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Sample records for brain diseased persons

  1. Personality Changes after Deep Brain Stimulation in Parkinson's Disease

    Science.gov (United States)

    Pham, Uyen; Solbakk, Anne-Kristin; Skogseid, Inger-Marie; Pripp, Are Hugo; Konglund, Ane Eidahl; Andersson, Stein; Haraldsen, Ira Ronit; Aarsland, Dag; Dietrichs, Espen; Malt, Ulrik Fredrik

    2015-01-01

    Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS) is a recognized therapy that improves motor symptoms in advanced Parkinson's disease (PD). However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI): the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS), and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L) before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P = 0.006; P = 0.024). Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P = 0.027). Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity. PMID:25705545

  2. Personality Changes after Deep Brain Stimulation in Parkinson’s Disease

    Directory of Open Access Journals (Sweden)

    Uyen Pham

    2015-01-01

    Full Text Available Objectives. Deep brain stimulation of the subthalamic nucleus (STN-DBS is a recognized therapy that improves motor symptoms in advanced Parkinson’s disease (PD. However, little is known about its impact on personality. To address this topic, we have assessed personality traits before and after STN-DBS in PD patients. Methods. Forty patients with advanced PD were assessed with the Temperament and Character Inventory (TCI: the Urgency, Premeditation, Perseverance, Sensation Seeking impulsive behaviour scale (UPPS, and the Neuroticism and Lie subscales of the Eysenck Personality Questionnaire (EPQ-N, EPQ-L before surgery and after three months of STN-DBS. Collateral information obtained from the UPPS was also reported. Results. Despite improvement in motor function and reduction in dopaminergic dosage patients reported lower score on the TCI Persistence and Self-Transcendence scales, after three months of STN-DBS, compared to baseline (P=0.006; P=0.024. Relatives reported significantly increased scores on the UPPS Lack of Premeditation scale at follow-up (P=0.027. Conclusion. STN-DBS in PD patients is associated with personality changes in the direction of increased impulsivity.

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

    Science.gov (United States)

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

    2014-01-01

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

  4. Brain Diseases

    Science.gov (United States)

    The brain is the control center of the body. It controls thoughts, memory, speech, and movement. It regulates the function of many organs. When the brain is healthy, it works quickly and automatically. However, ...

  5. PERSONALITY CHANGES IN BRAIN INJURY

    OpenAIRE

    Garcia, Patricia Gracia; Mielke, Michelle M.; Rosenberg, Paul; Bergey, Alyssa; Rao, Vani

    2011-01-01

    Traumatic brain injury (TBI) is frequently complicated by alterations in mood and behaviour and changes in personality. We report mild personality changes post-TBI as a possible indicator of traumatic brain injury, but not of injury severity or psychiatric complications.

  6. Gangliosides, NGF, brain aging and disease: a mini-review with personal reflections.

    Science.gov (United States)

    Cuello, A Claudio

    2012-06-01

    In this mini-review I summarize our research efforts in ascertaining the possible neuro-reparative properties of the GM1 ganglioside and its cooperative effects with NGF in stroke-lesion models. We also review aspects of our NGF investigations which have recently led to the discovery that NGF is released in an activity-dependent manner in the form of its precursor molecule, proNGF. These studies support the notion that in the CNS NGF metabolism conversion and degradation occur in the extracellular milieu. We have also validated this pathway in vivo demonstrating that the pharmacological inhibition of the pro-to mature NGF conversion results in the brain accumulation of proNGF and loss and atrophy of cortical cholinergic synapses. Furthermore, we have gathered neurochemical evidence for a compromise of this newly discovered NGF metabolic pathway in Alzheimer's disease, explaining the vulnerability of NGF-dependent forebrain cholinergic neurons in this disease despite normal NGF synthesis and abundance of NGF precursor.

  7. Mind, brain and person:

    African Journals Online (AJOL)

    Adele

    tools to explain the relationship between mind and brain in a sophisticated way that is .... i) Psychiatry as a subject in relation to psychology and neurology, or .... of discourse, or conceptual schemes.24 He portrayed this pluralism as lacking ...

