2016-11-01

    There is evidence that brain structure is abnormal in patients with bipolar disorder. Lithium intake appears to ׳normalise׳ global and local brain volumes, but effects of antipsychotic medication on brain volume or cortical thickness are less clear. Here, we aim to disentangle disease-specific brain deviations from those induced by antipsychotic medication and lithium intake using a large homogeneous sample of patients with bipolar disorder type I. Magnetic resonance imaging brain scans were obtained from 266 patients and 171 control subjects. Subcortical volumes and global and focal cortical measures (volume, thickness, and surface area) were compared between patients and controls. In patients, the association between lithium and antipsychotic medication intake and global, subcortical and cortical measures was investigated. Patients showed significantly larger lateral and third ventricles, smaller total brain, caudate nucleus, and pallidum volumes and thinner cortex in some small clusters in frontal, parietal and cingulate regions as compared with controls. Lithium-free patients had significantly smaller total brain, thalamus, putamen, pallidum, hippocampus and accumbens volumes compared to patients on lithium. In patients, use of antipsychotic medication was related to larger third ventricle and smaller hippocampus and supramarginal cortex volume. Patients with bipolar disorder show abnormalities in total brain, subcortical, and ventricle volume, particularly in the nucleus caudate and pallidum. Abnormalities in cortical thickness were scattered and clusters were relatively small. Lithium-free patients showed more pronounced abnormalities as compared with those on lithium. The associations between antipsychotic medication and brain volume are subtle and less pronounced than those of lithium. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

  7. Changes in brain activity of somatoform disorder patients during emotional empathy after multimodal psychodynamic psychotherapy

    OpenAIRE

    de Greck, Moritz; Bölter, Annette F.; Lehmann, Lisa; Ulrich, Cornelia; Stockum, Eva; Enzi, Björn; Hoffmann, Thilo; Tempelmann, Claus; Beutel, Manfred; Frommer, Jörg; Northoff, Georg

    2013-01-01

    Somatoform disorder patients show a variety of emotional disturbances including impaired emotion recognition and increased empathic distress. In a previous paper, our group showed that several brain regions involved in emotional processing, such as the parahippocampal gyrus and other regions, were less activated in pre-treatment somatoform disorder patients (compared to healthy controls) during an empathy task. Since the parahippocampal gyrus is involved in emotional memory, its decreased act...

  8. Changes in brain activity of somatoform disorder patients during emotional empathy after multimodal psychodynamic psychotherapy.

    OpenAIRE

    Moritz ede Greck; Bölter, Annette F.; Lisa eLehmann; Cornelia eUlrich; Eva eStockum; Björn eEnzi; Thilo eHoffmann; Claus eTempelmann; Manfred eBeutel; Jörg eFrommer; Georg eNorthoff

    2013-01-01

    Somatoform disorder patients show a variety of emotional disturbances including impaired emotion recognition and increased empathic distress. In a previous paper, our group showed that several brain regions involved in emotional processing, such as the parahippocampal gyrus and other regions, were less activated in pre-treatment somatoform disorder patients (compared to healthy controls) during an empathy task. Since the parahippocampal gyrus is involved in emotional memory, its decreased act...

  9. Anxiety disorders in children and adolescents in the second six months after traumatic brain injury.

    Science.gov (United States)

    Max, Jeffrey E; Lopez, Aholibama; Wilde, Elisabeth A; Bigler, Erin D; Schachar, Russell J; Saunders, Ann; Ewing-Cobbs, Linda; Chapman, Sandra B; Yang, Tony T; Levin, Harvey S

    2015-01-01

    The objective of this prospective longitudinal study was to assess the nature, rate, predictive variables, and neuroimaging characteristics of novel (new-onset) anxiety disorders (compared with no novel anxiety disorders) 6-12 months after pediatric traumatic brain injury (TBI). Psychiatric and psychosocial interviews were administered to children who sustained mild to severe TBI at baseline (soon after injury) and at the 12-month follow-up post-injury (n= 125). The psychiatric outcome of children 12-months post-injury revealed that novel anxiety disorders present in the second six months after TBI were heterogeneous and occurred in 13 (10.4%) participants. Novel anxiety disorder was significantly associated with concurrent novel depressive disorder and with novel personality change due to TBI. Novel anxiety disorder was marginally associated with younger age at injury and with pre-injury anxiety disorder in univariate analyses. Age at injury, pre-injury anxiety disorder, and personality change due to TBI were each significantly and independently related to novel anxiety disorder in a logistic regression analysis. There were no significant neuroimaging group differences. These findings suggest that the emergence of novel anxiety disorder after TBI might be related to a broader problem of affective dysregulation especially in younger children and those with a vulnerability even to pre-injury anxiety disorder.

  10. Uremic encephalopathy and other brain disorders associated with renal failure.

    Science.gov (United States)

    Seifter, Julian Lawrence; Samuels, Martin A

    2011-04-01

    Kidney failure is one of the leading causes of disability and death and one of the most disabling features of kidney failure and dialysis is encephalopathy. This is probably caused by the accumulation of uremic toxins. Other important causes are related to the underlying disorders that cause kidney failure, particularly hypertension. The clinical manifestations of uremic encephalopathy include mild confusional states to deep coma, often with associated movement disorders, such as asterixis. Most nephrologists consider cognitive impairment to be a major indication for the initiation of renal replacement therapy with dialysis with or without subsequent transplantation. Sleep disorders, including Ekbom's syndrome (restless legs syndrome) are also common in patients with kidney failure. Renal replacement therapies are also associated with particular neurologic complications including acute dialysis encephalopathy and chronic dialysis encephalopathy, formerly known as dialysis dementia. The treatments and prevention of each are discussed. © Thieme Medical Publishers.

  11. Abnormal brain activation in excoriation (skin-picking) disorder

    DEFF Research Database (Denmark)

    Odlaug, Brian L.; Hampshire, Adam; Chamberlain, Samuel R

    2016-01-01

    Background: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims: To probe the function of fronto-striatal circuitry in SPD. Method: Eighteen participants with SPD and 15 matched healthy controls undertook an executive...... involved in habit formation, action monitoring and inhibition appear involved in the pathophysiology of SPD. Implications exist for understanding the basis of excessive grooming and the relationship of SPD with putative obsessive-compulsive spectrum disorders.......Background: Excoriation (skin-picking) disorder (SPD) is a relatively common psychiatric condition whose neurobiological basis is unknown. Aims: To probe the function of fronto-striatal circuitry in SPD. Method: Eighteen participants with SPD and 15 matched healthy controls undertook an executive...

  12. Brain structure in post-traumatic stress disorder A voxel-based morphometry analysis**

    Institute of Scientific and Technical Information of China (English)

    Liwen Tan; Li Zhang; Rongfeng Qi; Guangming Lu; Lingjiang Li; Jun Liu; Weihui Li

    2013-01-01

    This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, us-ing the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, fol owed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occip-ital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities.

  13. Brain structure in post-traumatic stress disorder: A voxel-based morphometry analysis.

    Science.gov (United States)

    Tan, Liwen; Zhang, Li; Qi, Rongfeng; Lu, Guangming; Li, Lingjiang; Liu, Jun; Li, Weihui

    2013-09-15

    This study compared the difference in brain structure in 12 mine disaster survivors with chronic post-traumatic stress disorder, 7 cases of improved post-traumatic stress disorder symptoms, and 14 controls who experienced the same mine disaster but did not suffer post-traumatic stress disorder, using the voxel-based morphometry method. The correlation between differences in brain structure and post-traumatic stress disorder symptoms was also investigated. Results showed that the gray matter volume was the highest in the trauma control group, followed by the symptoms-improved group, and the lowest in the chronic post-traumatic stress disorder group. Compared with the symptoms-improved group, the gray matter volume in the lingual gyrus of the right occipital lobe was reduced in the chronic post-traumatic stress disorder group. Compared with the trauma control group, the gray matter volume in the right middle occipital gyrus and left middle frontal gyrus was reduced in the symptoms-improved group. Compared with the trauma control group, the gray matter volume in the left superior parietal lobule and right superior frontal gyrus was reduced in the chronic post-traumatic stress disorder group. The gray matter volume in the left superior parietal lobule was significantly positively correlated with the State-Trait Anxiety Inventory subscale score in the symptoms-improved group and chronic post-traumatic stress disorder group (r = 0.477, P = 0.039). Our findings indicate that (1) chronic post-traumatic stress disorder patients have gray matter structural damage in the prefrontal lobe, occipital lobe, and parietal lobe, (2) after post-traumatic stress, the disorder symptoms are improved and gray matter structural damage is reduced, but cannot recover to the trauma-control level, and (3) the superior parietal lobule is possibly associated with chronic post-traumatic stress disorder. Post-traumatic stress disorder patients exhibit gray matter abnormalities.

  14. Developmental disorders of speech and language: from genes to brain structure and function.

    Science.gov (United States)

    Watkins, Kate

    2011-01-01

    Functional and structural brain imaging studies of developmental disorders provide insights into their neural correlates and have potential to bridge the gap between genotype and phenotype. We have used such techniques to investigate the neural correlates of two developmental disorders of speech and language, in which a genetic etiology is either known or strongly suspected. The first disorder is one shared by the affected members of the KE family who have a mutation in the FOXP2 gene. The brain structural and functional correlates of this disorder help clarify the nature of the behavioral impairment. They confirm that a deficit in auditory-motor learning of articulation patterns is core to the behavioral phenotype. In the second disorder, developmental stuttering, brain imaging data reveal functional abnormalities consistent with theories that it is caused by a basal ganglia deficit and structural differences consistent with an impairment in auditory-motor integration necessary for fluent speech. The common finding of basal ganglia abnormality in two developmental disorders of speech and language is discussed. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. DISC1 pathway in brain development: exploring therapeutic targets for major psychiatric disorders

    Directory of Open Access Journals (Sweden)

    Atsushi eKamiya

    2012-03-01

    Full Text Available Genetic risk factors for major psychiatric disorders play key roles in neurodevelopment. Thus, exploring the molecular pathways of risk genes is important not only for understanding the molecular mechanisms underlying brain development, but also to decipher how genetic disturbances affect brain maturation and functioning relevant to major mental illnesses. During the last decade, there has been significant progress in determining the mechanisms whereby risk genes impact brain development. Nonetheless, given that the majority of psychiatric disorders have etiological complexities encompassing multiple risk genes and environmental factors, the biological mechanisms of these diseases remain poorly understood. How can we move forward in our research for discovery of the biological markers and novel therapeutic targets for major mental disorders? Here we review recent progress in the neurobiology of Disrupted in schizophrenia 1 (DISC1, a major risk gene for major mental disorders, with a particular focus on its roles in cerebral cortex development. Convergent findings implicate DISC1 as part of a large, multi-step pathway implicated in various cellular processes and signal transduction. We discuss links between the DISC1 pathway and environmental factors, such as immune/inflammatory responses, which may suggest novel therapeutic targets. Existing treatments for major mental disorders are hampered by a limited number of pharmacological targets. Consequently, elucidation of the DISC1 pathway, and its association with neuropsychiatric disorders, may offer hope for novel treatment interventions.

  16. Brain structure abnormalities in young women who presented conduct disorder in childhood/adolescence.

    Science.gov (United States)

    Budhiraja, Meenal; Savic, Ivanka; Lindner, Philip; Jokinen, Jussi; Tiihonen, Jari; Hodgins, Sheilagh

    2017-07-10

    The phenotype and genotype of antisocial behavior among females are different from those among males. Previous studies have documented structural brain alterations in males with antisocial behavior, yet little is known about the neural correlates of female antisocial behavior. The present study examined young women who had presented conduct disorder (CDW) prior to age 15 to determine whether brain abnormalities are present in adulthood and whether the observed abnormalities are associated with comorbid disorders or maltreatment that typically characterize this population. Using magnetic resonance imaging and voxel-based morphometry, we compared gray matter volumes (GMV) of 31 women who presented CD by midadolescence and 25 healthy women (HW), age, on average, 23 years. Participants completed structured, validated interviews to diagnose mental disorders, and validated questionnaires to document physical and sexual abuse. Relative to HW, CDW presented increased GMV in the left superior temporal gyrus that was associated with past alcohol and drug dependence, current use of alcohol and drugs, and current anxiety and depression symptoms and maltreatment. Additionally, CDW displayed reduced GMV in lingual gyrus, hippocampus, and anterior cingulate cortex that was associated with past comorbid disorders, current alcohol and drugs use, current anxiety and depression symptoms, and maltreatment. The CDW also presented reduced total GMV that was associated with past comorbid disorders and current anxiety/depression symptoms. Alterations of brain structure were observed among young adult females with prior CD, relative to HW, all of which were associated with internalizing and externalizing disorders and maltreatment that typically accompany CD.

  17. Is fetal brain monoamine oxidase inhibition the missing link between maternal smoking and conduct disorders?

    Science.gov (United States)

    Baler, Ruben D; Volkow, Nora D; Fowler, Joanna S; Benveniste, Helene

    2008-05-01

    Smoking is the leading cause of preventable illness in the world today. Prenatal cigarette smoke exposure (PCSE) is a particularly insidious form because so many of its associated health effects befall the unborn child and produce behavioural outcomes that manifest themselves only years later. Among these are the associations between PCSE and conduct disorders, which have been mostly ascribed to the deleterious effects of nicotine on the fetal brain. Here we hypothesize that inhibition of brain monoamine oxidase (MAO) during fetal brain development, secondary to maternal cigarette smoking and in addition to nicotine, is a likely contributor to this association. MAOs play a central role in monoaminergic balance in the brain, and their inhibition during fetal development - but not during adult life - is known to result in an aggressive phenotype in laboratory animals. This paper provides theoretical and experimental support for the notion that cigarette smoke-induced inhibition of MAO in the fetal brain, particularly when it occurs in combination with polymorphisms in the MAOA gene that lead to lower enzyme concentration in the brain, may result in brain morphologic and functional changes that enhance the risk of irritability, poor self-control and aggression in the offspring. It also encourages research to evaluate whether the interaction of smoking exposure during fetal development and MAOA genotype increases the risk for conduct disorder over that incurred by mere fetal exposure to tobacco smoke.

  18. Correlation of auditory brain stem response and the MRI measurements in neuro-degenerative disorders

    Energy Technology Data Exchange (ETDEWEB)

    Kamei, Hidekazu (Tokyo Women' s Medical Coll. (Japan))

    1989-06-01

    The purpose of this study is to elucidate correlations of several MRI measurements of the cranium and brain, functioning as a volume conductor, to the auditory brain stem response (ABR) in neuro-degenerative disorders. The subjects included forty-seven patients with spinocerebellar degeneration (SCD) and sixteen of amyotrophic lateral sclerosis (ALS). Statistically significant positive correlations were found between I-V and III-V interpeak latencies (IPLs) and the area of cranium and brain in the longitudinal section of SCD patients, and between I-III and III-V IPLs and the area in the longitudinal section of those with ALS. And, also there were statistically significant correlations between the amplitude of the V wave and the area of brain stem as well as that of the cranium in the longitudinal section of SCD patients, and between the amplitude of the V wave and the area of the cerebrum in the longitudinal section of ALS. In conclusion, in the ABR, the IPLs were prolonged and the amplitude of the V wave was decreased while the MRI size of the cranium and brain increased. When the ABR is applied to neuro-degenerative disorders, it might be important to consider not only the conduction of the auditory tracts in the brain stem, but also the correlations of the size of the cranium and brain which act as a volume conductor. (author).

  19. Inherited disorders of brain neurotransmitters: pathogenesis and diagnostic approach.

    Science.gov (United States)

    Szymańska, Krystyna; Kuśmierska, Katarzyna; Demkow, Urszula

    2015-01-01

    Neurotransmitters (NTs) play a central role in the efficient communication between neurons necessary for normal functioning of the nervous system. NTs can be divided into two groups: small molecule NTs and larger neuropeptide NTs. Inherited disorders of NTs result from a primary disturbance of NTs metabolism or transport. This group of disorders requires sophisticated diagnostic procedures. In this review we discuss disturbances in the metabolism of tetrahydrobiopterin, biogenic amines, γ-aminobutyric acid, foliate, pyridoxine-dependent enzymes, and also the glycine-dependent encephalopathy. We point to pathologic alterations of proteins involved in synaptic neurotransmission that may cause neurological and psychiatric symptoms. We postulate that synaptic receptors and transporter proteins for neurotransmitters should be investigated in unresolved cases. Patients with inherited neurotransmitters disorders present various clinical presentations such as mental retardation, refractory seizures, pyramidal and extrapyramidal syndromes, impaired locomotor patterns, and progressive encephalopathy. Every patient with suspected inherited neurotransmitter disorder should undergo a structured interview and a careful examination including neurological, biochemical, and imaging.

  20. A comparison of brain volume and cortical thickness in excoriation (skin picking) disorder and trichotillomania (hair pulling disorder) in women.

    Science.gov (United States)

    Roos, Annerine; Grant, Jon E; Fouche, Jean-Paul; Stein, Dan J; Lochner, Christine

    2015-02-15

    Skin picking disorder (SPD) and trichotillomania (hair pulling disorder, or HPD) significantly overlap in terms of clinical features. However, few studies have directly compared structural brain data in these disorders. The aim of this study was to compare volumes of brain structures and cortical thickness in patients with SPD and HPD, and determine involvement of fronto-striatal pathways. Seventeen female SPD, 17 HPD and 15 healthy age-matched controls underwent clinical assessment and structural MRI imaging. Group differences were determined in brain volume and cortical thickness, controlling for illness severity. Participants with SPD had greater volume of the ventral striatum bilaterally; and reduced cortical thickness in right hemisphere frontal areas, and greater thickness of the cuneus bilaterally compared to HPD and control participants. HPD participants demonstrated reduced thickness of the right parahippocampal gyrus compared to SPD and control participants. The findings here are partially consistent with previous structural work in SPD, and suggest some differences in the neurobiology of SPD and HPD. The more extensive involvement of the ventral striatum in SPD may suggest greater involvement of the reward system, while the more extensive involvement of the parahippocampal gyrus in HPD may be consistent with the dissociative symptoms often seen in these patients.

  1. Brain CB2 Receptors: Implications for Neuropsychiatric Disorders

    OpenAIRE

    Michelle Roche; Finn, David P.

    2010-01-01

    Although previously thought of as the peripheral cannabinoid receptor, it is now accepted that the CB2 receptor is expressed in the central nervous system on microglia, astrocytes and subpopulations of neurons. Expression of the CB2 receptor in the brain is significantly lower than that of the CB1 receptor. Conflicting findings have been reported on the neurological effects of pharmacological agents targeting the CB2 receptor under normal conditions. Under inflammatory conditions, CB2 recepto...

  2. Endocrine disorders following treatment of childhood brain tumours.

    OpenAIRE

    Livesey, E A; Hindmarsh, P C; Brook, C G; Whitton, A. C.; Bloom, H. J.; Tobias, J. S.; Godlee, J. N.; Britton, J.

    1990-01-01

    We have studied the long-term endocrine effects of treatment on 144 children treated for brain tumours. All received cranial irradiation, 86 also received spinal irradiation and 34 chemotherapy. Almost all patients (140 of 144) had evidence of growth hormone insufficiency. Treatment with growth hormone was effective in maintaining normal growth but could not restore a deficit incurred by delay in instituting treatment. The effect of spinal irradiation on spinal growth was not corrected by gro...

  3. Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence.

    Science.gov (United States)

    Stevens, Michael C; Haney-Caron, Emily

    2012-11-01

    Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically "pure" (i.e., no comorbidities) conduct disorder and ADHD samples. Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is associated with numerous frontal lobe structural deficits, a

  4. Affective-Motivational Brain Responses to Direct Gaze in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Kylliainen, Anneli; Wallace, Simon; Coutanche, Marc N.; Leppanen, Jukka M.; Cusack, James; Bailey, Anthony J.; Hietanen, Jari K.

    2012-01-01

    Background: It is unclear why children with autism spectrum disorders (ASD) tend to be inattentive to, or even avoid eye contact. The goal of this study was to investigate affective-motivational brain responses to direct gaze in children with ASD. To this end, we combined two measurements: skin conductance responses (SCR), a robust arousal…

  5. Social Outcomes in Childhood Brain Disorder: A Heuristic Integration of Social Neuroscience and Developmental Psychology

    Science.gov (United States)

    Yeates, Keith Owen; Bigler, Erin D.; Dennis, Maureen; Gerhardt, Cynthia A.; Rubin, Kenneth H.; Stancin, Terry; Taylor, H. Gerry; Vannatta, Kathryn

    2007-01-01

    The authors propose a heuristic model of the social outcomes of childhood brain disorder that draws on models and methods from both the emerging field of social cognitive neuroscience and the study of social competence in developmental psychology/psychopathology. The heuristic model characterizes the relationships between social adjustment, peer…

  6. The microbiota-gut-brain axis and its potential therapeutic role in autism spectrum disorder.

    Science.gov (United States)

    Li, Q; Zhou, J-M

    2016-06-02

    Autism spectrum disorder (ASD) is a series of neurodevelopmental disorders that are characterized by deficits in both social and cognitive functions. Although the exact etiology and pathology of ASD remain unclear, a disorder of the microbiota-gut-brain axis is emerging as a prominent factor in the generation of autistic behaviors. Clinical studies have shown that gastrointestinal symptoms and compositional changes in the gut microbiota frequently accompany cerebral disorders in patients with ASD. A disturbance in the gut microbiota, which is usually induced by a bacterial infection or chronic antibiotic exposure, has been implicated as a potential contributor to ASD. The bidirectional microbiota-gut-brain axis acts mainly through neuroendocrine, neuroimmune, and autonomic nervous mechanisms. Application of modulators of the microbiota-gut-brain axis, such as probiotics, helminthes and certain special diets, may be a promising strategy for the treatment of ASD. This review mainly discusses the salient observations of the disruptions of the microbiota-gut-brain axis in the pathogenesis of ASD and reveals its potential therapeutic role in autistic deficits.

  7. Structural brain network analysis in families multiply affected with bipolar I disorder

    NARCIS (Netherlands)

    Forde, Natalie J.; O'Donoghue, Stefani; Scanlon, Cathy; Emsell, Louise; Chaddock, Chris; Leemans, Alexander; Jeurissen, Ben; Barker, Gareth J.; Cannon, Dara M.; Murray, Robin M.; McDonald, Colm

    2015-01-01

    Disrupted structural connectivity is associated with psychiatric illnesses including bipolar disorder (BP). Here we use structural brain network analysis to investigate connectivity abnormalities in multiply affected BP type I families, to assess the utility of dysconnectivity as a biomarker and its

  8. Posttraumatic Stress Disorder, Traumatic Brain Injury, and Suicide Attempt History among Veterans Receiving Mental Health Services

    Science.gov (United States)

    Brenner, Lisa A.; Betthauser, Lisa M.; Homaifar, Beeta Y.; Villarreal, Edgar; Harwood, Jeri E. F.; Staves, Pamela J.; Huggins, Joseph A.

    2011-01-01

    History of posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI) has been found to increase risk of suicidal behavior. The association between suicide attempt history among veterans with PTSD and/or TBI was explored. Cases (N = 81) and 2:1 matched controls (N = 160) were randomly selected from a Veterans Affairs Medical Center…

  9. The application of deep brain stimulation in the treatment of psychiatric disorders

    NARCIS (Netherlands)

    Graat, Ilse; Figee, Martijn; Denys, D.

    2017-01-01

    Deep brain stimulation (DBS) is a last-resort treatment for neurological and psychiatric disorders that are refractory to standard treatment. Over the last decades, the progress of DBS in psychiatry has been slower than in neurology, in part owing to the heterogenic symptomatology and complex

  10. Brief Report: Abnormal Association between the Thalamus and Brain Size in Asperger's Disorder

    Science.gov (United States)

    Hardan, Antonio Y.; Girgis, Ragy R.; Adams, Jason; Gilbert, Andrew R.; Melhem, Nadine M.; Keshavan, Matcheri S.; Minshew, Nancy J.

    2008-01-01

    The objective of this study was to examine the relationship between thalamic volume and brain size in individuals with Asperger's disorder (ASP). Volumetric measurements of the thalamus were performed on MRI scans obtained from 12 individuals with ASP (age range: 10-35 years) and 12 healthy controls (age range: 9-33 years). A positive correlation…

  11. Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Paul E. Rapp

    2013-07-01

    Full Text Available Psychophysiological investigations of traumatic brain injury (TBI are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP component properties (e.g. timing, amplitude, scalp distribution, and a participant’s clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that traumatic brain injury is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing traumatic brain injury, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records.

  12. Determinants of Psychosocial Difficulties Experienced by Persons with Brain Disorders: Towards a 'Horizontal Epidemiology' Approach.

    Directory of Open Access Journals (Sweden)

    Carla Sabariego

    Full Text Available Persons with brain disorders experience significant psychosocial difficulties (PSD in daily life, e.g. problems with managing daily routine or emotional lability, and the level of the PSD depends on social, physical and political environments, and psychologic-personal determinants. Our objective is to determine a brief set of environmental and psychologic-personal factors that are shared determinants of PSD among persons with different brain disorders.Cross-sectional study, convenience sample of persons with either dementia, stroke, multiple sclerosis, epilepsy, migraine, depression, schizophrenia, substance dependence or Parkinson's disease. Random forest regression and classical linear regression were used in the analyses.722 subjects were interviewed in four European countries. The brief set of determinants encompasses presence of comorbidities, health status appraisal, stressful life events, personality changes, adaptation, self-esteem, self-worth, built environment, weather, and health problems in the family.The identified brief set of common determinants of PSD can be used to support the implementation of cross-cutting interventions, social actions and policy tools to lower PSD experienced by persons with brain disorders. This set complements a recently proposed reliable and valid direct metric of PSD for brain disorders called PARADISE24.

  13. Deep brain stimulation for treatment-refractory obsessive compulsive disorder : a systematic review

    NARCIS (Netherlands)

    Kohl, Sina; Schönherr, Deva M; Luigjes, Judy; Denys, D.; Mueller, Ulf J; Lenartz, Doris; Visser-Vandewalle, Veerle; Kuhn, Jens

    2014-01-01

    BACKGROUND: Obsessive-compulsive disorder is one of the most disabling of all psychiatric illnesses. Despite available pharmacological and psychotherapeutic treatments about 10% of patients remain severely affected and are considered treatment-refractory. For some of these patients deep brain

  14. Mixed acid-base disorder secondary to topiramate use in traumatic brain injury

    Directory of Open Access Journals (Sweden)

    S Golla

    2016-01-01

    Full Text Available We report a case of a man with traumatic brain injury. He was started on to prophylactic topiramate which led to a mixed acid-base disorder. He had severe metabolic acidosis secondary to renal tubular acidification defect and respiratory alkalosis secondary to hyperventilation. Withdrawal of the offending drug led to the prompt resolution of the acid-base disturbance.

  15. Nucleus accumbens deep brain stimulation as treatment option for binge eating disorder?

    NARCIS (Netherlands)

    Lok, R.; Verhagen, M.; Staal, L.; Van Dijk, J.; Van Beek, A.; Temel, Y.; Jahanshahi, A.; Staal, M.; Van Dijk, G.

    2014-01-01

    Introduction: Binge eating disorder (BED) has been postulated to arise from mesolimbic dopaminergic system changes, presumably homologous to those seen in drug addiction. Deep Brain Stimulation (DBS) is regarded as a relatively novel but promising surgical treatment of addiction. Because of

  16. Neuroimaging Correlates of Novel Psychiatric Disorders after Pediatric Traumatic Brain Injury

    Science.gov (United States)

    Max, Jeffrey E.; Wilde, Elisabeth A.; Bigler, Erin D.; Thompson, Wesley K.; MacLeod, Marianne; Vasquez, Ana C.; Merkley, Tricia L.; Hunter, Jill V.; Chu, Zili D.; Yallampalli, Ragini; Hotz, Gillian; Chapman, Sandra B.; Yang, Tony T.; Levin, Harvey S.

    2012-01-01

    Objective: To study magnetic resonance imaging (MRI) correlates of novel (new-onset) psychiatric disorders (NPD) after traumatic brain injury (TBI) and orthopedic injury (OI). Method: Participants were 7 to 17 years of age at the time of hospitalization for either TBI or OI. The study used a prospective, longitudinal, controlled design with…

  17. Classroom Strategies for Teaching Veterans with Post-Traumatic Stress Disorder and Traumatic Brain Injury

    Science.gov (United States)

    Sinski, Jennifer Blevins

    2012-01-01

    Postsecondary institutions currently face the largest influx of veteran students since World War II. As the number of veteran students who may experience learning problems caused by Post-Traumatic Stress Disorder and/or Traumatic Brain Injury continues to rise, the need for instructional strategies that address their needs increases. Educators may…

  18. Random matrix theory for analyzing the brain functional network in attention deficit hyperactivity disorder.

    Science.gov (United States)

    Wang, Rong; Wang, Li; Yang, Yong; Li, Jiajia; Wu, Ying; Lin, Pan

    2016-11-01

    Attention deficit hyperactivity disorder (ADHD) is the most common childhood neuropsychiatric disorder and affects approximately 6-7% of children worldwide. Here, we investigate the statistical properties of undirected and directed brain functional networks in ADHD patients based on random matrix theory (RMT), in which the undirected functional connectivity is constructed based on correlation coefficient and the directed functional connectivity is measured based on cross-correlation coefficient and mutual information. We first analyze the functional connectivity and the eigenvalues of the brain functional network. We find that ADHD patients have increased undirected functional connectivity, reflecting a higher degree of linear dependence between regions, and increased directed functional connectivity, indicating stronger causality and more transmission of information among brain regions. More importantly, we explore the randomness of the undirected and directed functional networks using RMT. We find that for ADHD patients, the undirected functional network is more orderly than that for normal subjects, which indicates an abnormal increase in undirected functional connectivity. In addition, we find that the directed functional networks are more random, which reveals greater disorder in causality and more chaotic information flow among brain regions in ADHD patients. Our results not only further confirm the efficacy of RMT in characterizing the intrinsic properties of brain functional networks but also provide insights into the possibilities RMT offers for improving clinical diagnoses and treatment evaluations for ADHD patients.

  19. Random matrix theory for analyzing the brain functional network in attention deficit hyperactivity disorder

    Science.gov (United States)

    Wang, Rong; Wang, Li; Yang, Yong; Li, Jiajia; Wu, Ying; Lin, Pan

    2016-11-01

    Attention deficit hyperactivity disorder (ADHD) is the most common childhood neuropsychiatric disorder and affects approximately 6 -7 % of children worldwide. Here, we investigate the statistical properties of undirected and directed brain functional networks in ADHD patients based on random matrix theory (RMT), in which the undirected functional connectivity is constructed based on correlation coefficient and the directed functional connectivity is measured based on cross-correlation coefficient and mutual information. We first analyze the functional connectivity and the eigenvalues of the brain functional network. We find that ADHD patients have increased undirected functional connectivity, reflecting a higher degree of linear dependence between regions, and increased directed functional connectivity, indicating stronger causality and more transmission of information among brain regions. More importantly, we explore the randomness of the undirected and directed functional networks using RMT. We find that for ADHD patients, the undirected functional network is more orderly than that for normal subjects, which indicates an abnormal increase in undirected functional connectivity. In addition, we find that the directed functional networks are more random, which reveals greater disorder in causality and more chaotic information flow among brain regions in ADHD patients. Our results not only further confirm the efficacy of RMT in characterizing the intrinsic properties of brain functional networks but also provide insights into the possibilities RMT offers for improving clinical diagnoses and treatment evaluations for ADHD patients.

  20. Brain Basics

    Medline Plus

    Full Text Available ... brain may play a role in disorders like schizophrenia or attention deficit hyperactivity disorder (ADHD) . Glutamate —the ... mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain Regions Just as many neurons ...

  1. Maternal Brain-Reactive Antibodies and Autism Spectrum Disorder

    Science.gov (United States)

    2015-10-01

    individuals. Dr. Peter Gregersen Completed Research: Biogen/IDEC Biomarkers of Anti-TNF-α Therapy Efficacy in Rheumatoid Arthritis to Define...Molecular and Cellular Dissection of Early Rheumatoid Arthritis DOD Betty Diamond Progress Report 14‐1‐0369          14    Gregersen (PI) 10/01...brain antigens were isolated with magnetic anti-biotin beads. Because we obtained blood years after the pregnancy that resulted in a child with ASD

  2. Transcranial sonography in brain disorders with trace metal accumulation.

    Science.gov (United States)

    Walter, Uwe

    2010-01-01

    Transcranial sonography (TCS) can detect trace metal accumulation in deep brain structures with higher sensitivity than conventional MRI. Especially, increased iron content in the substantia nigra in Parkinson's disease, increased copper content in the lenticular nucleus (LN) in Wilson's disease and idiopathic dystonia, and increased manganese content in the LN in manganese-induced Parkinsonism were detected with TCS, even in subjects with normal MRI. TCS, therefore, might be useful to detect an increased risk of developing neurological symptoms in relatives of patients with Parkinson's or Wilson's disease. The exact mechanism of how an elevated trace metal content leads to an increased echogenicity needs to be further elucidated.

  3. Elevated levels of plasma brain derived neurotrophic factor in rapid cycling bipolar disorder patients

    DEFF Research Database (Denmark)

    Munkholm, Klaus; Pedersen, Bente Klarlund; Kessing, Lars Vedel

    2014-01-01

    Impaired neuroplasticity may be implicated in the pathophysiology of bipolar disorder, involving peripheral alterations of the neurotrophins brain derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3). Evidence is limited by methodological issues and is based primarily on case......-control designs. The aim of this study was to investigate whether BDNF and NT-3 levels differ between patients with rapid cycling bipolar disorder and healthy control subjects and whether BDNF and NT-3 levels alter with affective states in rapid cycling bipolar disorder patients. Plasma levels of BDNF and NT-3...... were measured in 37 rapid cycling bipolar disorder patients and in 40 age- and gender matched healthy control subjects using enzyme-linked immunosorbent assay (ELISA). In a longitudinal design, repeated measurements of BDNF and NT-3 were evaluated in various affective states in bipolar disorder...

  4. Functional characteristics of the brain in college students with internet gaming disorder.

    Science.gov (United States)

    Liu, Jun; Li, Weihui; Zhou, Shunke; Zhang, Li; Wang, Zhiyuan; Zhang, Yan; Jiang, Yebin; Li, Lingjiang

    2016-03-01

    Internet gaming disorder (IGD) is a subtype of internet addiction disorder (IAD), but its pathogenesis remains unclear. This study investigated brain function in IGD individuals using task-state functional magnetic resonance imaging (fMRI). It is a prospective study in 19 IGD individuals and 19 matched healthy controls. They all received internet videogame stimuli while a 3.0 T fMRI was used to assess echo planar imaging. Brain activity was analyzed using the Brain Voyager software package. Functional data were spatially smoothed using Gaussian kernel. The threshold level was positioned at 10 pixels, and the activation range threshold was set to 10 voxels. Activated brain regions were compared between the two groups, as well as the amount of activated voxels. The internet videogame stimuli activated brain regions in both groups. Compared with controls, the IGD group showed increased activation in the right superior parietal lobule, right insular lobe, right precuneus, right cingulated gyrus, right superior temporal gyrus, and left brainstem. There was a significant difference in the number of activated voxels between the two groups. An average of 1078 voxels was activated in the IGD group compared with only 232 in the control group. Internet videogame play activates the vision, space, attention, and execution centers located in the occipital, temporal, parietal, and frontal gyri. Abnormal brain function was noted in IGD subjects, with hypofunction of the frontal cortex. IGD subjects showed laterality activation of the right cerebral hemisphere.

  5. Understanding principles of integration and segregation using whole-brain computational connectomics: implications for neuropsychiatric disorders.

    Science.gov (United States)

    Lord, Louis-David; Stevner, Angus B; Deco, Gustavo; Kringelbach, Morten L

    2017-06-28

    To survive in an ever-changing environment, the brain must seamlessly integrate a rich stream of incoming information into coherent internal representations that can then be used to efficiently plan for action. The brain must, however, balance its ability to integrate information from various sources with a complementary capacity to segregate information into modules which perform specialized computations in local circuits. Importantly, evidence suggests that imbalances in the brain's ability to bind together and/or segregate information over both space and time is a common feature of several neuropsychiatric disorders. Most studies have, however, until recently strictly attempted to characterize the principles of integration and segregation in static (i.e. time-invariant) representations of human brain networks, hence disregarding the complex spatio-temporal nature of these processes. In the present Review, we describe how the emerging discipline of whole-brain computational connectomics may be used to study the causal mechanisms of the integration and segregation of information on behaviourally relevant timescales. We emphasize how novel methods from network science and whole-brain computational modelling can expand beyond traditional neuroimaging paradigms and help to uncover the neurobiological determinants of the abnormal integration and segregation of information in neuropsychiatric disorders.This article is part of the themed issue 'Mathematical methods in medicine: neuroscience, cardiology and pathology'. © 2017 The Author(s).

  6. Towards the routine use of brain imaging to aid the clinical diagnosis of disorders of consciousness.

    Science.gov (United States)

    Coleman, M R; Davis, M H; Rodd, J M; Robson, T; Ali, A; Owen, A M; Pickard, J D

    2009-09-01

    Clinical audits have highlighted the many challenges and dilemmas faced by clinicians assessing persons with disorders of consciousness (vegetative state and minimally conscious state). The diagnostic decision-making process is highly subjective, dependent upon the skills of the examiner and invariably dictated by the patients' ability to move or speak. Whilst a considerable amount has been learnt since Jennett and Plum coined the term 'vegetative state', the assessment process remains largely unchanged; conducted at the bedside, using behavioural assessment tools, which are susceptible to environmental and physiological factors. This has created a situation where the rate of misdiagnosis is unacceptably high (up to 43%). In order to address these problems, various functional brain imaging paradigms, which do not rely upon the patient's ability to move or speak, have been proposed as a source of additional information to inform the diagnostic decision making process. Although accumulated evidence from brain imaging, particularly functional magnetic resonance imaging (fMRI), has been encouraging, the empirical evidence is still based on relatively small numbers of patients. It remains unclear whether brain imaging is capable of informing the diagnosis beyond the behavioural assessment and whether brain imaging has any prognostic utility. In this study, we describe the functional brain imaging findings from a group of 41 patients with disorders of consciousness, who undertook a hierarchical speech processing task. We found, contrary to the clinical impression of a specialist team using behavioural assessment tools, that two patients referred to the study with a diagnosis of vegetative state did in fact demonstrate neural correlates of speech comprehension when assessed using functional brain imaging. These fMRI findings were found to have no association with the patient's behavioural presentation at the time of investigation and thus provided additional diagnostic

  7. The DNA methylome and transcriptome of different brain regions in schizophrenia and bipolar disorder.

    Directory of Open Access Journals (Sweden)

    Yun Xiao

    Full Text Available Extensive changes in DNA methylation have been observed in schizophrenia (SC and bipolar disorder (BP, and may contribute to the pathogenesis of these disorders. Here, we performed genome-scale DNA methylation profiling using methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq on two brain regions (including frontal cortex and anterior cingulate in 5 SC, 7 BP and 6 normal subjects. Comparing with normal controls, we identified substantial differentially methylated regions (DMRs in these two brain regions of SC and BP. To our surprise, different brain regions show completely distinct distributions of DMRs across the genomes. In frontal cortex of both SC and BP subjects, we observed widespread hypomethylation as compared to normal controls, preferentially targeting the terminal ends of the chromosomes. In contrast, in anterior cingulate, both SC and BP subjects displayed extensive gain of methylation. Notably, in these two brain regions of SC and BP, only a few DMRs overlapped with promoters, whereas a greater proportion occurs in introns and intergenic regions. Functional enrichment analysis indicated that important psychiatric disorder-related biological processes such as neuron development, differentiation and projection may be altered by epigenetic changes located in the intronic regions. Transcriptome analysis revealed consistent dysfunctional processes with those determined by DMRs. Furthermore, DMRs in the same brain regions from SC and BP could successfully distinguish BP and/or SC from normal controls while differentially expressed genes could not. Overall, our results support a major role for brain-region-dependent aberrant DNA methylation in the pathogenesis of these two disorders.

  8. Brain studies may alter long-held concepts about likely causes of some voice disorders

    Energy Technology Data Exchange (ETDEWEB)

    1989-02-17

    Two voice disorders long considered to be psychological problems, stuttering and spasmodic dysphonia, have been shown in many persons to have a neurophysiological basis. Investigators at the 155th national meeting of the American Association for the Advancement of Science, in San Francisco, described their findings, which are based on new analytic techniques. The research is being done at the Dallas Center for Vocal Motor Control, Callier Center for Communication Disorders, University of Texas at Dallas Health Science Center. The technology employed to learn what's wrong with the brains, rather than the psyches, of persons with certain speech disorders includes magnetic resonance imaging (MRI), brain electrical activity mapping (BEAM), and single photon emission computerized tomography (SPECT). The results of applying these techniques are combined with quantitative behavioral measures of vocal and nonvocal motor control, language performance, and cognition to arrive at a better understanding of the problem.