  8. Inflammatory diseases of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Haehnel, Stefan (ed.) [University of Heidelberg Medical Center (Germany). Div. of Neuroradiology

    2009-07-01

    This book provides a comprehensive overview of inflammatory brain diseases from a neuroradiological point of view. Such diseases may be either infectious (e.g., viral encephalitis and pyogenic brain abscess) or non-infectious (e.g., multiple sclerosis), and many of these entities are becoming increasingly important for differential diagnosis, particularly in immunocompromised persons. Neuroimaging contributes greatly to the differentiation of infectious and noninfectious brain diseases and to the distinction between brain inflammation and other, for instance neoplastic, diseases. In order to ensure a standardized approach throughout the book, each chapter is subdivided into three principal sections: epidemiology, clinical presentation and therapy; imaging; and differential diagnosis. A separate chapter addresses technical and methodological issues and imaging protocols. All of the authors are recognized experts in their fields, and numerous high-quality and informative illustrations are included. This book will be of great value not only to neuroradiologists but also to neurologists, neuropediatricians, and general radiologists. (orig.)

  9. Plasma pro-brain natriuretic peptide and electrocardiographic changes in combination improve risk prediction in persons without known heart disease

    DEFF Research Database (Denmark)

    Jørgensen, Peter G; Jensen, Jan S; Appleyard, Merete

    2015-01-01

    BACKGROUND: Though the electrocardiogram(ECG) and plasma pro-brain-natriuretic-peptide (pro-BNP) are widely used markers of subclinical cardiac injury and can be used to predict future cardiovascular disease(CVD), they could merely be markers of the same underlying pathology. We aimed to determine...... cohort study. Median follow-up was 10.4 years. High pro-BNP was defined as above 90th percentile of age and sex adjusted levels. The end-points were all-cause mortality and the combination of admission with ischemic heart disease, heart failure or CVD death. RESULTS: ECG changes were present in 907...

  10. Mental Illness And Brain Disease.

    Science.gov (United States)

    Bedrick, Jeffrey D

    2014-01-01

    It has become common to say psychiatric illnesses are brain diseases. This reflects a conception of the mental as being biologically based, though it is also thought that thinking of psychiatric illness this way will reduce the stigma attached to psychiatric illness. If psychiatric illnesses are brain diseases, however, it is not clear why psychiatry should not collapse into neurology, and some argue for this course. Others try to maintain a distinction by saying that neurology deals with abnormalities of neural structure while psychiatry deals with specific abnormalities of neural functioning. It is not clear that neurologists would accept this division, nor that they should. I argue that if we take seriously the notion that psychiatric illnesses are mental illnesses we can draw a more defensible boundary between psychiatry and neurology. As mental illnesses, psychiatric illnesses must have symptoms that affect our mental capacities and that the sufferer is capable of being aware of, even if they are not always self-consciously aware of them. Neurological illnesses, such as stroke or multiple sclerosis, may be diagnosed even if they are silent, just as the person may not be aware of having high blood pressure or may suffer a silent myocardial infarction. It does not make sense to speak of panic disorder if the person has never had a panic attack, however, or of bipolar disorder in the absence of mood swings. This does not mean psychiatric illnesses are not biologically based. Mental illnesses are illnesses of persons, whereas other illnesses are illnesses of biological individuals.

  11. The cost of brain diseases

    DEFF Research Database (Denmark)

    DiLuca, Monica; Olesen, Jes

    2014-01-01

    Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists.......Brain diseases represent a considerable social and economic burden in Europe. With yearly costs of about 800 billion euros and an estimated 179 million people afflicted in 2010, brain diseases are an unquestionable emergency and a grand challenge for neuroscientists....

  12. Obsessive compulsive personality disorder and Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Alessandra Nicoletti

    Full Text Available OBJECTIVES: To evaluate the frequency of personality disorders in Parkinson's disease (PD patients and in a group of healthy controls. METHODS: Patients affected by PD diagnosed according to the United Kingdom Parkinson's disease Society Brain Bank diagnostic criteria and a group of healthy controls were enrolled in the study. PD patients with cognitive impairment were excluded from the study. Structured Clinical Interview for Personality Disorders-II (SCID-II has been performed to evaluate the presence of personality disorders. Presence of personality disorders, diagnosed according to the DSM-IV, was confirmed by a psychiatric interview. Clinical and pharmacological data were also recorded using a standardized questionnaire. RESULTS: 100 PD patients (57 men; mean age 59.0 ± 10.2 years and 100 healthy subjects (52 men; mean age 58.1 ± 11.4 years were enrolled in the study. The most common personality disorder was the obsessive-compulsive personality disorder diagnosed in 40 PD patients and in 10 controls subjects (p-value<0.0001 followed by the depressive personality disorder recorded in 14 PD patients and 4 control subjects (p-value 0.02. Obsessive-compulsive personality disorder was also found in 8 out of 16 de novo PD patients with a short disease duration. CONCLUSION: PD patients presented a high frequency of obsessive-compulsive personality disorder that does not seem to be related with both disease duration and dopaminergic therapy.

  13. The Brain Derived Neurotrophic Factor and Personality

    OpenAIRE

    Christian Montag

    2014-01-01

    The study of the biological basis of personality is a timely research endeavor, with the aim of deepening our understanding of human nature. In recent years, a growing body of research has investigated the role of the brain derived neurotrophic factor (BDNF) in the context of individual differences across human beings, with a focus on personality traits. A large number of different approaches have been chosen to illuminate the role of BDNF for personality, ranging from the measurement of BDNF...

  14. Simulations of exercise and brain effects of acute exposure to carbon monoxide in normal and vascular-diseased persons.

    Science.gov (United States)

    At some level, carboxyhemoglobin (RbCO) due to inhalation of carbon monoxide (CO) reduces maximum exercise duration in normal and ischemic heart patients. At high RbCO levels in normal subjects, brain function is also affected and behavioral performance is impaired. These are fin...

  15. Occupational Therapy and Community Reintegration of Persons with Brain Injury

    Science.gov (United States)

    Fact Sheet Occupational Therapy and Community Reintegration of Persons With Brain Injury Brain injuries can affect motor, sensory, cognitive, and behavioral functioning. A person who has sustained a brain ...

  16. Mental Illness And Brain Disease

    Directory of Open Access Journals (Sweden)

    Bedrick Jeffrey D.

    2014-12-01

    Full Text Available It has become common to say psychiatric illnesses are brain diseases. This reflects a conception of the mental as being biologically based, though it is also thought that thinking of psychiatric illness this way will reduce the stigma attached to psychiatric illness. If psychiatric illnesses are brain diseases, however, it is not clear why psychiatry should not collapse into neurology, and some argue for this course. Others try to maintain a distinction by saying that neurology deals with abnormalities of neural structure while psychiatry deals with specific abnormalities of neural functioning. It is not clear that neurologists would accept this division, nor that they should. I argue that if we take seriously the notion that psychiatric illnesses are mental illnesses we can draw a more defensible boundary between psychiatry and neurology. As mental illnesses, psychiatric illnesses must have symptoms that affect our mental capacities and that the sufferer is capable of being aware of, even if they are not always self-consciously aware of them. Neurological illnesses, such as stroke or multiple sclerosis, may be diagnosed even if they are silent, just as the person may not be aware of having high blood pressure or may suffer a silent myocardial infarction. It does not make sense to speak of panic disorder if the person has never had a panic attack, however, or of bipolar disorder in the absence of mood swings. This does not mean psychiatric illnesses are not biologically based. Mental illnesses are illnesses of persons, whereas other illnesses are illnesses of biological individuals.

  17. The Brain Derived Neurotrophic Factor and Personality

    Directory of Open Access Journals (Sweden)

    Christian Montag

    2014-01-01

    Full Text Available The study of the biological basis of personality is a timely research endeavor, with the aim of deepening our understanding of human nature. In recent years, a growing body of research has investigated the role of the brain derived neurotrophic factor (BDNF in the context of individual differences across human beings, with a focus on personality traits. A large number of different approaches have been chosen to illuminate the role of BDNF for personality, ranging from the measurement of BDNF in the serum/plasma to molecular genetics to (genetic brain imaging. The present review provides the reader with an overview of the current state of affairs in the context of BDNF and personality.