  9. Brain structure-function associations in multi-generational families genetically enriched for bipolar disorder.

    Science.gov (United States)

    Fears, Scott C; Schür, Remmelt; Sjouwerman, Rachel; Service, Susan K; Araya, Carmen; Araya, Xinia; Bejarano, Julio; Knowles, Emma; Gomez-Makhinson, Juliana; Lopez, Maria C; Aldana, Ileana; Teshiba, Terri M; Abaryan, Zvart; Al-Sharif, Noor B; Navarro, Linda; Tishler, Todd A; Altshuler, Lori; Bartzokis, George; Escobar, Javier I; Glahn, David C; Thompson, Paul M; Lopez-Jaramillo, Carlos; Macaya, Gabriel; Molina, Julio; Reus, Victor I; Sabatti, Chiara; Cantor, Rita M; Freimer, Nelson B; Bearden, Carrie E

    2015-07-01

    Recent theories regarding the pathophysiology of bipolar disorder suggest contributions of both neurodevelopmental and neurodegenerative processes. While structural neuroimaging studies indicate disease-associated neuroanatomical alterations, the behavioural correlates of these alterations have not been well characterized. Here, we investigated multi-generational families genetically enriched for bipolar disorder to: (i) characterize neurobehavioural correlates of neuroanatomical measures implicated in the pathophysiology of bipolar disorder; (ii) identify brain-behaviour associations that differ between diagnostic groups; (iii) identify neurocognitive traits that show evidence of accelerated ageing specifically in subjects with bipolar disorder; and (iv) identify brain-behaviour correlations that differ across the age span. Structural neuroimages and multi-dimensional assessments of temperament and neurocognition were acquired from 527 (153 bipolar disorder and 374 non-bipolar disorder) adults aged 18-87 years in 26 families with heavy genetic loading for bipolar disorder. We used linear regression models to identify significant brain-behaviour associations and test whether brain-behaviour relationships differed: (i) between diagnostic groups; and (ii) as a function of age. We found that total cortical and ventricular volume had the greatest number of significant behavioural associations, and included correlations with measures from multiple cognitive domains, particularly declarative and working memory and executive function. Cortical thickness measures, in contrast, showed more specific associations with declarative memory, letter fluency and processing speed tasks. While the majority of brain-behaviour relationships were similar across diagnostic groups, increased cortical thickness in ventrolateral prefrontal and parietal cortical regions was associated with better declarative memory only in bipolar disorder subjects, and not in non-bipolar disorder family

  10. [Early functional disorders of the brain in uncomplicated hypertensive patients].

    Science.gov (United States)

    De Quesada-Martínez, M E; Blanco-García, M; Díaz-De Quesada, L

    To detect the presence of changes in brain electrical activity that might be used as early markers in patients with risk factors for developing vascular encephalopathy. There were studied 84 uncomplicated hypertensive patients, with a normal neurological physical examination and mean age of 49 years compared to 35 functionally healthy subjects. The patients were divided into three groups: slight high blood pressure (SLHBP, n = 24) with diastolic blood pressure (DBP) between 90 and 100 mmHg, moderate high blood pressure (MHBP, n = 40) with DBP between 101 and 114 mmHg, and severe high blood pressure (SHBP, n = 20) with TAD of 115 mmHg or higher. All subjects underwent digital electroencephalogram (dEEG) with quantitative analysis (QEEG). The patients showed focal, especially frontal paroxysms, and diffuse polymorphic theta activity in these areas, mainly those with SLHBP. Posterior alpha rhythm disorganization, inter-hemispheric asymmetries and frontal monomorphic activity were more often found in SHBP patients. In QEEG was observed an increase in absolute and relative power of slow activities, and a decrease in power of alpha and beta activities. All these findings were more frequent in the left hemisphere. The hemodynamic characteristics of the Central Nervous System and the changes caused by HBP alter the functional organization of the brain cortex, especially in frontal and midline regions, irrigated by the anterior cerebral artery.

  11. [Development and developmental disorders of the human brain. III. Neuronal migration disorders of the cerebrum

    NARCIS (Netherlands)

    Donkelaar, H.J. ten; Lammens, M.M.Y.; Wesseling, P.; Thijssen, H.O.M.; Renier, W.O.; Gabreëls, F.J.M.

    2001-01-01

    Neuronal migration disorders of the cerebral cortex form a heterogeneous group of abnormalities, characterised by mental retardation, epilepsy and hypotonia. They are prevalent in 1% of the population and in 20-40% of the untreatable forms of epilepsy. Disorders at the start of the migration result

  12. Disruption in the Blood-Brain Barrier: The Missing Link between Brain and Body Inflammation in Bipolar Disorder?

    Directory of Open Access Journals (Sweden)

    Jay P. Patel

    2015-01-01

    Full Text Available The blood-brain barrier (BBB regulates the transport of micro- and macromolecules between the peripheral blood and the central nervous system (CNS in order to maintain optimal levels of essential nutrients and neurotransmitters in the brain. In addition, the BBB plays a critical role protecting the CNS against neurotoxins. There has been growing evidence that BBB disruption is associated with brain inflammatory conditions such as Alzheimer’s disease and multiple sclerosis. Considering the increasing role of inflammation and oxidative stress in the pathophysiology of bipolar disorder (BD, here we propose a novel model wherein transient or persistent disruption of BBB integrity is associated with decreased CNS protection and increased permeability of proinflammatory (e.g., cytokines, reactive oxygen species substances from the peripheral blood into the brain. These events would trigger the activation of microglial cells and promote localized damage to oligodendrocytes and the myelin sheath, ultimately compromising myelination and the integrity of neural circuits. The potential implications for research in this area and directions for future studies are discussed.

  13. Gut-brain peptides in corticostriatal-limbic circuitry and alcohol use disorders

    Directory of Open Access Journals (Sweden)

    Chelsea A Vadnie

    2014-09-01

    Full Text Available Peptides synthesized in endocrine cells in the gastrointestinal tract and neurons are traditionally considered regulators of metabolism, energy intake, and appetite. However, recent work has demonstrated that many of these peptides act on corticostriatal-limbic circuitry and, in turn, regulate addictive behaviors. Given that alcohol is a source of energy and an addictive substance, it is not surprising that increasing evidence supports a role for gut-brain peptides specifically in alcohol use disorders (AUD. In this review, we discuss the effects of several gut-brain peptides on alcohol-related behaviors and the potential mechanisms by which these gut-brain peptides may interfere with alcohol-induced changes in corticostriatal-limbic circuitry. This review provides a summary of current knowledge on gut-brain peptides focusing on five peptides: neurotensin, glucagon-like peptide 1, ghrelin, substance P, and neuropeptide Y. Our review will be helpful to develop novel therapeutic targets for AUD.

  14. Treatment of developmental stress disorder: mind, body and brain - analysis and pharmacology coupled.

    Science.gov (United States)

    McFadden, Joseph

    2017-11-01

    The schism between psychiatry, psychology and analysis, while long present, has widened even more in the past half-century with the advances in psychopharmacology. With the advances in electronic brain imaging, particularly in developmental and post-traumatic stress disorders, there has emerged both an understanding of brain changes resulting from severe, chronic stress and an ability to target brain chemistry in ways that can relieve clinical symptomatology. The use of alpha-1 adrenergic brain receptor antagonists decreases many of the manifestations of PTSD. Additionally, this paper discusses the ways in which dreaming, thinking and the analytic process are facilitated with this concomitant treatment and hypervigilence and hyper-arousal states are signficiantly decreased. © 2017, The Society of Analytical Psychology.

  15. Computational neuropsychiatry – schizophrenia as a cognitive brain network disorder

    Directory of Open Access Journals (Sweden)

    Maria R Dauvermann

    2014-03-01

    Full Text Available Computational modelling of functional brain networks has advanced the understanding of higher cognitive function. It is hypothesised that functional networks mediating higher cognitive processes are disrupted in people with schizophrenia. In this article, we review studies that applied measures of functional and effective connectivity to fMRI data during cognitive tasks, in particular working memory fMRI studies. We provide a conceptual summary of the main findings in fMRI data and their relationship with neurotransmitter systems, which are known to be altered in individuals with schizophrenia. We consider possible developments in computational neuropsychiatry, which are likely to further our understanding of how functional networks are altered in schizophrenia.

  16. Brain Basics

    Medline Plus

    Full Text Available ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  17. Brain Basics

    Science.gov (United States)

    ... News About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  18. Brain Basics

    Medline Plus

    Full Text Available ... Events About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain ... to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons are ...

  19. Enhanced brain signal variability in children with autism spectrum disorder during early childhood

    Science.gov (United States)

    Yoshimura, Yuko; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Munesue, Toshio; Higashida, Haruhiro; Minabe, Yoshio; Kikuchi, Mitsuru

    2016-01-01

    Abstract Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age‐related increase of brain signal variability in a specific timescale in TD children, whereas atypical age‐related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region‐specifically and timescale‐specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical‐developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. Hum Brain Mapp 37:1038–1050, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26859309

  20. The GABA excitatory/inhibitory shift in brain maturation and neurological disorders.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Khalilov, Ilgam; Kahle, Kristopher T; Cherubini, Enrico

    2012-10-01

    Ionic currents and the network-driven patterns they generate differ in immature and adult neurons: The developing brain is not a "small adult brain." One of the most investigated examples is the developmentally regulated shift of actions of the transmitter GABA that inhibit adult neurons but excite immature ones because of an initially higher intracellular chloride concentration [Cl(-)](i), leading to depolarizing and often excitatory actions of GABA instead of hyperpolarizing and inhibitory actions. The levels of [Cl(-)](i) are also highly labile, being readily altered transiently or persistently by enhanced episodes of activity in relation to synaptic plasticity or a variety of pathological conditions, including seizures and brain insults. Among the plethora of channels, transporters, and other devices involved in controlling [Cl(-)](i), two have emerged as playing a particularly important role: the chloride importer NKCC1 and the chloride exporter KCC2. Here, the authors stress the importance of determining how [Cl(-)](i) is dynamically regulated and how this affects brain operation in health and disease. In a clinical perspective, agents that control [Cl(-)](i) and reinstate inhibitory actions of GABA open novel therapeutic perspectives in many neurological disorders, including infantile epilepsies, autism spectrum disorders, and other developmental disorders.

  1. Dissociated Functional Brain Abnormalities of Inhibition in Boys With Pure Conduct Disorder and in Boys With Pure Attention Deficit Hyperactivity Disorder

    National Research Council Canada - National Science Library

    Scott, Steven; Smith, Anna B; Giampietro, Vincent; Taylor, Eric; Brammer, Michael J; Rubia, Katya; Mohammed, Majeed; Halari, Rozmin

    2008-01-01

    .... Method: Event-related fMRI was used to compare brain activation of 13 boys with noncomorbid conduct disorder, 20 with noncomorbid ADHD, and 20 normal boys during an individually adjusted tracking stop task...

  2. [Pediatric anesthetic during brain immaturity and neurodevelopment disorders].

    Science.gov (United States)

    Catré, Dora; Lopes, Maria Francelina; Cabrita, António Silvério; Silva Viana, Joaquim

    2014-01-01

    Introdução: Diversos estudos experimentais e clínicos sugerem que fármacos usados em anestesia pediátrica podem exercer efeitos indesejáveis sobre o sistema nervoso central imaturo. O objetivo desta revisão consistiu em avaliar os resultados e conclusões de estudos publicados na literatura sobre perturbações persistentes do neurodesenvolvimento após exposição a anestésicos de crianças em fase de imaturidade cerebral. Material e Métodos: Realizámos uma pesquisa bibliográfica em diversas bases de dados (PubMed, SciELO e Cochrane Library), utilizando os termos ‘Pediatric anesthesia OR Pediatric anesthetic OR Developing brain anesthetic OR Developing brain anesthesia AND behavior disorders’ e foram incluídos os estudos em humanos, referentes a efeitos persistentes no neurodesenvolvimento após exposição a anestésicos nos primeiros quatro anos de idade. Resultados: Dez estudos retrospetivos cumpriram os critérios de inclusão. Destes, sete sugerem alteração do neurodesenvolvimento por exposição de criança pequena à anestesia, por oposição aos resultados obtidos pelos restantes três. Discussão: Embora maioritariamente utilizem bases de dados amplas, os estudos encontrados são retrospetivos, variam nos grupos teste, incluem variáveis de confusão por vezes contornáveis e alguns apresentam incorreções na escolha da população teste e controlo que podem comprometer a fiabilidade dos resultados. Conclusão: As numerosas limitações dos poucos estudos clínicos disponíveis fazem com que a informação reportada ainda se considere insuficiente para mudar a prática clínica atual. No entanto, sendo indiscutível que se mantêm as recomendações para providenciar anestesia quando necessária, independentemente da idade, os alertas encontrados na literatura são preocupantes, existindo indicação para que sempre que possível sejam ponderadas alternativas que possam contribuir para diminuir os riscos da exposição anestésica.

  3. Arizona Study of Aging and Neurodegenerative Disorders and Brain and Body Donation Program.

    Science.gov (United States)

    Beach, Thomas G; Adler, Charles H; Sue, Lucia I; Serrano, Geidy; Shill, Holly A; Walker, Douglas G; Lue, LihFen; Roher, Alex E; Dugger, Brittany N; Maarouf, Chera; Birdsill, Alex C; Intorcia, Anthony; Saxon-Labelle, Megan; Pullen, Joel; Scroggins, Alexander; Filon, Jessica; Scott, Sarah; Hoffman, Brittany; Garcia, Angelica; Caviness, John N; Hentz, Joseph G; Driver-Dunckley, Erika; Jacobson, Sandra A; Davis, Kathryn J; Belden, Christine M; Long, Kathy E; Malek-Ahmadi, Michael; Powell, Jessica J; Gale, Lisa D; Nicholson, Lisa R; Caselli, Richard J; Woodruff, Bryan K; Rapscak, Steven Z; Ahern, Geoffrey L; Shi, Jiong; Burke, Anna D; Reiman, Eric M; Sabbagh, Marwan N

    2015-08-01

    The Brain and Body Donation Program (BBDP) at Banner Sun Health Research Institute (http://www.brainandbodydonationprogram.org) started in 1987 with brain-only donations and currently has banked more than 1600 brains. More than 430 whole-body donations have been received since this service was commenced in 2005. The collective academic output of the BBDP is now described as the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND). Most BBDP subjects are enrolled as cognitively normal volunteers residing in the retirement communities of metropolitan Phoenix, Arizona. Specific recruitment efforts are also directed at subjects with Alzheimer's disease, Parkinson's disease and cancer. The median age at death is 82. Subjects receive standardized general medical, neurological, neuropsychological and movement disorders assessments during life and more than 90% receive full pathological examinations by medically licensed pathologists after death. The Program has been funded through a combination of internal, federal and state of Arizona grants as well as user fees and pharmaceutical industry collaborations. Subsets of the Program are utilized by the US National Institute on Aging Arizona Alzheimer's Disease Core Center and the US National Institute of Neurological Disorders and Stroke National Brain and Tissue Resource for Parkinson's Disease and Related Disorders. Substantial funding has also been received from the Michael J. Fox Foundation for Parkinson's Research. The Program has made rapid autopsy a priority, with a 3.0-hour median post-mortem interval for the entire collection. The median RNA Integrity Number (RIN) for frozen brain and body tissue is 8.9 and 7.4, respectively. More than 2500 tissue requests have been served and currently about 200 are served annually. These requests have been made by more than 400 investigators located in 32 US states and 15 countries. Tissue from the BBDP has contributed to more than 350 publications and more than 200

  4. Expression weighted cell type enrichments reveal genetic and cellular nature of major brain disorders

    Directory of Open Access Journals (Sweden)

    Nathan Gerald Skene

    2016-01-01

    Full Text Available The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer’s disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer’s and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesised that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer’s disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models.

  5. Storm in My Brain: Kids and Mood Disorders (Bipolar Disorder and Depression)

    Science.gov (United States)

    ... yourself—Learn about mood disorders and the side effects of treatments prescribed for your student(s). • Identify and reduce stressors: sensory overload, boredom, bullying, homework, competition. • Suggest psychoeducational testing. • Identify a person ...

  6. The size and burden of mental disorders and other disorders of the brain in Europe 2010

    DEFF Research Database (Denmark)

    Wittchen, H U; Jacobi, F; Rehm, J;

    2011-01-01

    To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range...... of disorders than previously covered are needed for basic, clinical and public health research and policy decisions and to inform about the estimated number of persons affected in the EU....

  7. Abnormal brain activation and connectivity to standardized disorder-related visual scenes in social anxiety disorder.

    Science.gov (United States)

    Heitmann, Carina Yvonne; Feldker, Katharina; Neumeister, Paula; Zepp, Britta Maria; Peterburs, Jutta; Zwitserlood, Pienie; Straube, Thomas

    2016-04-01

    Our understanding of altered emotional processing in social anxiety disorder (SAD) is hampered by a heterogeneity of findings, which is probably due to the vastly different methods and materials used so far. This is why the present functional magnetic resonance imaging (fMRI) study investigated immediate disorder-related threat processing in 30 SAD patients and 30 healthy controls (HC) with a novel, standardized set of highly ecologically valid, disorder-related complex visual scenes. SAD patients rated disorder-related as compared with neutral scenes as more unpleasant, arousing and anxiety-inducing than HC. On the neural level, disorder-related as compared with neutral scenes evoked differential responses in SAD patients in a widespread emotion processing network including (para-)limbic structures (e.g. amygdala, insula, thalamus, globus pallidus) and cortical regions (e.g. dorsomedial prefrontal cortex (dmPFC), posterior cingulate cortex (PCC), and precuneus). Functional connectivity analysis yielded an altered interplay between PCC/precuneus and paralimbic (insula) as well as cortical regions (dmPFC, precuneus) in SAD patients, which emphasizes a central role for PCC/precuneus in disorder-related scene processing. Hyperconnectivity of globus pallidus with amygdala, anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) additionally underlines the relevance of this region in socially anxious threat processing. Our findings stress the importance of specific disorder-related stimuli for the investigation of altered emotion processing in SAD. Disorder-related threat processing in SAD reveals anomalies at multiple stages of emotion processing which may be linked to increased anxiety and to dysfunctionally elevated levels of self-referential processing reported in previous studies. © 2016 Wiley Periodicals, Inc.

  8. Uremic anorexia: a consequence of persistently high brain serotonin levels? The tryptophan/serotonin disorder hypothesis.

    Science.gov (United States)

    Aguilera, A; Selgas, R; Codoceo, R; Bajo, A

    2000-01-01

    Anorexia is a frequent part of uremic syndrome, contributing to malnutrition in dialysis patients. Many factors have been suggested as responsible for uremic anorexia. In this paper we formulate a new hypothesis to explain the appetite disorders in dialysis patients: "the tryptophan/serotonin disorder hypothesis." We review current knowledge of normal hunger-satiety cycle control and the disorders described in uremic patients. There are four phases in food intake regulation: (1) the gastric phase, during which food induces satiety through gastric distention and satiety peptide release; (2) the post absorptive phase, during which circulating compounds, including glucose and amino acids, cause satiety by hepatic receptors via the vagus nerve; (3) the hepatic phase, during which adenosine triphosphate (ATP) concentration is the main stimulus inducing hunger or satiety, with cytokines inhibiting ATP production; and (4) the central phase, during which appetite is regulated through peripheral (circulating plasma substances and neurotransmitters) and brain stimuli. Brain serotonin is the final target for peripheral mechanisms controlling appetite. High brain serotonin levels and a lower serotonin/dopamine ratio cause anorexia. Plasma and brain amino acid concentrations are recognized factors involved in neurotransmitter synthesis and appetite control. Tryptophan is the substrate of serotonin synthesis. High plasma levels of anorectics such as tryptophan (plasma and brain), cholecystokinin, tumor necrosis factor alpha, interleukin-1, and leptin, and deficiencies of nitric oxide and neuropeptide Y have been described in uremia; all increase intracerebral serotonin. We suggest that brain serotonin hyperproduction due to a uremic-dependent excess of tryptophan may be the final common pathway involved in the genesis of uremic anorexia. Various methods of ameliorating anorexia by decreasing the central effects of serotonin are proposed.

  9. The application of tDCS in psychiatric disorders: a brain imaging view

    Directory of Open Access Journals (Sweden)

    Chris Baeken

    2016-03-01

    Full Text Available Background: Transcranial direct current stimulation (tDCS is a non-invasive, non-convulsive technique for modulating brain function. In contrast to other non-invasive brain stimulation techniques, where costs, clinical applicability, and availability limit their large-scale use in clinical practices, the low-cost, portable, and easy-to-use tDCS devices may overcome these restrictions. Objective: Despite numerous clinical applications in large numbers of patients suffering from psychiatric disorders, it is not quite clear how tDCS influences the mentally affected human brain. In order to decipher potential neural mechanisms of action of tDCS in patients with psychiatric conditions, we focused on the combination of tDCS with neuroimaging techniques. Design: We propose a contemporary overview on the currently available neurophysiological and neuroimaging data where tDCS has been used as a research or treatment tool in patients with psychiatric disorders. Results: Over a reasonably short period of time, tDCS has been broadly used as a research tool to examine neuronal processes in the healthy brain. tDCS has also commonly been applied as a treatment application in a variety of mental disorders, with to date no straightforward clinical outcome and not always accompanied by brain imaging techniques. Conclusion: tDCS, as do other neuromodulation devices, clearly affects the underlying neuronal processes. However, research on these mechanisms in psychiatric patients is rather limited. A better comprehension of how tDCS modulates brain function will help us to define optimal parameters of stimulation in each indication and may result in the detection of biomarkers in favor of clinical response.

  10. Relationship between symptom dimensions and brain morphology in obsessive-compulsive disorder.

    Science.gov (United States)

    Hirose, Motohisa; Hirano, Yoshiyuki; Nemoto, Kiyotaka; Sutoh, Chihiro; Asano, Kenichi; Miyata, Haruko; Matsumoto, Junko; Nakazato, Michiko; Matsumoto, Koji; Masuda, Yoshitada; Iyo, Masaomi; Shimizu, Eiji; Nakagawa, Akiko

    2016-10-11

    Obsessive-compulsive disorder (OCD) is known as a clinically heterogeneous disorder characterized by symptom dimensions. Although substantial numbers of neuroimaging studies have demonstrated the presence of brain abnormalities in OCD, their results are controversial. The clinical heterogeneity of OCD could be one of the reasons for this. It has been hypothesized that certain brain regions contributed to the respective obsessive-compulsive dimensions. In this study, we investigated the relationship between symptom dimensions of OCD and brain morphology using voxel-based morphometry to discover the specific regions showing alterations in the respective dimensions of obsessive-compulsive symptoms. The severities of symptom dimensions in thirty-three patients with OCD were assessed using Obsessive-Compulsive Inventory-Revised (OCI-R). Along with numerous MRI studies pointing out brain abnormalities in autistic spectrum disorder (ASD) patients, a previous study reported a positive correlation between ASD traits and regional gray matter volume in the left dorsolateral prefrontal cortex and amygdala in OCD patients. We investigated the correlation between gray and white matter volumes at the whole brain level and each symptom dimension score, treating all remaining dimension scores, age, gender, and ASD traits as confounding covariates. Our results revealed a significant negative correlation between washing symptom dimension score and gray matter volume in the right thalamus and a significant negative correlation between hoarding symptom dimension score and white matter volume in the left angular gyrus. Although our result was preliminary, our findings indicated that there were specific brain regions in gray and white matter that contributed to symptom dimensions in OCD patients.

  11. Ibudilast: a non-selective phosphodiesterase inhibitor in brain disorders

    Directory of Open Access Journals (Sweden)

    Joanna Schwenkgrub

    2017-03-01

    Full Text Available Ibudilast (IBD is a non-selective (3, 4, 10, 11 phosphodiesterase (PDE inhibitor, used mainly as a bronchodilator for the treatment of bronchial asthma. PDE play a central role in cellular function (e.g. differentiation, synaptic plasticity and inflammatory response by metabolizing cyclic nucleotides. The results from preclinical and clinical studies indicate that IBD has a broader range of action through suppression of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, toll-like receptor 4 blockade (TLR-4, inhibition of a macrophage migration inhibitory factor (MIF, up-regulation the anti-inflammatory cytokine (IL-10, and promotion of neurotrophic factors (GDNF, NGF, NT-4. Recent data indicate that the efficacy of IBD appears to be independent from PDE inhibition activity and rather linked to glial activity attenuation. Additional advantages of IBD, such as crossing the blood–brain barrier, good tolerance and activity by oral administration, makes it a promising therapeutic candidate for treating neuroinflammatory conditions, where the currently available treatment remains unsatisfying due to poor tolerability and/or sub-optimal efficacy. IBD has no direct receptor affinity with exemption of some undefined effect on adenosine receptors that makes the drug devoid of its receptors-mediated adverse effects. Current article provides an overview of the pharmacology of IBD with a focus on preclinical and clinical data supporting its potential neuroprotective benefits for neurological conditions, including multiple sclerosis, neuropathic pain, medication overuse headache, stroke, opioid, alcohol and methamphetamine abuse.

  12. Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

    Institute of Scientific and Technical Information of China (English)

    Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

    2008-01-01

    BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

  13. Treatment of movement disorders using deep brain stimulation – illustrative case reports and technical notes

    Directory of Open Access Journals (Sweden)

    Tadej Strojnik

    2012-05-01

    Full Text Available Operative neuromodulation is the field of electrically or chemically altering the signal transmission in the nervous system by implanted devices in order to excite, inhibit or tune the activities of neurons or neural networks to produce therapeutic effects. Deep brain stimulation (DBS is an important component of the therapy of movement disorders and has almost completely replaced high-frequency coagulation of brain tissue in stereotactic neurosurgery. This article presents the first DBS cases in Slovenia. In the article the technical features and adjustments of magnetic resonance (MR imaging and development of a new microdrive, which was clinically successfully tested, are described and discussed.

  14. Posttraumatic Stress Disorder in patients with traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Schmidt Roger

    2004-03-01

    Full Text Available Abstract Background Severe traumatic stressors such as war, rape, or life-threatening accidents can result in a debilitating psychopathological development conceptualised as Posttraumatic Stress Disorder (PTSD. Pathological memory formation during an alarm response may set the precondition for PTSD to occur. If true, a lack of memory formation by extended unconsciousness in the course of the traumatic experience should preclude PTSD. Methods 46 patients from a neurological rehabilitation clinic were examined by means of questionnaires and structured clinical interviews. All patients had suffered a TBI due to an accident, but varied with respect to falling unconscious during the traumatic event. Results 27% of the sub-sample who were not unconscious for an extended period but only 3% (1 of 31 patients who were unconscious for more than 12 hours as a result of the accident were diagnosed as having current PTSD (P Conclusion TBI and PTSD are not mutually exclusive. However, victims of accidents are unlikely to develop a PTSD if the impact to the head had resulted in an extended period of unconsciousness.

  15. Brain injury in premature neonates: A primary cerebral dysmaturation disorder?

    Science.gov (United States)

    Back, Stephen A; Miller, Steven P

    2014-04-01

    With advances in neonatal care, preterm neonates are surviving with an evolving constellation of motor and cognitive disabilities that appear to be related to widespread cellular maturational disturbances that target cerebral gray and white matter. Whereas preterm infants were previously at high risk for destructive brain lesions that resulted in cystic white matter injury and secondary cortical and subcortical gray matter degeneration, contemporary cohorts of preterm survivors commonly display less severe injury that does not appear to involve pronounced glial or neuronal loss. Nevertheless, these milder forms of injury are also associated with reduced cerebral growth. Recent human and experimental studies support that impaired cerebral growth is related to disparate responses in gray and white matter. Myelination disturbances in cerebral white matter are related to aberrant regeneration and repair responses to acute death of premyelinating late oligodendrocyte progenitors (preOLs). In response to preOL death, early oligodendrocyte progenitors rapidly proliferate and differentiate, but the regenerated preOLs fail to normally mature to myelinating cells required for white matter growth. Although immature neurons appear to be more resistant to cell death from hypoxia-ischemia than glia, they display widespread disturbances in maturation of their dendritic arbors, which further contribute to impaired cerebral growth. These complex and disparate responses of neurons and preOLs thus result in large numbers of cells that fail to fully mature during a critical window in development of neural circuitry. These recently recognized forms of cerebral gray and white matter dysmaturation raise new diagnostic challenges and suggest new therapeutic directions centered on reversal of the processes that promote dysmaturation.

  16. Changes in brain activity of somatoform disorder patients during emotional empathy after multimodal psychodynamic psychotherapy.

    Directory of Open Access Journals (Sweden)

    Moritz ede Greck

    2013-08-01

    Full Text Available Somatoform disorder patients show a variety of emotional disturbances including impaired emotion recognition and increased empathic distress. In a previous paper, our group showed that several brain regions involved in emotional processing, such as the parahippocampal gyrus and other regions, were less activated in pre-treatment somatoform disorder patients (compared to healthy controls during an empathy task. Since the parahippocampal gyrus is involved in emotional memory, its decreased activation might reflect the repression of emotional memories (which - according to psychoanalytical concepts - plays an important role in somatoform disorder. Psychodynamic psychotherapy aims at increasing the understanding of emotional conflicts as well as uncovering repressed emotions. We were interested, whether brain activity in the parahippocampal gyrus normalized after (inpatient multimodal psychodynamic psychotherapy. Using fMRI, subjects were scanned while they shared the emotional states of presented facial stimuli expressing anger, disgust, joy and a neutral expression; distorted stimuli with unrecognizable content served as control condition. 15 somatoform disorder patients were scanned twice, pre and post multimodal psychodynamic psychotherapy; in addition, 15 age-matched healthy control subjects were investigated. Effects of psychotherapy on hemodynamic responses were analyzed implementing two approaches: (i an a priori region of interest approach and (ii a voxelwise whole brain analysis.Both analyses revealed increased hemodynamic responses in the left and right parahippocampal gyrus (and other regions after multimodal psychotherapy in the contrast ‘empathy with anger’-‘control’. Our results are in line with psychoanalytical concepts about somatoform disorder. They suggest the parahippocampal gyrus is crucially involved in the neurobiological mechanisms which underly the emotional deficits of somatoform disorder patients.

  17. Changes in brain activity of somatoform disorder patients during emotional empathy after multimodal psychodynamic psychotherapy.

    Science.gov (United States)

    de Greck, Moritz; Bölter, Annette F; Lehmann, Lisa; Ulrich, Cornelia; Stockum, Eva; Enzi, Björn; Hoffmann, Thilo; Tempelmann, Claus; Beutel, Manfred; Frommer, Jörg; Northoff, Georg

    2013-01-01

    Somatoform disorder patients show a variety of emotional disturbances including impaired emotion recognition and increased empathic distress. In a previous paper, our group showed that several brain regions involved in emotional processing, such as the parahippocampal gyrus and other regions, were less activated in pre-treatment somatoform disorder patients (compared to healthy controls) during an empathy task. Since the parahippocampal gyrus is involved in emotional memory, its decreased activation might reflect the repression of emotional memories (which-according to psychoanalytical concepts-plays an important role in somatoform disorder). Psychodynamic psychotherapy aims at increasing the understanding of emotional conflicts as well as uncovering repressed emotions. We were interested, whether brain activity in the parahippocampal gyrus normalized after (inpatient) multimodal psychodynamic psychotherapy. Using fMRI, subjects were scanned while they shared the emotional states of presented facial stimuli expressing anger, disgust, joy, and a neutral expression; distorted stimuli with unrecognizable content served as control condition. 15 somatoform disorder patients were scanned twice, pre and post multimodal psychodynamic psychotherapy; in addition, 15 age-matched healthy control subjects were investigated. Effects of psychotherapy on hemodynamic responses were analyzed implementing two approaches: (1) an a priori region of interest approach and (2) a voxelwise whole brain analysis. Both analyses revealed increased hemodynamic responses in the left and right parahippocampal gyrus (and other regions) after multimodal psychotherapy in the contrast "empathy with anger"-"control." Our results are in line with psychoanalytical concepts about somatoform disorder. They suggest the parahippocampal gyrus is crucially involved in the neurobiological mechanisms which underly the emotional deficits of somatoform disorder patients.

  18. Enhanced brain signal variability in children with autism spectrum disorder during early childhood.

    Science.gov (United States)

    Takahashi, Tetsuya; Yoshimura, Yuko; Hiraishi, Hirotoshi; Hasegawa, Chiaki; Munesue, Toshio; Higashida, Haruhiro; Minabe, Yoshio; Kikuchi, Mitsuru

    2016-03-01

    Extensive evidence shows that a core neurobiological mechanism of autism spectrum disorder (ASD) involves aberrant neural connectivity. Recent advances in the investigation of brain signal variability have yielded important information about neural network mechanisms. That information has been applied fruitfully to the assessment of aging and mental disorders. Multiscale entropy (MSE) analysis can characterize the complexity inherent in brain signal dynamics over multiple temporal scales in the dynamics of neural networks. For this investigation, we sought to characterize the magnetoencephalography (MEG) signal variability during free watching of videos without sound using MSE in 43 children with ASD and 72 typically developing controls (TD), emphasizing early childhood to older childhood: a critical period of neural network maturation. Results revealed an age-related increase of brain signal variability in a specific timescale in TD children, whereas atypical age-related alteration was observed in the ASD group. Additionally, enhanced brain signal variability was observed in children with ASD, and was confirmed particularly for younger children. In the ASD group, symptom severity was associated region-specifically and timescale-specifically with reduced brain signal variability. These results agree well with a recently reported theory of increased brain signal variability during development and aberrant neural connectivity in ASD, especially during early childhood. Results of this study suggest that MSE analytic method might serve as a useful approach for characterizing neurophysiological mechanisms of typical-developing and its alterations in ASD through the detection of MEG signal variability at multiple timescales. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  19. Brain functional connectivity in stimulant drug dependence and obsessive-compulsive disorder.

    Science.gov (United States)

    Meunier, David; Ersche, Karen D; Craig, Kevin J; Fornito, Alex; Merlo-Pich, Emilio; Fineberg, Naomi A; Shabbir, Shaila S; Robbins, Trevor W; Bullmore, Edward T

    2012-01-16

    There are reasons for thinking that obsessive-compulsive disorder (OCD) and drug dependence, although conventionally distinct diagnostic categories, might share important cognitive and neurobiological substrates. We tested this hypothesis directly by comparing brain functional connectivity measures between patients with OCD, stimulant dependent individuals (SDIs; many of whom were non-dependent users of other recreational drugs) and healthy volunteers. We measured functional connectivity between each possible pair of 506 brain regional functional MRI time series representing low frequency (0.03-0.06 Hz) spontaneous brain hemodynamics in healthy volunteers (N=18), patients with OCD (N=18) and SDIs (N=18). We used permutation tests to identify i) brain regions where strength of connectivity was significantly different in both patient groups compared to healthy volunteers; and ii) brain regions and connections which had significantly different functional connectivity between patient groups. We found that functional connectivity of right inferior and superior orbitofrontal cortex (OFC) was abnormally reduced in both disorders. Whether diagnosed as OCD or SDI, patients with higher scores on measures of compulsive symptom severity showed greater reductions of right orbitofrontal connectivity. Functional connections specifically between OFC and dorsal medial pre-motor and cingulate cortex were attenuated in both patient groups. However, patients with OCD demonstrated more severe and extensive reductions of functional connectivity compared to SDIs. OCD and stimulant dependence are not identical at the level of brain functional systems but they have some important abnormalities in common compared with healthy volunteers. Orbitofrontal connectivity may serve as a human brain systems biomarker for compulsivity across diagnostic categories.

  20. Progress in the genetics of polygenic brain disorders: significant new challenges for neurobiology.

    Science.gov (United States)

    McCarroll, Steven A; Hyman, Steven E

    2013-10-30

    Advances in genome analysis, accompanied by the assembly of large patient cohorts, are making possible successful genetic analyses of polygenic brain disorders. If the resulting molecular clues, previously hidden in the genomes of affected individuals, are to yield useful information about pathogenesis and inform the discovery of new treatments, neurobiology will have to rise to many difficult challenges. Here we review the underlying logic of the genetic investigations, describe in more detail progress in schizophrenia and autism, and outline the challenges for neurobiology that lie ahead. We argue that technologies at the disposal of neuroscience are adequately advanced to begin to study the biology of common and devastating polygenic disorders.

  1. BRAIN DYSFUNCTION OF PATIENTS WITH QIGONG INDUCED MENTAL DISORDER REVEALED BY EVOKED POTENTIALS RECORDING

    Institute of Scientific and Technical Information of China (English)

    LU Yingzhi; ZONG Wenbin; CHEN Xingshi

    2003-01-01

    Objective: In order to investigate the brain function of patients with Qigong induced mental disorder (QIMD), this study was carried out. Methods: Four kinds of evoked potentials, including contingent negative variation (CNV), auditory evoked potentials (AEP), visual evoked potentials (VEP), and somatosensory evoked potentials (SEP), were recorded from 12 patients with Qigong induced mental disorder.Comparison of their evoked potentials with the data from some normal controls was made. Results: The results revealed that there were 3 kinds of abnormal changes in evoked potentials of patients with QIMD that is latency prolongation, amplitude increase and amplitude decrease, as compared with normal controls. Conclusion: Brain dysfunction of patients with QIMD was confirmed. Its biological mechanism needs further studying.

  2. Neuroethics and Disorders of Consciousness: Discerning Brain States in Clinical Practice and Research.

    Science.gov (United States)

    Fins, Joseph J

    2016-12-01

    Decisions about end-of-life care and participation in clinical research for patients with disorders of consciousness begin with diagnostic discernment. Accurately distinguishing between brain states clarifies clinicians' ethical obligations and responsibilities. Central to this effort is the obligation to provide neuropalliative care for patients in the minimally conscious state who can perceive pain and to restore functional communication through neuroprosthetics, drugs, and rehabilitation to patients with intact but underactivated neural networks. Efforts to bring scientific advances to patients with disorders of consciousness are reviewed, including the investigational use of deep brain stimulation in patients in the minimally conscious state. These efforts help to affirm the civil rights of a population long on the margins.

  3. MR spectroscopy in metabolic disorders of the brain; MR-Spektroskopie bei Stoffwechselerkrankungen des Gehirns

    Energy Technology Data Exchange (ETDEWEB)

    Yilmaz, U. [Universitaetsklinikum des Saarlandes, Klinik fuer Diagnostische und Interventionelle Neuroradiologie, Homburg/Saar (Germany)

    2017-06-15

    Metabolic disorders of the brain often present a particular challenge for the neuroradiologist, since the disorders are rare, changes on conventional MR are often non-specific and there are numerous differential diagnoses for the white substance lesions. As a complementary method to conventional brain MRI, MR spectroscopy may help to reduce the scope of the differential diagnosis. Entities with specific MR spectroscopy patterns are Canavan disease, maple syrup urine disease, nonketotic hyperglycinemia and creatine deficiency. (orig.) [German] Die Diagnostik metabolischer Erkrankungen des Gehirns stellt eine besondere Herausforderung in der Neuroradiologie dar, da die Erkrankungen insgesamt selten, die bildmorphologischen Befunde haeufig unspezifisch sind und es eine Vielzahl von Differenzialdiagnosen fuer die Veraenderungen der weissen Substanz gibt. Als zusaetzliche Technik kann die MR-Spektroskopie bei Stoffwechselerkrankungen helfen, die Diagnose einzugrenzen. Krankheitsentitaeten, die spezifische Veraenderungen in der Spektroskopie aufweisen, sind der Morbus Canavan, die Ahornsirupkrankheit, die nichtketotische Hyperglyzinaemie und Kreatinmangelsyndrome. (orig.)

  4. Abnormal early brain responses during visual search are evident in schizophrenia but not bipolar affective disorder.

    Science.gov (United States)

    VanMeerten, Nicolaas J; Dubke, Rachel E; Stanwyck, John J; Kang, Seung Suk; Sponheim, Scott R

    2016-01-01

    People with schizophrenia show deficits in processing visual stimuli but neural abnormalities underlying the deficits are unclear and it is unknown whether such functional brain abnormalities are present in other severe mental disorders or in individuals who carry genetic liability for schizophrenia. To better characterize brain responses underlying visual search deficits and test their specificity to schizophrenia we gathered behavioral and electrophysiological responses during visual search (i.e., Span of Apprehension [SOA] task) from 38 people with schizophrenia, 31 people with bipolar disorder, 58 biological relatives of people with schizophrenia, 37 biological relatives of people with bipolar disorder, and 65 non-psychiatric control participants. Through subtracting neural responses associated with purely sensory aspects of the stimuli we found that people with schizophrenia exhibited reduced early posterior task-related neural responses (i.e., Span Endogenous Negativity [SEN]) while other groups showed normative responses. People with schizophrenia exhibited longer reaction times than controls during visual search but nearly identical accuracy. Those individuals with schizophrenia who had larger SENs performed more efficiently (i.e., shorter reaction times) on the SOA task suggesting that modulation of early visual cortical responses facilitated their visual search. People with schizophrenia also exhibited a diminished P300 response compared to other groups. Unaffected first-degree relatives of people with bipolar disorder and schizophrenia showed an amplified N1 response over posterior brain regions in comparison to other groups. Diminished early posterior brain responses are associated with impaired visual search in schizophrenia and appear to be specifically associated with the neuropathology of schizophrenia. Published by Elsevier B.V.

  5. Adrenal Disorders and the Paediatric Brain: Pathophysiological Considerations and Clinical Implications

    Directory of Open Access Journals (Sweden)

    Vincenzo Salpietro

    2014-01-01

    Full Text Available Various neurological and psychiatric manifestations have been recorded in children with adrenal disorders. Based on literature review and on personal case-studies and case-series we focused on the pathophysiological and clinical implications of glucocorticoid-related, mineralcorticoid-related, and catecholamine-related paediatric nervous system involvement. Childhood Cushing syndrome can be associated with long-lasting cognitive deficits and abnormal behaviour, even after resolution of the hypercortisolism. Exposure to excessive replacement of exogenous glucocorticoids in the paediatric age group (e.g., during treatments for adrenal insufficiency has been reported with neurological and magnetic resonance imaging (MRI abnormalities (e.g., delayed myelination and brain atrophy due to potential corticosteroid-related myelin damage in the developing brain and the possible impairment of limbic system ontogenesis. Idiopathic intracranial hypertension (IIH, a disorder of unclear pathophysiology characterised by increased cerebrospinal fluid (CSF pressure, has been described in children with hypercortisolism, adrenal insufficiency, and hyperaldosteronism, reflecting the potential underlying involvement of the adrenal-brain axis in the regulation of CSF pressure homeostasis. Arterial hypertension caused by paediatric adenomas or tumours of the adrenal cortex or medulla has been associated with various hypertension-related neurological manifestations. The development and maturation of the central nervous system (CNS through childhood is tightly regulated by intrinsic, paracrine, endocrine, and external modulators, and perturbations in any of these factors, including those related to adrenal hormone imbalance, could result in consequences that affect the structure and function of the paediatric brain. Animal experiments and clinical studies demonstrated that the developing (i.e., paediatric CNS seems to be particularly vulnerable to alterations induced by

  6. Brain Activity toward Gaming-Related Cues in Internet Gaming Disorder during an Addiction Stroop Task

    OpenAIRE

    Zhang, Yifen; Lin, Xiao; Zhou, Hongli; Xu, Jiaojing; Du, XiaoXia; Dong, Guangheng

    2016-01-01

    Background and Aims: Attentional bias for drug-related stimuli is a key characteristic for drug addiction. Characterizing the relationship between attentional bias and brain reactivity to Internet gaming-related stimuli may help in identifying the neural substrates that critical to Internet gaming disorder (IGD). Methods: 19 IGD and 21 healthy control (HC) subjects were scanned with functional magnetic resonance imaging while they were performing an addiction Stroop task. Results: Compared wi...

  7. Brain activity towards gaming-related cues in Internet gaming disorder during an addiction Stroop task

    OpenAIRE

    Yifen eZhang; Xiao eLin; Hongli eZhou; Xiaoxia eDu; Guangheng eDong

    2016-01-01

    Background and aims: Attentional bias for drug-related stimuli is a key characteristic for drug addiction. Characterizing the relationship between attentional bias and brain reactivity to Internet gaming-related stimuli may help in identifying the neural substrates that critical to Internet gaming disorder (IGD).Methods: 19 IGD and 21 healthy control (HC) subjects were scanned with functional magnetic resonance imaging while they were performing an addiction Stroop task.Results: Compared with...

  8. Behavioral and affective disorders after brain injury: French guidelines for prevention and community supports.

    Science.gov (United States)

    Luauté, J; Hamonet, J; Pradat-Diehl, P

    2016-02-01

    The purpose of this study was to elaborate practice guidelines for the prevention of behavioral and affective disorders in adult outpatients after traumatic brain injury (TBI); but also to identify the support systems available for family, caregivers of patients with TBI within the community. The elaboration of these guidelines followed the procedure validated by the French health authority for good practice recommendations, close to the Prisma statement. This involved a systematic and critical review of the literature looking for studies that investigated the impact of programs in community settings directed to behavioral and affective disorders post-TBI. Recommendations were than elaborated by a group of professionals and family representatives. Only six articles were found comprising 4 studies with a control group. Two studies showed a beneficial effect of personalized behavior management program delivered within natural community settings for persons with brain injury and their caregivers. Two other studies showed the relevance of scheduled telephone interventions to improve depressive symptoms and one study emphasized the usefulness of physical training. One study investigated the relevance of an outreach program; this study showed an improvement of the patients' independence but did not yield any conclusions regarding anxiety and depression. In addition to the application of care pathways already established by the SOFMER, prevention of behavioral and affective disorders for brain-injured outpatients should involve pain management, as well as development of therapeutic partnerships. It is recommended to inform patients, their family and caregivers regarding the local organization and facilities involved in the management of traumatic brain injury. The relevance of therapeutic education for implementing coping strategies, educating caregivers on behavioral disorder management, follow-up telephone interventions, and holistic therapy seems established. The

  9. An Update Overview on Brain Imaging Studies of Internet Gaming Disorder

    Directory of Open Access Journals (Sweden)

    Aviv M. Weinstein

    2017-09-01

    Full Text Available There are a growing number of studies on structural and functional brain mechanisms underlying Internet gaming disorder (IGD. Recent functional magnetic resonance imaging studies showed that IGD adolescents and adults had reduced gray matter volume in regions associated with attention motor coordination executive function and perception. Adolescents with IGD showed lower white matter (WM integrity measures in several brain regions that are involved in decision-making, behavioral inhibition, and emotional regulation. IGD adolescents had also disruption in the functional connectivity in areas responsible for learning memory and executive function, processing of auditory, visual, and somatosensory stimuli and relay of sensory and motor signals. IGD adolescents also had decreased functional connectivity of PFC-striatal circuits, increased risk-taking choices, and impaired ability to control their impulses similar to other impulse control disorders. Recent studies indicated that altered executive control mechanisms in attention deficit hyperactivity disorder (ADHD would be a predisposition for developing IGD. Finally, patients with IGD have also shown an increased functional connectivity of several executive control brain regions that may related to comorbidity with ADHD and depression. The behavioral addiction model argues that IGD shows the features of excessive use despite adverse consequences, withdrawal phenomena, and tolerance that characterize substance use disorders. The evidence supports the behavioral addiction model of IGD by showing structural and functional changes in the mechanisms of reward and craving (but not withdrawal in IGD. Future studies need to investigate WM density and functional connectivity in IGD in order to validate these findings. Furthermore, more research is required about the similarity in neurochemical and neurocognitive brain circuits in IGD and comorbid conditions such as ADHD and depression.

  10. Electroencephalographic neurofeedback: Level of evidence in mental and brain disorders and suggestions for good clinical practice.

    Science.gov (United States)

    Micoulaud-Franchi, J-A; McGonigal, A; Lopez, R; Daudet, C; Kotwas, I; Bartolomei, F

    2015-12-01

    The technique of electroencephalographic neurofeedback (EEG NF) emerged in the 1970s and is a technique that measures a subject's EEG signal, processes it in real time, extracts a parameter of interest and presents this information in visual or auditory form. The goal is to effectuate a behavioural modification by modulating brain activity. The EEG NF opens new therapeutic possibilities in the fields of psychiatry and neurology. However, the development of EEG NF in clinical practice requires (i) a good level of evidence of therapeutic efficacy of this technique, (ii) a good practice guide for this technique. Firstly, this article investigates selected trials with the following criteria: study design with controlled, randomized, and open or blind protocol, primary endpoint related to the mental and brain disorders treated and assessed with standardized measurement tools, identifiable EEG neurophysiological targets, underpinned by pathophysiological relevance. Trials were found for: epilepsies, migraine, stroke, chronic insomnia, attentional-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, major depressive disorder, anxiety disorders, addictive disorders, psychotic disorders. Secondly, this article investigates the principles of neurofeedback therapy in line with learning theory. Different underlying therapeutic models are presented didactically between two continua: a continuum between implicit and explicit learning and a continuum between the biomedical model (centred on "the disease") and integrative biopsychosocial model of health (centred on "the illness"). The main relevant learning model is to link neurofeedback therapy with the field of cognitive remediation techniques. The methodological specificity of neurofeedback is to be guided by biologically relevant neurophysiological parameters. Guidelines for good clinical practice of EEG NF concerning technical issues of electrophysiology and of learning are suggested. These require validation by

  11. The size and burden of mental disorders and other disorders of the brain in Europe 2010

    DEFF Research Database (Denmark)

    Wittchen, H U; Jacobi, F; Rehm, J

    2011-01-01

    To provide 12-month prevalence and disability burden estimates of a broad range of mental and neurological disorders in the European Union (EU) and to compare these findings to previous estimates. Referring to our previous 2005 review, improved up-to-date data for the enlarged EU on a broader range...

  12. The Effects of Video Games on Cognition and Brain Structure: Potential Implications for Neuropsychiatric Disorders.

    Science.gov (United States)

    Shams, Tahireh A; Foussias, George; Zawadzki, John A; Marshe, Victoria S; Siddiqui, Ishraq; Müller, Daniel J; Wong, Albert H C

    2015-09-01

    Video games are now a ubiquitous form of entertainment that has occasionally attracted negative attention. Video games have also been used to test cognitive function, as therapeutic interventions for neuropsychiatric disorders, and to explore mechanisms of experience-dependent structural brain changes. Here, we review current research on video games published from January 2011 to April 2014 with a focus on studies relating to mental health, cognition, and brain imaging. Overall, there is evidence that specific types of video games can alter brain structure or improve certain aspects of cognitive functioning. Video games can also be useful as neuropsychological assessment tools. While research in this area is still at a very early stage, there are interesting results that encourage further work in this field, and hold promise for utilizing this technology as a powerful therapeutic and experimental tool.

  13. The effects of lithium and anticonvulsants on brain structure in bipolar disorder.

    Science.gov (United States)

    Germaná, C; Kempton, M J; Sarnicola, A; Christodoulou, T; Haldane, M; Hadjulis, M; Girardi, P; Tatarelli, R; Frangou, S

    2010-12-01

    To investigate the effect of lithium, anticonvulsants and antipsychotics on brain structure in bipolar disorder (BD). A cross-sectional structural brain magnetic resonance imaging study of 74 remitted patients with BD, aged 18-65, who were receiving long-term prophylactic treatment with lithium or anticonvulsants or antipsychotics. Global and regional grey matter, white matter, and cerebrospinal fluid volumes were compared between treatment groups. Grey matter in the subgenual anterior cingulate gyrus on the right (extending into the hypothalamus) and in the postcentral gyrus, the hippocampus/amygdale complex and the insula on the left was greater in BD patients on lithium treatment compared to all other treatment groups. Lithium treatment in BD has a significant effect on brain structure particularly in limbic/paralimbic regions associated with emotional processing. © 2010 John Wiley & Sons A/S.

  14. Characteristics of Hemodynamic Disorders in Patients with Severe Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Ryta E. Rzheutskaya

    2012-01-01

    Full Text Available Purpose. To define specific features of central hemodynamic parameter changes in patients with isolated severe traumatic brain injury (STBI and in patients with clinically established brain death and to determine the required course of treatment for their correction. Data and Research Methods. A close study of central hemodynamic parameters was undertaken. The study involved 13 patients with isolated STBI (group STBI and 15 patients with isolated STBI and clinically established brain death (group STBI-BD. The parameters of central hemodynamics were researched applying transpulmonary thermodilution. Results. In the present study, various types of hemodynamic reaction (normodynamic, hyperdynamic, and hypodynamic were identified in patients with isolated STBI in an acute period of traumatic disease. Hyperdynamic type of blood circulation was not observed in patients with isolated STBI and clinically established brain death. Detected hemodynamic disorders led to the correction of the ongoing therapy under the control of central hemodynamic parameters. Conclusions. Monitoring of parameters of central hemodynamics allows to detect the cause of disorders, to timely carry out the required correction, and to coordinate infusion, inotropic, and vasopressor therapy.

  15. Aging Effects on Whole-Brain Functional Connectivity in Adults Free of Cognitive and Psychiatric Disorders.

    Science.gov (United States)

    Ferreira, Luiz Kobuti; Regina, Ana Carolina Brocanello; Kovacevic, Natasa; Martin, Maria da Graça Morais; Santos, Pedro Paim; Carneiro, Camila de Godoi; Kerr, Daniel Shikanai; Amaro, Edson; McIntosh, Anthony Randal; Busatto, Geraldo F

    2016-09-01

    Aging is associated with decreased resting-state functional connectivity (RSFC) within the default mode network (DMN), but most functional imaging studies have restricted the analysis to specific brain regions or networks, a strategy not appropriate to describe system-wide changes. Moreover, few investigations have employed operational psychiatric interviewing procedures to select participants; this is an important limitation since mental disorders are prevalent and underdiagnosed and can be associated with RSFC abnormalities. In this study, resting-state fMRI was acquired from 59 adults free of cognitive and psychiatric disorders according to standardized criteria and based on extensive neuropsychological and clinical assessments. We tested for associations between age and whole-brain RSFC using Partial Least Squares, a multivariate technique. We found that normal aging is not only characterized by decreased RSFC within the DMN but also by ubiquitous increases in internetwork positive correlations and focal internetwork losses of anticorrelations (involving mainly connections between the DMN and the attentional networks). Our results reinforce the notion that the aging brain undergoes a dedifferentiation processes with loss of functional diversity. These findings advance the characterization of healthy aging effects on RSFC and highlight the importance of adopting a broad, system-wide perspective to analyze brain connectivity.

  16. Experiments in evaluation capacity building: Enhancing brain disorders research impact in Ontario.

    Science.gov (United States)

    Nylen, Kirk; Sridharan, Sanjeev

    2017-05-08

    This paper is the introductory paper on a forum on evaluation capacity building for enhancing impacts of research on brain disorders. It describes challenges and opportunities of building evaluation capacity among community-based organizations in Ontario involved in enhancing brain health and supporting people living with a brain disorder. Using an example of a capacity building program called the "Evaluation Support Program", which is run by the Ontario Brain Institute, this forum discusses multiple themes including evaluation capacity building, evaluation culture and evaluation methodologies appropriate for evaluating complex community interventions. The goal of the Evaluation Support Program is to help community-based organizations build the capacity to demonstrate the value that they offer in order to improve, sustain, and spread their programs and activities. One of the features of this forum is that perspectives on the Evaluation Support Program are provided by multiple stakeholders, including the community-based organizations, evaluation team members involved in capacity building, thought leaders in the fields of evaluation capacity building and evaluation culture, and the funders. Copyright © 2017. Published by Elsevier Ltd.

  17. Blockade of N-acetylaspartylglutamate peptidases: a novel protective strategy for brain injuries and neurological disorders.

    Science.gov (United States)

    Zhong, Chunlong; Luo, Qizhong; Jiang, Jiyao

    2014-12-01

    The peptide neurotransmitter N-acetylaspartylglutamate (NAAG) is reported to suppress glutamate release mainly through selective activation of presynaptic Group II metabotropic glutamate receptor subtype 3 (mGluR3). Therefore, strategies of inhibition of NAAG peptidases and subsequent NAAG hydrolysis to elevate levels of NAAG could reduce glutamate release under pathological conditions and be neuroprotective by attenuating excitotoxic cell injury. A series of potent inhibitors of NAAG peptidases has been synthesized and demonstrated efficacy in experimental models of ischemic-hypoxic brain injury, traumatic brain injury, inflammatory pain, diabetic neuropathy, amyotrophic lateral sclerosis and phencyclidine-induced schizophrenia-like behaviors. The excessive glutamatergic transmission has been implicated in all of these neurological disorders. Thus, blockade of NAAG peptidases may augment an endogenous protective mechanism and afford neuroprotection in the brain. This review aims to summarize and provide insight into the current understanding of the novel neuroprotective strategy based on limiting glutamate excitotoxicity for a wide variety of brain injuries and neurological disorders.

  18. Brain Basics

    Medline Plus

    Full Text Available ... some point. Such disorders include depression , anxiety disorders , bipolar disorder , attention deficit hyperactivity disorder (ADHD) , and many ... differences in brain development in children who develop bipolar disorder than children who do not. Studies comparing ...

  19. MR imaging of the effects of methylphenidate on brain structure and function in Attention-Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    Schweren, Lizanne J. S.; de Zeeuw, Patrick; Durston, Sarah

    2013-01-01

    Methylphenidate is the first-choice pharmacological intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The pharmacological and behavioral effects of methylphenidate are well described, but less is known about neurochemical brain changes induced by methylphenidate. Thi

  20. MR imaging of the effects of methylphenidate on brain structure and function in Attention-Deficit/Hyperactivity Disorder

    NARCIS (Netherlands)

    Schweren, Lizanne J. S.; de Zeeuw, Patrick; Durston, Sarah

    2013-01-01

    Methylphenidate is the first-choice pharmacological intervention for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). The pharmacological and behavioral effects of methylphenidate are well described, but less is known about neurochemical brain changes induced by methylphenidate.

  1. Patient Characterization Protocols for Psychophysiological Studies of Traumatic Brain Injury and Post-TBI Psychiatric Disorders.

    Science.gov (United States)

    Rapp, Paul E; Rosenberg, Brenna M; Keyser, David O; Nathan, Dominic; Toruno, Kevin M; Cellucci, Christopher J; Albano, Alfonso M; Wylie, Scott A; Gibson, Douglas; Gilpin, Adele M K; Bashore, Theodore R

    2013-01-01

    Psychophysiological investigations of traumatic brain injury (TBI) are being conducted for several reasons, including the objective of learning more about the underlying physiological mechanisms of the pathological processes that can be initiated by a head injury. Additional goals include the development of objective physiologically based measures that can be used to monitor the response to treatment and to identify minimally symptomatic individuals who are at risk of delayed-onset neuropsychiatric disorders following injury. Research programs studying TBI search for relationships between psychophysiological measures, particularly ERP (event-related potential) component properties (e.g., timing, amplitude, scalp distribution), and a participant's clinical condition. Moreover, the complex relationships between brain injury and psychiatric disorders are receiving increased research attention, and ERP technologies are making contributions to this effort. This review has two objectives supporting such research efforts. The first is to review evidence indicating that TBI is a significant risk factor for post-injury neuropsychiatric disorders. The second objective is to introduce ERP researchers who are not familiar with neuropsychiatric assessment to the instruments that are available for characterizing TBI, post-concussion syndrome, and psychiatric disorders. Specific recommendations within this very large literature are made. We have proceeded on the assumption that, as is typically the case in an ERP laboratory, the investigators are not clinically qualified and that they will not have access to participant medical records.

  2. Brain connectivity and psychiatric comorbidity in adolescents with Internet gaming disorder.

    Science.gov (United States)

    Han, Doug Hyun; Kim, Sun Mi; Bae, Sujin; Renshaw, Perry F; Anderson, Jeffrey S

    2017-05-01

    Prolonged Internet video game play may have multiple and complex effects on human cognition and brain development in both negative and positive ways. There is not currently a consensus on the principle effects of video game play neither on brain development nor on the relationship to psychiatric comorbidity. In this study, 78 adolescents with Internet gaming disorder (IGD) and 73 comparison subjects without IGD, including subgroups with no other psychiatric comorbid disease, with major depressive disorder and with attention deficit hyperactivity disorder (ADHD), were included in a 3 T resting state functional magnetic resonance imaging analysis. The severity of Internet gaming disorder, depression, anxiety and ADHD symptoms were assessed with the Young Internet Addiction Scale, the Beck Depression Inventory, the Beck Anxiety Inventory and the Korean ADHD rating scales, respectively. Patients with IGD showed an increased functional correlation between seven pairs of regions, all satisfying q game play and suggest a risk or predisposition in game players for over-connectivity of the default mode and executive control networks that may relate to psychiatric comorbidity.

  3. Learning, memory and brain plasticity in posttraumatic stress disorder: context matters.

    Science.gov (United States)

    Flor, Herta; Nees, Frauke

    2014-01-01

    We review evidence from our laboratory that suggests that in addition to enhanced cue conditioning and delayed cue extinction disturbed contextual learning may play an important role in the development and maintenance of posttraumatic stress disorder. Based on data from a longitudinal sample of rescue workers at high risk for posttraumatic stress disorder and data on single trauma exposed persons with and without posttraumatic stress disorder we show the crucial role of the hippocampus for contextual memory and impaired contextual learning along with enhanced cue conditioning and delayed extinction in PTSD. Using structural and functional magnetic resonance imaging we confirmed animal data on the role of the hippocampus in contextual and the importance of the amygdala in cue conditioning and the role of the frontal cortex in extinction. Genetic variants related to the modulation of the hypothalamus-pituitary-adrenal axis are associated with cue and genetic variants related to calcium signaling and memory processes and the regulation of the stress response are associated with context conditioning. These genes also play a role in PTSD. Further research needs to identify the predictive nature of these learning processes and plastic brain changes and their interaction with genetic characteristics changes for the transition into PTSD and its maintenance. A further focus needs to be on the identification of learning and memory mechanisms and the associated brain plasticity across disorders.

  4. Functional genomics of human brain development and implications for autism spectrum disorders.

    Science.gov (United States)

    Ziats, M N; Grosvenor, L P; Rennert, O M

    2015-10-27

    Transcription of the inherited DNA sequence into copies of messenger RNA is the most fundamental process by which the genome functions to guide development. Encoded sequence information, inherited epigenetic marks and environmental influences all converge at the level of mRNA gene expression to allow for cell-type-specific, tissue-specific, spatial and temporal patterns of expression. Thus, the transcriptome represents a complex interplay between inherited genomic structure, dynamic experiential demands and external signals. This property makes transcriptome studies uniquely positioned to provide insight into complex genetic-epigenetic-environmental processes such as human brain development, and disorders with non-Mendelian genetic etiologies such as autism spectrum disorders. In this review, we describe recent studies exploring the unique functional genomics profile of the human brain during neurodevelopment. We then highlight two emerging areas of research with great potential to increase our understanding of functional neurogenomics-non-coding RNA expression and gene interaction networks. Finally, we review previous functional genomics studies of autism spectrum disorder in this context, and discuss how investigations at the level of functional genomics are beginning to identify convergent molecular mechanisms underlying this genetically heterogeneous disorder.

  5. Zinc in Gut-Brain Interaction in Autism and Neurological Disorders

    Science.gov (United States)

    Vela, Guillermo; Stark, Peter; Socha, Michael; Sauer, Ann Katrin; Hagmeyer, Simone; Grabrucker, Andreas M.

    2015-01-01

    A growing amount of research indicates that abnormalities in the gastrointestinal (GI) system during development might be a common factor in multiple neurological disorders and might be responsible for some of the shared comorbidities seen among these diseases. For example, many patients with Autism Spectrum Disorder (ASD) have symptoms associated with GI disorders. Maternal zinc status may be an important factor given the multifaceted effect of zinc on gut development and morphology in the offspring. Zinc status influences and is influenced by multiple factors and an interdependence of prenatal and early life stress, immune system abnormalities, impaired GI functions, and zinc deficiency can be hypothesized. In line with this, systemic inflammatory events and prenatal stress have been reported to increase the risk for ASD. Thus, here, we will review the current literature on the role of zinc in gut formation, a possible link between gut and brain development in ASD and other neurological disorders with shared comorbidities, and tie in possible effects on the immune system. Based on these data, we present a novel model outlining how alterations in the maternal zinc status might pathologically impact the offspring leading to impairments in brain functions later in life. PMID:25878905

  6. Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

    Science.gov (United States)

    Wichmann, Thomas; DeLong, Mahlon R

    2016-04-01

    Deep brain stimulation (DBS) is highly effective for both hypo- and hyperkinetic movement disorders of basal ganglia origin. The clinical use of DBS is, in part, empiric, based on the experience with prior surgical ablative therapies for these disorders, and, in part, driven by scientific discoveries made decades ago. In this review, we consider anatomical and functional concepts of the basal ganglia relevant to our understanding of DBS mechanisms, as well as our current understanding of the pathophysiology of two of the most commonly DBS-treated conditions, Parkinson's disease and dystonia. Finally, we discuss the proposed mechanism(s) of action of DBS in restoring function in patients with movement disorders. The signs and symptoms of the various disorders appear to result from signature disordered activity in the basal ganglia output, which disrupts the activity in thalamocortical and brainstem networks. The available evidence suggests that the effects of DBS are strongly dependent on targeting sensorimotor portions of specific nodes of the basal ganglia-thalamocortical motor circuit, that is, the subthalamic nucleus and the internal segment of the globus pallidus. There is little evidence to suggest that DBS in patients with movement disorders restores normal basal ganglia functions (e.g., their role in movement or reinforcement learning). Instead, it appears that high-frequency DBS replaces the abnormal basal ganglia output with a more tolerable pattern, which helps to restore the functionality of downstream networks.

  7. The anteromedial GPi as a new target for deep brain stimulation in obsessive compulsive disorder.

    Science.gov (United States)

    Nair, Girish; Evans, Andrew; Bear, Renee E; Velakoulis, Dennis; Bittar, Richard G

    2014-05-01

    Deep brain stimulation (DBS) is now well established in the treatment of intractable movement disorders. Over the past decade the clinical applications have expanded into the realm of psychosurgery, including depression and obsessive compulsive disorder (OCD). The optimal targets for electrode placement in psychosurgery remain unclear, with numerous anatomical targets reported for the treatment of OCD. We present four patients with Tourette's syndrome and prominent features of OCD who underwent DBS of the anteromedial globus pallidus internus (GPi) to treat their movement disorder. Their pre-operative and post-operative OCD symptoms were compared, and responded dramatically to surgery. On the basis of these results, we propose the anteromedial (limbic) GPi as a potential surgical target for the treatment of OCD, and furnish data supporting its further investigation as a DBS target for the treatment of psychiatric conditions. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. From One Extreme to the Other: Negative Evaluation Anxiety and Disordered Eating as Candidates for the Extreme Female Brain

    Directory of Open Access Journals (Sweden)

    Jennifer A. Bremser

    2012-07-01

    Full Text Available Simon Baron-Cohen pioneered the idea that different brain types evolved to process information in gender specific ways. Here we expand this approach to looking at eating disorders as a byproduct of the extreme female brain. The incidence of eating disorders is higher among females, and recent findings show that hormones may play a role in eating disorders. We present new evidence from four studies that both an empathizing bias and hyper-mentalizing (as measures of the extreme female brain; EFB are related to disordered eating and negative evaluation anxiety in women. We also advance the novel hypothesis that concerns about animal welfare (a unique expression of the EFB may account for the relationship between vegetarianism and eating disorders.

  9. Brain parenchymal damage in neuromyelitis optica spectrum disorder - A multimodal MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Pache, F.; Paul, F. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Zimmermann, H.; Lacheta, A.; Papazoglou, S.; Kuchling, J.; Wuerfel, J.; Brandt, A.U. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Finke, C. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Humboldt-Universitaet zu Berlin, Berlin School of Mind and Brain, Berlin (Germany); Hamm, B. [Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Ruprecht, K. [Charite Universitaetsmedizin Berlin, Department of Neurology, Berlin (Germany); Scheel, M. [Max Delbrueck Center for Molecular Medicine and Charite Universitaetsmedizin Berlin, NeuroCure Clinical Research Center and Experimental and Clinical Research Center, Berlin (Germany); Charite Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany)

    2016-12-15

    To investigate different brain regions for grey (GM) and white matter (WM) damage in a well-defined cohort of neuromyelitis optica spectrum disorder (NMOSD) patients and compare advanced MRI techniques (VBM, Subcortical and cortical analyses (Freesurfer), and DTI) for their ability to detect damage in NMOSD. We analyzed 21 NMOSD patients and 21 age and gender matched control subjects. VBM (GW/WM) and DTI whole brain (TBSS) analyses were performed at different statistical thresholds to reflect different statistical approaches in previous studies. In an automated atlas-based approach, Freesurfer and DTI results were compared between NMOSD and controls. DTI TBSS and DTI atlas based analysis demonstrated microstructural impairment only within the optic radiation or in regions associated with the optic radiation (posterior thalamic radiation p < 0.001, 6.9 % reduction of fractional anisotropy). VBM demonstrated widespread brain GM and WM reduction, but only at exploratory statistical thresholds, with no differences remaining after correction for multiple comparisons. Freesurfer analysis demonstrated no group differences. NMOSD specific parenchymal brain damage is predominantly located in the optic radiation, likely due to a secondary degeneration caused by ON. In comparison, DTI appears to be the most reliable and sensitive technique for brain damage detection in NMOSD. (orig.)

  10. Atypical developmental trajectory of local spontaneous brain activity in autism spectrum disorder

    Science.gov (United States)

    Guo, Xiaonan; Chen, Heng; Long, Zhiliang; Duan, Xujun; Zhang, Youxue; Chen, Huafu

    2017-01-01

    Autism spectrum disorder (ASD) is marked by atypical trajectory of brain maturation, yet the developmental abnormalities in brain function remain unclear. The current study examined the effect of age on amplitude of low-frequency fluctuations (ALFF) in ASD and typical controls (TC) using a cross-sectional design. We classified all the participants into three age cohorts: child (<11 years, 18ASD/20TC), adolescent (11–18 years, 28ASD/26TC) and adult (≥18 years, 18ASD/18TC). Two-way analysis of variance (ANOVA) was performed to ascertain main effects and interaction effects on whole brain ALFF maps. Results exhibited significant main effect of diagnosis in ASD with decreased ALFF in the right precuneus and left middle occipital gyrus during all developmental stages. Significant diagnosis-by-age interaction was observed in the medial prefrontal cortex (mPFC) with ALFF lowered in autistic children but highered in autistic adolescents and adults. Specifically, remarkable quadratic change of ALFF with increasing age in mPFC presented in TC group was absent in ASD. Additionally, abnormal ALFF values in diagnosis-related brain regions predicted the social deficits in ASD. Our findings indicated aberrant developmental patterns of spontaneous brain activity associated with social deficits in ASD and highlight the crucial role of the default mode network in the development of disease. PMID:28057930

  11. Machine learning classifier using abnormal brain network topological metrics in major depressive disorder.

    Science.gov (United States)

    Guo, Hao; Cao, Xiaohua; Liu, Zhifen; Li, Haifang; Chen, Junjie; Zhang, Kerang

    2012-12-05

    Resting state functional brain networks have been widely studied in brain disease research. However, it is currently unclear whether abnormal resting state functional brain network metrics can be used with machine learning for the classification of brain diseases. Resting state functional brain networks were constructed for 28 healthy controls and 38 major depressive disorder patients by thresholding partial correlation matrices of 90 regions. Three nodal metrics were calculated using graph theory-based approaches. Nonparametric permutation tests were then used for group comparisons of topological metrics, which were used as classified features in six different algorithms. We used statistical significance as the threshold for selecting features and measured the accuracies of six classifiers with different number of features. A sensitivity analysis method was used to evaluate the importance of different features. The result indicated that some of the regions exhibited significantly abnormal nodal centralities, including the limbic system, basal ganglia, medial temporal, and prefrontal regions. Support vector machine with radial basis kernel function algorithm and neural network algorithm exhibited the highest average accuracy (79.27 and 78.22%, respectively) with 28 features (Pnetwork topological metrics and statistically significant nodal metrics can be successfully used for feature selection in classification algorithms.

  12. Corpus Callosum Area and Brain Volume in Autism Spectrum Disorder: Quantitative Analysis of Structural MRI from the ABIDE Database

    Science.gov (United States)

    Kucharsky Hiess, R.; Alter, R.; Sojoudi, S.; Ardekani, B. A.; Kuzniecky, R.; Pardoe, H. R.

    2015-01-01

    Reduced corpus callosum area and increased brain volume are two commonly reported findings in autism spectrum disorder (ASD). We investigated these two correlates in ASD and healthy controls using T1-weighted MRI scans from the Autism Brain Imaging Data Exchange (ABIDE). Automated methods were used to segment the corpus callosum and intracranial…

  13. Influence of genes and environment on brain volumes in twin pairs concordant and discordant for bipolar disorder

    NARCIS (Netherlands)

    Schot, van der A.C.; Vonk, R.; Brans, R.G.H.; Haren, van N.E.M.; Koolschijn, P.C.; Nuboer, V.; Schnack, H.G.; Baal, van G.C.M.; Boomsma, D.I.; Nolen, W.A.; Hulshoff Pol, H.E.; Kahn, R.S.

    2009-01-01

    CONTEXT: Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. OBJECTIVE: To investigate the contribution of genetic and environmenta

  14. Influence of Genes and Environment on Brain Volumes in Twin Pairs Concordant and Discordant for Bipolar Disorder

    NARCIS (Netherlands)

    van der Schot, Astrid C.; Vonk, Ronald; Brans, Rachel G. H.; van Haren, Neeltje E. M.; Koolschijn, P. Cedric M. P.; Nuboer, Valerie; Schnack, Hugo G.; van Baal, G. Caroline M.; Boomsma, Dorret I.; Nolen, Willem A.; Pol, Hilleke E. Hulshoff; Kahn, Rene S.

    2009-01-01

    Context: Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. Objective: To investigate the contribution of genetic and environmenta

  15. Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

    2012-01-01

    Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

  16. Smoking and the Developing Brain : Altered White Matter Microstructure in Attention-Deficit/Hyperactivity Disorder and Healthy Controls

    NARCIS (Netherlands)

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

    2015-01-01

    Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated

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

    NARCIS (Netherlands)

    Ewijk, H. van; Groenman, A.P.; Zwiers, M.P.; Heslenfeld, D.J.; Faraone, S.V; Hartman, C.A.; Luman, M.; Greven, C.U.; Hoekstra, P.J.; Franke, B.; Buitelaar, J.; Oosterlaan, J.

    2015-01-01

    Brain white matter (WM) tracts, playing a vital role in the communication between brain regions, undergo important maturational changes during adolescence and young adulthood, a critical period for the development of nicotine dependence. Attention-deficit/hyperactivity disorder (ADHD) is associated

  18. Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder

    Science.gov (United States)

    Corrigan, Neva M.; Shaw, Dennis. W. W.; Richards, Todd L.; Estes, Annette M.; Friedman, Seth D.; Petropoulos, Helen; Artru, Alan A.; Dager, Stephen R.

    2012-01-01

    Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ([superscript 1]HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally…

  19. 78 FR 42795 - Submission for OMB review; 30-Day Comment Request: Evaluation of the Brain Disorders in the...

    Science.gov (United States)

    2013-07-17

    ...: Evaluation of the Brain Disorders in the Developing World Program of the John E. Fogarty International Center... Health, may not conduct or sponsor, and the respondent is not required to respond to, an information... plans and instruments must be requested in writing. Proposed Collection: Evaluation of the Brain...

  20. Brain activation during self- and other-reflection in bipolar disorder with a history of psychosis : Comparison to schizophrenia

    NARCIS (Netherlands)

    Zhang, Liwen; Opmeer, Esther M.; Ruhe, Henricus G.; Aleman, Andre; van der Meer, Lisette

    2015-01-01

    Objectives: Reflecting on the self and on others activates specific brain areas and contributes to metacognition and social cognition. The aim of the current study is to investigate brain activation during self-and other-reflection in patients with bipolar disorder (BD). In addition, we examined whe

  1. Influence of genes and environment on brain volumes in twin pairs concordant and discordant for bipolar disorder

    NARCIS (Netherlands)

    Schot, van der A.C.; Vonk, R.; Brans, R.G.H.; Haren, van N.E.M.; Koolschijn, P.C.; Nuboer, V.; Schnack, H.G.; Baal, van G.C.M.; Boomsma, D.I.; Nolen, W.A.; Hulshoff Pol, H.E.; Kahn, R.S.

    2009-01-01

    CONTEXT: Structural neuroimaging studies suggest the presence of subtle abnormalities in the brains of patients with bipolar disorder. The influence of genetic and/or environmental factors on these brain abnormalities is unknown. OBJECTIVE: To investigate the contribution of genetic and

  2. Longitudinal Volumetric Brain Changes in Autism Spectrum Disorder Ages 6–35 Years

    Science.gov (United States)

    Lange, Nicholas; Travers, Brittany G.; Bigler, Erin D.; Prigge, Molly B.D.; Froehlich, Alyson L.; Nielsen, Jared A.; Cariello, Annahir N.; Zielinski, Brandon A.; Anderson, Jeffrey S.; Fletcher, P. Thomas; Alexander, Andrew A.; Lainhart, Janet E.

    2014-01-01

    LAY ABSTRACT Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality MRI scans) compared to 56 typically developing male controls (TDCs) (117 high-quality scans) from childhood into adulthood, for a total of 156 participants scanned over an eight-year period. We provide volumetric growth curves for the entire brain, total gray matter (GM), frontal GM, temporal GM, parietal GM, occipital GM, total cortical white matter (WM), corpus callosum, caudate, thalamus, total cerebellum, and total ventricles. Mean volume of cortical WM was reduced significantly. Decreases in regional mean volumes in the ASD sample were most often due to decreases during late adolescence and adulthood. The growth curve of whole-brain volume showed increased volumes in young children with autism and subsequently decreased during adolescence to meet the TDC curve between 10 and 15 years of age. The volume of many structures continued to decline atypically into adulthood in the ASD sample. The data suggest that ASD is a dynamic disorder with complex changes in whole and regional brain volumes that change over time from childhood into adulthood. SCIENTIFIC ABSTRACT Since the impairments associated with autism spectrum disorder (ASD) tend to persist or worsen from childhood into adulthood, it is of critical importance to examine how the brain develops over this growth epoch. We report initial findings on whole and regional longitudinal brain development in 100 male participants with ASD (226 high-quality MRI scans; mean inter-scan interval 2.7 years) compared to 56 typically developing male controls (TDCs) (117 high-quality scans; mean inter-scan interval 2.6 years) from childhood into adulthood, for a total of 156

  3. Brain substrates of social decision-making in dual diagnosis: cocaine dependence and personality disorders.

    Science.gov (United States)

    Verdejo-Garcia, Antonio; Verdejo-Román, Juan; Albein-Urios, Natalia; Martínez-González, José M; Soriano-Mas, Carles

    2017-03-01

    Cocaine dependence frequently co-occurs with personality disorders, leading to increased interpersonal problems and greater burden of disease. Personality disorders are characterised by patterns of thinking and feeling that divert from social expectations. However, the comorbidity between cocaine dependence and personality disorders has not been substantiated by measures of brain activation during social decision-making. We applied functional magnetic resonance imaging to compare brain activations evoked by a social decision-making task-the Ultimatum Game-in 24 cocaine dependents with personality disorders (CDPD), 19 cocaine dependents without comorbidities and 19 healthy controls. In the Ultimatum Game participants had to accept or reject bids made by another player to split monetary stakes. Offers varied in fairness (in fair offers the proposer shares ~50 percent of the money; in unfair offers the proposer shares <30 percent of the money), and participants were told that if they accept both players get the money, and if they reject both players lose it. We contrasted brain activations during unfair versus fair offers and accept versus reject choices. During evaluation of unfair offers CDPD displayed lower activation in the insula and the anterior cingulate cortex and higher activation in the lateral orbitofrontal cortex and superior frontal and temporal gyri. Frontal activations negatively correlated with emotion recognition. During rejection of offers CDPD displayed lower activation in the anterior cingulate cortex, striatum and midbrain. Dual diagnosis is linked to hypo-activation of the insula and anterior cingulate cortex and hyper-activation of frontal-temporal regions during social decision-making, which associates with poorer emotion recognition.

  4. AN IMPROVED TECHNIQUE FOR IDENTIFICATION AND CLASSIFICATION OF BRAIN DISORDER FROM MRI BRAIN IMAGE

    Directory of Open Access Journals (Sweden)

    Finitha Joseph

    2015-11-01

    Full Text Available Medical image processing is developing recently due to its wide applications. An efficient MRI image segmentation is needed at present. In this paper, MRI brain segmentation is done by Semi supervised learning which does not require pathology modelling and, thus, allows high degree of automation. In abnormality detection, a vector is characterized as anomalous if it does not comply with the probability distribution obtained from normal data. The estimation of the probability density function, however, is usually not feasible due to large data dimensionality. In order to overcome this challenge, we treat every image as a network of locally coherent image partitions (overlapping blocks. We formulate and maximize a strictly concave likelihood function estimating abnormality for each partition and fuse the local estimates into a globally optimal estimate that satisfies the consistency constraints, based on a distributed estimation algorithm. After this features are extracted by Gray-Level Co-occurrence Matrices (GLCM algorithm and those features are given to Particle Spam Optimization (PSO and finally classification is done by using Library Support Vector Machine (LIBSVM.Thus results are evaluated and proved its efficiency using accuracy.

  5. Neurorehabilitation and cognitive-behaviour therapy of anxiety disorders after brain injury: An overview and a case illustration of obsessive-compulsive disorder.

    Science.gov (United States)

    Williams, W H; Evans, J J; Fleminger, S

    2003-01-01

    Survivors of acquired and traumatic brain injuries may often experience anxiety states. Psychological reactions to neurological trauma may be caused by a complex interaction of a host of factors. We explore how anxiety states may be understood in terms of a biopsychosocial formulation of such factors. We also review the current evidence for the presence of specific anxiety disorders after brain injury. We then describe how cognitive-behaviour therapy (CBT), a treatment of choice for many anxiety disorders, may be integrated with cognitive rehabilitation (CR), for the management of anxiety disorders in brain injury. We illustrate how CBT and CR may be delivered with a case of a survivor of traumatic brain injury (TBI) who had developed obsessive compulsive disorder and health anxiety. We show how CBT plus CR allows a biopsychosocial formulation to be developed of the survivor's concerns for guiding a goal-based intervention. The survivor made significant gains from intervention in terms of goals achieved and changes on clinical measures. We argue that large-scale research is needed for developing an evidence base for managing emotional disorders in brain injury.

  6. Inverse changes in L1 retrotransposons between blood and brain in major depressive disorder.

    Science.gov (United States)

    Liu, Shu; Du, Tingfu; Liu, Zeyue; Shen, Yan; Xiu, Jianbo; Xu, Qi

    2016-11-22

    Long interspersed nuclear element-1 (LINE-1 or L1) is a type of retrotransposons comprising 17% of the human and mouse genome, and has been found to be associated with several types of neurological disorders. Previous post-mortem brain studies reveal increased L1 copy number in the prefrontal cortex from schizophrenia patients. However, whether L1 retrotransposition occurs similarly in major depressive disorder (MDD) is unknown. Here, L1 copy number was measured by quantitative PCR analysis in peripheral blood of MDD patients (n = 105) and healthy controls (n = 105). The results showed that L1 copy number was increased in MDD patients possibly due to its hypomethylation. Furthermore, L1 copy number in peripheral blood and five brain regions (prefrontal cortex, hippocampus, amygdala, nucleus accumbens and paraventricular hypothalamic nucleus) was measured in the chronic unpredictable mild stress (CUMS) model of depression in mice. Intriguingly, increased L1 copy number in blood and the decreased L1 copy number in the prefrontal cortex were observed in stressed mice, while no change was found in other brain regions. Our results suggest that the changes of L1 may be associated with the pathophysiology of MDD, but the biological mechanism behind dysfunction of L1 retrotransposition in MDD remains to be further investigated.