  18. Rehabilitation of persons with traumatic brain injury.

    Science.gov (United States)

    The objective of this NIH Consensus Statement is to inform the biomedical research and clinical practice communities of the results of the NIH Consensus Development Conference on Rehabilitation of Persons with Traumatic Brain Injury. The statement provides state-of-the-art information regarding effective rehabilitation measures for persons who have suffered a traumatic brain injury (TBI) and presents the conclusions and recommendations of the consensus panel regarding these issues. In addition, the statement identifies those areas that deserve further investigation. Upon completion of this educational activity, the reader should possess a clear working clinical knowledge of the state of the art regarding this topic. The target audience for this statement includes, but is not limited to, pediatricians, family practitioners, internists, neurologists, physiatrists, psychologists, and behavioral medicine specialists. Participants were a non-Federal, nonadvocate, 16-member panel representing the fields of neuropsychology, neurology, psychiatry, behavioral medicine, family medicine, pediatrics, physical medicine and rehabilitation, speech and hearing, occupational therapy, nursing, epidemiology, biostatistics and the public. In addition, 23 experts from these same fields presented data to the panel and a conference audience of 883. The literature was searched through Medline and an extensive bibliography of references was provided to the panel and the conference audience. Experts prepared abstracts with relevant citations from the literature. A compendium of evidence was prepared by the panel which included a contribution from a patient with TBI, a report from an Evidence Based Practice Center of the Agency for Health Care Policy and Research, and a report from the National Center for Injury Prevention and Control at the Centers for Disease Control and Prevention. Scientific evidence was given precedence over clinical anecdotal experience. The panel, answering predefined

  19. Brain MRI in Parkinson's disease

    NARCIS (Netherlands)

    Meijer, F.J.A.; Goraj, B.M.

    2014-01-01

    In this review article, conventional brain MRI and advanced MRI techniques in Parkinson`s disease (PD) are discussed, with emphasis on clinical relevance. Conventional brain MRI sequences generally demonstrate limited abnormalities specific for PD and in clinical practice brain MRI is mainly used to

  20. PERSONAL RESPONSIBILITY AND LIFESTYLE DISEASES

    DEFF Research Database (Denmark)

    Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2015-01-01

    , to be responsible for behaviors leading to increased risks of diseases. We show that only what we call the causal approach can adequately accommodate widely shared intuitions to the effect that certain causal influences, such as genetic make-up or certain social circumstances, diminishes or undermines personal......What does it take for an individual to be personally responsible for behaviors that lead to increased risks of diseases? We examine three approaches to responsibility that cover the most important aspects of the discussion of responsibility, and spell out what it takes, according to each of them...... responsibility. However, accepting the causal approach most likely makes personal responsibility impossible. We therefore need either to reject these widely shared intuitions about what counts as responsibility-softening or -undermining, or accept that personal responsibility for behaviors leading to increased...

  1. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  2. Personalized medicine in cardiovascular diseases.

    Science.gov (United States)

    Lee, Moo-Sik; Flammer, Andreas J; Lerman, Lilach O; Lerman, Amir

    2012-09-01

    Personalized medicine is a novel medical model with all decisions and practices being tailored to individual patients in whatever ways possible. In the era of genomics, personalized medicine combines the genetic information for additional benefit in preventive and therapeutic strategies. Personalized medicine may allow the physician to provide a better therapy for patients in terms of efficiency, safety and treatment length to reduce the associated costs. There was a remarkable growth in scientific publication on personalized medicine within the past few years in the cardiovascular field. However, so far, only very few cardiologists in the USA are incorporating personalized medicine into clinical treatment. We review the concepts, strengths, limitations and challenges of personalized medicine with a particular focus on cardiovascular diseases (CVDs). There are many challenges from both scientific and policy perspectives to personalized medicine, which can overcome them by comprehensive concept and understanding, clinical application, and evidence based practices. Individualized medicine serves a pivotal role in the evolution of national and global healthcare reform, especially, in the CVDs fields. Ultimately, personalized medicine will affect the entire landscape of health care system in the near future.