  7. Closed-loop brain-machine-body interfaces for noninvasive rehabilitation of movement disorders.

    Science.gov (United States)

    Broccard, Frédéric D; Mullen, Tim; Chi, Yu Mike; Peterson, David; Iversen, John R; Arnold, Mike; Kreutz-Delgado, Kenneth; Jung, Tzyy-Ping; Makeig, Scott; Poizner, Howard; Sejnowski, Terrence; Cauwenberghs, Gert

    2014-08-01

    Traditional approaches for neurological rehabilitation of patients affected with movement disorders, such as Parkinson's disease (PD), dystonia, and essential tremor (ET) consist mainly of oral medication, physical therapy, and botulinum toxin injections. Recently, the more invasive method of deep brain stimulation (DBS) showed significant improvement of the physical symptoms associated with these disorders. In the past several years, the adoption of feedback control theory helped DBS protocols to take into account the progressive and dynamic nature of these neurological movement disorders that had largely been ignored so far. As a result, a more efficient and effective management of PD cardinal symptoms has emerged. In this paper, we review closed-loop systems for rehabilitation of movement disorders, focusing on PD, for which several invasive and noninvasive methods have been developed during the last decade, reducing the complications and side effects associated with traditional rehabilitation approaches and paving the way for tailored individual therapeutics. We then present a novel, transformative, noninvasive closed-loop framework based on force neurofeedback and discuss several future developments of closed-loop systems that might bring us closer to individualized solutions for neurological rehabilitation of movement disorders.

  8. Serum concentrations of brain-derived neurotrophic factor and mental disorders in imprisoned women

    Directory of Open Access Journals (Sweden)

    Renata M. Dotta-Panichi

    2015-06-01

    Full Text Available Objective:Mental disorders and early trauma are highly prevalent in female inmates. Brain-derived neurotrophic factor (BDNF plays an important role in learning, memory processes, and mood regulation. The aim of this study was to evaluate the relationship between serum BDNF levels and mental disorders among imprisoned women as compared with age- and education-matched controls.Methods:A consecutively recruited sample of 18 female prisoners with mental disorders was assessed for sociodemographic, criminal, and clinical variables using standardized instruments, the Mini International Neuropsychiatric Interview Plus (MINI Plus, and serum BDNF levels.Results:High rates of childhood sexual abuse and posttraumatic stress disorder (PTSD were found in the group of forensic patients. Serum BDNF levels in the forensic group did not differ from those of healthy controls, and were significantly higher when compared with those of women with mental disorders hospitalized in a general hospital.Conclusion:Elevated serum BDNF levels were found in imprisoned women. The results of this study may suggest neurobiological mechanisms similar to those seen in previous clinical and preclinical studies showing the involvement of BDNF in the pathophysiology of PTSD.

  9. Differences between effects of psychological versus pharmacological treatments on functional and morphological brain alterations in anxiety disorders and major depressive disorder: a systematic review.

    Science.gov (United States)

    Quidé, Yann; Witteveen, Anke B; El-Hage, Wissam; Veltman, Dick J; Olff, Miranda

    2012-01-01

    The most prevalent mental disorders, anxiety and mood disorders, are associated with both functional and morphological brain changes that commonly involve the 'fear network' including the (medial) prefrontal cortex, hippocampus and amygdala. Patients suffering from anxiety disorders and major depressive disorder often show excessive amygdala and reduced prefrontal cortex functioning. It is, however, still unclear whether these brain abnormalities disappear or diminish following effective treatment. This review aims to compare the effects of psychotherapy and pharmacotherapy on functional and morphological brain measures in these disorders. Sixty-three studies were included, 30 investigating psychotherapy effects and 33 investigating pharmacotherapy effects. Despite methodological differences, results suggest a functional normalization of the 'fear network'. Pharmacotherapy particularly decreases over-activity of limbic structures (bottom-up effect) while psychotherapy tends to increase activity and recruitment of frontal areas (top-down effect), especially the anterior cingulate cortex. Additionally, pharmacotherapy, but not psychotherapy, has been associated with morphological changes, depending on the disorder. These findings suggest that both types of treatments normalize (functional) brain abnormalities each in specific ways.

  10. Cognitive profile and disorders affecting higher brain functions in paediatric patients with neurofibromatosis type 1.

    Science.gov (United States)

    Vaucheret Paz, E; López Ballent, A; Puga, C; García Basalo, M J; Baliarda, F; Ekonen, C; Ilari, R; Agosta, G

    2017-04-18

    Neurofibromatosis type 1 (NF1) is a common neurocutaneous syndrome often associated with specific cognitive deficits that are rarely monitored during follow-up of these patients. The purpose of our study is two-fold. First, we aimed to describe the cognitive profile of patients with NF1 and detect disorders in higher brain functions associated with the disease. Second, we identified the reasons for consultation associated with school performance in these patients. We conducted a descriptive cross-sectional study of 24 paediatric patients (ages 5 to 16) with NF1 who underwent neuropsychological assessment. The most frequent reasons for consultation were attention deficits (58.33%), learning disorders (25%), poor motor coordination (25%), and language impairment (0.8%). Although 96% of the patients displayed impairments in at least one of the assessed areas, only 83.34% of the parents had reported such impairments. Attention-deficit/hyperactivity disorder was present in 58.33% of the patients, whereas 33.33% had nonverbal learning disabilities, 20.83% had expressive language disorder, 8.33% had borderline intellectual functioning, 4.16% had mental retardation, and only 4.16% showed no cognitive impairment. Higher brain functions are frequently impaired in paediatric patients with NF1. Although many parents report such disorders, they can go undetected in some cases. Neuropsychological assessment is recommended for all paediatric patients with NF1 to detect cognitive impairment and provide early, effective rehabilitation treatment. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  11. Brain abnormalities in bipolar disorder detected by quantitative T1ρ mapping.

    Science.gov (United States)

    Johnson, C P; Follmer, R L; Oguz, I; Warren, L A; Christensen, G E; Fiedorowicz, J G; Magnotta, V A; Wemmie, J A

    2015-02-01

    Abnormal metabolism has been reported in bipolar disorder, however, these studies have been limited to specific regions of the brain. To investigate whole-brain changes potentially associated with these processes, we applied a magnetic resonance imaging technique novel to psychiatric research, quantitative mapping of T1 relaxation in the rotating frame (T1ρ). This method is sensitive to proton chemical exchange, which is affected by pH, metabolite concentrations and cellular density with high spatial resolution relative to alternative techniques such as magnetic resonance spectroscopy and positron emission tomography. Study participants included 15 patients with bipolar I disorder in the euthymic state and 25 normal controls balanced for age and gender. T1ρ maps were generated and compared between the bipolar and control groups using voxel-wise and regional analyses. T1ρ values were found to be elevated in the cerebral white matter and cerebellum in the bipolar group. However, volumes of these areas were normal as measured by high-resolution T1- and T2-weighted magnetic resonance imaging. Interestingly, the cerebellar T1ρ abnormalities were normalized in participants receiving lithium treatment. These findings are consistent with metabolic or microstructural abnormalities in bipolar disorder and draw attention to roles of the cerebral white matter and cerebellum. This study highlights the potential utility of high-resolution T1ρ mapping in psychiatric research.

  12. Review of transcranial photobiomodulation for major depressive disorder: targeting brain metabolism, inflammation, oxidative stress, and neurogenesis.

    Science.gov (United States)

    Cassano, Paolo; Petrie, Samuel R; Hamblin, Michael R; Henderson, Theodore A; Iosifescu, Dan V

    2016-07-01

    We examined the use of near-infrared and red radiation (photobiomodulation, PBM) for treating major depressive disorder (MDD). While still experimental, preliminary data on the use of PBM for brain disorders are promising. PBM is low-cost with potential for wide dissemination; further research on PBM is sorely needed. We found clinical and preclinical studies via PubMed search (2015), using the following keywords: "near-infrared radiation," "NIR," "low-level light therapy," "low-level laser therapy," or "LLLT" plus "depression." We chose clinically focused studies and excluded studies involving near-infrared spectroscopy. In addition, we used PubMed to find articles that examine the link between PBM and relevant biological processes including metabolism, inflammation, oxidative stress, and neurogenesis. Studies suggest the processes aforementioned are potentially effective targets for PBM to treat depression. There is also clinical preliminary evidence suggesting the efficacy of PBM in treating MDD, and comorbid anxiety disorders, suicidal ideation, and traumatic brain injury. Based on the data collected to date, PBM appears to be a promising treatment for depression that is safe and well-tolerated. However, large randomized controlled trials are still needed to establish the safety and effectiveness of this new treatment for MDD.

  13. Neurosurgical treatment of mood disorders: traditional psychosurgery and the advent of deep brain stimulation.

    Science.gov (United States)

    Sachdev, Perminder S; Chen, Xiaohua

    2009-01-01

    From its peak in the 1940s and 1950s, psychosurgery (or, neurosurgery for psychiatric disorders) has had a gradual decline, with only a few centers around the world continuing with the procedure into the 1980s and 1990s. With recent developments in brain stimulation techniques, the continuing relevance of psychosurgery in the treatment of psychiatric disorders is worthy of examination. A review of databases (PubMed, Medline, Current Contents and Embase) suggests that psychosurgery in the form of stereotactic focal ablation is still practiced in a few centers, although the number has decreased further from the 1990s. Procedures have not changed substantively, although modern imaging and stereotaxy have made them more precise. No good predictors of treatment response have been identified. There is a major shift in interest to deep brain stimulation (DBS) instead of ablative surgery. Studies of DBS in resistant depression and obsessive-compulsive disorder have been few and have involved small numbers, but this field is growing rapidly. Although ablative psychosurgery using stereotactic procedures continues to be used to a small extent, psychiatrists remain ambivalent about this procedure. The baton of psychosurgery, however, appears to have been passed on to DBS, but more data are needed on technical details and outcomes before the possible therapeutic role of DBS can be established.

  14. Deep brain stimulation for movement disorders: update on recent discoveries and outlook on future developments.

    Science.gov (United States)

    Mahlknecht, Philipp; Limousin, Patricia; Foltynie, Thomas

    2015-11-01

    Modern deep brain stimulation (DBS) has become a routine therapy for patients with movement disorders such as Parkinson's disease, generalized or segmental dystonia and for multiple forms of tremor. Growing numbers of publications also report beneficial effects in other movement disorders such as Tourette's syndrome, various forms of chorea and DBS is even being studied for Parkinson's-related dementia. While exerting remarkable effects on many motor symptoms, DBS does not restore normal neurophysiology and therefore may also have undesirable side effects including speech and gait deterioration. Furthermore, its efficacy might be compromised in the long term, due to progression of the underlying disease. Various programming strategies have been studied to try and address these issues, e.g., the use of low-frequency rather than high-frequency stimulation or the targeting of alternative brain structures such as the pedunculopontine nucleus. In addition, further technical developments will soon provide clinicians with an expanded choice of hardware such as segmented electrodes allowing for a steering of the current to optimize beneficial effects and reduce side effects as well as the possibility of adaptive stimulation systems based on closed-loop concepts with or without accompanying advances in programming and imaging software. In the present article, we will provide an update on the most recent achievements and discoveries relevant to the application of DBS in the treatment of movement disorder patients and give an outlook on future clinical and technical developments.

  15. Brain-derived neurotrophic factor as a drug target for CNS disorders.

    Science.gov (United States)

    Pezet, Sophie; Malcangio, Marzia

    2004-10-01

    Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family of trophic factors. BDNF is widely and abundantly expressed in the CNS and is available to some peripheral nervous system neurons that uptake the neurotrophin produced by peripheral tissues. BDNF promotes survival and differentiation of certain neuronal populations during development. In adulthood, BDNF can modulate neuronal synaptic strength and has been implicated in hippocampal mechanisms of learning and memory and spinal mechanisms for pain. Several CNS disorders are associated with a decrease in trophic support. As BDNF and its high affinity receptor are abundant throughout the whole CNS, and BDNF is a potent neuroprotective agent, this trophic factor is a good candidate for therapeutic treatment of some of CNS disorders. This review aims to correlate the features of some CNS disorders (Parkinson's disease, Alzheimer's disease, depression, epilepsy and chronic pain) to changes in BDNF expression in the brain. The cellular and molecular mechanism by which BDNF might be a therapeutic strategy are critically examined.

  16. Chondroitin Sulfate Proteoglycans: Structure-Function Relationship with Implication in Neural Development and Brain Disorders

    Directory of Open Access Journals (Sweden)

    Speranta Avram

    2014-01-01

    Full Text Available Chondroitin sulfate proteoglycans (CSPGs are extracellular matrix components that contain two structural parts with distinct functions: a protein core and glycosaminoglycan (GAG side chains. CSPGs are known to be involved in important cell processes like cell adhesion and growth, receptor binding, or cell migration. It is recognized that the presence of CSPGs is critical in neuronal growth mechanisms including axon guidance following injury of nervous system components such as spinal cord and brain. CSPGs are upregulated in the central nervous system after injury and participate in the inhibition of axon regeneration mainly through their GAG side chains. Recently, it was shown that some CSPGs members like aggrecan, versican, and neurocan were strongly involved in brain disorders like bipolar disorder (BD, schizophrenia, and ADHD. In this paper, we present the chemical structure-biological functions relationship of CSPGs, both in health state and in genetic disorders, addressing methods represented by genome-wide and crystallographic data as well as molecular modeling and quantitative structure-activity relationship.

  17. Beyond Neural Cubism: Promoting a Multidimensional View of Brain Disorders by Enhancing the Integration of Neurology and Psychiatry in Education

    OpenAIRE

    2015-01-01

    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 d...

  18. Benefits of agomelatine in behavioral, neurochemical and blood brain barrier alterations in prenatal valproic acid induced autism spectrum disorder.

    Science.gov (United States)

    Kumar, Hariom; Sharma, B M; Sharma, Bhupesh

    2015-12-01

    Valproic acid administration during gestational period causes behavior and biochemical deficits similar to those observed in humans with autism spectrum disorder. Although worldwide prevalence of autism spectrum disorder has been increased continuously, therapeutic agents to ameliorate the social impairment are very limited. The present study has been structured to investigate the therapeutic potential of melatonin receptor agonist, agomelatine in prenatal valproic acid (Pre-VPA) induced autism spectrum disorder in animals. Pre-VPA has produced reduction in social interaction (three chamber social behavior apparatus), spontaneous alteration (Y-Maze), exploratory activity (Hole board test), intestinal motility, serotonin levels (prefrontal cortex and ileum) and prefrontal cortex mitochondrial complex activity (complex I, II, IV). Furthermore, Pre-VPA has increased locomotor activity (actophotometer), anxiety, brain oxidative stress (thiobarbituric acid reactive species, glutathione, and catalase), nitrosative stress (nitrite/nitrate), inflammation (brain and ileum myeloperoxidase activity), calcium levels and blood brain barrier leakage in animals. Treatment with agomelatine has significantly attenuated Pre-VPA induced reduction in social interaction, spontaneous alteration, exploratory activity intestinal motility, serotonin levels and prefrontal cortex mitochondrial complex activity. Furthermore, agomelatine also attenuated Pre-VPA induced increase in locomotion, anxiety, brain oxidative stress, nitrosative stress, inflammation, calcium levels and blood brain barrier leakage. It is concluded that, Pre-VPA has induced autism spectrum disorder, which was attenuated by agomelatine. Agomelatine has shown ameliorative effect on behavioral, neurochemical and blood brain barrier alteration in Pre-VPA exposed animals. Thus melatonin receptor agonists may provide beneficial therapeutic strategy for managing autism spectrum disorder.

  19. Impaired social brain network for processing dynamic facial expressions in autism spectrum disorders

    Directory of Open Access Journals (Sweden)

    Sato Wataru

    2012-08-01

    Full Text Available Abstract Background Impairment of social interaction via facial expressions represents a core clinical feature of autism spectrum disorders (ASD. However, the neural correlates of this dysfunction remain unidentified. Because this dysfunction is manifested in real-life situations, we hypothesized that the observation of dynamic, compared with static, facial expressions would reveal abnormal brain functioning in individuals with ASD. We presented dynamic and static facial expressions of fear and happiness to individuals with high-functioning ASD and to age- and sex-matched typically developing controls and recorded their brain activities using functional magnetic resonance imaging (fMRI. Result Regional analysis revealed reduced activation of several brain regions in the ASD group compared with controls in response to dynamic versus static facial expressions, including the middle temporal gyrus (MTG, fusiform gyrus, amygdala, medial prefrontal cortex, and inferior frontal gyrus (IFG. Dynamic causal modeling analyses revealed that bi-directional effective connectivity involving the primary visual cortex–MTG–IFG circuit was enhanced in response to dynamic as compared with static facial expressions in the control group. Group comparisons revealed that all these modulatory effects were weaker in the ASD group than in the control group. Conclusions These results suggest that weak activity and connectivity of the social brain network underlie the impairment in social interaction involving dynamic facial expressions in individuals with ASD.

  20. Intelligent Technique for Signal Processing to Identify the Brain Disorder for Epilepsy Captures Using Fuzzy Systems

    Directory of Open Access Journals (Sweden)

    Gurumurthy Sasikumar

    2016-01-01

    Full Text Available The new direction of understand the signal that is created from the brain organization is one of the main chores in the brain signal processing. Amid all the neurological disorders the human brain epilepsy is measured as one of the extreme prevalent and then programmed artificial intelligence detection technique is an essential due to the crooked and unpredictable nature of happening of epileptic seizures. We proposed an Improved Fuzzy firefly algorithm, which would enhance the classification of the brain signal efficiently with minimum iteration. An important bunching technique created on fuzzy logic is the Fuzzy C means. Together in the feature domain with the spatial domain the features gained after multichannel EEG signals remained combined by means of fuzzy algorithms. And for better precision segmentation process the firefly algorithm is applied to optimize the Fuzzy C-means membership function. Simultaneously for the efficient clustering method the convergence criteria are set. On the whole the proposed technique yields more accurate results and that gives an edge over other techniques. This proposed algorithm result compared with other algorithms like fuzzy c means algorithm and PSO algorithm.

  1. Multifrequency magnetic resonance elastography of the brain reveals tissue degeneration in neuromyelitis optica spectrum disorder

    Energy Technology Data Exchange (ETDEWEB)

    Streitberger, Kaspar-Josche [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Fehlner, Andreas; Sack, Ingolf [Charite - Universitaetsmedizin Berlin, Department of Radiology, Berlin (Germany); Pache, Florence [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Lacheta, Anna; Papazoglou, Sebastian; Brandt, Alexander [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Bellmann-Strobl, Judith [Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Ruprecht, Klemens [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Braun, Juergen [Charite - Universitaetsmedizin Berlin, Institute of Medical Informatics, Berlin (Germany); Paul, Friedemann [Charite - Universitaetsmedizin Berlin, Department of Neurology with Experimental Neurology, Berlin (Germany); Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Wuerfel, Jens [Charite - Universitaetsmedizin Berlin, NeuroCure Clinical Research Center, Berlin (Germany); Max Delbrueck Center for Molecular Medicine and Charite - Universitaetsmedizin Berlin, Experimental and Clinical Research Center, Berlin (Germany); Medical Image Analysis Center (MIAC AG), Basel (Switzerland)

    2017-05-15

    Application of multifrequency magnetic resonance elastography (MMRE) of the brain parenchyma in patients with neuromyelitis optica spectrum disorder (NMOSD) compared to age matched healthy controls (HC). 15 NMOSD patients and 17 age- and gender-matched HC were examined using MMRE. Two three-dimensional viscoelastic parameter maps, the magnitude G* and phase angle φ of the complex shear modulus were reconstructed by simultaneous inversion of full wave-field data in 1.9-mm isotropic resolution at 7 harmonic drive frequencies from 30 to 60 Hz. In NMOSD patients, a significant reduction of G* was observed within the white matter fraction (p = 0.017), predominantly within the thalamic regions (p = 0.003), compared to HC. These parameters exceeded the reduction in brain volume measured in patients versus HC (p = 0.02 whole-brain volume reduction). Volumetric differences in white matter fraction and the thalami were not detectable between patients and HC. However, phase angle φ was decreased in patients within the white matter (p = 0.03) and both thalamic regions (p = 0.044). MMRE reveals global tissue degeneration with accelerated softening of the brain parenchyma in patients with NMOSD. The predominant reduction of stiffness is found within the thalamic region and related white matter tracts, presumably reflecting Wallerian degeneration. (orig.)

  2. Addressing reverse inference in psychiatric neuroimaging: Meta‐analyses of task‐related brain activation in common mental disorders

    Science.gov (United States)

    Sprooten, Emma; Rasgon, Alexander; Goodman, Morgan; Carlin, Ariella; Leibu, Evan; Lee, Won Hee

    2017-01-01

    Abstract Functional magnetic resonance imaging (fMRI) studies in psychiatry use various tasks to identify case‐control differences in the patterns of task‐related brain activation. Differently activated regions are often ascribed disorder‐specific functions in an attempt to link disease expression and brain function. We undertook a systematic meta‐analysis of data from task‐fMRI studies to examine the effect of diagnosis and study design on the spatial distribution and direction of case‐control differences on brain activation. We mapped to atlas regions coordinates of case‐control differences derived from 537 task‐fMRI studies in schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, and obsessive compulsive disorder comprising observations derived from 21,427 participants. The fMRI tasks were classified according to the Research Domain Criteria (RDoC). We investigated whether diagnosis, RDoC domain or construct and use of regions‐of‐interest or whole‐brain analyses influenced the neuroanatomical pattern of results. When considering all primary studies, we found an effect of diagnosis for the amygdala and caudate nucleus and an effect of RDoC domains and constructs for the amygdala, hippocampus, putamen and nucleus accumbens. In contrast, whole‐brain studies did not identify any significant effect of diagnosis or RDoC domain or construct. These results resonate with prior reports of common brain structural and genetic underpinnings across these disorders and caution against attributing undue specificity to brain functional changes when forming explanatory models of psychiatric disorders. Hum Brain Mapp 38:1846–1864, 2017. © 2017 Wiley Periodicals, Inc. PMID:28067006

  3. Classification of Autism Spectrum Disorder Using Supervised Learning of Brain Connectivity Measures Extracted from Synchrostates

    CERN Document Server

    Jamal, Wasifa; Oprescu, Ioana-Anastasia; Maharatna, Koushik; Apicella, Fabio; Sicca, Federico

    2014-01-01

    Objective. The paper investigates the presence of autism using the functional brain connectivity measures derived from electro-encephalogram (EEG) of children during face perception tasks. Approach. Phase synchronized patterns from 128-channel EEG signals are obtained for typical children and children with autism spectrum disorder (ASD). The phase synchronized states or synchrostates temporally switch amongst themselves as an underlying process for the completion of a particular cognitive task. We used 12 subjects in each group (ASD and typical) for analyzing their EEG while processing fearful, happy and neutral faces. The minimal and maximally occurring synchrostates for each subject are chosen for extraction of brain connectivity features, which are used for classification between these two groups of subjects. Among different supervised learning techniques, we here explored the discriminant analysis and support vector machine both with polynomial kernels for the classification task. Main results. The leave ...

  4. Brain-derived neurotrophic factor in mood disorders and antidepressant treatments.

    Science.gov (United States)

    Castrén, Eero; Kojima, Masami

    2017-01-01

    Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment. These data, together with a wealth of reports using different animal models with depression-like behavior or manipulation of expression of BDNF or its receptor TrkB have implicated BDNF in the pathophysiology of depression as well as in the mechanism of action of antidepressant treatments. Recent findings have shown that posttranslational processing of BDNF gene product can yield different molecular entities that differently influence signaling through BNDF receptor TrkB and the pan-neurotrophin receptor p75(NTR). We will here review these data and discuss new insights into the possible pathophysiological roles of those new BDNF subtypes as well as recent findings on the role of BDNF mediated neuronal plasticity in mood disorders and their treatments.

  5. Joint source based analysis of multiple brain structures in studying major depressive disorder

    Science.gov (United States)

    Ramezani, Mahdi; Rasoulian, Abtin; Hollenstein, Tom; Harkness, Kate; Johnsrude, Ingrid; Abolmaesumi, Purang

    2014-03-01

    We propose a joint Source-Based Analysis (jSBA) framework to identify brain structural variations in patients with Major Depressive Disorder (MDD). In this framework, features representing position, orientation and size (i.e. pose), shape, and local tissue composition are extracted. Subsequently, simultaneous analysis of these features within a joint analysis method is performed to generate the basis sources that show signi cant di erences between subjects with MDD and those in healthy control. Moreover, in a cross-validation leave- one-out experiment, we use a Fisher Linear Discriminant (FLD) classi er to identify individuals within the MDD group. Results show that we can classify the MDD subjects with an accuracy of 76% solely based on the information gathered from the joint analysis of pose, shape, and tissue composition in multiple brain structures.

  6. Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder.

    Science.gov (United States)

    Zhang, A; Leow, A; Zhan, L; GadElkarim, J; Moody, T; Khalsa, S; Strober, M; Feusner, J D

    2016-10-01

    Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. The aim of the study was to compare modular organization of brain structural connectivity. We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n = 29), weight-restored AN (n = 24) and healthy controls (HC) (n = 31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups. AN showed abnormal modularity involving frontal, basal ganglia and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate. Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection.

  7. Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder

    Science.gov (United States)

    Zhang, A; Leow, A; Zhan, L; GadElkarim, J; Moody, T; Khalsa, S; Strober, M; Feusner, JD

    2017-01-01

    Background Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. Aims To compare modular organization of brain structural connectivity. Methods We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n=29), weight-restored AN (n=24), and healthy controls (HC) (n=31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups. Results AN showed abnormal modularity involving frontal, basal ganglia, and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate. Conclusions Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection. PMID:27429183

  8. Treat the brain and treat the periphery: toward a holistic approach to major depressive disorder.

    Science.gov (United States)

    Zheng, Xiao; Zhang, Xueli; Wang, Guangji; Hao, Haiping

    2015-05-01

    The limited medication for major depressive disorder (MDD) against an ever-rising disease burden presents an urgent need for therapeutic innovations. During recent years, studies looking at the systems regulation of mental health and disease have shown a remarkably powerful control of MDD by systemic signals. Meanwhile, the identification of a host of targets outside the brain opens the way to treat MDD by targeting systemic signals. We examine these emerging findings and consider the implications for current thinking regarding MDD pathogenesis and treatment. We highlight the opportunities and challenges of a periphery-targeting strategy and propose its incorporation into a holistic approach.

  9. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders

    Directory of Open Access Journals (Sweden)

    Kristen J. Brennand

    2015-12-01

    Full Text Available As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  10. Creating Patient-Specific Neural Cells for the In Vitro Study of Brain Disorders.

    Science.gov (United States)

    Brennand, Kristen J; Marchetto, M Carol; Benvenisty, Nissim; Brüstle, Oliver; Ebert, Allison; Izpisua Belmonte, Juan Carlos; Kaykas, Ajamete; Lancaster, Madeline A; Livesey, Frederick J; McConnell, Michael J; McKay, Ronald D; Morrow, Eric M; Muotri, Alysson R; Panchision, David M; Rubin, Lee L; Sawa, Akira; Soldner, Frank; Song, Hongjun; Studer, Lorenz; Temple, Sally; Vaccarino, Flora M; Wu, Jun; Vanderhaeghen, Pierre; Gage, Fred H; Jaenisch, Rudolf

    2015-12-01

    As a group, we met to discuss the current challenges for creating meaningful patient-specific in vitro models to study brain disorders. Although the convergence of findings between laboratories and patient cohorts provided us confidence and optimism that hiPSC-based platforms will inform future drug discovery efforts, a number of critical technical challenges remain. This opinion piece outlines our collective views on the current state of hiPSC-based disease modeling and discusses what we see to be the critical objectives that must be addressed collectively as a field.

  11. Diffusion Magnetic Resonance Imaging Patterns in Metabolic and Toxic Brain Disorders

    Energy Technology Data Exchange (ETDEWEB)

    Sener, R.N. [Ege Univ. Hospital, Bornova, Izmir (Turkey). Dept. of Radiology

    2004-08-01

    Purpose: To evaluate metabolic and toxic brain disorders that manifest with restricted, elevated, or both restricted and elevated diffusion patterns on diffusion magnetic resonance imaging (MRI). Material and Methods: Echo-planar diffusion MRI examinations were obtained in 34 pediatric patients with metabolic and toxic brain disorders proved by appropriate laboratory studies. The MRI unit operated at 1.5T with a gradient strength of 30 mT/meter, and a rise time of 600 s. b=1000 s/mm{sup 2} images and apparent diffusion coefficient (ADC) maps with ADC values were studied. Results: Three patterns were observed: 1. A restricted diffusion pattern (high signal on b=1000 s/mm{sup 2} images and low ADC values); 2. an elevated diffusion pattern (normal signal on b=1000 s/mm2 images and high ADC values); and 3. a mixed pattern (coexistent restricted and increased diffusion patterns in the same patient). Disorders manifesting with a restricted diffusion pattern included metachromatic leukodystrophy (n=2), phenylketonuria (n=3), maple syrup urine disease (intermediate form) (n=1), infantile neuroaxonal dystrophy (n=1), Leigh (n=2), Wilson (n=3), and Canavan disease (n=1). Disorders with an elevated diffusion pattern included phenylketonuria (n=1), adrenoleukodystrophy (n=1), merosin-deficient congenital muscular dystrophy (n=2), mucopolysaccharidosis (n=2), Lowe syndrome (n=1), Leigh (n=2), Alexander (n=1), Pelizaeus-Merzbacher (n=1), and Wilson (n=3) disease. Disorders with a mixed pattern included L-2 hydroxyglutaric aciduria (n=2), non-ketotic hyperglycinemia (n=1), infantile neuroaxonal dystrophy (n=2), maple syrup urine disease (n=1), and Leigh (n=1) disease. Conclusion: The findings suggested that the three different diffusion patterns reflect the histopathological changes associated with the disorders and different stages of a particular disorder. It is likely that the restricted diffusion pattern corresponds to abnormalities related to myelin, and the elevated

  12. Different brain responses during empathy in autism spectrum disorders versus conduct disorder and callous-unemotional traits.

    Science.gov (United States)

    Klapwijk, Eduard T; Aghajani, Moji; Colins, Olivier F; Marijnissen, Godfried M; Popma, Arne; van Lang, Natasja D J; van der Wee, Nic J A; Vermeiren, Robert R J M

    2016-06-01

    Deficits in empathy are reported in autism spectrum disorders (ASD) and also underlie antisocial behavior of individuals with conduct disorder and callous-unemotional traits (CD/CU+). Many studies suggest that individuals with ASD are typically impaired in cognitive aspects of empathy, and individuals with CD/CU+ typically in affective aspects. In the current study, we compared the neural correlates of cognitive and affective aspects of empathy between youth with ASD and youth with CD/CU+. Functional magnetic resonance imaging (fMRI) was used to assess boys with ASD (N = 23), boys with CD/CU+ (N = 23), and typically developing (TD) boys (N = 33), aged 15-19 years. Angry and fearful faces were presented and participants were asked to either infer the emotional state from the face (other-task; emotion recognition) or to judge their own emotional response to the face (self-task; emotional resonance). During emotion recognition, boys with ASD showed reduced responses compared to the other groups in the ventromedial prefrontal cortex (vmPFC). During emotional resonance, the CD/CU+ and ASD groups showed reduced amygdala responses compared to the TD controls, boys with ASD showed reduced responses in bilateral hippocampus, and the CD/CU+ boys showed reduced responses in the inferior frontal gyrus (IFG) and anterior insula (AI). Results suggest differential abnormal brain responses associated with specific aspects of empathic functioning in ASD and CD/CU+. Decreased amygdala responses in ASD and CD/CU+ might point to impaired emotion processing in both disorders, whereas reduced vmPFC responses suggest problems in processing cognitive aspects of empathy in ASD. Reduced IFG/AI responses, finally, suggest decreased emotional resonance in CD/CU+. © 2015 Association for Child and Adolescent Mental Health.

  13. Update on pharmaceutical intervention for disorders of consciousness and agitation after traumatic brain injury in children.

    Science.gov (United States)

    Suskauer, Stacy J; Trovato, Melissa K

    2013-02-01

    Responsiveness and agitation are common targets for pharmaceutical intervention after traumatic brain injury (TBI) in children. This focused review presents a critical discussion of the limited literature available on the use of medications for disorders of consciousness and agitation in children with TBI. For disorders of consciousness, evidence from several small studies supports a potential benefit of dopaminergic agents for improving responsiveness in some children with lower levels of function after TBI. Larger studies, likely requiring multicenter collaborations, are needed to more definitively address questions regarding the use of medications for responsiveness in children with TBI. The literature regarding use of pharmaceutical agents for agitation in children with TBI is even more limited. The dearth of literature regarding the effects of medications used for agitation in children with TBI highlights the need for additional basic and clinical science contributions in this area. Copyright © 2013 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.

  14. Pros and Cons of Medical Cannabis use by People with Chronic Brain Disorders.

    Science.gov (United States)

    Suryadevara, Uma; Bruijnzeel, Dawn M; Nuthi, Meena; Jagnarine, Darin A; Tandon, Rajiv; Bruijnzeel, Adriaan W

    2017-01-01

    Cannabis is the most widely used illicit drug in the world and there is growing concern about the mental health effects of cannabis use. These concerns are at least partly due to the strong increase in recreational and medical cannabis use and the rise in tetrahydrocannabinol (THC) levels. Cannabis is widely used to self-medicate by older people and people with brain disorders such as amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's disease (PD), bipolar disorder, and schizophrenia. This review provides an overview of the perceived benefits and adverse mental health effects of cannabis use in people with ALS, MS, AD, PD, bipolar disorder, and schizophrenia. The reviewed studies indicate that cannabis use diminishes some symptoms associated with these disorders. Cannabis use decreases pain and spasticity in people with MS, decreases tremor, rigidity, and pain in people with PD, and improves the quality of life of ALS patients by improving appetite, and decreasing pain and spasticity. Cannabis use is more common among people with schizophrenia than healthy controls. Cannabis use is a risk factor for schizophrenia which increases positive symptoms in schizophrenia patients and diminishes negative symptoms. Cannabis use worsens bipolar disorder and there is no evidence that bipolar patients derive any benefit from cannabis. In late stage Alzheimer's patients, cannabis products may improve food intake, sleep quality, and diminish agitation. Cannabis use diminishes some of the adverse effects of neurological and psychiatric disorders. However, chronic cannabis use may lead to cognitive impairments and dependence. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Abnormal resting-state brain activities in patients with first-episode obsessive-compulsive disorder

    Science.gov (United States)

    Niu, Qihui; Yang, Lei; Song, Xueqin; Chu, Congying; Liu, Hao; Zhang, Lifang; Li, Yan; Zhang, Xiang; Cheng, Jingliang; Li, Youhui

    2017-01-01

    Objective This paper attempts to explore the brain activity of patients with obsessive-compulsive disorder (OCD) and its correlation with the disease at resting duration in patients with first-episode OCD, providing a forceful imaging basis for clinic diagnosis and pathogenesis of OCD. Methods Twenty-six patients with first-episode OCD and 25 healthy controls (HC group; matched for age, sex, and education level) underwent functional magnetic resonance imaging (fMRI) scanning at resting state. Statistical parametric mapping 8, data processing assistant for resting-state fMRI analysis toolkit, and resting state fMRI data analysis toolkit packages were used to process the fMRI data on Matlab 2012a platform, and the difference of regional homogeneity (ReHo) values between the OCD group and HC group was detected with independent two-sample t-test. With age as a concomitant variable, the Pearson correlation analysis was adopted to study the correlation between the disease duration and ReHo value of whole brain. Results Compared with HC group, the ReHo values in OCD group were decreased in brain regions, including left thalamus, right thalamus, right paracentral lobule, right postcentral gyrus, and the ReHo value was increased in the left angular gyrus region. There was a negative correlation between disease duration and ReHo value in the bilateral orbitofrontal cortex (OFC). Conclusion OCD is a multifactorial disease generally caused by abnormal activities of many brain regions at resting state. Worse brain activity of the OFC is related to the OCD duration, which provides a new insight to the pathogenesis of OCD. PMID:28243104

  16. Differential brain development with low and high IQ in attention-deficit/hyperactivity disorder.

    Directory of Open Access Journals (Sweden)

    Patrick de Zeeuw

    Full Text Available Attention-Deficit/Hyperactivity Disorder (ADHD and intelligence (IQ are both heritable phenotypes. Overlapping genetic effects have been suggested to influence both, with neuroimaging work suggesting similar overlap in terms of morphometric properties of the brain. Together, this evidence suggests that the brain changes characteristic of ADHD may vary as a function of IQ. This study investigated this hypothesis in a sample of 108 children with ADHD and 106 typically developing controls, who participated in a cross-sectional anatomical MRI study. A subgroup of 64 children also participated in a diffusion tensor imaging scan. Brain volumes, local cortical thickness and average cerebral white matter microstructure were analyzed in relation to diagnostic group and IQ. Dimensional analyses investigated possible group differences in the relationship between anatomical measures and IQ. Second, the groups were split into above and below median IQ subgroups to investigate possible differences in the trajectories of cortical development. Dimensionally, cerebral gray matter volume and cerebral white matter microstructure were positively associated with IQ for controls, but not for ADHD. In the analyses of the below and above median IQ subgroups, we found no differences from controls in cerebral gray matter volume in ADHD with below-median IQ, but a delay of cortical development in a number of regions, including prefrontal areas. Conversely, in ADHD with above-median IQ, there were significant reductions from controls in cerebral gray matter volume, but no local differences in the trajectories of cortical development.In conclusion, the basic relationship between IQ and neuroanatomy appears to be altered in ADHD. Our results suggest that there may be multiple brain phenotypes associated with ADHD, where ADHD combined with above median IQ is characterized by small, more global reductions in brain volume that are stable over development, whereas ADHD with

  17. PET brain imaging in HIV-associated neurocognitive disorders (HAND) in the era of combination antiretroviral therapy

    Energy Technology Data Exchange (ETDEWEB)

    Vera, Jaime H. [Brighton and Sussex Medical School, Department of Infection and Global Health, Brighton (United Kingdom); Brighton and Sussex University Hospitals NHS Trust, HIV Department, Brighton (United Kingdom); Ridha, Basil [Brighton and Sussex University Hospitals NHS Trust, Neurology Department, Brighton (United Kingdom); Gilleece, Yvonne; Amlani, Aliza [Brighton and Sussex University Hospitals NHS Trust, HIV Department, Brighton (United Kingdom); Thorburn, Patrick; Dizdarevic, Sabina [Brighton and Sussex University Hospitals NHS Trust, Imaging and Nuclear Medicine Department, Brighton (United Kingdom); Brighton and Sussex Medical School, Clinical Imaging Science Centre, Brighton (United Kingdom)

    2017-05-15

    Effective combination antiretroviral therapy (cART) has lead to a significant reduction in the prevalence and incidence of central nervous system (CNS) HIV-associated brain disease, particularly CNS opportunistic infections and HIV encephalitis. Despite this, cognitive deficits in people living with HIV, also known as HIV-associated neurocognitive disorders (HAND) have become more prevalent in recent years. The pathogenesis of HAND is likely to be multifactorial, however recent evidence suggests that brain microglial activation is the most likely pathogenic mechanism. Recent developments in positron emission tomography (PET) brain neuroimaging using novel brain radioligands targeting a variety of physiological changes in the brains of HIV-positive individuals have improved our understanding of the mechanisms associated with the development of HAND. This review will highlight recent PET brain neuroimaging studies in the cART era, focusing on physiological and neurochemical changes associated with HAND in people living with HIV. (orig.)

  18. Failure of the Nemo trial: bumetanide is a promising agent to treat many brain disorders but not newborn seizures

    Directory of Open Access Journals (Sweden)

    Yehezkel eBen-Ari

    2016-04-01

    Full Text Available The diuretic bumetanide failed to treat acute seizures due to hypoxic ischemic encephalopathy (HIE in newborn babies and was associated with hearing loss (NEMO trial; 1. On the other hand, clinical and experimental observations suggest that the diuretic might provide novel therapy for many brain disorders including autistic spectrum disorder, schizophrenia, Rett syndrome and Parkinson disease. Here, we discuss the differences between the pathophysiology of severe recurrent seizures in the neonates and neurological and psychiatric disorders stressing the uniqueness of severe seizures in newborn in comparison to other disorders.

  19. Failure of the Nemo Trial: Bumetanide Is a Promising Agent to Treat Many Brain Disorders but Not Newborn Seizures.

    Science.gov (United States)

    Ben-Ari, Yehezkel; Damier, Philippe; Lemonnier, Eric

    2016-01-01

    The diuretic bumetanide failed to treat acute seizures due to hypoxic ischemic encephalopathy (HIE) in newborn babies and was associated with hearing loss (NEMO trial, Pressler et al., 2015). On the other hand, clinical and experimental observations suggest that the diuretic might provide novel therapy for many brain disorders including Autism Spectrum Disorders (ASD), schizophrenia, Rett syndrome, and Parkinson disease. Here, we discuss the differences between the pathophysiology of severe recurrent seizures in the neonates and neurological and psychiatric disorders stressing the uniqueness of severe seizures in newborn in comparison to other disorders.

  20. Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder.

    Science.gov (United States)

    Soloff, Paul; White, Richard; Diwadkar, Vaibhav A

    2014-06-30

    Impulsivity and aggressiveness are trait dispositions associated with the vulnerability to suicidal behavior across diagnoses. They are associated with structural and functional abnormalities in brain networks involved in regulation of mood, impulse and behavior. They are also core characteristics of borderline personality disorder (BPD), a disorder defined, in part, by recurrent suicidal behavior. We assessed the relationships between personality traits, brain structure and lethality of suicide attempts in 51 BPD attempters using multiple regression analyses on structural MRI data. BPD was diagnosed by the Diagnostic Interview for Borderline Patients-revised, impulsivity by the Barratt Impulsiveness Scale (BIS), aggression by the Brown-Goodwin Lifetime History of Aggression (LHA), and high lethality by a score of 4 or more on the Lethality Rating Scale (LRS). Sixteen High Lethality attempters were compared to 35 Low Lethality attempters, with no significant differences noted in gender, co-morbidity, childhood abuse, BIS or LHA scores. Degree of medical lethality (LRS) was negatively related to gray matter volumes across multiple fronto-temporal-limbic regions. Effects of impulsivity and aggression on gray matter volumes discriminated High from Low Lethality attempters and differed markedly within lethality groups. Lethality of suicide attempts in BPD may be related to the mediation of these personality traits by specific neural networks. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. Targeting neural endophenotypes of eating disorders with non-invasive brain stimulation

    Directory of Open Access Journals (Sweden)

    Katharine A Dunlop

    2016-02-01

    Full Text Available The term eating disorders (ED encompasses a wide variety of disordered eating and compensatory behaviors, and so the term is associated with considerable clinical and phenotypic heterogeneity. This heterogeneity makes optimizing treatment techniques difficult. One class of treatments is non-invasive brain stimulation (NIBS. NIBS, including repetitive transcranial magnetic stimulation (rTMS and transcranial direct current stimulation (tDCS are accessible forms of neuromodulation that alter the cortical excitability of a target brain region. It is crucial for NIBS to be successful that the target is well selected for the patient population in question. Targets may best be selected by stepping back from conventional DSM-5 diagnostic criteria to identify neural substrates of more basic phenotypes, including behavior related rewards and punishment cognitive control, and social processes. These phenotypic dimensions have been recently laid out by the Research Domain Criteria (RDoC initiative. Consequently, this review is intended to identify potential dimensions as outlined by the RDoC and their underlying behavioral and neurobiological targets associated with ED as potential candidates for NIBS and review the available literature on rTMS and tDCS in ED. This review systematically reviews abnormal neural circuitry in ED within the RDoC framework, and also systematically reviews the available literature investigating NIBS as a treatment for ED.

  2. Susceptibility-weighted MRI of extrapyramidal brain structures in Parkinsonian disorders.

    Science.gov (United States)

    Schneider, Eva; Ng, Kia-Min; Yeoh, Chooi-Sum; Rumpel, Helmut; Fook-Chong, Stephanie; Li, Hui-Hua; Tan, Eng-King; Chan, Ling-Ling

    2016-06-01

    Susceptibility-weighted MRI (SWI) is sensitive to T2 effects and mineralization.We investigated differences in the extrapyramidal brain structures on SWI between Parkinson disease (PD) and postural instability gait disorder (PIGD) patients and correlated the SWI values with the degree of gait dysfunction.Forty patients diagnosed with PD and PIGD underwent 3 Tesla magnetic resonance imaging (MRI) brain study. An SWI sequence (TE/TR/FA 20/33/15) was used. Ten regions of interest were placed in the midbrain and basal ganglia by 2 independent raters blinded to subject data and quantitatively evaluated.The inter-rater reliability between the raters was excellent (interclass correlation coefficient >0.8). The SWI intensity values in all regions were on average lower in PIGD than in PD patients, with the lowest results found in globus pallidus.Multivariate analysis showed a lower SWI hypointensity in the putamen and globus pallidus in PIGD compared with PD patients, with a similar trend for the other basal ganglia nuclei. Pearson correlation analysis showed a statistically significant positive correlation between SWI putaminal hypointensity and the Tinetti total score (r = 0.39, P = 0.01) in both PD and PIGD.SWI putaminal hypointensity may be a useful imaging marker in prospective evaluation for clinical progression for Parkinsonian disorders.

  3. Eating disorder psychopathology, brain structure, neuropsychological correlates and risk mechanisms in very preterm young adults.

    Science.gov (United States)

    Micali, Nadia; Kothari, Radha; Nam, Kie Woo; Gioroukou, Elena; Walshe, Muriel; Allin, Matthew; Rifkin, Larry; Murray, Robin M; Nosarti, Chiara

    2015-03-01

    This study investigates the prevalence of eating disorder (ED) psychopathology, neuropsychological function, structural brain correlates and risk mechanisms in a prospective cohort of very preterm (VPT) young adults. We assessed ED psychopathology and neuropsychological correlates in 143 cohort individuals born at childhood and adolescence, were investigated using prospectively collected data throughout childhood/adolescence. VPT-born individuals had high levels of ED psychopathology at age 21 years. Executive function did not correlate with ED symptomatology. VPT adults presenting with ED psychopathology had smaller grey matter volume at age 14/15 years in the left posterior cerebellum and smaller white matter volume in the fusiform gyrus bilaterally, compared with VPT adults with no ED psychopathology. Caesarean delivery predicted engaging in compensatory behaviours, and severe eating difficulty at age 14 years predicted ED symptomatology in young adulthood. VPT individuals are at risk for ED symptomatology, with evidence of associated structural alterations in posterior brain regions. Further prospective studies are needed to clarify the pathways that lead from perinatal/obstetric complications to ED and relevant neurobiological mechanisms. © 2015 The Authors. European Eating Disorders Review published by John Wiley &Sons, Ltd.

  4. HIV alters neuronal mitochondrial fission/fusion in the brain during HIV-associated neurocognitive disorders.

    Science.gov (United States)

    Fields, Jerel Adam; Serger, Elisabeth; Campos, Sofia; Divakaruni, Ajit S; Kim, Changyoun; Smith, Kendall; Trejo, Margarita; Adame, Anthony; Spencer, Brian; Rockenstein, Edward; Murphy, Anne N; Ellis, Ronald J; Letendre, Scott; Grant, Igor; Masliah, Eliezer

    2016-02-01

    HIV-associated neurocognitive disorders (HAND) still occur in approximately 50% of HIV patients, and therapies to combat HAND progression are urgently needed. HIV proteins are released from infected cells and cause neuronal damage, possibly through mitochondrial abnormalities. Altered mitochondrial fission and fusion is implicated in several neurodegenerative disorders. Here, we hypothesized that mitochondrial fission/fusion may be dysregulated in neurons during HAND. We have identified decreased mitochondrial fission protein (dynamin 1-like; DNM1L) in frontal cortex tissues of HAND donors, along with enlarged and elongated mitochondria localized to the soma of damaged neurons. Similar pathology was observed in the brains of GFAP-gp120 tg mice. In vitro, recombinant gp120 decreased total and active DNM1L levels, reduced the level of Mitotracker staining, and increased extracellular acidification rate (ECAR) in primary neurons. DNM1L knockdown enhanced the effects of gp120 as measured by reduced Mitotracker signal in the treated cells. Interestingly, overexpression of DNM1L increased the level of Mitotracker staining in primary rat neurons and reduced neuroinflammation and neurodegeneration in the GFAP-gp120-tg mice. These data suggest that mitochondrial biogenesis dynamics are shifted towards mitochondrial fusion in brains of HAND patients and this may be due to gp120-induced reduction in DNM1L activity. Promoting mitochondrial fission during HIV infection of the CNS may restore mitochondrial biogenesis and prevent neurodegeneration.

  5. Susceptibility-weighted MRI of extrapyramidal brain structures in Parkinsonian disorders

    Science.gov (United States)

    Schneider, Eva; Ng, Kia-Min; Yeoh, Chooi-Sum; Rumpel, Helmut; Fook-Chong, Stephanie; Li, Hui-Hua; Tan, Eng-King; Chan, Ling-Ling

    2016-01-01

    Abstract Susceptibility-weighted MRI (SWI) is sensitive to T2∗ effects and mineralization. We investigated differences in the extrapyramidal brain structures on SWI between Parkinson disease (PD) and postural instability gait disorder (PIGD) patients and correlated the SWI values with the degree of gait dysfunction. Forty patients diagnosed with PD and PIGD underwent 3 Tesla magnetic resonance imaging (MRI) brain study. An SWI sequence (TE/TR/FA 20/33/15) was used. Ten regions of interest were placed in the midbrain and basal ganglia by 2 independent raters blinded to subject data and quantitatively evaluated. The inter-rater reliability between the raters was excellent (interclass correlation coefficient >0.8). The SWI intensity values in all regions were on average lower in PIGD than in PD patients, with the lowest results found in globus pallidus. Multivariate analysis showed a lower SWI hypointensity in the putamen and globus pallidus in PIGD compared with PD patients, with a similar trend for the other basal ganglia nuclei. Pearson correlation analysis showed a statistically significant positive correlation between SWI putaminal hypointensity and the Tinetti total score (r = 0.39, P = 0.01) in both PD and PIGD. SWI putaminal hypointensity may be a useful imaging marker in prospective evaluation for clinical progression for Parkinsonian disorders. PMID:27367979

  6. Dissociated functional brain abnormalities of inhibition in boys with pure conduct disorder and in boys with pure attention deficit hyperactivity disorder.

    Science.gov (United States)

    Rubia, Katya; Halari, Rozmin; Smith, Anna B; Mohammed, Majeed; Scott, Steven; Giampietro, Vincent; Taylor, Eric; Brammer, Michael J

    2008-07-01

    Inhibitory dysfunction may be a transdiagnostic etiopathophysiology of disruptive behavior disorders. Functional magnetic resonance imaging (fMRI) of inhibitory control has only been investigated in patients with attention deficit hyperactivity disorder (ADHD), including comorbidity with conduct disorder, showing frontal-striatal dysfunction. This study investigates differences and commonalities in functional neural networks mediating inhibitory control between medication-naive adolescents with pure conduct disorder and those with pure ADHD to identify biological markers that distinguish these clinically overlapping disorders. Event-related fMRI was used to compare brain activation of 13 boys with noncomorbid conduct disorder, 20 with noncomorbid ADHD, and 20 normal boys during an individually adjusted tracking stop task that measures the neural substrates of inhibition and stopping failure. During successful inhibition, only patients with ADHD showed reduced activation in the left dorsolateral prefrontal cortex in relation to comparison subjects and patients with conduct disorder. During inhibition failures compared to go responses, both patient groups shared underactivation in the posterior cingulate gyrus in relation to comparison subjects. Patients with conduct disorder showed reduced activation in bilateral temporal-parietal regions compared to the other groups, which did not differ in this measure. Patients with pure ADHD or pure conduct disorder show qualitative differences in their brain abnormality patterns during inhibitory control. Inhibition-mediating prefrontal regions appear to be specifically reduced in ADHD, whereas posterior temporal-parietal, performance monitoring networks are specifically dysfunctional in conduct disorder. The findings provide pioneering evidence that distinct neurobiological abnormalities may be underlying the overlapping behavioral phenotype of the two disruptive disorders.

  7. A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder.

    Directory of Open Access Journals (Sweden)

    Sagari Sarkar

    Full Text Available The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD have significantly increased fractional anisotropy (FA of the uncinate fasciculus (a white matter (WM tract that connects the amygdala to the frontal lobe compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear.We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history.The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1 the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2 right superior longitudinal fasciculus; and 3 left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone.Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM 'connectivity'.

  8. Structural brain aberrations associated with the dissociative subtype of post-traumatic stress disorder.

    Science.gov (United States)

    Daniels, J K; Frewen, P; Theberge, J; Lanius, R A

    2016-03-01

    One factor potentially contributing to the heterogeneity of previous results on structural grey matter alterations in adult participants suffering from post-traumatic stress disorder (PTSD) is the varying levels of dissociative symptomatology. The aim of this study was therefore to test whether the recently defined dissociative subtype of PTSD characterized by symptoms of depersonalization and derealization is characterized by specific differences in volumetric brain morphology. Whole-brain MRI data were acquired for 59 patients with PTSD. Voxel-based morphometry was carried out to test for group differences between patients classified as belonging (n = 15) vs. not belonging (n = 44) to the dissociative subtype of PTSD. The correlation between dissociation (depersonalization/derealization) severity and grey matter volume was computed. Patients with PTSD classified as belonging to the dissociative subtype exhibited greater grey matter volume in the right precentral and fusiform gyri as well as less volume in the right inferior temporal gyrus. Greater dissociation severity was associated with greater volume in the right middle frontal gyrus. The results of this first whole-brain investigation of specific grey matter volume in dissociative subtype PTSD indentified structural aberrations in regions subserving the processing and regulation of emotional arousal. These might constitute characteristic biomarkers for the dissociative subtype PTSD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder.

    Science.gov (United States)

    Sarkar, Sagari; Dell'Acqua, Flavio; Froudist Walsh, Seán; Blackwood, Nigel; Scott, Stephen; Craig, Michael C; Deeley, Quinton; Murphy, Declan G M

    2016-01-01

    The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear. We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history. The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone. Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM 'connectivity'.

  10. Altered brain functional connectivity in relation to perception of scrutiny in social anxiety disorder.

    Science.gov (United States)

    Giménez, Mónica; Pujol, Jesús; Ortiz, Hector; Soriano-Mas, Carles; López-Solà, Marina; Farré, Magí; Deus, Joan; Merlo-Pich, Emilio; Martín-Santos, Rocio

    2012-06-30

    Although the fear of being scrutinized by others in a social context is a key symptom in social anxiety disorder (SAD), the neural processes underlying the perception of scrutiny have not previously been studied by functional magnetic resonance imaging (fMRI). We used fMRI to map brain activation during a perception-of-scrutiny task in 20 SAD patients and 20 controls. A multi-dimensional analytic approach was used. Scrutiny perception was mediated by activation of the medial frontal cortex, insula-operculum region and cerebellum, and the additional recruitment of visual areas and the thalamus in patients. Between-group comparison demonstrated significantly enhanced brain activation in patients in the primary visual cortex and cerebellum. Functional connectivity mapping demonstrated an abnormal connectivity between regions underlying general arousal and attention. SAD patients showed significantly greater task-induced functional connectivity in the thalamo-cortical and the fronto-striatal circuits. A statistically significant increase in task-induced functional connectivity between the anterior cingulate cortex and scrutiny-perception-related regions was observed in the SAD patients, suggesting the existence of enhanced behavior-inhibitory control. The presented data indicate that scrutiny perception in SAD enhances brain activity in arousal-attention systems, suggesting that fMRI may be a useful tool to explore such a behavioral dimension.

  11. Brain Biomarkers of Long-Term Outcome of Neonatal Onset Urea Cycle Disorder

    Directory of Open Access Journals (Sweden)

    Maha Mourad

    2016-11-01

    Full Text Available Urea cycle disorders (UCDs are common inborn errors of metabolism, with an incidence of one in 30,000 births. They are caused by deficiencies in any of six enzymes and two carrier proteins, the most common being Ornithine Transcarbamylase Deficiency (OTCD. OTCD results in impairment to excrete nitrogen, causing toxic buildup of ammonia with resultant encephalopathy. Hyperammonemia (HA induces the conversion of glutamate to glutamine in the brain. Excess glutamine in the brain causes osmotic changes, cerebral edema, changes in astrocyte morphology, and cell death. Acute symptoms of HA include vomiting, hyperventilation, seizures, and irritability. Long-term neurological effects include deficits in working memory and executive function. To date, there are no predictors of prognosis of infants with neonatal onset OTCD outside of the plasma ammonia level at presentation and duration of a hyperammonemic coma. We provide a comprehensive analysis of a 16-year-old male with neonatal onset of OTCD as an example of how brain biomarkers may be useful to monitor disease course and outcome. This male presented at 8 days of life with plasma ammonia and glutamine of 677 and 4024 micromol/L respectively, and was found to have a missense mutation in Exon 4 (p. R129H. Treatment included protein restriction, sodium benzoate, and citrulline, arginine, and iron. Despite compliance, he suffered recurrent acute hyperammonemic episodes triggered by infections or catabolic stressors. We discuss the long-term effects of the hyperammonemic episodes by following MRI-based disease biomarkers.

  12. Brain structural alterations in obsessive-compulsive disorder patients with autogenous and reactive obsessions.

    Directory of Open Access Journals (Sweden)

    Marta Subirà

    Full Text Available Obsessive-compulsive disorder (OCD is a clinically heterogeneous condition. Although structural brain alterations have been consistently reported in OCD, their interaction with particular clinical subtypes deserves further examination. Among other approaches, a two-group classification in patients with autogenous and reactive obsessions has been proposed. The purpose of the present study was to assess, by means of a voxel-based morphometry analysis, the putative brain structural correlates of this classification scheme in OCD patients. Ninety-five OCD patients and 95 healthy controls were recruited. Patients were divided into autogenous (n = 30 and reactive (n = 65 sub-groups. A structural magnetic resonance image was acquired for each participant and pre-processed with SPM8 software to obtain a volume-modulated gray matter map. Whole-brain and voxel-wise comparisons between the study groups were then performed. In comparison to the autogenous group, reactive patients showed larger gray matter volumes in the right Rolandic operculum. When compared to healthy controls, reactive patients showed larger volumes in the putamen (bilaterally, while autogenous patients showed a smaller left anterior temporal lobe. Also in comparison to healthy controls, the right middle temporal gyrus was smaller in both patient subgroups. Our results suggest that autogenous and reactive obsessions depend on partially dissimilar neural substrates. Our findings provide some neurobiological support for this classification scheme and contribute to unraveling the neurobiological basis of clinical heterogeneity in OCD.

  13. A Whole-Brain Investigation of White Matter Microstructure in Adolescents with Conduct Disorder

    Science.gov (United States)

    Sarkar, Sagari; Dell’Acqua, Flavio; Froudist Walsh, Seán; Blackwood, Nigel; Scott, Stephen; Craig, Michael C.

    2016-01-01

    Background The biological basis of severe antisocial behaviour in adolescents is poorly understood. We recently reported that adolescents with conduct disorder (CD) have significantly increased fractional anisotropy (FA) of the uncinate fasciculus (a white matter (WM) tract that connects the amygdala to the frontal lobe) compared to their non-CD peers. However, the extent of WM abnormality in other brain regions is currently unclear. Methods We used tract-based spatial statistics to investigate whole brain WM microstructural organisation in 27 adolescent males with CD, and 21 non-CD controls. We also examined relationships between FA and behavioural measures. Groups did not differ significantly in age, ethnicity, or substance use history. Results The CD group, compared to controls, had clusters of significantly greater FA in 7 brain regions corresponding to: 1) the bilateral inferior and superior cerebellar peduncles, corticopontocerebellar tract, posterior limb of internal capsule, and corticospinal tract; 2) right superior longitudinal fasciculus; and 3) left cerebellar WM. Severity of antisocial behavior and callous-unemotional symptoms were significantly correlated with FA in several of these regions across the total sample, but not in the CD or control groups alone. Conclusions Adolescents with CD have significantly greater FA than controls in WM regions corresponding predominantly to the fronto-cerebellar circuit. There is preliminary evidence that variation in WM microstructure may be dimensionally related to behaviour problems in youngsters. These findings are consistent with the hypothesis that antisocial behaviour in some young people is associated with abnormalities in WM ‘connectivity’. PMID:27271503

  14. Frontal brain dysfunction in alcoholism with and without antisocial personality disorder

    Directory of Open Access Journals (Sweden)

    Marlene Oscar-Berman

    2009-05-01

    Full Text Available Marlene Oscar-Berman1,2, Mary M Valmas1,2, Kayle s Sawyer1,2, Shalene M Kirkley1, David A Gansler3, Diane Merritt1,2, Ashley Couture11Department of Veterans Affairs Healthcare System, Boston Campus, Boston, MA, USA; 2Boston University School of Medicine, Boston, MA, USA; 3Suffolk University, Boston, MA, USAAbstract: Alcoholism and antisocial personality disorder (ASPD often are comorbid conditions. Alcoholics, as well as nonalcoholic individuals with ASPD, exhibit behaviors associated with prefrontal brain dysfunction such as increased impulsivity and emotional dysregulation. These behaviors can influence drinking motives and patterns of consumption. Because few studies have investigated the combined association between ASPD and alcoholism on neuropsychological functioning, this study examined the influence of ASPD symptoms and alcoholism on tests sensitive to frontal brain deficits. The participants were 345 men and women. Of them, 144 were abstinent alcoholics (66 with ASPD symptoms, and 201 were nonalcoholic control participants (24 with ASPD symptoms. Performances among the groups were examined with Trails A and B tests, the Wisconsin Card Sorting Test, the Controlled Oral Word Association Test, the Ruff Figural Fluency Test, and Performance subtests of the Wechsler Adult Intelligence Scale. Measures of affect also were obtained. Multiple regression analyses showed that alcoholism, specific drinking variables (amount and duration of heavy drinking, and ASPD were significant predictors of frontal system and affective abnormalities. These effects were different for men and women. The findings suggested that the combination of alcoholism and ASPD leads to greater deficits than the sum of each.  Keywords: alcoholism, antisocial personality disorder (ASPD, frontal brain system, neuropsychological deficits, reward system

  15. Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits

    Directory of Open Access Journals (Sweden)

    Sarah Kathleen Bourne

    2012-06-01

    Full Text Available Deep brain stimulation (DBS has emerged as a safe, effective, and reversible treatment for a number of movement disorders. This has prompted investigation of its use for other applications including psychiatric disorders. In recent years, DBS has been introduced for the treatment of obsessive-compulsive disorder (OCD, which is characterized by recurrent unwanted thoughts or ideas (obsessions and repetitive behaviors or mental acts performed in order to relieve these obsessions (compulsions. Abnormal activity in cortico-striato-thalamo-cortical (CSTC circuits including the orbitofrontal cortex, anterior cingulate cortex, ventral striatum, and mediodorsal thalamus has been implicated in OCD. To this end a number of DBS targets including the anterior limb of the internal capsule, ventral capsule/ventral striatum, ventral caudate nucleus, subthalamic nucleus, nucleus accumbens, and the inferior thalamic peduncle have been investigated for the treatment of OCD. Despite its efficacy and widespread use in movement disorders, the mechanism of DBS is not fully understood, especially as it relates to psychiatric disorders. While initially thought to create a functional lesion akin to ablative procedures, it is increasingly clear that DBS may induce clinical benefit through activation of axonal fibers spanning the CSTC circuits, alteration of oscillatory activity within this network, and/or release of critical neurotransmitters. In this article we review how the use of DBS for OCD informs our understanding of both the mechanisms of DBS and the circuitry of OCD. We review the literature on DBS for OCD and discuss potential mechanisms of action at the neuronal level as well as the broader circuit level.

  16. The Evolution of Post-Traumatic Stress Disorder following Moderate-to-Severe Traumatic Brain Injury.

    Science.gov (United States)

    Alway, Yvette; Gould, Kate Rachel; McKay, Adam; Johnston, Lisa; Ponsford, Jennie

    2016-05-01

    Increasing evidence indicates that post-traumatic stress disorder (PTSD) may develop following traumatic brain injury (TBI), despite most patients having no conscious memory of their accident. This prospective study examined the frequency, timing of onset, symptom profile, and trajectory of PTSD and its psychiatric comorbidities during the first 4 years following moderate-to-severe TBI. Participants were 85 individuals (78.8% male) with moderate or severe TBI recruited following admission to acute rehabilitation between 2005 and 2010. Using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Disorders (SCID-I), participants were evaluated for pre- and post-injury PTSD soon after injury and reassessed at 6 months, 12 months, 2 years, 3 years, and 4 years post-injury. Over the first 4 years post-injury, 17.6% developed injury-related PTSD, none of whom had PTSD prior to injury. PTSD onset peaked between 6 and 12 months post-injury. The majority of PTSD cases (66.7%) had a delayed-onset, which for a third was preceded by subsyndromal symptoms in the first 6 months post-injury. PTSD frequency increased over the first year post-injury, remained stable during the second year, and gradually declined thereafter. The majority of subjects with PTSD experienced a chronic symptom course and all developed one or more than one comorbid psychiatric disorder, with mood, other anxiety, and substance-use disorders being the most common. Despite event-related amnesia, post-traumatic stress symptoms, including vivid re-experiencing phenomena, may develop following moderate-to-severe TBI. Onset is typically delayed and symptoms may persist for several years post-injury.

  17. Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

    Science.gov (United States)

    Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

    2014-01-01

    Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

  18. Meta-Analyses of Developing Brain Function in High-Risk and Emerged Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Moon-Soo eLee

    2014-11-01

    Full Text Available Objectives: Identifying early markers of brain function among those at high risk for pediatric bipolar disorder (PBD could serve as a screening measure when children and adolescents present with sub-syndromal clinical symptoms prior to the conversion to bipolar disorder. Studies on the offspring of patients with bipolar disorder who are genetically at high risk (HR have each been limited in establishing a biomarker, while an analytic review in summarizing the findings offers an improvised opportunity towards that goal. Methods: An activation likelihood estimation meta-analysis of mixed cognitive and emotional activities using the GingerALE software from the BrainMap Project was completed. The meta-analysis of all fMRI studies contained a total of 29 reports and included PBD, HR and typically developing (TD groups.Results: The HR group showed significantly greater activation relative to the TD group in the right DLPFC-insular-parietal-cerebellar regions. Similarly, the HR group exhibited greater activity in the right DLPFC and insula as well as the left cerebellum compared to patients with PBD. Patients with PBD, relative to TD, showed greater activation in regions of the right amygdala, parahippocampal gyrus, medial PFC, left ventral striatum, and cerebellum and lower activation in the right VLPFC and the DLPFC.Conclusions: The HR population showed increased activity, presumably indicating greater compensatory deployment, in relation to both the TD and the PBD, in the key cognition and emotion processing regions, such as the DLPFC, insula and parietal cortex. In contrast, patients with PBD, relative to HR and TD, showed decreased activity, which could indicate a decreased effort in multiple PFC regions in addition to widespread subcortical abnormalities, which are suggestive of a more entrenched disease process.

  19. Meta-analyses of developing brain function in high-risk and emerged bipolar disorder.

    Science.gov (United States)

    Lee, Moon-Soo; Anumagalla, Purnima; Talluri, Prasanth; Pavuluri, Mani N

    2014-01-01

    Identifying early markers of brain function among those at high risk (HR) for pediatric bipolar disorder (PBD) could serve as a screening measure when children and adolescents present with subsyndromal clinical symptoms prior to the conversion to bipolar disorder. Studies on the offspring of patients with bipolar disorder who are genetically at HR have each been limited in establishing a biomarker, while an analytic review in summarizing the findings offers an improvised opportunity toward that goal. An activation likelihood estimation (ALE) meta-analysis of mixed cognitive and emotional activities using the GingerALE software from the BrainMap Project was completed. The meta-analysis of all fMRI studies contained a total of 29 reports and included PBD, HR, and typically developing (TD) groups. The HR group showed significantly greater activation relative to the TD group in the right DLPFC-insular-parietal-cerebellar regions. Similarly, the HR group exhibited greater activity in the right DLPFC and insula as well as the left cerebellum compared to patients with PBD. Patients with PBD, relative to TD, showed greater activation in regions of the right amygdala, parahippocampal gyrus, medial PFC, left ventral striatum, and cerebellum and lower activation in the right VLPFC and the DLPFC. The HR population showed increased activity, presumably indicating greater compensatory deployment, in relation to both the TD and the PBD, in the key cognition and emotion-processing regions, such as the DLPFC, insula, and parietal cortex. In contrast, patients with PBD, relative to HR and TD, showed decreased activity, which could indicate a decreased effort in multiple PFC regions in addition to widespread subcortical abnormalities, which are suggestive of a more entrenched disease process.

  20. A review of attention-deficit/hyperactivity disorder from the perspective of brain networks

    Directory of Open Access Journals (Sweden)

    Angelica eDe La Fuente

    2013-05-01

    Full Text Available Attention-Deficit/Hyperactivity disorder (ADHD is the most commonly diagnosed neurodevelopmental disorder in childhood, which affects more than 5% of the population worldwide. ADHD is characterized by developmentally inappropriate behaviors of inattention, and/or impulsivity and hyperactivity. These behavioral manifestations contribute to diminished academic, occupational and social functioning, and have neurobiological bases. Neuronal deficits, especially in the attention and executive function processing networks, have been implicated in both children and adults with ADHD by using sophisticated structural and functional neuroimaging approaches. These structural and functional abnormalities in the brain networks have been associated with the impaired cognitive, affective, and motor behaviors seen in the disorder. The goal of this review is to summarize and integrate emerging themes from the existing neuroimaging connectivity studies based on advanced imaging techniques, applied in data of structural Magnetic Resonance Imaging (MRI, functional MRI (fMRI, Diffusion Tensor Imaging (DTI, Electroencephalography (EEG and Event Related Potential (ERP; and to discuss the results of these studies when considering future directions for understanding pathophysiological mechanisms and developmental trajectories of the behavioral manifestations in ADHD. We conclude this review by suggesting that future research should put more effort on understanding the roles of the subcortical structures and their structural/functional pathways in ADHD.

  1. Traumatic Brain Injury and Substance Related Disorder: A 10-Year Nationwide Cohort Study in Taiwan

    Directory of Open Access Journals (Sweden)

    Chieh-Hsin Wu

    2016-01-01

    Full Text Available Whether traumatic brain injury (TBI is causally related to substance related disorder (SRD is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events.

  2. Alcohol use and craving among Veterans with mental health disorders and mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Amy A. Herrold, PhD

    2015-02-01

    Full Text Available Mental health disorders (MHDs, mild traumatic brain injury (mTBI, and alcohol use disorder (AUD are endemic among recent Veterans, resulting in a population with heterogeneous, co-occurring conditions. While alcohol craving negatively affects rehabilitation and leads to relapse, no studies have examined alcohol craving among Veterans with co-occurring MHDs and mTBI. The purpose of this preliminary cohort study is to describe alcohol craving in a convenience sample of Iraq and Afghanistan Veterans (n = 48, including those exposed to traumatic events and experiencing active symptoms. Veterans completed weekly telephone interviews that included the Alcohol Use Disorder Identification Test, consumption questions (AUDIT-C (week 1 and the Penn Alcohol Craving Scale (PACS (weeks 1–6. Sixty percent of the sample screened positive on the AUDIT-C for probable AUD. Using Rasch analysis, the person separation reliability of the PACS was strong (0.87 among AUDIT-C positive Veterans. Higher PACS scores were reported among AUDIT-C positive versus AUDIT-C negative Veterans (mixed effects analysis, p < 0.001. PACS scores were higher among AUDIT-C positive Veterans with MHDs with and without mTBI versus AUDIT-C positive combat comparison Veterans (pairwise comparison, p < 0.001. Rates of hazardous alcohol use are high among Iraq and Afghanistan conflict Veterans and suggest that alcohol craving is elevated among those with MHDs with and without mTBI.

  3. Traumatic Brain Injury and Substance Related Disorder: A 10-Year Nationwide Cohort Study in Taiwan

    Science.gov (United States)

    Wu, Chieh-Hsin; Tsai, Tai-Hsin; Zhang, Zi-Hao; Liu, Wei; Wu, Ming-Kung; Chang, Chih-Hui; Kuo, Keng-Liang

    2016-01-01

    Whether traumatic brain injury (TBI) is causally related to substance related disorder (SRD) is still debatable, especially in persons with no history of mental disorders at the time of injury. This study analyzed data in the Taiwan National Health Insurance Research Database for 19,109 patients aged ≥18 years who had been diagnosed with TBI during 2000–2010. An additional 19,109 randomly selected age and gender matched patients without TBI (1 : 1 ratio) were enrolled in the control group. The relationship between TBI and SRD was estimated with Cox proportional hazard regression models. During the follow-up period, SRD developed in 340 patients in the TBI group and in 118 patients in the control group. After controlling for covariates, the overall incidence of SRD was 3.62-fold higher in the TBI group compared to the control group. Additionally, patients in the severe TBI subgroup were 9.01 times more likely to have SRD compared to controls. Notably, patients in the TBI group were prone to alcohol related disorders. The data in this study indicate that TBI is significantly associated with the subsequent risk of SRD. Physicians treating patients with TBI should be alert to this association to prevent the occurrence of adverse events.

  4. Deep brain stimulation for psychiatric disorders--state of the art.

    Science.gov (United States)

    Schläpfer, T E; Bewernick, B H

    2009-01-01

    A substantial number of patients suffering from severe neuropsychiatric disorders do not respond to conventional therapeutic approaches. Results from functional neuroimaging research and the development of neuromodulatory treatments lead to novel putative strategies. Recently, one of those methods, deep brain stimulation (DBS) has been applied in selected patient with major depression and obsessive-compulsive disorder (OCD) and major depression. We summarize in this review, the state of art of knowledge about the neurobiology of depression and OCD and historical treatment methods. Principles of DBS and reasons for the use of DBS in neuropsychiatry are discussed. Different targets have been chosen in a hypothesis-guided way and first results have demonstrated that DBS might be able to modulate dysfunctional neural networks in both major depression and OCD. Although DBS is a unique and promising method for otherwise treatment resistant psychiatric patients, mandatory treatment standards have to be applied for patient and target selection. Therefore, a distinct focus of this review lies on ethical aspects for DBS in neuropsychiatric disorders.

  5. Brain Activity Classifies Adolescents with and without a Familial History of Substance Use Disorders

    Directory of Open Access Journals (Sweden)

    Jianping eQiao

    2015-04-01

    Full Text Available We aimed to uncover differences in brain circuits of adolescents with parental positive or negative histories of substance use disorders (SUD, when performing a task that elicits emotional conflict, testing whether the brain circuits could serve as endophenotype markers to distinguish these adolescents. We acquired functional magnetic resonance imaging data from 11 adolescents with a positive familial history of SUD (FH+ group and 7 adolescents with a negative familial history of SUD (FH- group when performing an emotional stroop task. We extracted brain features from the conflict-related contrast images in group level analyses and granger causality indices (GCIs that measure the causal interactions among regions. Support vector machine was applied to classify the FH+ and FH- adolescents. Adolescents with FH+ showed greater activity and weaker connectivity related to emotional conflict, decision making and reward system including anterior cingulate cortex (ACC, prefrontal cortex (PFC and ventral tegmental area (VTA. High classification accuracies were achieved with leave-one-out cross validation (89.75% for the maximum conflict, 96.71% when combining maximum conflict and general conflict contrast, 97.28% when combining activity of the two contrasts and GCIs. Individual contributions of the brain features to the classification were further investigated, indicating that activation in PFC, ACC, VTA and effective connectivity from PFC to ACC play the most important roles. We concluded that fundamental differences of neural substrates underlying cognitive behaviors of adolescents with parental positive or negative histories of SUD provide new insight into potential neurobiological mechanisms contributing to the elevated risk of FH+ individuals for developing SUD.

  6. Additional brain functional network in adults with attention-deficit/hyperactivity disorder: a phase synchrony analysis.

    Directory of Open Access Journals (Sweden)

    Dongchuan Yu

    Full Text Available We develop a method to construct a new type of functional networks by the usage of phase synchrony degree that is different from the widely used Pearson's correlation approach. By a series of very strict statistical tests, we found that there is an additional network in attention-deficit/hyperactivity disorder (ADHD subjects, superimposing the original (normal brain functional network corresponding to healthy controls. The additional network leads to the increase in clustering coefficient, cost, local efficiency, and global efficiency. Our findings are inconsistent with many previous researches (using the Pearson's correlation approach revealing both increased and decreased functional connections between brain regions and many reports revealing that the brain functional networks of ADHD patients have slow information flow and low global efficiency. We also confirm that the additional network in ADHD subjects contains 6 communities, and three of them are associated with emotional control, sensory information integration, and motor control, respectively. Furthermore, we find that there is a pathway connecting the left insula and left anterior cingular gyrus via the frontal gyrus and putamen in the additional network in ADHD subjects. This implies that due to the pathway connecting brain regions in the salience network, the ADHD patients are more sensitive to external stimuli or internal thoughts and are easier to switch to the executive network and hence harder to inhibit. For clinical diagnostic purposes, we apply the k-means clustering method to distinguish ADHD patients with healthy controls at the individual subject level, and obtain a meaningful diagnostic result. More interestingly, we find that the suggested technique using phase synchrony degree to construct functional networks may obtain higher classification accuracy than the method using the Pearson's correlation coefficient.

  7. Targeted Polymeric Nanoparticles for Brain Delivery of High Molecular Weight Molecules in Lysosomal Storage Disorders.

    Directory of Open Access Journals (Sweden)

    Marika Salvalaio

    Full Text Available Lysosomal Storage Disorders (LSDs are a group of metabolic syndromes, each one due to the deficit of one lysosomal enzyme. Many LSDs affect most of the organ systems and overall about 75% of the patients present neurological impairment. Enzyme Replacement Therapy, although determining some systemic clinical improvements, is ineffective on the CNS disease, due to enzymes' inability to cross the blood-brain barrier (BBB. With the aim to deliver the therapeutic enzymes across the BBB, we here assayed biodegradable and biocompatible PLGA-nanoparticles (NPs in two murine models for LSDs, Mucopolysaccharidosis type I and II (MPS I and MPS II. PLGA-NPs were modified with a 7-aminoacid glycopeptide (g7, yet demonstrated to be able to deliver low molecular weight (MW molecules across the BBB in rodents. We specifically investigated, for the first time, the g7-NPs ability to transfer a model drug (FITC-albumin with a high MW, comparable to the enzymes to be delivered for LSDs brain therapy. In vivo experiments, conducted on wild-type mice and knockout mouse models for MPS I and II, also included a whole series of control injections to obtain a broad preliminary view of the procedure efficiency. Results clearly showed efficient BBB crossing of albumin in all injected mice, underlying the ability of NPs to deliver high MW molecules to the brain. These results encourage successful experiments with enzyme-loaded g7-NPs to deliver sufficient amounts of the drug to the brain district on LSDs, where exerting a corrective effect on the pathological phenotype.

  8. Brain activation predicts treatment improvement in patients with major depressive disorder.

    LENUS (Irish Health Repository)

    Samson, Andrea C

    2012-02-01

    Major depressive disorder (MDD) is associated with alterations in brain function that might be useful for therapy evaluation. The current study aimed to identify predictors for therapy improvement and to track functional brain changes during therapy. Twenty-one drug-free patients with MDD underwent functional MRI twice during performance of an emotional perception task: once before and once after 4 weeks of antidepressant treatment (mirtazapine or venlafaxine). Twelve healthy controls were investigated once with the same methods. A significant difference between groups was a relative greater activation of the right dorsolateral prefrontal cortex (dlPFC) in the patients vs. controls. Before treatment, patients responding better to pharmacological treatment showed greater activation in the dorsomedial PFC (dmPFC), posterior cingulate cortex (pCC) and superior frontal gyrus (SFG) when viewing of negative emotional pictures was compared with the resting condition. Activations in the caudate nucleus and insula contrasted for emotional compared to neutral stimuli were also associated with successful treatment. Responders had also significantly higher levels of activation, compared to non-responders, in a range of other brain regions. Brain activation related to treatment success might be related to altered self-referential processes and a differential response to external emotional stimuli, suggesting differences in the processing of emotionally salient stimuli between those who are likely to respond to pharmacological treatment and those who will not. The present investigation suggests the pCC, dmPFC, SFG, caudate nucleus and insula may have a key role as a biological marker for treatment response and predictor for therapeutic success.

  9. Neural, electrophysiological and anatomical basis of brain-network variability and its characteristic changes in mental disorders.

    Science.gov (United States)

    Zhang, Jie; Cheng, Wei; Liu, Zhaowen; Zhang, Kai; Lei, Xu; Yao, Ye; Becker, Benjamin; Liu, Yicen; Kendrick, Keith M; Lu, Guangming; Feng, Jianfeng

    2016-08-01

    ratio of intra- to inter-community structural connectivity. Application of the mesoscale variability measure to multicentre datasets of three mental disorders and matched controls involving 1180 subjects reveals that those regions demonstrating extreme, i.e. highest/lowest variability in controls are most liable to change in mental disorders. Specifically, we draw attention to the identification of diametrically opposing patterns of variability changes between schizophrenia and attention deficit hyperactivity disorder/autism. Regions of the default-mode network demonstrate lower variability in patients with schizophrenia, but high variability in patients with autism/attention deficit hyperactivity disorder, compared with respective controls. In contrast, subcortical regions, especially the thalamus, show higher variability in schizophrenia patients, but lower variability in patients with attention deficit hyperactivity disorder. The changes in variability of these regions are also closely related to symptom scores. Our work provides insights into the dynamic organization of the resting brain and how it changes in brain disorders. The nodal variability measure may also be potentially useful as a predictor for learning and neural rehabilitation.

  10. Deep brain stimulation for severe treatment-resistant obsessive-compulsive disorder: An open-label case series.

    Science.gov (United States)

    Farrand, Sarah; Evans, Andrew H; Mangelsdorf, Simone; Loi, Samantha M; Mocellin, Ramon; Borham, Adam; Bevilacqua, JoAnne; Blair-West, Scott; Walterfang, Mark A; Bittar, Richard G; Velakoulis, Dennis

    2017-09-01

    Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8-54 months). The sample included four females and three males, with a mean age of 46 years (range, 37-59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15-38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Deep

  11. 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.