  3. Personal Responsibility and Lifestyle Diseases.

    Science.gov (United States)

    Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2016-10-01

    What does it take for an individual to be personally responsible for behaviors that lead to increased risk of disease? We examine three approaches to responsibility that cover the most important aspects of the discussion of responsibility and spell out what it takes, according to each of them, to be responsible for behaviors leading to increased risk of disease. We show that only what we call the causal approach can adequately accommodate widely shared intuitions to the effect that certain causal influences-such as genetic make-up or certain social circumstances-diminish, or undermine personal responsibility. However, accepting the causal approach most likely makes personal responsibility impossible. We therefore need either to reject these widely shared intuitions about what counts as responsibility-softening or undermining or to accept that personal responsibility for behaviors leading to increased risk of disease rests on premises so shaky that personal responsibility is probably impossible. © The Author 2016. Published by Oxford University Press, on behalf of the Journal of Medicine and Philosophy Inc. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Deep Brain Stimulation for Parkinson's Disease

    Science.gov (United States)

    ... You are here Home » Disorders » All Disorders Deep Brain Stimulation for Parkinson's Disease Information Page Deep Brain Stimulation for Parkinson's Disease Information Page Search Disorders ...

  5. Personal Responsibility and Lifestyle Diseases

    DEFF Research Database (Denmark)

    Andersen, Martin Marchman; Nielsen, Morten Ebbe Juul

    2016-01-01

    , to be responsible for behaviors leading to increased risk of disease. We show that only what we call the causal approach can adequately accommodate widely shared intuitions to the effect that certain causal influences—such as genetic make-up or certain social circumstances—diminish, or undermine personal...

  6. Foundation for PSP/CBD and Related Brain Diseases

    Science.gov (United States)

    Donate I want to learn Overview Progressive Supranuclear Palsy (PSP) Prime of life brain diseases FAQ About Our Research Research Initiatives Investigator Resources Healthcare Professional Resources I need Support Overview Personal ...

  7. Obsessive Compulsive Personality Disorder and Parkinson’s Disease

    OpenAIRE

    Alessandra Nicoletti; Antonina Luca; Loredana Raciti; Donatella Contrafatto; Elisa Bruno; Valeria Dibilio; Giorgia Sciacca; Giovanni Mostile; Antonio Petralia; Mario Zappia

    2013-01-01

    OBJECTIVES: To evaluate the frequency of personality disorders in Parkinson's disease (PD) patients and in a group of healthy controls. METHODS: Patients affected by PD diagnosed according to the United Kingdom Parkinson's disease Society Brain Bank diagnostic criteria and a group of healthy controls were enrolled in the study. PD patients with cognitive impairment were excluded from the study. Structured Clinical Interview for Personality Disorders-II (SCID-II) has been performed to evaluate...

  8. Brain Diseases in Mesopotamian Societies

    Directory of Open Access Journals (Sweden)

    Piedad Yuste

    2010-04-01

    Full Text Available In ancient Mesopotamia were not practiced neither autopsies nor dissections, so the internal organs of human body were known only from occasional inspections on wounds and injuries. The
    brain was considered as a part of the head and was not related to mental activity. However, Babylonian and Assyrian physicians were able to identify the symptoms of many diseases that affect this organ. We will make here a brief overview of them.

  9. THE PERSONALITY AND THE BRAIN: AN INEVITABLE ENCOUNTER

    Directory of Open Access Journals (Sweden)

    Eduardo J. Pedrero Pérez

    2015-01-01

    Full Text Available Personality is a construct that, until recent years, had not attracted much interest among neurologists and neuropsychologists. However, during the past decade, studies have proliferated that seek brain, structural and functional correlates of personality traits proposed by different theories, especially the Big Five model of personality. These studies have accumulated evidence about the fact that the five traits are related to specific brain locations, allowing us, at the present time, to be able to draw a brain map associated with each trait. More recent studies relate these features with the brain default mode network, where the compendium of implicit rules of management which we call personality resides. This will gradually take shape throughout one’s lifetime through mechanisms of "experience-dependent plasticity". These proposals represent the threshold of a paradigm shift that may lead the study of "mental disorders" to the territory of alterations in brain connectivity, which is an immediate challenge for neuroscience.