  12. Meta-analysis and association of brain-derived neurotrophic factor (BDNF) gene with obsessive-compulsive disorder.

    Science.gov (United States)

    Zai, Gwyneth; Zai, Clement C; Arnold, Paul D; Freeman, Natalie; Burroughs, Eliza; Kennedy, James L; Richter, Margaret A

    2015-04-01

    Obsessive-compulsive disorder (OCD) is a severe psychiatric condition with a clear genetic component (Nicolini et al., 2009) in which neurodevelopmental mechanisms may be etiologically important. Brain-derived neurotrophic factor (BDNF) is an interesting candidate for molecular analysis in OCD on the basis of potential functional relevance, positive association studies, and reported interaction between this gene and other neurotransmitters implicated in this disorder.

  13. Temporal, Diagnostic, and Tissue-Specific Regulation of NRG3 Isoform Expression in Human Brain Development and Affective Disorders.

    Science.gov (United States)

    Paterson, Clare; Wang, Yanhong; Hyde, Thomas M; Weinberger, Daniel R; Kleinman, Joel E; Law, Amanda J

    2017-03-01

    Genes implicated in schizophrenia are enriched in networks differentially regulated during human CNS development. Neuregulin 3 (NRG3), a brain-enriched neurotrophin, undergoes alternative splicing and is implicated in several neurological disorders with developmental origins. Isoform-specific increases in NRG3 are observed in schizophrenia and associated with rs10748842, a NRG3 risk polymorphism, suggesting NRG3 transcriptional dysregulation as a molecular mechanism of risk. The authors quantitatively mapped the temporal trajectories of NRG3 isoforms (classes I-IV) in the neocortex throughout the human lifespan, examined whether tissue-specific regulation of NRG3 occurs in humans, and determined if abnormalities in NRG3 transcriptomics occur in mood disorders and are genetically determined. NRG3 isoform classes I-IV were quantified using quantitative real-time polymerase chain reaction in human postmortem dorsolateral prefrontal cortex from 286 nonpsychiatric control individuals, from gestational week 14 to 85 years old, and individuals diagnosed with either bipolar disorder (N=34) or major depressive disorder (N=69). Tissue-specific mapping was investigated in several human tissues. rs10748842 was genotyped in individuals with mood disorders, and association with NRG3 isoform expression examined. NRG3 classes displayed individually specific expression trajectories across human neocortical development and aging; classes I, II, and IV were significantly associated with developmental stage. NRG3 class I was increased in bipolar and major depressive disorder, consistent with observations in schizophrenia. NRG3 class II was increased in bipolar disorder, and class III was increased in major depression. The rs10748842 risk genotype predicted elevated class II and III expression, consistent with previous reports in the brain, with tissue-specific analyses suggesting that classes II and III are brain-specific isoforms of NRG3. Mapping the temporal expression of genes

  14. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  15. Brain Basics

    Medline Plus

    Full Text Available ... have been linked to many mental disorders, including autism , obsessive compulsive disorder (OCD) , schizophrenia , and depression . Brain ... studies show that brain growth in children with autism appears to peak early. And as they grow ...

  16. Social anxiety disorder: radio electric asymmetric conveyor brain stimulation versus sertraline

    Directory of Open Access Journals (Sweden)

    Fontani V

    2011-11-01

    Full Text Available Vania Fontani1, Piero Mannu1,2, Alessandro Castagna1, Salvatore Rinaldi11Department of Neuro Psycho Physio Pathology, Rinaldi Fontani Institute, Florence; 2Psychic Studies Center, Cagliari, ItalyPurpose: Social anxiety disorder (SAD is a disabling condition that affects almost 5% of the general population. Many types of drugs have shown their efficacy in the treatment of SAD. There are also some data regarding psychotherapies, but no data are available today about the efficacy of brain stimulation techniques. The aim of the study is to compare the efficacy of noninvasive brain stimulation neuro psycho physical optimization (NPPO protocol performed by radio electric asymmetric conveyor (REAC with that of sertraline in adults with SAD.Patients and methods: Twenty SAD patients on sertraline were compared with 23 SAD patients who refused any drug treatment and who chose to be treated with NPPO-REAC brain stimulation. This was a 6-month, open-label, naturalistic study. Patients on sertraline received flexible doses, whereas NPPO-REAC patients received two 18-session cycles of treatment. Clinical Global Improvement scale items "much improved" or "very much improved" and Liebowitz Social Anxiety Scale total score variation on fear and avoidance components were used to detect the results. The statistical analysis was performed with t-test. All measures <0.05 have been considered statistically significant.Results: Ten of 23 subjects on NPPO-REAC and six of the 20 taking sertraline were much improved or very much improved 1 month after the first NPPO-REAC cycle (t1. Sixteen of the subjects on NPPO-REAC and ten of the subjects taking sertraline were much improved or very much improved 1 month after the second NPPO-REAC cycle (t2. In respect of the Liebowitz Social Anxiety Scale, at t1 NPPO-REAC resulted in statistically more efficacy for sertraline on both fear and avoidance total scores. At t2, NPPO-REAC resulted in statistically more efficacy for

  17. Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.

    Directory of Open Access Journals (Sweden)

    Alejandra Borjabad

    2011-09-01

    Full Text Available Antiretroviral therapy (ART has reduced morbidity and mortality in HIV-1 infection; however HIV-1-associated neurocognitive disorders (HAND persist despite treatment. The reasons for the limited efficacy of ART in the brain are unknown. Here we used functional genomics to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART. We performed genome-wide microarray analysis using Affymetrix U133 Plus 2.0 Arrays, real-time PCR, and immunohistochemistry in brain tissues from seven treated and eight untreated HAND patients and six uninfected controls. We also determined brain virus burdens by real-time PCR. Treated and untreated HAND brains had distinct gene expression profiles with ART transcriptomes clustering with HIV-1-negative controls. The molecular disease profile of untreated HAND showed dysregulated expression of 1470 genes at p<0.05, with activation of antiviral and immune responses and suppression of synaptic transmission and neurogenesis. The overall brain transcriptome changes in these patients were independent of histological manifestation of HIV-1 encephalitis and brain virus burdens. Depending on treatment compliance, brain transcriptomes from patients on ART had 83% to 93% fewer dysregulated genes and significantly lower dysregulation of biological pathways compared to untreated patients, with particular improvement indicated for nervous system functions. However a core of about 100 genes remained similarly dysregulated in both treated and untreated patient brain tissues. These genes participate in adaptive immune responses, and in interferon, cell cycle, and myelin pathways. Fluctuations of cellular gene expression in the brain correlated in Pearson's formula analysis with plasma but not brain virus burden. Our results define for the first time an aberrant genome-wide brain transcriptome of untreated HAND and they suggest that antiretroviral treatment can be broadly effective in reducing

  18. Evaluation of dysthymic disorder with technetium-99 m hexamethylpropylene amine oxime brain single-photon emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sarikaya, A.; Cermik, T.F. [Department of Nuclear Medicine, Trakya University, Faculty of Medicine, Edirne (Turkey); Karasin, E.; Abay, E. [Department of Psychiatry, Trakya University, Faculty of Medicine, Edirne (Turkey); Berkarda, S.

    1999-03-01

    Dysthymic disorder is a chronic disorder characterised by the presence of a depressed mood and is classified as a distinct category in DSM-IV, separately from major depression. Although brain imaging studies have been performed in major depressive disease, there have to date been no reports of such studies in dysthymic disorder. In this study 36 patients with dysthymic disorder were compared with 16 normal subjects using technetium-99m hexamethylpropylene amine oxime brain single-photon emission tomography. A relative blood flow ratio was calculated for each region of interest using the average tissue activity in the region divided by activity in the cerebellum. There were significant differences in the bilateral inferior frontal, bilateral parietal, right superior frontal and left posterior temporal regions in the patients with dysthymic disorder compared with the healthy controls. These findings support the hypothesis that the biological bases for dysthymic disorder and major depression are similar. Recognition of these regional abnormalities may have clinical utility in both the diagnosis and the treatment of dysthymic disorder. Further studies are needed to confirm our results and to assess the influence of treatment in patients with dysthymic disorder. (orig.) With 1 fig., 1 tab., 26 refs.

  19. The alexithymic brain: the neural pathways linking alexithymia to physical disorders.

    Science.gov (United States)

    Kano, Michiko; Fukudo, Shin

    2013-01-09

    Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala) and the prefrontal cortex when alexithymics attempt to feel other people's feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT) was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The neural machinery in

  20. The alexithymic brain: the neural pathways linking alexithymia to physical disorders

    Directory of Open Access Journals (Sweden)

    Kano Michiko

    2013-01-01

    Full Text Available Abstract Alexithymia is a personality trait characterized by difficulties in identifying and describing feelings and is associated with psychiatric and psychosomatic disorders. The mechanisms underlying the link between emotional dysregulation and psychosomatic disorders are unclear. Recent progress in neuroimaging has provided important information regarding emotional experience in alexithymia. We have conducted three brain imaging studies on alexithymia, which we describe herein. This article considers the role of emotion in the development of physical symptoms and discusses a possible pathway that we have identified in our neuroimaging studies linking alexithymia with psychosomatic disorders. In terms of socio-affective processing, alexithymics demonstrate lower reactivity in brain regions associated with emotion. Many studies have reported reduced activation in limbic areas (e.g., cingulate cortex, anterior insula, amygdala and the prefrontal cortex when alexithymics attempt to feel other people’s feelings or retrieve their own emotional episodes, compared to nonalexithymics. With respect to primitive emotional reactions such as the response to pain, alexithymics show amplified activity in areas considered to be involved in physical sensation. In addition to greater hormonal arousal responses in alexithymics during visceral pain, increased activity has been reported in the insula, anterior cingulate cortex, and midbrain. Moreover, in complex social situations, alexithymics may not be able to use feelings to guide their behavior appropriately. The Iowa gambling task (IGT was developed to assess decision-making processes based on emotion-guided evaluation. When alexithymics perform the IGT, they fail to learn an advantageous decision-making strategy and show reduced activity in the medial prefrontal cortex, a key area for successful performance of the IGT, and increased activity in the caudate, a region associated with impulsive choice. The

  1. The Effects of Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Combined Mild Traumatic Brain Injury/Post-Traumatic Stress Disorder on Returning Veterans.

    Science.gov (United States)

    Combs, Hannah L; Berry, David T R; Pape, Theresa; Babcock-Parziale, Judith; Smith, Bridget; Schleenbaker, Randal; Shandera-Ochsner, Anne; Harp, Jordan P; High, Walter M

    2015-07-01

    United States veterans of the Iraqi (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]) conflicts have frequently returned from deployment after sustaining mild traumatic brain injury (mTBI) and enduring stressful events resulting in post-traumatic stress disorder (PTSD). A large number of returning service members have been diagnosed with both a history of mTBI and current PTSD. Substantial literature exists on the neuropsychological factors associated with mTBI and PTSD occurring separately; far less research has explored the combined effects of PTSD and mTBI. The current study employed neuropsychological and psychological measures in a sample of 251 OIF/OEF veterans to determine whether participants with a history of mTBI and current PTSD (mTBI+PTSD) have poorer cognitive and psychological outcomes than participants with mTBI only (mTBI-o), PTSD only (PTSD-o), or veteran controls (VC), when groups are comparable on intelligence quotient, education, and age. The mTBI+PTSD group performed more poorly than VC, mTBI-o, and PTSD-o groups on several neuropsychological measures. Effect size comparisons suggest small deleterious effects for mTBI-o on measures of processing speed and visual attention and small effects for PTSD-o on measures of verbal memory, with moderate effects for mTBI+PTSD on the same variables. Additionally, the mTBI+PTSD group was significantly more psychologically distressed than the PTSD-o group, and PTSD-o group was more distressed than VC and mTBI-o groups. These findings suggest that veterans with mTBI+PTSD perform significantly lower on neuropsychological and psychiatric measures than veterans with mTBI-o or PTSD-o. The results also raise the possibility of mild but persisting cognitive changes following mTBI sustained during deployment.

  2. Using Brain Connectivity Measure of EEG Synchrostates for Discriminating Typical and Autism Spectrum Disorder

    CERN Document Server

    Jamal, Wasifa; Maharatna, Koushik; Kuyucu, Doga; Sicca, Federico; Billeci, Lucia; Apicella, Fabio; Muratori, Filippo

    2016-01-01

    In this paper we utilized the concept of stable phase synchronization topography - synchrostates - over the scalp derived from EEG recording for formulating brain connectivity network in Autism Spectrum Disorder (ASD) and typically-growing children. A synchronization index is adapted for forming the edges of the connectivity graph capturing the stability of each of the synchrostates. Such network is formed for 11 ASD and 12 control group children. Comparative analyses of these networks using graph theoretic measures show that children with autism have a different modularity of such networks from typical children. This result could pave the way to a new modality for possible identification of ASD from non-invasively recorded EEG data.

  3. Face and Word Recognition Can Be Selectively Affected by Brain Injury or Developmental Disorders

    DEFF Research Database (Denmark)

    Robotham, Ro J.; Starrfelt, Randi

    2017-01-01

    face recognition deficit, and pure alexia, a selective word recognition deficit. Together, the patterns of impaired reading with preserved face recognition and impaired face recognition with preserved reading constitute a double dissociation. The existence of these selective deficits has been...... also have deficits in the other. The implications of this would be immense, with most textbooks in cognitive neuropsychology requiring drastic revisions. In order to evaluate the evidence for dissociations, we review studies that specifically investigate whether face or word recognition can...... be selectively affected by acquired brain injury or developmental disorders. We only include studies published since 2004, as comprehensive reviews of earlier studies are available. Most of the studies assess the supposedly preserved functions using sensitive measurements. We found convincing evidence...

  4. Postconcussive symptoms and posttraumatic stress disorder after mild traumatic brain injury.

    Science.gov (United States)

    Bryant, R A; Harvey, A G

    1999-05-01

    Postconcussive symptoms after mild traumatic brain injury (MTBI) may be exacerbated by anxiety associated with posttraumatic stress. The aim of this study was to investigate the relationship between postconcussive symptoms and posttraumatic stress disorder (PTSD) in an MTBI population. Survivors of motor vehicle accidents who either sustained an MTBI (N = 46) or no TBI (N = 59) were assessed 6 months posttrauma for PTSD and postconcussive symptoms. Postconcussive symptoms were more evident in MTBI patients with PTSD than those without PTSD, and in MTBI patients than non-TBI patients. Further, postconcussive symptoms were significantly correlated with PTSD symptoms. These findings indicate that postconcussive symptoms may be mediated by an interaction of neurological and psychological factors after MTBI.

  5. A Heme Oxygenase-1 Transducer Model of Degenerative and Developmental Brain Disorders

    Directory of Open Access Journals (Sweden)

    Hyman M. Schipper

    2015-03-01

    Full Text Available Heme oxygenase-1 (HO-1 is a 32 kDa protein which catalyzes the breakdown of heme to free iron, carbon monoxide and biliverdin. The Hmox1 promoter contains numerous consensus sequences that render the gene exquisitely sensitive to induction by diverse pro-oxidant and inflammatory stimuli. In “stressed” astroglia, HO-1 hyperactivity promotes mitochondrial iron sequestration and macroautophagy and may thereby contribute to the pathological iron deposition and bioenergetic failure documented in Alzheimer disease, Parkinson disease and certain neurodevelopmental conditions. Glial HO-1 expression may also impact neuroplasticity and cell survival by modulating brain sterol metabolism and the proteasomal degradation of neurotoxic proteins. The glial HO-1 response may represent a pivotal transducer of noxious environmental and endogenous stressors into patterns of neural damage and repair characteristic of many human degenerative and developmental CNS disorders.

  6. Remodeling Pearson's Correlation for Functional Brain Network Estimation and Autism Spectrum Disorder Identification

    Directory of Open Access Journals (Sweden)

    Weikai Li

    2017-08-01

    Full Text Available Functional brain network (FBN has been becoming an increasingly important way to model the statistical dependence among neural time courses of brain, and provides effective imaging biomarkers for diagnosis of some neurological or psychological disorders. Currently, Pearson's Correlation (PC is the simplest and most widely-used method in constructing FBNs. Despite its advantages in statistical meaning and calculated performance, the PC tends to result in a FBN with dense connections. Therefore, in practice, the PC-based FBN needs to be sparsified by removing weak (potential noisy connections. However, such a scheme depends on a hard-threshold without enough flexibility. Different from this traditional strategy, in this paper, we propose a new approach for estimating FBNs by remodeling PC as an optimization problem, which provides a way to incorporate biological/physical priors into the FBNs. In particular, we introduce an L1-norm regularizer into the optimization model for obtaining a sparse solution. Compared with the hard-threshold scheme, the proposed framework gives an elegant mathematical formulation for sparsifying PC-based networks. More importantly, it provides a platform to encode other biological/physical priors into the PC-based FBNs. To further illustrate the flexibility of the proposed method, we extend the model to a weighted counterpart for learning both sparse and scale-free networks, and then conduct experiments to identify autism spectrum disorders (ASD from normal controls (NC based on the constructed FBNs. Consequently, we achieved an 81.52% classification accuracy which outperforms the baseline and state-of-the-art methods.

  7. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  8. Brain Basics

    Medline Plus

    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  9. Brain Basics

    Medline Plus

    Full Text Available ... brain's structure, studies show that brain growth in children with autism appears to peak early. And as ... grow there are differences in brain development in children who develop bipolar disorder than children who do ...

  10. Brain Basics

    Medline Plus

    Full Text Available ... science, such as: How the brain develops How genes and the environment affect the brain The basic ... that with brain development in people mental disorders. Genes and environmental cues both help to direct this ...

  11. Brain Basics

    Medline Plus

    Full Text Available ... lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits Neurons ... affects the Brain Meet Sarah Sarah is a middle-aged woman who seemed to have it all. ...

  12. Brain Basics

    Medline Plus

    Full Text Available ... can lead to mental disorders, such as depression. The Growing Brain Inside the Brain: Neurons & Neural Circuits ... tailored treatments, and possibly prevention of such illnesses. The Working Brain Neurotransmitters Everything we do relies on ...

  13. Classification of autism spectrum disorder using supervised learning of brain connectivity measures extracted from synchrostates

    Science.gov (United States)

    Jamal, Wasifa; Das, Saptarshi; Oprescu, Ioana-Anastasia; Maharatna, Koushik; Apicella, Fabio; Sicca, Federico

    2014-08-01

    Objective. The paper investigates the presence of autism using the functional brain connectivity measures derived from electro-encephalogram (EEG) of children during face perception tasks. Approach. Phase synchronized patterns from 128-channel EEG signals are obtained for typical children and children with autism spectrum disorder (ASD). The phase synchronized states or synchrostates temporally switch amongst themselves as an underlying process for the completion of a particular cognitive task. We used 12 subjects in each group (ASD and typical) for analyzing their EEG while processing fearful, happy and neutral faces. The minimal and maximally occurring synchrostates for each subject are chosen for extraction of brain connectivity features, which are used for classification between these two groups of subjects. Among different supervised learning techniques, we here explored the discriminant analysis and support vector machine both with polynomial kernels for the classification task. Main results. The leave one out cross-validation of the classification algorithm gives 94.7% accuracy as the best performance with corresponding sensitivity and specificity values as 85.7% and 100% respectively. Significance. The proposed method gives high classification accuracies and outperforms other contemporary research results. The effectiveness of the proposed method for classification of autistic and typical children suggests the possibility of using it on a larger population to validate it for clinical practice.

  14. Brain activity towards gaming-related cues in Internet gaming disorder during an addiction Stroop task

    Directory of Open Access Journals (Sweden)

    Yifen eZhang

    2016-05-01

    Full Text Available Background and aims: Attentional bias for drug-related stimuli is a key characteristic for drug addiction. Characterizing the relationship between attentional bias and brain reactivity to Internet gaming-related stimuli may help in identifying the neural substrates that critical to Internet gaming disorder (IGD.Methods: 19 IGD and 21 healthy control (HC subjects were scanned with functional magnetic resonance imaging while they were performing an addiction Stroop task.Results: Compared with HC group, IGD subjects showed higher activations when facing Internet gaming-related stimuli in regions including the inferior parietal lobule, the middle occipital gyrus and the dorsolateral prefrontal cortex. These brain areas were thought to be involved in selective attention, visual processing, working memory and cognitive control.Discussion and Conclusions: The results demonstrated that compared with HC group, IGD subjects show impairment in both visual and cognitive control ability while dealing with gaming-related words. This finding might be helpful in understanding the underlying neural basis of IGD.

  15. Brain activation for response inhibition under gaming cue distraction in internet gaming disorder.

    Science.gov (United States)

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

    2014-01-01

    We evaluated neural substrates related to the loss of control in college students with internet gaming disorder (IGD). We hypothesized that deficit in response inhibition under gaming cue distraction was the possible mechanism for the loss of control internet use. Eleven cases of IGD and 11 controls performed Go/NoGo tasks with/without gaming distraction in the functional magnetic resonance imaging scanner. When the gaming picture was shown as background while individuals were performing Go/NoGo tasks, the IGD group committed more commission errors. The control group increased their brain activations more over the right dorsolateral prefrontal cortex (DLPFC) and superior parietal lobe under gaming cue distraction in comparison with the IGD group. Furthermore, brain activation of the right DLPFC and superior parietal lobe were negatively associated with performance of response inhibition among the IGD group. The results suggest that the function of response inhibition was impaired under gaming distraction among the IGD group, and individuals with IGD could not activate right DLPFC and superior parietal lobe to keep cognitive control and attention allocation for response inhibition under gaming cue distraction. This mechanism should be addressed in any intervention for IGD.

  16. Functional and dysfunctional brain circuits underlying emotional processing of music in autism spectrum disorders.

    Science.gov (United States)

    Caria, Andrea; Venuti, Paola; de Falco, Simona

    2011-12-01

    Despite intersubject variability, dramatic impairments of socio-communicative skills are core features of autistic spectrum disorder (ASD). A deficit in the ability to express and understand emotions has often been hypothesized to be an important correlate of such impairments. Little is known about individuals with ASD's ability to sense emotions conveyed by nonsocial stimuli such as music. Music has been found to be capable of evoking and conveying strong and consistent positive and negative emotions in healthy subjects. The ability to process perceptual and emotional aspects of music seems to be maintained in ASD. Individuals with ASD and neurotypical (NT) controls underwent a single functional magnetic resonance imaging (fMRI) session while processing happy and sad music excerpts. Overall, fMRI results indicated that while listening to both happy and sad music, individuals with ASD activated cortical and subcortical brain regions known to be involved in emotion processing and reward. A comparison of ASD participants with NT individuals demonstrated decreased brain activity in the premotor area and in the left anterior insula, especially in response to happy music excerpts. Our findings shed new light on the neurobiological correlates of preserved and altered emotional processing in ASD.

  17. Deep brain stimulation for treatment refractory obsessive-compulsive disorder--a case report.

    Science.gov (United States)

    Csigó, Katalin; Dome, Lászó; Valálik, I; Harsányi, András; Demeter, Gyula; Racsmány, Mihály

    2010-03-30

    In the past 30 years it has been a great development in the unders-anding and therapy of obsessive-compulsive disorder. Adequate pharmaco- and cognitive-behavior therapies reduce the symptoms in 40-60% of patients, so a remarkable portion of patients still remains refractory to conventional treatment. Neurosurgery--with it's reversible and irreversible techniques--brought a breakthrough in the therapy of treatment refractory patients. In the present case, we represent a 3 months follow-up of an obsessive-compulsive pctient treated by deep brain stimulation. In our case, the stimulation target was the anterior limb of internal capsule. The clinical symptoms were measured by Y-BOCS. In addition various neuropsychological tests were used to monitor patient's executive functions before and 3 months after the deep brain stimulation. We found that obsessive-compu sive symptoms improved after three months of the stimulation. The neuropsychological tests showed improvement in some executive functions (e.g. fluency, set-shifting, decision making). On the other hand our results revealed severe neurocognitive--mainly attention skill--deficits in a treatment refractory obsessive-compulsive patient.

  18. The relationship of brain structure to age and executive functioning in adolescent disruptive behavior disorder.

    Science.gov (United States)

    Hummer, Tom A; Wang, Yang; Kronenberger, William G; Dunn, David W; Mathews, Vincent P

    2015-03-30

    Characterizing brain maturation in adolescents with disruptive behavior disorders (DBDs) may provide insight into the progression of their behavioral deficits. Therefore, this study examined how age and executive functioning were related to structural neural characteristics in DBD. Thirty-three individuals (aged 13-17) with a DBD, along with a matched control sample, completed neuropsychological testing and underwent magnetic resonance imaging (MRI) to measure gray matter volume and microstructural white matter properties. Voxel-based morphometry quantified gray matter volume, and diffusion tensor imaging measured fractional anisotropy (FA) in white matter tracts. In the anterior cingulate, gray matter volume decreased with age in healthy controls but showed no such change in the DBD sample. In the corpus callosum and superior longitudinal fasciculus (SLF), FA increased with age in the control sample significantly more than in the DBD sample. Executive functioning, particularly working memory, was associated with SLF FA bilaterally. However, the relationship of SLF FA to working memory performance was weaker in the DBD sample. These data suggest that youth with DBD have altered brain development compared with typically developing youth. The abnormal maturation of the anterior cingulate and frontoparietal tracts during adolescence may contribute to the persistence of behavioral deficits in teens with a DBD. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Structural and Functional Brain Correlates of Cognitive Impairment in Euthymic Patients with Bipolar Disorder

    Science.gov (United States)

    Goikolea, José M.; Bonnin, Caterina M.; Sarró, Salvador; Segura, Barbara; Amann, Benedikt L.; Monté, Gemma C.; Moro, Noemi; Fernandez-Corcuera, Paloma; Maristany, Teresa; Salvador, Raymond; Vieta, Eduard; Pomarol-Clotet, Edith; McKenna, Peter J.

    2016-01-01

    Introduction Cognitive impairment in the euthymic phase is a well-established finding in bipolar disorder. However, its brain structural and/or functional correlates are uncertain. Methods Thirty-three euthymic bipolar patients with preserved memory and executive function and 28 euthymic bipolar patients with significant memory and/or executive impairment, as defined using two test batteries, the Rivermead Behavioural Memory Test (RBMT) and the Behavioural Assessment of the Dysexecutive Syndrome (BADS), plus 28 healthy controls underwent structural MRI using voxel-based morphometry (VBM). Twenty-seven of the cognitively preserved patients, 23 of the cognitively impaired patients and 28 controls also underwent fMRI during performance of the n-back working memory task. Results No clusters of grey or white matter volume difference were found between the two patient groups. During n-back performance, the cognitively impaired patients showed hypoactivation compared to the cognitively preserved patients in a circumscribed region in the right dorsolateral prefrontal cortex. Both patient groups showed failure of de-activation in the medial frontal cortex compared to the healthy controls. Conclusions Cognitive impairment in euthymic bipolar patients appears from this study to be unrelated to structural brain abnormality, but there was some evidence for an association with altered prefrontal function. PMID:27448153

  20. Brain SPECT analysis using statistical parametric mapping in patients with posttraumatic stress disorder

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Euy Neyng; Sohn, Hyung Sun; Kim, Sung Hoon; Chung, Soo Kyo; Yang, Dong Won [College of Medicine, The Catholic Univ. of Korea, Seoul (Korea, Republic of)

    2001-07-01

    This study investigated alterations in regional cerebral blood flow (rCBF) in patients with posttraumatic stress disorder (PTSD) using statistical parametric mapping (SPM99). Noninvasive rCBF measurements using {sup 99m}Tc-ethyl cysteinate dimer (ECD) SPECT were performed on 23 patients with PTSD and 21 age matched normal controls without re-exposure to accident-related stimuli. The relative rCBF maps in patients with PTSD and controls were compared. In patients with PTSD, significant increased rCBF was found along the limbic system in the brain. There were a few foci of decreased rCBF in the superior frontal gyrus, parietal and temporal region. PTSD is associated with increased rCBF in limbic areas compared with age-matched normal controls. These findings implicate regions of the limbic brain, which may mediate the response to aversive stimuli in healthy individuals, play on important role in patients suffering from PTSD and suggest that ongoing hyperfunction of 'overlearned survival response' or flashbacks response in these regions after painful, life threatening, or horrifying events without re-exposure to same traumatic stimulus.

  1. Meta-analysis of brain activation in depressive patients with emotional perception disorders

    Institute of Scientific and Technical Information of China (English)

    Chenwang Jin; Ming Zhang; Dan Li; Shaohui Ma; Yuan Wang; Min Li; Lihua Liu

    2011-01-01

    OBJECTIVE: To elucidate the distribution of abnormally activated brain regions in depressive patients during emotional perception processing using activation likelihood estimation, a quantitative meta-analytic technique. DATA SOURCES: Computer-based online retrieval was conducted using the PscyINFO, Pubmed and CNKI databases, searching literature from the establishment of each database until June 2010.STUDY SELECTION: Inclusion criteria: (1) studies examined emotion perception tasks using functional magnetic resonance imaging; (2) studies indicated regional brain activation abnormalities in depressive patients compared with controls in standard Talairach or MNI coordinates. Any analyzed coordinates based on the MNI system were converted to Talairach space with icbm2tal software. The map of activation likelihood estimation was finally created through the Gaussian smooth (full-width half-maximum = 8 mm), permutation test and corrected for multiple comparisons using the false discovery rate method (q = 0.05) with Ginger-ALE 2.0 software. MAIN OUTCOME MEASURES: Activation of brain regions in patients.RESULTS: Seventeen studies were identified, involving a total of 261 patients, 273 healthy controls and 201 foci. Meta-analysis revealed a dysfunctional emotion regulation loop in depressive patients, comprised of the prefrontal cortex, the basal ganglia and the limbic lobe, in which the amygdala was a key component. During emotion processing, the left prefrontal cortex and basal ganglia were hypoactive among depressive patients, whereas the opposite change was found in the limbic lobe. CONCLUSION: Abnormal connections among the prefrontal cortex, basal ganglia and limbic lobe may be involved in the pathophysiology of depressive disorder.

  2. The military's approach to traumatic brain injury and post-traumatic stress disorder

    Science.gov (United States)

    Ling, Geoffrey S. F.; Grimes, Jamie; Ecklund, James M.

    2014-06-01

    Traumatic brain injury (TBI) and Post Traumatic Stress Disorder (PTSD) are common conditions. In Iraq and Afghanistan, explosive blast related TBI became prominent among US service members but the vast majority of TBI was still due to typical causes such as falls and sporting events. PTS has long been a focus of the US military mental health providers. Combat Stress Teams have been integral to forward deployed units since the beginning of the Global War on Terror. Military medical management of disease and injury follows standard of care clinical practice guidelines (CPG) established by civilian counterparts. However, when civilian CPGs do not exist or are not applicable to the military environment, new practice standards are created. Such is the case for mild TBI. In 2009, the VA-DoD CPG for management of mild TBI/concussion was published and a system-wide clinical care program for mild TBI/concussion was introduced. This was the first large scale effort on an entire medical care system to address all severities of TBI in a comprehensive organized way. In 2010, the VA-DoD CPG for management of PTSD was published. Nevertheless, both TBI and PTS are still incompletely understood. Investment in terms of money and effort has been committed by the DoD to their study. The Defense and Veterans Brain Injury Center, National Intrepid Center of Excellence and the Defense Centers of Excellence for Psychological Health and Traumatic Brain Injury are prominent examples of this effort. These are just beginnings, a work in progress ready to leverage advances made scientifically and always striving to provide the very best care to its military beneficiaries.

  3. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, S.C.; Schouten-van Meeteren, A.Y.; Boot, A.M.; Claahsen-van der Grinten, H.L.; Granzen, B.; Han, K.; Janssens, G.O.; Michiels, E.M.; Trotsenburg, A.S. van; Vandertop, W.P.; Vuurden, D.G. van; Kremer, L.C.; Caron, H.N.; Santen, H.M. van

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >/= 2 years after diagnosis.

  4. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients

  5. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boots, Annemieke; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >= 2 years after diagnosis. Patients

  6. Etiologic subtypes of attention-deficit/hyperactivity disorder : Brain imaging, molecular genetic and environmental factors and the dopamine hypothesis

    NARCIS (Netherlands)

    Swanson, James M.; Kinsbourne, Marcel; Nigg, Joel; Lanphear, Bruce; Stefanatos, Gerry A.; Volkow, Nora; Taylor, Eric; Casey, B. J.; Castellanos, F. Xavier; Wadhwa, Pathik D.

    2007-01-01

    Multiple theories of Attention-Deficit/Hyperactivity Disorder (ADHD) have been proposed, but one that has stood the test of time is the dopamine deficit theory. We review the narrow literature from recent brain imaging and molecular genetic studies that has improved our understanding of the role of

  7. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boots, Annemieke; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >= 2 years after diagnosis. Patients wi

  8. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients wit

  9. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, S.C.; Schouten-van Meeteren, A.Y.; Boot, A.M.; Claahsen-van der Grinten, H.L.; Granzen, B.; Han, K.; Janssens, G.O.; Michiels, E.M.; Trotsenburg, A.S. van; Vandertop, W.P.; Vuurden, D.G. van; Kremer, L.C.; Caron, H.N.; Santen, H.M. van

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >/= 2 years after diagnosis. Patient

  10. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients wit

  11. Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

    NARCIS (Netherlands)

    Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boots, Annemieke; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.

    2016-01-01

    Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >= 2 years after diagnosis. Patients wi

  12. Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

    Science.gov (United States)

    Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

    2012-01-01

    Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

  13. Traumatic brain injury, posttraumatic stress disorder, and pain diagnoses in OIF/OEF/OND Veterans

    Directory of Open Access Journals (Sweden)

    David X. Cifu, MD

    2013-12-01

    Full Text Available To identify the prevalence of traumatic brain injury (TBI, posttraumatic stress disorder (PTSD, and pain in Veterans from Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND, Veterans who received any inpatient or outpatient care from Veterans Health Administration (VHA facilities from 2009 to 2011 were studied. A subset of Veterans was identified who were diagnosed with TBI, PTSD, and/or pain (head, neck, or back as determined by their International Classification of Diseases-9th Revision-Clinical Modification codes. Between fiscal years 2009 and 2011, 613,391 Veterans accessed VHA services at least once (age: 31.9 +/– 9.6 yr. TBI diagnosis in any 1 year was slightly less than 7%. When data from 3 years were pooled, 9.6% were diagnosed with TBI, 29.3% were diagnosed with PTSD, and 40.2% were diagnosed with pain. The full polytrauma triad expression (TBI, PTSD, and pain was diagnosed in 6.0%. Results show that increasing numbers of Veterans from OIF/OEF/OND accessed VHA over a 3 year period. Among those with a TBI diagnosis, the majority also had a mental health disorder, with approximately half having both PTSD and pain. While the absolute number of Veterans increased by over 40% from 2009 to 2011, the proportion of Veterans diagnosed with TBI and the high rate of comorbid PTSD and pain in this population remained relatively stable.

  14. Neuropathological similarities and differences between schizophrenia and bipolar disorder: a flow cytometric postmortem brain study.

    Directory of Open Access Journals (Sweden)

    Yoshitaka Hayashi

    Full Text Available Recent studies suggest that schizophrenia (SCH and bipolar disorder (BPD may share a similar etiopathology. However, their precise neuropathological natures have rarely been characterized in a comprehensive and quantitative fashion. We have recently developed a rapid, quantitative cell-counting method for frozen unfixed postmortem brains using a flow cytometer. In the present study, we not only counted stained nuclei, but also measured their sizes in the gray matter of frontopolar cortices (FPCs and inferior temporal cortices (ITCs from patients with SCH or BPD, as well as in that from normal controls. In terms of NeuN(+ neuronal nuclei size, particularly in the reduced densities of small NeuN(+ nuclei, we found abnormal distributions present in the ITC gray matter of both patient groups. These same abnormalities were also found in the FPCs of SCH patients, whereas in the FPCs of BPD patients, a reduction in oligodendrocyte lineage (olig2(+ cells was much more common. Surprisingly, in the SCH FPC, normal left-greater-than-right asymmetry in neural nuclei densities was almost completely reversed. In the BPD FPC, this asymmetry, though not obvious, differed significantly from that in the SCH FPC. These findings indicate that while similar neuropathological abnormalities are shared by patients with SCH or BPD, differences also exist, mainly in the FPC, which may at least partially explain the differences observed in many aspects in these disorders.

  15. Psychiatric Disorders in Children and Adolescents 24 Months After Mild Traumatic Brain Injury

    Science.gov (United States)

    Max, Jeffrey E.; Friedman, Keren; Wilde, Elisabeth A.; Bigler, Erin D.; Hanten, Gerri; Schachar, Russell J.; Saunders, Ann E.; Dennis, Maureen; Ewing-Cobbs, Linda; Chapman, Sandra B.; Yang, Tony T.; Levin, Harvey S.

    2016-01-01

    This study aimed to better understand the occurrence of novel psychiatric disorders (NPDs) in children with mild traumatic brain injury (mTBI) in relation to preinjury variables, injury-related variables, and concurrent neurocognitive outcome. Eighty-seven children aged 5–14 years who had experienced mTBI were studied from consecutive hospital admissions with semistructured psychiatric interviews soon after injury (baseline). Fifty-four children were reassessed 24 months postinjury. Standardized instruments were used to evaluate injury severity, lesion characteristics, preinjury variables (lifetime psychiatric disorder, family psychiatric history, family function, socioeconomic status, psychosocial adversity, adaptive function, and academic function), and finally, postinjury neurocognitive and adaptive function. At 24 months postinjury, NPDs had occurred in 17 of 54 (31%) participants. NPD at 24 months was related to frontal white matter lesions and was associated with estimated preinjury reading, preinjury adaptive function, and concurrent deficits in reading, processing speed, and adaptive function. These findings extend earlier reports that the psychiatric morbidity after mTBI in children is more common than previously thought, and moreover, it is linked to preinjury individual variables and injury characteristics and is associated with postinjury adaptive and neurocognitive functioning. PMID:25923850

  16. Small-World Brain Functional Networks in Children With Attention-Deficit/Hyperactivity Disorder Revealed by EEG Synchrony.

    Science.gov (United States)

    Liu, Tian; Chen, Yanni; Lin, Pan; Wang, Jue

    2015-07-01

    We investigated the topologic properties of human brain attention-related functional networks associated with Multi-Source Interference Task (MSIT) performance using electroencephalography (EEG). Data were obtained from 13 children diagnosed with attention-deficit/hyperactivity disorder (ADHD) and 13 normal control children. Functional connectivity between all pairwise combinations of EEG channels was established by calculating synchronization likelihood (SL). The cluster coefficients and path lengths were computed as a function of degree K. The results showed that brain attention functional networks of normal control subjects had efficient small-world topologic properties, whereas these topologic properties were altered in ADHD. In particular, increased local characteristics combined with decreased global characteristics in ADHD led to a disorder-related shift of the network topologic structure toward ordered networks. These findings are consistent with a hypothesis of dysfunctional segregation and integration of the brain in ADHD, and enhance our understanding of the underlying pathophysiologic mechanism of this illness.

  17. Aberrant Global and Regional Topological Organization of the Fractional Anisotropy-weighted Brain Structural Networks in Major Depressive Disorder

    Institute of Scientific and Technical Information of China (English)

    Jian-Huai Chen; Zhi-Jian Yao; Jiao-Long Qin; Rui Yan; Ling-Ling Hua; Qing Lu

    2016-01-01

    Background:Most previous neuroimaging studies have focused on the structural and functional abnormalities of local brain regions in major depressive disorder (MDD).Moreover,the exactly topological organization of networks underlying MDD remains unclear.This study examined the aberrant global and regional topological patterns of the brain white matter networks in MDD patients.Methods:The diffusion tensor imaging data were obtained from 27 patients with MDD and 40 healthy controls.The brain fractional anisotropy-weighted structural networks were constructed,and the global network and regional nodal metrics of the networks were explored by the complex network theory.Results:Compared with the healthy controls,the brain structural network of MDD patients showed an intact small-world topology,but significantly abnormal global network topological organization and regional nodal characteristic of the network in MDD were found.Our findings also indicated that the brain structural networks in MDD patients become a less strongly integrated network with a reduced central role of some key brain regions.Conclusions:All these resulted in a less optimal topological organization of networks underlying MDD patients,including an impaired capability of local information processing,reduced centrality of some brain regions and limited capacity to integrate information across different regions.Thus,these global network and regional node-level aberrations might contribute to understanding the pathogenesis of MDD from the view of the brain network.

  18. Distinct phenotypes of speech and voice disorders in Parkinson's disease after subthalamic nucleus deep brain stimulation.

    Science.gov (United States)

    Tsuboi, Takashi; Watanabe, Hirohisa; Tanaka, Yasuhiro; Ohdake, Reiko; Yoneyama, Noritaka; Hara, Kazuhiro; Nakamura, Ryoichi; Watanabe, Hazuki; Senda, Jo; Atsuta, Naoki; Ito, Mizuki; Hirayama, Masaaki; Yamamoto, Masahiko; Fujimoto, Yasushi; Kajita, Yasukazu; Wakabayashi, Toshihiko; Sobue, Gen

    2015-08-01

    To elucidate the phenotypes and pathophysiology of speech and voice disorders in Parkinson's disease (PD) with subthalamic nucleus deep brain stimulation (STN-DBS). We conducted a cross-sectional study on 76 PD patients treated with bilateral STN-DBS (PD-DBS) and 33 medically treated PD patients (PD-Med). Speech and voice functions, electrode positions, motor function and cognitive function were comprehensively assessed. Moreover, speech and voice functions were compared between the on-stimulation and off-stimulation conditions in 42 PD-DBS patients. Speech and voice disorders in PD-DBS patients were significantly worse than those in PD-Med patients. Factor analysis and subsequent cluster analysis classified PD-DBS patients into five clusters: relatively good speech and voice function type, 25%; stuttering type, 24%; breathy voice type, 16%; strained voice type, 18%; and spastic dysarthria type, 17%. STN-DBS ameliorated voice tremor or low volume; however, it deteriorated the overall speech intelligibility in most patients. Breathy voice did not show significant changes and stuttering exhibited slight improvement after stopping stimulation. In contrast, patients with strained voice type or spastic dysarthria type showed a greater improvement after stopping stimulation. Spastic dysarthria type patients showed speech disorders similar to spastic dysarthria, which is associated with bilateral upper motor neuron involvement. Strained voice type and spastic dysarthria type appeared to be related to current diffusion to the corticobulbar fibres. Stuttering and breathy voice can be aggravated by STN-DBS, but are mainly due to aging or PD itself. Strained voice and spastic dysarthria are considered corticobulbar side effects. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  19. Altered Microstructural Caudate Integrity in Posttraumatic Stress Disorder but Not Traumatic Brain Injury

    Science.gov (United States)

    Waltzman, Dana; Soman, Salil; Fairchild, J. Kaci; Kinoshita, Lisa M.; Wintermark, Max; Ashford, J. Wesson; Yesavage, Jerome; Williams, Leanne

    2017-01-01

    Objective Given the high prevalence and comorbidity of combat-related PTSD and TBI in Veterans, it is often difficult to disentangle the contributions of each disorder. Examining these pathologies separately may help to understand the neurobiological basis of memory impairment in PTSD and TBI independently of each other. Thus, we investigated whether a) PTSD and TBI are characterized by subcortical structural abnormalities by examining diffusion tensor imaging (DTI) metrics and volume and b) if these abnormalities were specific to PTSD versus TBI. Method We investigated whether individuals with PTSD or TBI display subcortical structural abnormalities in memory regions by examining DTI metrics and volume of the hippocampus and caudate in three groups of Veterans: Veterans with PTSD, Veterans with TBI, and Veterans with neither PTSD nor TBI (Veteran controls). Results While our results demonstrated no macrostructural differences among the groups in these regions, there were significant alterations in microstructural DTI indices in the caudate for the PTSD group but not the TBI group compared to Veteran controls. Conclusions The result of increased mean, radial, and axial diffusivity, and decreased fractional anisotropy in the caudate in absence of significant volume atrophy in the PTSD group suggests the presence of subtle abnormalities evident only at a microstructural level. The caudate is thought to play a role in the physiopathology of PTSD, and the habit-like behavioral features of the disorder could be due to striatal-dependent habit learning mechanisms. Thus, DTI appears to be a vital tool to investigate subcortical pathology, greatly enhancing the ability to detect subtle brain changes in complex disorders. PMID:28114393

  20. Brain circuits implicated in psychogenic paralysis in conversion disorders and hypnosis.

    Science.gov (United States)

    Vuilleumier, P

    2014-10-01

    Conversion disorders are defined as neurological symptoms arising without organic damage to the nervous system, presumably in relation to various emotional stress factors, but the exact neural substrates of these symptoms and the mechanisms responsible for their production remain poorly understood. In the past 15 years, novel insights have been gained with the advent of functional neuroimaging studies in patients suffering from conversion disorders in both motor and non-motor (e.g. somatosensory, visual) domains. Several studies have also compared brain activation patterns in conversion to those observed during hypnosis, where similar functional losses can be evoked by suggestion. The current review summarizes these recent results and the main neurobiological hypotheses proposed to account for conversion symptoms, in particular motor deficits. An emerging model points to an important role of ventromedial prefrontal cortex (VMPFC), precuneus, and perhaps other limbic structures (including amygdala), all frequently found to be hyperactivated in conversion disorders in parallel to impaired recruitment of primary motor and/or sensory pathways at the cortical or subcortical (basal ganglia) level. These findings are only partly shared with hypnosis, where increases in precuneus predominate, together with activation of attentional control systems, but without any activation of VMPFC. Both VMPFC and precuneus are key regions for access to internal representations about the self, integrating information from memory and imagery with affective relevance (in VMPFC) and sensory or agency representations (in precuneus). It is therefore postulated that conversion deficits might result from an alteration of conscious sensorimotor functions and self-awareness under the influence of affective and sensory representations generated in these regions, which might promote certain patterns of behaviors in response to self-relevant emotional states.

  1. Moving forward: advances in the treatment of movement disorders with deep brain stimulation

    Directory of Open Access Journals (Sweden)

    Terry K Schiefer

    2011-11-01

    Full Text Available The modern era of stereotactic and functional neurosurgery has ushered in state of the art technologies for the treatment of movement disorders, particularly Parkinson’s disease (PD, tremor, and dystonia. After years of experience with various surgical therapies, the eventual shortcomings of both medical and surgical treatments, and several serendipitous discoveries, deep brain stimulation (DBS has risen to the forefront as a highly effective, safe, and reversible treatment for these conditions. Idiopathic advanced Parkinson’s disease can be treated with thalamic, globus pallidus internus (GPi, or subthalamic nucleus (STN DBS. Thalamic DBS primarily relieves tremor while GPi and STN DBS alleviate a wide range of Parkinsonian symptoms. Thalamic DBS is also used in the treatment of other types of tremor, particularly essential tremor, with excellent results. Both primary and various types of secondary dystonia can be treated very effectively with GPi DBS. The variety of anatomical targets for these movement disorders is indicative of the network-level dysfunction mediating these movement disturbances. Despite an increasing understanding of the clinical benefits of DBS, little is known about how DBS can create such wide sweeping neuromodulatory effects. The key to improving this therapeutic modality and discovering new ways to treat these and other neurologic conditions lies in better understanding the intricacies of DBS. Here we review the history and pertinent clinical data for DBS treatment of PD, tremor, and dystonia. Our search criteria for PubMed included combinations of the following terms: DBS, neuromodulation, movement disorders, PD, tremor, dystonia, and history. Dates were not restricted.

  2. Decreased plasma brain-derived neurotrophic factor levels in institutionalized elderly with depressive disorder.

    Science.gov (United States)

    Chu, Chin-Liang; Liang, Chih-Kuang; Chou, Ming-Yueh; Lin, Yu-Te; Pan, Chih-Chuan; Lu, Ti; Chen, Liang-Kung; Chow, Philip C

    2012-06-01

    To compare the differences in plasma brain-derived neurotrophic factor (BDNF) levels among institutionalized ethnic Chinese elderly participants with major depression, those with subclinical depression, and a nondepressed control group. A cross-sectional study. The veterans' home in southern Taiwan. One hundred sixty-seven residents. Questionnaires including the Minimum Data Set Nursing Home 2.1, Chinese-language version, and the short-form Geriatric Depression Scale, Chinese-language version. Depressive disorder was diagnosed by a well-trained psychiatrist using DSM-IV-TR (Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision) criteria. We measured plasma BDNF levels in the following 3 groups: nondepressive subjects (n = 122), subclinically depressive subjects (n = 33), and subjects with major depression (n = 12). Plasma BDNF was assayed using the sandwich ELISA method. We noted a significantly negative association between age and plasma BDNF in the regression model. There was no significant correlation between BDNF plasma levels and body weight or platelet counts. We found that plasma BDNF was significantly lower in the major depressive group (mean, 115.1 pg/mL; SD, 57.2) than in the nondepressive group (mean, 548.8 pg/mL; SD, 370.6; P depressive group (mean, 231.8 pg/mL; SD, 92.4; P depressive disorder but also in those with subclinical depression. This makes the plasma BDNF level a potential biological marker for clinical or subclinical depression. Copyright © 2012 American Medical Directors Association, Inc. Published by Elsevier Inc. All rights reserved.

  3. Altered brain functional networks in people with Internet gaming disorder: Evidence from resting-state fMRI.

    Science.gov (United States)

    Wang, Lingxiao; Wu, Lingdan; Lin, Xiao; Zhang, Yifen; Zhou, Hongli; Du, Xiaoxia; Dong, Guangheng

    2016-08-30

    Although numerous neuroimaging studies have detected structural and functional abnormality in specific brain regions and connections in subjects with Internet gaming disorder (IGD), the topological organization of the whole-brain network in IGD remain unclear. In this study, we applied graph theoretical analysis to explore the intrinsic topological properties of brain networks in Internet gaming disorder (IGD). 37 IGD subjects and 35 matched healthy control (HC) subjects underwent a resting-state functional magnetic resonance imaging scan. The functional networks were constructed by thresholding partial correlation matrices of 90 brain regions. Then we applied graph-based approaches to analysis their topological attributes, including small-worldness, nodal metrics, and efficiency. Both IGD and HC subjects show efficient and economic brain network, and small-world topology. Although there was no significant group difference in global topology metrics, the IGD subjects showed reduced regional centralities in the prefrontal cortex, left posterior cingulate cortex, right amygdala, and bilateral lingual gyrus, and increased functional connectivity in sensory-motor-related brain networks compared to the HC subjects. These results imply that people with IGD may be associated with functional network dysfunction, including impaired executive control and emotional management, but enhanced coordination among visual, sensorimotor, auditory and visuospatial systems.

  4. The Relationship Between Brain Oscillatory Activity and Therapeutic Effectiveness of Transcranial Magnetic Stimulation in the Treatment of Major Depressive Disorder

    Directory of Open Access Journals (Sweden)

    Andrew Francis Leuchter

    2013-02-01

    Full Text Available Major Depressive Disorder (MDD is marked by disturbances in brain functional connectivity. This connectivity is modulated by rhythmic oscillations of brain electrical activity, which enable coordinated functions across brain regions. Oscillatory activity plays a central role in regulating thinking and memory, mood, cerebral blood flow, and neurotransmitter levels, and restoration of normal oscillatory patterns is associated with effective treatment of MDD. Repetitive Transcranial Magnetic Stimulation (rTMS is a robust treatment for MDD, but the mechanism of action (MOA of its benefits for mood disorders remains incompletely understood. Benefits of rTMS have been tied to enhanced neuroplasticity in specific brain pathways. We summarize here the evidence that rTMS entrains and resets thalamocortical oscillators, normalizes regulation and facilitates reemergence of intrinsic cerebral rhythms, and through this mechanism restores normal brain function. This entrainment and resetting may be a critical step in engendering neuroplastic changes and the antidepressant effects of rTMS. It may be possible to modify the method of rTMS administration to enhance this mechanism of action and achieve better antidepressant effectiveness. We propose that rTMS can be administered: 1 synchronized to a patient’s individual alpha rhythm (IAF, or synchronized rTMS (sTMS; 2 as a low magnetic field strength sinusoidal wave form; and, 3 broadly to multiple brain areas simultaneously. We present here the theory and evidence indicating that these modifications could enhance the therapeutic effectiveness of rTMS for the treatment of MDD.

  5. State of the Art for Deep Brain Stimulation Therapy in Movement Disorders: A Clinical and Technological Perspective.

    Science.gov (United States)

    Wagle Shukla, Aparna; Okun, Michael S

    2016-01-01

    Deep brain stimulation (DBS) therapy is a widely used brain surgery that can be applied for many neurological and psychiatric disorders. DBS is American Food and Drug Administration approved for medication refractory Parkinson's disease, essential tremor and dystonia. Although DBS has shown consistent success in many clinical trials, the therapy has limitations and there are well-recognized complications. Thus, only carefully selected patients are ideal candidates for this surgery. Over the last two decades, there have been significant advances in clinical knowledge on DBS. In addition, the surgical techniques and technology related to DBS has been rapidly evolving. The goal of this review is to describe the current status of DBS in the context of movement disorders, outline the mechanisms of action for DBS in brief, discuss the standard surgical and imaging techniques, discuss the patient selection and clinical outcomes in each of the movement disorders, and finally, introduce the recent advancements from a clinical and technological perspective.

  6. Symptom Complaints Following Combat-Related Traumatic Brain Injury: Relationship to Traumatic Brain Injury Severity and Posttraumatic Stress Disorder

    Science.gov (United States)

    2009-08-01

    being less competent (Sawchyn, Mateer, & Suffi eld, 2005 ). Mild TBI has also been associated with greater emotional distress ( Leininger , Kreutzer...brain injury . Brain Injury , 23 , 83 – 91 . Leininger , B.E. , Kreutzer , J.S. , & Hill , M.R . ( 1991 ). Comparison of minor and severe

  7. Organic and Non-Organic Language Disorders after Awake Brain Surgery

    Directory of Open Access Journals (Sweden)

    Elke De Witte

    2014-04-01

    Full Text Available INTRODUCTION: Awake surgery with Direct Electrical Stimulation (DES is considered the ‘gold standard’ to resect brain tumours in the language dominant hemisphere (De Witte & Mariën, 2013. Although transient language impairments are common in the immediate postoperative phase, permanent postoperative language deficits seem to be rare (Duffau, 2007. Milian et al. (2014 stated that most patients tolerate the awake procedure well and would undergo a similar procedure again. However, postoperative psychological symptoms including recurrent distressing dreams and persistent avoidance of stimuli have been recorded following awake surgery (Goebel, Nabavi, Schubert, & Mehdorn, 2010; Milian et al., 2014. To the best of our knowledge, psychogenic language disturbances have never been described after awake surgery. In general, only a handful of non-organic, psychogenic language disorders have been reported in the literature (De Letter et al., 2012. We report three patients with left brain tumours (see table 1 who presented linguistic symptoms after awake surgery that were incompatible with the lesion location, suggesting a psychogenic origin. METHODS: Neurocognitive (language, memory, executive functions investigations were carried out before, during and after awake surgery (6 weeks, 6 months postsurgery on the basis of standardised tests. Pre- and postoperative (fMRI images, DTI results and intraoperative DES findings were analysed. A selection of tasks was used to map language intraoperatively (De Witte et al., 2013. In the postoperative phase spontaneous speech and behavioural phenomena to errors were video-recorded. RESULTS: Preoperative language tests did not reveal any speech or language problems. Intraoperatively, eloquent sites were mapped and preserved enabling good language skills at the end of the awake procedure. However, assessments in the first weeks postsurgery disclosed language and behavioural symptoms that support the hypothesis of a

  8. Brain Basics

    Medline Plus

    Full Text Available ... better understand and treat disorders. Mental disorders are common. You may have a friend, colleague, or relative ... attention deficit hyperactivity disorder (ADHD) . Glutamate —the most common neurotransmitter, glutamate has many roles throughout the brain ...

  9. Cardiorespiratory concerns shape brain responses during automatic panic-related scene processing in patients with panic disorder.

    Science.gov (United States)

    Feldker, Katharina; Heitmann, Carina Yvonne; Neumeister, Paula; Brinkmann, Leonie; Bruchmann, Maximillan; Zwitserlood, Pienie; Straube, Thomas

    2017-09-26

    Increased automatic processing of threat-related stimuli has been proposed as a key element in panic disorder. Little is known about the neural basis of automatic processing, in particular to task-irrelevant, panic-related, ecologically valid stimuli, or about the association between brain activation and symptomatology in patients with panic disorder. The present event-related fMRI study compared brain responses to task-irrelevant, panic-related and neutral visual stimuli in medication-free patients with panic disorder and healthy controls. Panic-related and neutral scenes were presented while participants performed a spatially nonoverlapping bar orientation task. Correlation analyses investigated the association between brain responses and panic-related aspects of symptomatology, measured using the Anxiety Sensitivity Index (ASI). We included 26 patients with panic disorder and 26 heatlhy controls in our analysis. Compared with controls, patients with panic disorder showed elevated activation in the amygdala, brainstem, thalamus, insula, anterior cingulate cortex and midcingulate cortex in response to panic-related versus neutral task-irrelevant stimuli. Furthermore, fear of cardiovascular symptoms (a subcomponent of the ASI) was associated with insula activation, whereas fear of respiratory symptoms was associated with brainstem hyperactivation in patients with panic disorder. The additional implementation of measures of autonomic activation, such as pupil diameter, heart rate, or electrodermal activity, would have been informative during the fMRI scan as well as during the rating procedure. Results reveal a neural network involved in the processing of panic-related distractor stimuli in patients with panic disorder and suggest an automatic weighting of panic-related information depending on the magnitude of cardiovascular and respiratory symptoms. Insula and brainstem activations show function-related associations with specific components of panic symptomatology.

  10. Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI.

    Science.gov (United States)

    Prasad, Kedar N; Bondy, Stephen C

    2015-03-02

    Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

  11. Distinct multivariate brain morphological patterns and their added predictive value with cognitive and polygenic risk scores in mental disorders.

    Science.gov (United States)

    Doan, Nhat Trung; Kaufmann, Tobias; Bettella, Francesco; Jørgensen, Kjetil Nordbø; Brandt, Christine Lycke; Moberget, Torgeir; Alnæs, Dag; Douaud, Gwenaëlle; Duff, Eugene; Djurovic, Srdjan; Melle, Ingrid; Ueland, Torill; Agartz, Ingrid; Andreassen, Ole A; Westlye, Lars T

    2017-01-01

    The brain underpinnings of schizophrenia and bipolar disorders are multidimensional, reflecting complex pathological processes and causal pathways, requiring multivariate techniques to disentangle. Furthermore, little is known about the complementary clinical value of brain structural phenotypes when combined with data on cognitive performance and genetic risk. Using data-driven fusion of cortical thickness, surface area, and gray matter density maps (GMD), we found six biologically meaningful patterns showing strong group effects, including four statistically independent multimodal patterns reflecting co-occurring alterations in thickness and GMD in patients, over and above two other independent patterns of widespread thickness and area reduction. Case-control classification using cognitive scores alone revealed high accuracy, and adding imaging features or polygenic risk scores increased performance, suggesting their complementary predictive value with cognitive scores being the most sensitive features. Multivariate pattern analyses reveal distinct patterns of brain morphology in mental disorders, provide insights on the relative importance between brain structure, cognitive and polygenetic risk score in classification of patients, and demonstrate the importance of multivariate approaches in studying the pathophysiological substrate of these complex disorders.

  12. Preliminary Evidence for Impaired Brain Activity of Neural Reward Processing in Children and Adolescents with Reactive Attachment Disorder.

    Science.gov (United States)

    Tomoda, Akemi

    2016-01-01

    Childhood maltreatment, which markedly increases risks for psychopathology, is associated with structural and functional brain differences. Especially, exposure to parental verbal abuse (PVA) or interparental violence during childhood is associated with negative outcomes such as depression, posttraumatic stress disorder (PTSD), and reduced cognitive abilities. Other forms of childhood maltreatment have been associated with brain structure or developmental alteration. Our earlier studies elucidated potential discernible effects of PVA and witnessing domestic violence during childhood on brain morphology, including gray matter volume or cortical thickness. Brain regions that process and convey the adverse sensory input of the abuse might be modified specifically by such experiences, particularly in subjects exposed to a single type of maltreatment. Exposure to multiple types of maltreatment is more commonly associated with morphological alterations in the corticolimbic regions. These findings fit with preclinical studies showing that sensory cortices are highly plastic structures. Using tasks with high and low monetary rewards while subjects underwent functional MRI, we also examined whether neural activity during reward processing was altered, or not, in children and adolescents with reactive attachment disorder (RAD). Significantly reduced activity in the caudate and nucleus accumbens was observed during a high monetary reward condition in the RAD group compared to the typically developed group. The striatal neural reward activity in the RAD group was also markedly decreased. The present results suggest that dopaminergic dysfunction occurred in the striatum in children and adolescents with RAD, potentially leading to a future risk of psychiatric disorders such as dependence.

  13. Occurrence of Asymptomatic Acute Neuromyelitis Optica Spectrum Disorder-Typical Brain Lesions during an Attack of Optic Neuritis or Myelitis

    Science.gov (United States)

    Kim, Su-Hyun; Hyun, Jae-Won; Joung, AeRan; Lee, Sang Hyun; Kim, Ho Jin

    2016-01-01

    We aimed to investigate the frequency of asymptomatic acute brain MRI abnormalities accompanying optic neuritis (ON) or myelitis in neuromyelitis optica spectrum disorder (NMOSD) patients with aquaporin-4 antibodies (AQP4-Ab). We reviewed 324 brain MRI scans that were obtained during acute attacks of ON or myelitis, in 165 NMOSD patients with AQP4-Ab. We observed that acute asymptomatic NMOSD-typical brain lesions accompanied 27 (8%) acute attacks of ON or myelitis in 24 (15%) patients. The most common asymptomatic brain abnormalities included edematous corpus callosum lesions (n = 17), followed by lesions on the internal capsule and/or cerebral peduncle lesions (n = 9), periependymal surfaces of the fourth ventricle (n = 5), large deep white matter lesions (n = 4), periependymal cerebral lesions surrounding the lateral ventricles (n = 3), and hypothalamic lesions (n = 1). If asymptomatic NMOSD-typical brain abnormalities were considered as evidence for DIS, while also assuming that the AQP4-IgG status was unknown, the median time to diagnosis using the 2015 diagnosis criteria for NMOSD was shortened from 28 months to 6 months (p = 0.008). Asymptomatic acute NMOSD-typical brain lesions can be accompanied by an acute attack of ON or myelitis. Identifying these asymptomatic brain lesions may help facilitate earlier diagnosis of NMOSD. PMID:27936193

  14. Occurrence of Asymptomatic Acute Neuromyelitis Optica Spectrum Disorder-Typical Brain Lesions during an Attack of Optic Neuritis or Myelitis.

    Science.gov (United States)

    Kim, Su-Hyun; Hyun, Jae-Won; Joung, AeRan; Lee, Sang Hyun; Kim, Ho Jin

    2016-01-01

    We aimed to investigate the frequency of asymptomatic acute brain MRI abnormalities accompanying optic neuritis (ON) or myelitis in neuromyelitis optica spectrum disorder (NMOSD) patients with aquaporin-4 antibodies (AQP4-Ab). We reviewed 324 brain MRI scans that were obtained during acute attacks of ON or myelitis, in 165 NMOSD patients with AQP4-Ab. We observed that acute asymptomatic NMOSD-typical brain lesions accompanied 27 (8%) acute attacks of ON or myelitis in 24 (15%) patients. The most common asymptomatic brain abnormalities included edematous corpus callosum lesions (n = 17), followed by lesions on the internal capsule and/or cerebral peduncle lesions (n = 9), periependymal surfaces of the fourth ventricle (n = 5), large deep white matter lesions (n = 4), periependymal cerebral lesions surrounding the lateral ventricles (n = 3), and hypothalamic lesions (n = 1). If asymptomatic NMOSD-typical brain abnormalities were considered as evidence for DIS, while also assuming that the AQP4-IgG status was unknown, the median time to diagnosis using the 2015 diagnosis criteria for NMOSD was shortened from 28 months to 6 months (p = 0.008). Asymptomatic acute NMOSD-typical brain lesions can be accompanied by an acute attack of ON or myelitis. Identifying these asymptomatic brain lesions may help facilitate earlier diagnosis of NMOSD.

  15. Altered behavior and neural activity in conspecific cagemates co-housed with mouse models of brain disorders.

    Science.gov (United States)

    Yang, Hyunwoo; Jung, Seungmoon; Seo, Jinsoo; Khalid, Arshi; Yoo, Jung-Seok; Park, Jihyun; Kim, Soyun; Moon, Jangsup; Lee, Soon-Tae; Jung, Keun-Hwa; Chu, Kon; Lee, Sang Kun; Jeon, Daejong

    2016-09-01

    The psychosocial environment is one of the major contributors of social stress. Family members or caregivers who consistently communicate with individuals with brain disorders are considered at risk for physical and mental health deterioration, possibly leading to mental disorders. However, the underlying neural mechanisms of this phenomenon remain poorly understood. To address this, we developed a social stress paradigm in which a mouse model of epilepsy or depression was housed long-term (>4weeks) with normal conspecifics. We characterized the behavioral phenotypes and electrophysiologically investigated the neural activity of conspecific cagemate mice. The cagemates exhibited deficits in behavioral tasks assessing anxiety, locomotion, learning/memory, and depression-like behavior. Furthermore, they showed severe social impairment in social behavioral tasks involving social interaction or aggression. Strikingly, behavioral dysfunction remained in the cagemates 4weeks following co-housing cessation with the mouse models. In an electrophysiological study, the cagemates showed an increased number of spikes in medial prefrontal cortex (mPFC) neurons. Our results demonstrate that conspecifics co-housed with mouse models of brain disorders develop chronic behavioral dysfunctions, and suggest a possible association between abnormal mPFC neural activity and their behavioral pathogenesis. These findings contribute to the understanding of the psychosocial and psychiatric symptoms frequently present in families or caregivers of patients with brain disorders.

  16. Brain SPECT guided repetitive transcranial magnetic stimulation (rTMS) in treatment resistant major depressive disorder.

    Science.gov (United States)

    Jha, Shailesh; Chadda, Rakesh K; Kumar, Nand; Bal, C S

    2016-06-01

    Repetitive transcranial magnetic stimulation (rTMS) has emerged as a potential treatment in treatment resistant major depressive disorder (MDD). However, there is no consensus about the exact site of stimulation for rTMS. Single-photon emission computed tomography (SPECT) offers a potential technique in deciding the site of stimulation. The present study was conducted to assess the difference in outcome of brain SPECT assisted rTMS versus standard protocol of twenty sessions of high frequency rTMS as add on treatment in 20 patients with treatment resistant MDD, given over a period of 4 weeks. Thirteen subjects (group I) received high frequency rTMS over an area of hypoperfusion in the prefrontal cortex, as identified on SPECT, whereas 7 subjects (group II) were administered rTMS in the left dorsoslateral prefrontal cortex (DLPFC) area. Improvement was monitored using standardized instruments. Patients in the group I showed a significantly better response compared to those in the group II. In group I, 46% of the subjects were responders on MADRS, 38% on BDI and 77% on CGI. The parallel figures of responders in Group II were 0% on MADRS, 14% on BDI and 43% on CGI. There were no remitters in the study. No significant untoward side effects were noticed. The study had limitations of a small sample size and non-controlled design, and all the subjects were also receiving the standard antidepressant therapy. Administration of rTMS over brain SPECT specified area of hypoperfusion may have a better clinical outcome compared to the standard protocol.

  17. Restoring cognitive functions using non-invasive brain stimulation techniques in patients with cerebellar disorders

    Directory of Open Access Journals (Sweden)

    Paul A Pope

    2014-04-01

    Full Text Available Numerous studies have highlighted the possibility of modulating the excitability of cerebro-cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral-lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato-rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro-cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided towards neuro-enhancement in certain patient populations, using what is commonly termed 'non-invasive brain stimulation' as a cognitive rehabilitation tool to modulate cerebro-cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo

  18. Restoring cognitive functions using non-invasive brain stimulation techniques in patients with cerebellar disorders.

    Science.gov (United States)

    Pope, Paul A; Miall, R Chris

    2014-01-01

    Numerous studies have highlighted the possibility of modulating the excitability of cerebro-cerebellar circuits bi-directionally using transcranial electrical brain stimulation, in a manner akin to that observed using magnetic stimulation protocols. It has been proposed that cerebellar stimulation activates Purkinje cells in the cerebellar cortex, leading to inhibition of the dentate nucleus, which exerts a tonic facilitatory drive onto motor and cognitive regions of cortex through a synaptic relay in the ventral-lateral thalamus. Some cerebellar deficits present with cognitive impairments if damage to non-motor regions of the cerebellum disrupts the coupling with cerebral cortical areas for thinking and reasoning. Indeed, white matter changes in the dentato-rubral tract correlate with cognitive assessments in patients with Friedreich ataxia, suggesting that this pathway is one component of the anatomical substrate supporting a cerebellar contribution to cognition. An understanding of the physiology of the cerebro-cerebellar pathway previously helped us to constrain our interpretation of results from two recent studies in which we showed cognitive enhancements in healthy participants during tests of arithmetic after electrical stimulation of the cerebellum, but only when task demands were high. Others studies have also shown how excitation of the prefrontal cortex can enhance performance in a variety of working memory tasks. Thus, future efforts might be guided toward neuro-enhancement in certain patient populations, using what is commonly termed "non-invasive brain stimulation" as a cognitive rehabilitation tool to modulate cerebro-cerebellar circuits, or for stimulation over the cerebral cortex to compensate for decreased cerebellar drive to this region. This article will address these possibilities with a review of the relevant literature covering ataxias and cerebellar cognitive affective disorders, which are characterized by thalamo-cortical disturbances.

  19. Detecting awareness in patients with disorders of consciousness using a hybrid brain-computer interface

    Science.gov (United States)

    Pan, Jiahui; Xie, Qiuyou; He, Yanbin; Wang, Fei; Di, Haibo; Laureys, Steven; Yu, Ronghao; Li, Yuanqing

    2014-10-01

    Objective. The bedside detection of potential awareness in patients with disorders of consciousness (DOC) currently relies only on behavioral observations and tests; however, the misdiagnosis rates in this patient group are historically relatively high. In this study, we proposed a visual hybrid brain-computer interface (BCI) combining P300 and steady-state evoked potential (SSVEP) responses to detect awareness in severely brain injured patients. Approach. Four healthy subjects, seven DOC patients who were in a vegetative state (VS, n = 4) or minimally conscious state (MCS, n = 3), and one locked-in syndrome (LIS) patient attempted a command-following experiment. In each experimental trial, two photos were presented to each patient; one was the patient's own photo, and the other photo was unfamiliar. The patients were instructed to focus on their own or the unfamiliar photos. The BCI system determined which photo the patient focused on with both P300 and SSVEP detections. Main results. Four healthy subjects, one of the 4 VS, one of the 3 MCS, and the LIS patient were able to selectively attend to their own or the unfamiliar photos (classification accuracy, 66-100%). Two additional patients (one VS and one MCS) failed to attend the unfamiliar photo (50-52%) but achieved significant accuracies for their own photo (64-68%). All other patients failed to show any significant response to commands (46-55%). Significance. Through the hybrid BCI system, command following was detected in four healthy subjects, two of 7 DOC patients, and one LIS patient. We suggest that the hybrid BCI system could be used as a supportive bedside tool to detect awareness in patients with DOC.

  20. Integration of ultra-high field MRI and histology for connectome based research of brain disorders

    Science.gov (United States)

    Yang, Shan; Yang, Zhengyi; Fischer, Karin; Zhong, Kai; Stadler, Jörg; Godenschweger, Frank; Steiner, Johann; Heinze, Hans-Jochen; Bernstein, Hans-Gert; Bogerts, Bernhard; Mawrin, Christian; Reutens, David C.; Speck, Oliver; Walter, Martin

    2013-01-01

    Ultra-high field magnetic resonance imaging (MRI) became increasingly relevant for in vivo neuroscientific research because of improved spatial resolutions. However, this is still the unchallenged domain of histological studies, which long played an important role in the investigation of neuropsychiatric disorders. While the field of biological psychiatry strongly advanced on macroscopic levels, current developments are rediscovering the richness of immunohistological information when attempting a multi-level systematic approach to brain function and dysfunction. For most studies, histology sections lost information on three-dimensional reconstructions. Translating histological sections to 3D-volumes would thus not only allow for multi-stain and multi-subject alignment in post mortem data, but also provide a crucial step in big data initiatives involving the network analyses currently performed with in vivo MRI. We therefore investigated potential pitfalls during integration of MR and histological information where no additional blockface information is available. We demonstrated that strengths and requirements from both methods can be effectively combined at a spatial resolution of 200 μm. However, the success of this approach is heavily dependent on choices of hardware, sequence and reconstruction. We provide a fully automated pipeline that optimizes histological 3D reconstructions, providing a potentially powerful solution not only for primary human post mortem research institutions in neuropsychiatric research, but also to help alleviate the massive workloads in neuroanatomical atlas initiatives. We further demonstrate (for the first time) the feasibility and quality of ultra-high spatial resolution (150 μm isotopic) imaging of the entire human brain MRI at 7T, offering new opportunities for analyses on MR-derived information. PMID:24098272

  1. Integration of ultra-high field MRI and histology for connectome based research of brain disorders

    Directory of Open Access Journals (Sweden)

    Shan eYang

    2013-09-01

    Full Text Available Ultra-high field magnetic resonance imaging (MRI became increasingly relevant for in vivo neuroscientific research because of improved spatial resolutions. However, this is still the unchallenged domain of histological studies, which long played an important role in the investigation of neuropsychiatric disorders. While the field of biological psychiatry strongly advanced on macroscopic levels, current developments are rediscovering the richness of immunohistological information when attempting a multi-level systematic approach to brain function and dysfunction. For most studies, histology sections lost information on three-dimensional reconstructions. Translating histological sections to 3D-volumes would thus not only allow for multi-stain and multi-subject alignment in post mortem data, but also provide a crucial step in big data initiatives involving the network analyses currently performed with in vivo MRI. We therefore investigated potential pitfalls during integration of MR and histological information where no additional blockface information is available. We demonstrated that strengths and requirements from both methods seem to be ideally merged at a spatial resolution of 200 μm. However, the success of this approach is heavily dependent on choices of hardware, sequence and reconstruction. We provide a fully automated pipeline that optimizes histological 3D reconstructions, providing a potentially powerful solution not only for primary human post mortem research institutions in neuropsychiatric research, but also to help alleviate the massive workloads in neuroanatomical atlas initiatives. We further demonstrate (for the first time the feasibility and quality of ultra-high spatial resolution (150 µm isotopic imaging of the entire human brain MRI at 7T, offering new opportunities for analyses on MR-derived information.

  2. Effects of STN and GPi deep brain stimulation on impulse control disorders and dopamine dysregulation syndrome.

    Directory of Open Access Journals (Sweden)

    Sarah J Moum

    Full Text Available OBJECTIVE: Impulse control disorders (ICDs and dopamine dysregulation syndrome (DDS are important behavioral problems that affect a subpopulation of patients with Parkinson's disease (PD and typically result in markedly diminished quality of life for patients and their caregivers. We aimed to investigate the effects of subthalamic nucleus (STN and internal globus pallidus (GPi deep brain stimulation (DBS on ICD/DDS frequency and dopaminergic medication usage. METHODS: A retrospective chart review was performed on 159 individuals who underwent unilateral or bilateral PD DBS surgery in either STN or GPi. According to published criteria, pre- and post-operative records were reviewed to categorize patients both pre- and post-operatively as having ICD, DDS, both ICD and DDS, or neither ICD nor DDS. Group differences in patient demographics, clinical presentations, levodopa equivalent dose (LED, and change in diagnosis following unilateral/bilateral by brain target (STN or GPi DBS placement were examined. RESULTS: 28 patients met diagnostic criteria for ICD or DDS pre- or post-operatively. ICD or DDS classification did not differ by GPi or STN target stimulation. There was no change in DDS diagnosis after unilateral or bilateral stimulation. For ICD, diagnosis resolved in 2 of 7 individuals after unilateral or bilateral DBS. Post-operative development of these syndromes was significant; 17 patients developed ICD diagnoses post-operatively with 2 patients with pre-operative ICD developing DDS post-operatively. CONCLUSIONS: Unilateral or bilateral DBS did not significantly treat DDS or ICD in our sample, even though a few cases of ICD resolved post-operatively. Rather, our study provides preliminary evidence that DDS and ICD diagnoses may emerge following DBS surgery.

  3. Investigation of the Changes in the Power Distribution in Resting-State Brain Networks Associated with Pure Conduct Disorder.

    Science.gov (United States)

    Zhang, Jiang; Zhou, Jiansong; Lu, Fengmei; Chen, Liangyin; Huang, Yunzhi; Chen, Huafu; Xiang, Yutao; Yang, Gang; Yuan, Zhen

    2017-07-17

    Conduct disorder (CD) is a psychiatric disorder in children and adolescence. To investigate changes in the power distribution in brain networks between CD and typically developing (TD) groups, resting-state functional magnetic resonance imaging (rsfMRI) data of thirty-six subjects were first recorded, and then the data were preprocessed using DPARSF and SPM8. Meanwhile, the power of the blood oxygenation level-dependent (BOLD) signals of ninety brain regions was acquired using the integral of the Welch power spectral density (PSD). Additionally, the powers of the brain regions that reached significance (p brain regions between the CD and TD groups, indicating a change in the power distribution. In addition, the results also suggest that the total power consumption of brain networks in CD patients is less than that observed in the TD group. Consequently, the study provided a paradigm for establishing quantifiable indicators via the power spectrum approach for the comparison and analysis of the BOLD signal power between CD patients and healthy controls.

  4. The medial forebrain bundle as a target for deep brain stimulation for obsessive-compulsive disorder.

    Science.gov (United States)

    Coenen, Volker A; Schlaepfer, Thomas E; Goll, Peter; Reinacher, Peter C; Voderholzer, Ulrich; Tebartz van Elst, Ludger; Urbach, Horst; Freyer, Tobias

    2017-06-01

    Deep brain stimulation (DBS) is a promising putative modality for the treatment of refractory psychiatric disorders such as major depression and obsessive-compulsive disorder (OCD). Several targets have been posited; however, a clear consensus on differential efficacy and possible modes of action remain unclear. DBS to the supero-lateral branch of the medial forebrain bundle (slMFB) has recently been introduced for major depression (MD). Due to our experience with slMFB stimulation for MD, and because OCD might be related to similar dysfunctions of the reward system, treatment with slMFB DBS seams meaningful. Here we describe our first 2 cases together with a hypothetical mode of action. We describe diffusion tensor imaging (DTI) fiber tractographically (FT)-assisted implantation of the bilateral DBS systems in 2 male patients. In a selected literature overview, we discuss the possible mode of action. Both patients were successfully implanted and stimulated. The follow-up time was 12 months. One patient showed a significant response (Yale-Brown Obsessive-Compulsive Scale [YBOCS] reduction by 35%); the other patient reached remission criteria 3 months after surgery (YBOCS<14) and showed mild OCD just above the remission criterion at 12 months follow-up. While the hypermetabolism theory for OCD involves the cortico-striato-thalamo-cortical (CSTC) network, we think that there is clinical evidence that the reward system plays a crucial role. Our findings suggest an important role of this network in mechanisms of disease development and recovery. In this uncontrolled case series, continuous bilateral DBS to the slMFB led to clinically significant improvements of ratings of OCD severity. Ongoing research focuses on the role of the reward system in OCD, and its yet-underestimated role in this underlying neurobiology of the disease.

  5. Brain order disorder 2nd group report of f-EEG

    Science.gov (United States)

    Lalonde, Francois; Gogtay, Nitin; Giedd, Jay; Vydelingum, Nadarajen; Brown, David; Tran, Binh Q.; Hsu, Charles; Hsu, Ming-Kai; Cha, Jae; Jenkins, Jeffrey; Ma, Lien; Willey, Jefferson; Wu, Jerry; Oh, Kenneth; Landa, Joseph; Lin, C. T.; Jung, T. P.; Makeig, Scott; Morabito, Carlo Francesco; Moon, Qyu; Yamakawa, Takeshi; Lee, Soo-Young; Lee, Jong-Hwan; Szu, Harold H.; Kaur, Balvinder; Byrd, Kenneth; Dang, Karen; Krzywicki, Alan; Familoni, Babajide O.; Larson, Louis; Harkrider, Susan; Krapels, Keith A.; Dai, Liyi

    2014-05-01

    Since the Brain Order Disorder (BOD) group reported on a high density Electroencephalogram (EEG) to capture the neuronal information using EEG to wirelessly interface with a Smartphone [1,2], a larger BOD group has been assembled, including the Obama BRAIN program, CUA Brain Computer Interface Lab and the UCSD Swartz Computational Neuroscience Center. We can implement the pair-electrodes correlation functions in order to operate in a real time daily environment, which is of the computation complexity of O(N3) for N=102~3 known as functional f-EEG. The daily monitoring requires two areas of focus. Area #(1) to quantify the neuronal information flow under arbitrary daily stimuli-response sources. Approach to #1: (i) We have asserted that the sources contained in the EEG signals may be discovered by an unsupervised learning neural network called blind sources separation (BSS) of independent entropy components, based on the irreversible Boltzmann cellular thermodynamics(ΔS correlation function. (i) Although the entropy itself is not the information per se, but the concurrence of the entropy sources is the information flow as a functional-EEG, sketched in this 2nd BOD report. Area #(2) applying EEG bio-feedback will improve collective decision making (TBD). Approach to #2: We introduce a novel performance quality metrics, in terms of the throughput rate of faster (Δt) & more accurate (ΔA) decision making, which applies to individual, as well as team brain dynamics. Following Nobel Laureate Daniel Kahnmen's novel "Thinking fast and slow", through the brainwave biofeedback we can first identify an individual's "anchored cognitive bias sources". This is done in order to remove the biases by means of individually tailored pre-processing. Then the training effectiveness can be maximized by the collective product Δt * ΔA. For Area #1, we compute a spatiotemporally windowed EEG in vitro average using adaptive time-window sampling. The sampling rate depends on the type of

  6. Application of machine learning classification for structural brain MRI in mood disorders: Critical review from a clinical perspective.

    Science.gov (United States)

    Kim, Yong-Ku; Na, Kyoung-Sae

    2018-01-03

    Mood disorders are a highly prevalent group of mental disorders causing substantial socioeconomic burden. There are various methodological approaches for identifying the underlying mechanisms of the etiology, symptomatology, and therapeutics of mood disorders; however, neuroimaging studies have provided the most direct evidence for mood disorder neural substrates by visualizing the brains of living individuals. The prefrontal cortex, hippocampus, amygdala, thalamus, ventral striatum, and corpus callosum are associated with depression and bipolar disorder. Identifying the distinct and common contributions of these anatomical regions to depression and bipolar disorder have broadened and deepened our understanding of mood disorders. However, the extent to which neuroimaging research findings contribute to clinical practice in the real-world setting is unclear. As traditional or non-machine learning MRI studies have analyzed group-level differences, it is not possible to directly translate findings from research to clinical practice; the knowledge gained pertains to the disorder, but not to individuals. On the other hand, a machine learning approach makes it possible to provide individual-level classifications. For the past two decades, many studies have reported on the classification accuracy of machine learning-based neuroimaging studies from the perspective of diagnosis and treatment response. However, for the application of a machine learning-based brain MRI approach in real world clinical settings, several major issues should be considered. Secondary changes due to illness duration and medication, clinical subtypes and heterogeneity, comorbidities, and cost-effectiveness restrict the generalization of the current machine learning findings. Sophisticated classification of clinical and diagnostic subtypes is needed. Additionally, as the approach is inevitably limited by sample size, multi-site participation and data-sharing are needed in the future. Copyright

  7. Brain disease, connectivity, plasticity and cognitive therapy: A neurological view of mental disorders.

    Science.gov (United States)

    Lubrini, G; Martín-Montes, A; Díez-Ascaso, O; Díez-Tejedor, E

    2017-04-25

    Our conception of the mind-brain relationship has evolved from the traditional idea of dualism to current evidence that mental functions result from brain activity. This paradigm shift, combined with recent advances in neuroimaging, has led to a novel definition of brain functioning in terms of structural and functional connectivity. The purpose of this literature review is to describe the relationship between connectivity, brain lesions, cerebral plasticity, and functional recovery. Assuming that brain function results from the organisation of the entire brain in networks, brain dysfunction would be a consequence of altered brain network connectivity. According to this approach, cognitive and behavioural impairment following brain damage result from disrupted functional organisation of brain networks. However, the dynamic and versatile nature of these circuits makes recovering brain function possible. Cerebral plasticity allows for functional reorganisation leading to recovery, whether spontaneous or resulting from cognitive therapy, after brain disease. Current knowledge of brain connectivity and cerebral plasticity provides new insights into normal brain functioning, the mechanisms of brain damage, and functional recovery, which in turn serve as the foundations of cognitive therapy. Copyright © 2017 Sociedad Española de Neurología. Publicado por Elsevier España, S.L.U. All rights reserved.

  8. Volume of discrete brain structures in complex dissociative disorders : preliminary findings

    NARCIS (Netherlands)

    Ehling, T.; Nijenhuis, E. R. S.; Krikke, A. P.; DeKloet, ER; Vermetten, E

    2007-01-01

    Based on findings in traumatized animals and patients with posttraumatic stress disorder, and on traumatogenic models of complex dissociative disorders, it was hypothesized that (1) patients with complex dissociative disorders have smaller volumes of hippocampus, parahippocampal gyrus, and amygdala

  9. Volume of discrete brain structures in complex dissociative disorders : preliminary findings

    NARCIS (Netherlands)

    Ehling, T.; Nijenhuis, E. R. S.; Krikke, A. P.; DeKloet, ER; Vermetten, E

    2007-01-01

    Based on findings in traumatized animals and patients with posttraumatic stress disorder, and on traumatogenic models of complex dissociative disorders, it was hypothesized that (1) patients with complex dissociative disorders have smaller volumes of hippocampus, parahippocampal gyrus, and amygdala

  10. Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

    OpenAIRE

    Elder, Gregory A; Dorr, Nathan P.; De Gasperi, Rita; Gama Sosa, Miguel A.; Shaughness, Michael C.; Maudlin-Jeronimo, Eric; Hall, Aaron A; McCarron, Richard M.; Ahlers, Stephen T

    2012-01-01

    Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety ...

  11. The effect of recombinant erythropoietin on plasma brain derived neurotrophic factor levels in patients with affective disorders

    DEFF Research Database (Denmark)

    Vinberg, Maj; Miskowiak, Kamilla; Hoejman, Pernille

    2015-01-01

    UNLABELLED: The study aims to investigate the effect of repeated infusions of recombinant erythropoietin (EPO) on plasma brain derived neurotrophic factor (BDNF) levels in patients with affective disorders. In total, 83 patients were recruited: 40 currently depressed patients with treatment......-resistant depression (TRD) (Hamilton Depression Rating Scale-17 items (HDRS-17) score >17) (study 1) and 43 patients with bipolar disorder (BD) in partial remission (HDRS-17 and Young Mania Rating Scale (YMRS) ≤ 14) (study 2). In both studies, patients were randomised to receive eight weekly EPO (Eprex; 40,000 IU...

  12. Technetium-99m HMPAO brain SPECT in children with attention deficit hyperactivity disorder

    Energy Technology Data Exchange (ETDEWEB)

    Kaya, G.C.; Pekcanlar, A.; Bekis, R.; Ada, E.; Miral, S.; Emiroglu, N.; Durak, H. [Dokuz Eylul Univ., Izmir (Turkey). School of Medicine

    2002-12-01

    Attention deficit hyperactivity disorder (ADHD) is a developmental, neurobehavioral syndrome with an onset in childhood. The aim of this study was to investigate the existence of regional perfusion changes in ADHD by means of Tc-99m HMPAO brain SPECT. Thirteen children with a diagnosis of ADHD and 7 healthy, age-matched controls were included in this study. Hypoperfusion was observed on the right temporal cortex in 9, and on the left temporal cortex in 3 children. The distribution of the lesions showed right lateral temporal cortex involvement in 3, right medial temporal cortex in 9 and left medial temporal cortex in 8 children. Asymmetric perfusion was seen on the caudate nucleus in 4, on the thalamus in 3 and on the frontal cortex in 6 children. There was a significant difference between children with ADHD and controls in right medial temporal cortex: cerebellum and right lateral temporal cortex: cerebellum ratios. Hypoperfusion in the right medial temporal cortex was significantly and inversely correlated with Du Paul teachers' questionnaire rating scale (r=-0.71, p=0.006). It has been postulated that difficulty in self regulating response to stimuli in ADHD is mediated by underfunctioning of the orbital frontal cortex and subsequent connection to the limbic system. Decreased temporal cortex perfusion may dysfunction of the limbic system or the orbito-frontal-limbic axis. (author)

  13. Predictors of Recovery from Traumatic Brain Injury-Induced Prolonged Consciousness Disorder

    Directory of Open Access Journals (Sweden)

    Hiroaki Abe

    2017-01-01

    Full Text Available We investigated the clinical predictors of the degree of recovery in patients with prolonged disorders of consciousness (PDC caused by traumatic brain injury. Fourteen patients with PDC underwent two diffusion tensor imaging (DTI studies; the first and second scans were performed at 345.6±192.6 and 689.1±272.2 days after the injury, respectively. In addition to the temporal changes in each of these diffusion parameters, fractional anisotropy (FA, mean diffusivity, axial diffusivity (AD, and radial diffusivity were assessed over a 1-year period. Relationship of clinical and DTI parameters with recovery from PDC (RPDC was evaluated using Spearman’s rank-correlation and stepwise multiple linear regression analysis. The mean FA and number of voxels with FA values > 0.4 (VsFA0.4 were significantly decreased at the second scan. A significant positive correlation was observed between the degree of RPDC and mean FA (r=0.60 and VsFA0.4 (r=0.68 as well as between the difference in VsFA0.4 (r=0.63 and AD (r=0.54 between the first and second scans. On multiple linear regression analysis, initial severity of PDC and the difference in AD remained significantly associated with the degree of RPDC. The microstructural white matter changes observed in this study indicate their potential relation with the degree of RPDC over the longer term.

  14. Serum brain-derived neurotrophic factor (BDNF) levels in attention deficit-hyperactivity disorder (ADHD).

    Science.gov (United States)

    Scassellati, Catia; Zanardini, Roberta; Tiberti, Alessandra; Pezzani, Marco; Valenti, Vera; Effedri, Paola; Filippini, Elena; Conte, Stefano; Ottolini, Alberto; Gennarelli, Massimo; Bocchio-Chiavetto, Luisella

    2014-03-01

    It has been proposed that the neurotrophin brain-derived neurotrophic factor (BDNF) may be involved in attention deficit-hyperactivity disorder (ADHD) etiopathogenesis. Alterations in BDNF serum levels have been observed in childhood/adulthood neurodevelopmental pathologies, but no evidence is available for BDNF serum concentrations in ADHD. The study includes 45 drug-naïve ADHD children and 45 age-sex matched healthy subjects. Concentration of serum BDNF was determined by the ELISA method. BDNF serum levels in patients with ADHD were not different from those of controls (mean ± SD; ADHD: 39.33 ± 10.41 ng/ml; controls: 38.82 ± 8.29 ng/ml, t = -0.26, p = 0.80). Our findings indicate no alteration of serum BDNF levels in untreated patients with ADHD. A further stratification for cognitive, neuropsychological and psychopathological assessment in a larger sample could be useful to clarify the role of BDNF in the endophenotype characterization of ADHD.

  15. Old Things New View: Ascorbic Acid Protects the Brain in Neurodegenerative Disorders

    Directory of Open Access Journals (Sweden)

    Adriana Covarrubias-Pinto

    2015-11-01

    Full Text Available Ascorbic acid is a key antioxidant of the Central Nervous System (CNS. Under brain activity, ascorbic acid is released from glial reservoirs to the synaptic cleft, where it is taken up by neurons. In neurons, ascorbic acid scavenges reactive oxygen species (ROS generated during synaptic activity and neuronal metabolism where it is then oxidized to dehydroascorbic acid and released into the extracellular space, where it can be recycled by astrocytes. Other intrinsic properties of ascorbic acid, beyond acting as an antioxidant, are important in its role as a key molecule of the CNS. Ascorbic acid can switch neuronal metabolism from glucose consumption to uptake and use of lactate as a metabolic substrate to sustain synaptic activity. Multiple evidence links oxidative stress with neurodegeneration, positioning redox imbalance and ROS as a cause of neurodegeneration. In this review, we focus on ascorbic acid homeostasis, its functions, how it is used by neurons and recycled to ensure antioxidant supply during synaptic activity and how this antioxidant is dysregulated in neurodegenerative disorders.

  16. Mild Traumatic Brain Injury and Attention-Deficit Hyperactivity Disorder in Young Student Athletes.

    Science.gov (United States)

    Biederman, Joseph; Feinberg, Leah; Chan, James; Adeyemo, Bamidele O; Woodworth, K Yvonne; Panis, Walter; McGrath, Neal; Bhatnagar, Saurabha; Spencer, Thomas J; Uchida, Mai; Kenworthy, Tara; Grossman, Rebecca; Zafonte, Ross; Faraone, Stephen V

    2015-11-01

    A recent meta-analysis documented a significant statistical association between mild traumatic brain injury (mTBI) and attention deficit hyperactivity disorder (ADHD) (Adeyemo et al., 2014), but the direction of this effect was unclear. In this study, we hypothesized that ADHD would be an antecedent risk factor for mTBI. Participants were student athletes ages 12 to 25 who had sustained a mTBI and Controls of similar age and sex selected from studies of youth with and without ADHD. Subjects were assessed for symptoms of ADHD, concussion severity, and cognitive function. mTBI subjects had a significantly higher rate of ADHD than Controls, and in all cases the age of onset of ADHD was before mTBI onset. mTBI+ADHD subjects also had more severe concussion symptoms (fatigue and poor concentration) than mTBI-ADHD subjects. These results support ADHD as an antecedent risk factor for mTBI in student athletes and that its presence complicates the course of mTBI.

  17. Hemostatic system changes predictive value in patients with ischemic brain disorders

    Directory of Open Access Journals (Sweden)

    Raičević Ranko

    2002-01-01

    Full Text Available The aim of this research was to determine the importance of tracking the dynamics of changes of the hemostatic system factors (aggregation of thrombocytes, D-dimer, PAI-1, antithrombin III, protein C and protein S, factor VII and factor VIII, fibrin degradation products, euglobulin test and the activated partial thromboplastin time – aPTPV in relation to the level of the severity of ischemic brain disorders (IBD and the level of neurological and functional deficiency in the beginning of IBD manifestation from 7 to 10 days, 19 to 21 day, and after 3 to 6 months. The research results confirmed significant predictive value of changes of hemostatic system with the predomination of procoagulant factors, together with the insufficiency of fibrinolysis. Concerning the IBD severity and it's outcome, the significant predictive value was shown in the higher levels of PAI-1 and the lower level of antithrombin III, and borderline significant value was shown in the accelerated aggregation of thrombocytes and the increased concentration of D-dimer. It could be concluded that the tracking of the dynamics of changes in parameters of hemostatic system proved to be an easily accessible method with the significant predictive value regarding the development of more severe. IBD cases and the outcome of the disease itself.

  18. Regional brain electrical activity in posttraumatic stress disorder after motor vehicle accident.

    Science.gov (United States)

    Rabe, Sirko; Beauducel, André; Zöllner, Tanja; Maercker, Andreas; Karl, Anke

    2006-11-01

    This study examined whether patients with posttraumatic stress disorder (PTSD) related to motor vehicle accidents (MVAs) would show an abnormal pattern of electroencephalographic (EEG) alpha asymmetries, which has been proposed for particular types of anxiety. Patients with PTSD (n = 22) or subsyndromal PTSD (n = 21), traumatized controls without PTSD (non-PTSD with MVA; n = 21), and healthy controls without MVA (n = 23) underwent measurement of EEG activity during baseline and exposure to a neutral, a positive, a negative, and an accident-related picture. Differences in brain asymmetry between groups were observed only during exposure to trauma-related material. PTSD and subsyndromal PTSD patients showed a pattern of enhanced right anterior and posterior activation, whereas non-PTSD with MVA participants showed the opposite pattern. Furthermore, posterior asymmetry in nontraumatized healthy controls varied with gender, with female participants showing a pattern of higher right posterior activation. The results support the hypothesis that symptomatic MVA survivors are characterized by a pattern of right hemisphere activation that is associated with anxious arousal and symptoms of PTSD during processing of trauma-specific information. (c) 2006 APA, all rights reserved.

  19. SIRT1 in the Brain – Connections with Aging-associated Disorders and Lifespan

    Directory of Open Access Journals (Sweden)

    Fanny eNg

    2015-03-01

    Full Text Available The silent mating type information regulation 2 proteins (sirtuins 1 of class III histone deacetylases have been associated with health span and longevity. SIRT1, the best studied member of the mammalian sirtuins, has a myriad of roles in multiple tissues and organs. However, a significant part of SIRT1’s role that impinges on aging and lifespan may lie in its activities in the central nervous system (CNS neurons. Systemically, SIRT1 influences energy metabolism and circadian rhythm through its activity in the hypothalamic nuclei. From a cell biological perspective, SIRT1 is a crucial component of multiple interconnected regulatory networks that modulate dendritic and axonal growth, as well as survival against stress. This neuronal cell autonomous activity of SIRT1 is also important for neuronal plasticity, cognitive functions, as well as protection against aging-associated neuronal degeneration and cognitive decline. We discuss recent findings that have shed light on the various activities of SIRT1 in the brain, which collectively impinge on aging-associated disorders and lifespan.

  20. [Psychopathological disorders and quality of life in patients with brain infarction].

    Science.gov (United States)

    Castellanos Pinedo, F; Hernández Pérez, J M; Zurdo, M; Rodríguez Fúnez, B; García Fernández, C; Cueli Rincón, B; Hernández Bayo, J M; Bejarano Parra, M; Rodríguez Manchón, V

    2012-03-01

    To study the influence of various factors on the health related quality of life (HRQOL) of patients who have suffered a brain infarction (BI), with special attention to psychopathological disorders (PD). Prospective observational study on 45 patients admitted due to a BI, evaluated at 4, 12 and 26 weeks of the acute event. Social and demographic data, and medical history were collected; the SF-36 scale was used for the assessment of HRQOL, and the Neuropsychiatric Inventory (NPI), MMSE, Canadian Neurological Scale, Modified Rankin Scale and other instruments for assessing psychopathological, cognitive, neurological and functional status. A linear regression analysis was performed to identify potential predictors of the SF-36 scores at 26 weeks, introducing, as independent variables, medical and psychiatric history, demographic characteristics and the functional, neuropsychological and psychopathological assessments at 4 weeks. Valid predictive models for all the SF-36 domains were obtained, in which a history of pre-morbid depression, higher scores in the NPI and Rankin Scale, and lowest in the Canadian Neurological Scale were the main predictors of a worse HRQOL in the long term. Psychopathology related caregiver's distress (assessed with the NPI) was associated with a lower score in the social function index. PDs and functional status were the main determinants of HRQOL in patients with BI. Copyright © 2011 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  1. Keeping time in the brain: Autism spectrum disorder and audiovisual temporal processing.

    Science.gov (United States)

    Stevenson, Ryan A; Segers, Magali; Ferber, Susanne; Barense, Morgan D; Camarata, Stephen; Wallace, Mark T

    2016-07-01

    A growing area of interest and relevance in the study of autism spectrum disorder (ASD) focuses on the relationship between multisensory temporal function and the behavioral, perceptual, and cognitive impairments observed in ASD. Atypical sensory processing is becoming increasingly recognized as a core component of autism, with evidence of atypical processing across a number of sensory modalities. These deviations from typical processing underscore the value of interpreting ASD within a multisensory framework. Furthermore, converging evidence illustrates that these differences in audiovisual processing may be specifically related to temporal processing. This review seeks to bridge the connection between temporal processing and audiovisual perception, and to elaborate on emerging data showing differences in audiovisual temporal function in autism. We also discuss the consequence of such changes, the specific impact on the processing of different classes of audiovisual stimuli (e.g. speech vs. nonspeech, etc.), and the presumptive brain processes and networks underlying audiovisual temporal integration. Finally, possible downstream behavioral implications, and possible remediation strategies are outlined. Autism Res 2016, 9: 720-738. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

  2. A brain-computer interface based attention training program for treating attention deficit hyperactivity disorder.

    Directory of Open Access Journals (Sweden)

    Choon Guan Lim

    Full Text Available UNLABELLED: Attention deficit hyperactivity disorder (ADHD symptoms can be difficult to treat. We previously reported that a 20-session brain-computer interface (BCI attention training programme improved ADHD symptoms. Here, we investigated a new more intensive BCI-based attention training game system on 20 unmedicated ADHD children (16 males, 4 females with significant inattentive symptoms (combined and inattentive ADHD subtypes. This new system monitored attention through a head band with dry EEG sensors, which was used to drive a feed forward game. The system was calibrated for each user by measuring the EEG parameters during a Stroop task. Treatment consisted of an 8-week training comprising 24 sessions followed by 3 once-monthly booster training sessions. Following intervention, both parent-rated inattentive and hyperactive-impulsive symptoms on the ADHD Rating Scale showed significant improvement. At week 8, the mean improvement was -4.6 (5.9 and -4.7 (5.6 respectively for inattentive symptoms and hyperactive-impulsive symptoms (both p<0.01. Cohen's d effect size for inattentive symptoms was large at 0.78 at week 8 and 0.84 at week 24 (post-boosters. Further analysis showed that the change in the EEG based BCI ADHD severity measure correlated with the change ADHD Rating Scale scores. The BCI-based attention training game system is a potential new treatment for ADHD. TRIAL REGISTRATION: ClinicalTrials.gov NCT01344044.

  3. Brain-Derived Neurotrophic Factor (BDNF protein levels in anxiety disorders: systematic review and meta-regression analysis

    Directory of Open Access Journals (Sweden)

    Sharain eSuliman

    2013-07-01

    Full Text Available Background: Brain-Derived Neurotrophic Factor (BDNF is a neurotrophin that is involved in the synaptic plasticity and survival of neurons. BDNF is believed to be involved in the pathogenesis of several neuropsychiatric disorders. As findings of BDNF levels in the anxiety disorders have been inconsistent, we undertook to conduct a systematic review and meta-analysis of studies that assessed BDNF protein levels in anxiety disorders. Methods: We conducted the review using electronic databases and searched reference lists of relevant articles for any further studies. Studies that measured BDNF protein levels in any anxiety disorder and compared these to a control group were included. Effect sizes of the differences in BDNF levels between anxiety disorder and control groups were calculated. Results: Eight studies with a total of 1179 participants were included. Initial findings suggested that BDNF levels were lower in individuals with any anxiety disorder compared to those without (Standard Mean Difference [SMD]=-0.94 [-1.75, -0.12], p≤0.05. This, however, differed with regards to source of BDNF protein (plasma: SMD=-1.31 [-1.69, -0.92], p≤0.01; serum: SMD=-1.06 [-2.27, 0.16], p≥0.01 and type of anxiety disorder (PTSD: SMD=-0.05 [-1.66, 1.75], p≥0.01; OCD: SMD=-2.33 [-4.21, -0.45], p≤0.01. Conclusion: Although BDNF levels appear to be reduced in individuals with an anxiety disorder, this is not consistent across the various anxiety disorders and may largely be explained by the significantly lowered BDNF levels found in OCD. Results further appear to be mediated by differences in sampling methods. Findings are, however, limited by the lack of research in this area, and given the potential for BDNF as a biomarker of anxiety disorders it would be useful to clarify the relationship further.

  4. A case study of a multiply talented savant with an autism spectrum disorder: neuropsychological functioning and brain morphometry

    OpenAIRE

    Wallace, Gregory L.; Happé, Francesca; Giedd, Jay N

    2009-01-01

    Neuropsychological functioning and brain morphometry in a savant (case GW) with an autism spectrum disorder (ASD) and both calendar calculation and artistic skills are quantified and compared with small groups of neurotypical controls. Good memory, mental calculation and visuospatial processing, as well as (implicit) knowledge of calendar structure and ‘weak’ central coherence characterized the cognitive profile of case GW. Possibly reflecting his savant skills, the superior parietal region o...

  5. Effect of brain structure and function on reward anticipation in children and adults with attention deficit hyperactivity disorder combined subtype

    OpenAIRE

    Kappel, Viola; Lorenz, Robert C.; Streifling, Martina; Renneberg, Babette; Lehmkuhl, Ulrike; Ströhle, Andreas; Salbach-Andrae, Harriet; Beck, Anne

    2014-01-01

    Attention deficit hyperactivity disorder (ADHD) is associated with decreased ventral-striatal responsiveness during reward anticipation. However, previous research mostly focused on adults with heterogeneous ADHD subtype and divers drug treatment status while studies in children with ADHD are sparse. Moreover, it remains unclear to what degree ADHD is characterized by a delay of normal brain structure or function maturation. We therefore attempt to determine whether results from structural an...

  6. Mapping the structural organization of the brain in conduct disorder: replication of findings in two independent samples.

    Science.gov (United States)

    Fairchild, Graeme; Toschi, Nicola; Sully, Kate; Sonuga-Barke, Edmund J S; Hagan, Cindy C; Diciotti, Stefano; Goodyer, Ian M; Calder, Andrew J; Passamonti, Luca

    2016-09-01

    Neuroimaging methods that allow researchers to investigate structural covariance between brain regions are increasingly being used to study psychiatric disorders. Structural covariance analyses are particularly well suited for studying disorders with putative neurodevelopmental origins as they appear sensitive to changes in the synchronized maturation of different brain regions. We assessed interregional correlations in cortical thickness as a measure of structural covariance, and applied this method to investigate the coordinated development of different brain regions in conduct disorder (CD). We also assessed whether structural covariance measures could differentiate between the childhood-onset (CO-CD) and adolescence-onset (AO-CD) subtypes of CD, which may differ in terms of etiology and adult outcomes. We examined interregional correlations in cortical thickness in male youths with CO-CD or AO-CD relative to healthy controls (HCs) in two independent datasets. The age range in the Cambridge sample was 16-21 years (mean: 18.0), whereas the age range of the Southampton sample was 13-18 years (mean: 16.7). We used FreeSurfer to perform segmentations and applied structural covariance methods to the resulting parcellations. In both samples, CO-CD participants displayed a strikingly higher number of significant cross-cortical correlations compared to HC or AO-CD participants, whereas AO-CD participants presented fewer significant correlations than HCs. Group differences in the strength of the interregional correlations were observed in both samples, and each set of results remained significant when controlling for IQ and comorbid attention-deficit/hyperactivity disorder symptoms. This study provides new evidence for quantitative differences in structural brain organization between the CO-CD and AO-CD subtypes, and supports the hypothesis that both subtypes of CD have neurodevelopmental origins. © 2016 The Authors. Journal of Child Psychology and Psychiatry

  7. Influence of post-traumatic stress disorder on neuroinflammation and cell proliferation in a rat model of traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Sandra A Acosta

    Full Text Available Long-term consequences of traumatic brain injury (TBI are closely associated with the development of severe psychiatric disorders, such as post-traumatic stress disorder (PTSD, yet preclinical studies on pathological changes after combined TBI with PTSD are lacking. In the present in vivo study, we assessed chronic neuroinflammation, neuronal cell loss, cell proliferation and neuronal differentiation in specific brain regions of adult Sprague-Dawley male rats following controlled cortical impact model of moderate TBI with or without exposure to PTSD. Eight weeks post-TBI, stereology-based histological analyses revealed no significant differences between sham and PTSD alone treatment across all brain regions examined, whereas significant exacerbation of OX6-positive activated microglial cells in the striatum, thalamus, and cerebral peduncle, but not cerebellum, in animals that received TBI alone and combined TBI-PTSD compared with PTSD alone and sham treatment. Additional immunohistochemical results revealed a significant loss of CA3 pyramidal neurons in the hippocampus of TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Further examination of neurogenic niches revealed a significant downregulation of Ki67-positive proliferating cells, but not DCX-positive neuronally migrating cells in the neurogenic subgranular zone and subventricular zone for both TBI alone and TBI-PTSD compared to PTSD alone and sham treatment. Comparisons of levels of neuroinflammation and neurogenesis between TBI alone and TBI+PTSD revealed that PTSD did not exacerbate the neuropathological hallmarks of TBI. These results indicate a progressive deterioration of the TBI brain, which, under the conditions of the present approach, was not intensified by PTSD, at least within our time window and within the examined areas of the brain. Although the PTSD manipulation employed here did not exacerbate the pathological effects of TBI, the observed long

  8. Structural and functional connectivity of the human brain in autism spectrum disorders and attention-deficit/hyperactivity disorder: A rich club organization study

    Science.gov (United States)

    Ray, Siddharth; Miller, Meghan; Karalunas, Sarah; Robertson, C.J.; Grayson, David; Cary, Paul; Hawkey, Elizabeth; Painter, Julia G.; Kriz, Daniel; Fombonne, Eric; Nigg, Joel T.; Fair, Damien A.

    2015-01-01

    Attention deficit hyperactive disorder (ADHD) and Autism spectrum disorders (ASD) are two of the most common and vexing neurodevelopmental disorders among children. Although the two disorders share many behavioral and neuropsychological characteristics, most MRI studies examine only one of the disorders at a time. Using graph theory combined with structural and functional connectivity, we examined the large-scale network organization among three groups of children: a group with ADHD (8-12 years, n = 20), a group with ASD (7-13 years, n = 16), and typically developing controls (TD) (8-12 years, n = 20). We apply the concept of the rich-club organization, whereby central, highly connected hub regions are also highly connected to themselves. We examine the brain into two different network domains: (1) inside a rich-club network phenomena, and (2) outside a rich-club network phenomena. ASD and ADHD populations had markedly different patterns of rich club and non rich-club connections in both functional and structural data. The ASD group exhibited higher connectivity in structural and functional networks but only inside the rich-club networks. These findings were replicated using the autism brain imaging data exchange (ABIDE) dataset with ASD (n = 85) and TD (n = 101). The ADHD group exhibited a lower generalized fractional anisotropy (GFA) and functional connectivity inside the rich-club networks, but a higher number of axonal fibers and correlation coefficient values outside the rich-club. Despite some shared biological features and frequent comorbity, these data suggest ADHD and ASD exhibit distinct large-scale connectivity patterns in middle childhood. PMID:25116862

  9. Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder

    Directory of Open Access Journals (Sweden)

    Tatiana Lauxen Peruzzolo

    2015-01-01

    Full Text Available Pediatric bipolar disorder (PBD is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder. We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm3, respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

  10. Correlation between Peripheral Levels of Brain-Derived Neurotrophic Factor and Hippocampal Volume in Children and Adolescents with Bipolar Disorder.

    Science.gov (United States)

    Lauxen Peruzzolo, Tatiana; Anes, Mauricio; Kohmann, Andre de Moura; Souza, Ana Claudia Mércio Loredo; Rodrigues, Ramiro Borges; Brun, Juliana Basso; Peters, Roberta; de Aguiar, Bianca Wollenhaupt; Kapczinski, Flavio; Tramontina, Silzá; Rohde, Luis Augusto Paim; Zeni, Cristian Patrick

    2015-01-01

    Pediatric bipolar disorder (PBD) is a serious mental disorder that affects the development and emotional growth of affected patients. The brain derived neurotrophic factor (BDNF) is recognized as one of the possible markers of the framework and its evolution. Abnormalities in BDNF signaling in the hippocampus could explain the cognitive decline seen in patients with TB. Our aim with this study was to evaluate possible changes in hippocampal volume in children and adolescents with BD and associate them to serum BDNF. Subjects included 30 patients aged seven to seventeen years from the ProCAB (Program for Children and Adolescents with Bipolar Disorder). We observed mean right and left hippocampal volumes of 41910.55 and 41747.96 mm(3), respectively. No statistically significant correlations between peripheral BDNF levels and hippocampal volumes were found. We believe that the lack of correlation observed in this study is due to the short time of evolution of BD in children and adolescents. Besides studies with larger sample sizes to confirm the present findings and longitudinal assessments, addressing brain development versus a control group and including drug-naive patients in different mood states may help clarify the role of BDNF in the brain changes consequent upon BD.

  11. Brain changes in early-onset bipolar and unipolar depressive disorders: a systematic review in children and adolescents.

    Science.gov (United States)

    Serafini, Gianluca; Pompili, Maurizio; Borgwardt, Stefan; Houenou, Josselin; Geoffroy, Pierre Alexis; Jardri, Renaud; Girardi, Paolo; Amore, Mario

    2014-11-01

    Pediatric bipolar disorder (BD) and unipolar disorder (UD) share common symptomatic and functional impairments. Various brain imaging techniques have been used to investigate the integrity of brain white matter (WM) and gray matter (GM) in these disorders. Despite promising preliminary findings, it is still unclear whether these alterations may be considered as common trait markers or may be used to distinguish BD from UD. A systematic literature search of studies between 1980 and September 2013 which reported WM/GM changes in pediatric and adolescent BD/UD, as detected by diffusion tensor imaging and voxel-based analysis was conducted. Of the 34 articles judged as eligible, 17 fulfilled our inclusion criteria and were finally retained in this review. More abnormalities have been documented in the brains of children and adolescents with BD than UD. Reductions in the volume of basal ganglia and the hippocampus appeared more specific for pediatric UD, whereas reduced corpus callosum volume and increased rates of deep WM hyperintensities were more specific for pediatric BD. Seminal papers failed to address the possibility that the differences between unipolar and bipolar samples might be related to illness severity, medication status, comorbidity or diagnosis. UD and BD present both shared and distinctive impairments in the WM and GM compartments. More WM abnormalities have been reported in children and adolescents with bipolar disease than in those with unipolar disease, maybe as a result of a low number of DTI studies in pediatric UD. Future longitudinal studies should investigate whether neurodevelopmental changes are diagnosis-specific.

  12. Noninvasive brain stimulation to suppress craving in substance use disorders: review of human evidence and methodological considerations for future work

    Science.gov (United States)

    Hone-Blanchet, Antoine; Ciraulo, Domenic A; Pascual-Leone, Alvaro; Fecteau, Shirley

    2016-01-01

    Substance use disorders (SUDs) can be viewed as a pathology of neuroadaptation. The pharmacological overstimulation of neural mechanisms of reward, motivated learning and memory leads to drug-seeking behavior. A critical characteristic of SUDs is the appearance of craving, the motivated desire and urge to use, which is a main focus of current pharmacological and behavioral therapies. Recent proof-of-concept studies have tested the effects of non-invasive brain stimulation on craving. Although its mechanisms of action are not fully understood, this approach shows interesting potential in tuning down craving and possibly consumption of diverse substances. This article reviews available results on the use of repetitive transcranial magnetic stimulation (rTMS) and transcranial electrical stimulation (tES) in SUDs, specifically tobacco, alcohol and psychostimulant use disorders. We discuss several important factors that need to be addressed in future works to improve clinical assessment and effects of non-invasive brain stimulation in SUDs. Factors discussed include brain stimulation devices and parameters, study designs, brain states and subjects’ characteristics. PMID:26449761

  13. A Computational Model for the Automatic Diagnosis of Attention Deficit Hyperactivity Disorder Based on Functional Brain Volume

    Directory of Open Access Journals (Sweden)

    Lirong Tan

    2017-09-01

    Full Text Available In this paper, we investigated the problem of computer-aided diagnosis of Attention Deficit Hyperactivity Disorder (ADHD using machine learning techniques. With the ADHD-200 dataset, we developed a Support Vector Machine (SVM model to classify ADHD patients from typically developing controls (TDCs, using the regional brain volumes as predictors. Conventionally, the volume of a brain region was considered to be an anatomical feature and quantified using structural magnetic resonance images. One major contribution of the present study was that we had initially proposed to measure the regional brain volumes using fMRI images. Brain volumes measured from fMRI images were denoted as functional volumes, which quantified the volumes of brain regions that were actually functioning during fMRI imaging. We compared the predictive power of functional volumes with that of regional brain volumes measured from anatomical images, which were denoted as anatomical volumes. The former demonstrated higher discriminative power than the latter for the classification of ADHD patients vs. TDCs. Combined with our two-step feature selection approach which integrated prior knowledge with the recursive feature elimination (RFE algorithm, our SVM classification model combining functional volumes and demographic characteristics achieved a balanced accuracy of 67.7%, which was 16.1% higher than that of a relevant model published previously in the work of Sato et al. Furthermore, our classifier highlighted 10 brain regions that were most discriminative in distinguishing between ADHD patients and TDCs. These 10 regions were mainly located in occipital lobe, cerebellum posterior lobe, parietal lobe, frontal lobe, and temporal lobe. Our present study using functional images will likely provide new perspectives about the brain regions affected by ADHD.

  14. Hemicrania Continua Headache in a Veteran with Posttraumatic Stress Disorder and Major Depressive Disorder without Traumatic Brain Injury.

    Science.gov (United States)

    Kohrt, Brandon A; Duncan, Erica

    2012-01-01

    Hemicrania continua is a headache characterized by chronic unremitting unilateral pain associated with ipsilateral autonomic findings. This type of headache responds to high-flow oxygen and indomethacin. This case report describes a male veteran with posttraumatic stress disorder (PTSD) and major depressive disorder who suffers from comorbid hemicrania continua. The psychiatric symptoms were recalcitrant to psychopharmacological intervention. However, when the patient's hemicrania continua was treated appropriately, the patient's psychiatric symptoms also abated. This case demonstrates the need to address physical comorbidities that may exacerbate psychiatric disorders, such as PTSD.

  15. Hemicrania Continua Headache in a Veteran with Posttraumatic Stress Disorder and Major Depressive Disorder without Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Brandon A. Kohrt

    2012-01-01

    Full Text Available Hemicrania continua is a headache characterized by chronic unremitting unilateral pain associated with ipsilateral autonomic findings. This type of headache responds to high-flow oxygen and indomethacin. This case report describes a male veteran with posttraumatic stress disorder (PTSD and major depressive disorder who suffers from comorbid hemicrania continua. The psychiatric symptoms were recalcitrant to psychopharmacological intervention. However, when the patient's hemicrania continua was treated appropriately, the patient's psychiatric symptoms also abated. This case demonstrates the need to address physical comorbidities that may exacerbate psychiatric disorders, such as PTSD.

  16. Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults : a cross-sectional mega-analysis

    NARCIS (Netherlands)

    Hoogman, Martine; Bralten, Janita; Hibar, Derrek P; Mennes, Maarten; Zwiers, Marcel P; Schweren, Lizanne S J; van Hulzen, Kimm J E|info:eu-repo/dai/nl/314410120; Medland, Sarah E; Shumskaya, Elena; Jahanshad, Neda; Zeeuw, Patrick de|info:eu-repo/dai/nl/304812692; Szekely, Eszter; Sudre, Gustavo; Wolfers, Thomas; Onnink, Alberdingk M H; Dammers, Janneke T; Mostert, Jeanette C; Vives-Gilabert, Yolanda; Kohls, Gregor; Oberwelland, Eileen; Seitz, Jochen; Schulte-Rüther, Martin; Ambrosino, Sara; Doyle, Alysa E; Høvik, Marie F; Dramsdahl, Margaretha; Tamm, Leanne; van Erp, Theo G M; Dale, Anders; Schork, Andrew; Conzelmann, Annette; Zierhut, Kathrin; Baur, Ramona; McCarthy, Hazel; Yoncheva, Yuliya N; Cubillo, Ana; Chantiluke, Kaylita; Mehta, Mitul A; Paloyelis, Yannis; Hohmann, Sarah; Baumeister, Sarah; Bramati, Ivanei; Mattos, Paulo; Tovar-Moll, Fernanda; Douglas, Pamela; Banaschewski, Tobias; Brandeis, Daniel; Kuntsi, Jonna; Asherson, Philip; Rubia, Katya; Kelly, Clare; Martino, Adriana Di; Milham, Michael P; Castellanos, Francisco X; Frodl, Thomas; Zentis, Mariam; Lesch, Klaus-Peter; Reif, Andreas; Pauli, Paul; Jernigan, Terry L; Haavik, Jan; Plessen, Kerstin J; Lundervold, Astri J; Hugdahl, Kenneth; Seidman, Larry J; Biederman, Joseph; Rommelse, Nanda; Heslenfeld, Dirk J; Hartman, Catharina A; Hoekstra, Pieter J; Oosterlaan, Jaap; Polier, Georg von; Konrad, Kerstin; Vilarroya, Oscar; Ramos-Quiroga, Josep Antoni; Soliva, Joan Carles; Durston, Sarah; Buitelaar, Jan K; Faraone, Stephen V; Shaw, Philip; Thompson, Paul M; Franke, Barbara

    BACKGROUND: Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies

  17. Neurocognitive impairment of mental rotation in major depressive disorder: evidence from event-related brain potentials.

    Science.gov (United States)

    Chen, Jiu; Ma, Wentao; Zhang, Yan; Yang, Lai-Qi; Zhang, Zhijun; Wu, Xingqu; Deng, Zihe

    2014-08-01

    Mental rotation performance may be used as an index of mental slowing or bradyphrenia and may reflect speed of motor preparation. Previous studies suggest that major depressive disorder (MDD) presents correlates of impaired behavioral performance for mental rotation and psychomotor disturbance. Very little is known about the electrophysiological mechanism underlying this deficit. The present study was the first to investigate the event-related brain potential (ERP) correlates of mental rotation and their mental slowing or bradyphrenia in MDD. ERPs were recorded while we tested 25 MDD patients and 26 healthy controls by evaluating the performance of MDD patients on hand and letter rotation tasks at different orientations, and their 400-to-600-msec time window was measured and analyzed for latencies and peak amplitudes over the electrodes. First, individuals with MDD were slower and made more errors in mentally rotating hands and letters than healthy controls did, and individuals with MDD exhibited a greater difference in response times and errors than controls did between hands and letters. Second, the mean peak amplitude was significantly lower and the mean latency was significantly longer in the 400-to-600-msec time window at the parietal site in the hand tasks in MDD patients than in controls, but this was not seen in the letter task, with only lower mean peak amplitude. MDD patients present the absence of a typical mental rotation function for the amplitude of the rotation-related negativity in the hand and letter tasks. Third, the scalp activity maps in MDD patients exhibited the absence of activation in the left parietal site for the mental rotation of hands, as shown in healthy participants. In contrast, their brain activation for the letter task was similar to those of healthy participants. These data suggest that mental imagery of hands and letters relies on different cognitive and neural mechanisms and indicate that the left posterior parietal lobe is a

  18. Response to Deep Brain Stimulation in Three Brain Targets with Implications in Mental Disorders: A PET Study in Rats

    Science.gov (United States)

    Casquero-Veiga, Marta; Hadar, Ravit; Pascau, Javier; Winter, Christine; Desco, Manuel; Soto-Montenegro, María Luisa

    2016-01-01

    Objective To investigate metabolic changes in brain networks by deep brain stimulation (DBS) of the medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) and dorsomedial thalamus (DM) using positron emission tomography (PET) in naïve rats. Methods 43 male Wistar rats underwent stereotactic surgery and concentric bipolar platinum-iridium electrodes were bilaterally implanted into one of the three brain sites. [18F]-fluoro-2-deoxy-glucose-PET (18FDG-PET) and computed tomography (CT) scans were performed at the 7th (without DBS) and 9th day (with DBS) after surgery. Stimulation period matched tracer uptake period. Images were acquired with a small-animal PET-CT scanner. Differences in glucose uptake between groups were assessed with Statistical Parametric Mapping. Results DBS induced site-specific metabolic changes, although a common increased metabolic activity in the piriform cortex was found for the three brain targets. mPFC-DBS increased metabolic activity in the striatum, temporal and amygdala, and reduced it in the cerebellum, brainstem (BS) and periaqueductal gray matter (PAG). NAcc-DBS increased metabolic activity in the subiculum and olfactory bulb, and decreased it in the BS, PAG, septum and hypothalamus. DM-DBS increased metabolic activity in the striatum, NAcc and thalamus and decreased it in the temporal and cingulate cortex. Conclusions DBS induced significant changes in 18FDG uptake in brain regions associated with the basal ganglia-thalamo-cortical circuitry. Stimulation of mPFC, NAcc and DM induced different patterns of 18FD