  10. Linking person perception and person knowledge in the human brain.

    Science.gov (United States)

    Greven, Inez M; Downing, Paul E; Ramsey, Richard

    2016-04-01

    Neuroscience research has examined separately how we detect human agents on the basis of their face and body (person perception) and how we reason about their thoughts, traits or intentions (person knowledge). Neuroanatomically distinct networks have been associated with person perception and person knowledge, but it remains unknown how multiple features of a person (e.g. thin and kind) are linked to form a holistic identity representation. In this fMRI experiment, we investigated the hypothesis that when encountering another person specialised person perception circuits would be functionally coupled with circuits involved in person knowledge. In a factorial design, we paired bodies or names with trait-based or neutral statements, and independent localiser scans identified body-selective and mentalising networks. When observing a body paired with a trait-implying statement, functional connectivity analyses demonstrated that body-selective patches in bilateral fusiform gyri were functionally coupled with nodes of the mentalising network. We demonstrate that when forming a representation of a person circuits for representing another person's physical appearance are linked to circuits that are engaged when reasoning about trait-based character. These data support the view that a 'who' system for social cognition involves communication between perceptual and inferential mechanisms when forming a representation of another's identity.

  11. Brain Imaging in Alzheimer Disease

    Science.gov (United States)

    Johnson, Keith A.; Fox, Nick C.; Sperling, Reisa A.; Klunk, William E.

    2012-01-01

    Imaging has played a variety of roles in the study of Alzheimer disease (AD) over the past four decades. Initially, computed tomography (CT) and then magnetic resonance imaging (MRI) were used diagnostically to rule out other causes of dementia. More recently, a variety of imaging modalities including structural and functional MRI and positron emission tomography (PET) studies of cerebral metabolism with fluoro-deoxy-d-glucose (FDG) and amyloid tracers such as Pittsburgh Compound-B (PiB) have shown characteristic changes in the brains of patients with AD, and in prodromal and even presymptomatic states that can help rule-in the AD pathophysiological process. No one imaging modality can serve all purposes as each have unique strengths and weaknesses. These modalities and their particular utilities are discussed in this article. The challenge for the future will be to combine imaging biomarkers to most efficiently facilitate diagnosis, disease staging, and, most importantly, development of effective disease-modifying therapies. PMID:22474610

  12. Prevalence and Predictors of Personality Change After Severe Brain Injury

    DEFF Research Database (Denmark)

    Norup, Anne; Mortensen, Erik Lykke

    2015-01-01

    of the Medical Outcomes Study 36-Item Short-Form Health Survey. Results Of the sample, 59.1% experienced personality change after acquired brain injury, and the most dominant changes were observed in the personality traits of neuroticism, extraversion, and conscientiousness. Changes in neuroticism were most...

  13. Brain aging, Alzheimer's disease, and mitochondria

    OpenAIRE

    Swerdlow, Russell H.

    2011-01-01

    The relationship between brain aging and Alzheimer’s disease (AD) is contentious. One view holds AD results when brain aging surpasses a threshold. The other view postulates AD is not a consequence of brain aging. This review discusses this conundrum from the perspective of different investigative lines that have tried to address it, as well as from the perspective of the mitochondrion, an organelle that appears to play a role in both AD and brain aging. Specific issues addressed include the ...

  14. Brain Diseases - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Supplements Videos & Tools You Are Here: Home → Multiple Languages → All Health Topics → Brain Diseases URL of this page: https://medlineplus.gov/ ... V W XYZ List of All Topics All Brain Diseases - Multiple Languages To use the sharing features on this page, ...

  15. 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.

  16. Personalized medicine in neurodegenerative diseases: how far away?

    Science.gov (United States)

    Gotovac, Kristina; Hajnšek, Sanja; Pašić, Marija Bošnjak; Pivac, Nela; Borovečki, Fran

    2014-02-01

    Neurodegenerative diseases are characterized by progressive dysfunction of the nervous system as a result of neuronal loss in the brain and spinal cord. Despite extensive research efforts aimed at development of new disease-modifying therapeutics, there is still no effective treatment to halt neurodegenerative processes. Thus, modification of current therapeutic and diagnostic research strategies is a goal of increasing urgency. The biggest limitation in neurodegenerative disease research is the lack of appropriate biomarkers. Discovery of universal biomarkers capable of diagnosing patients with neurodegenerative diseases, monitoring their response to therapy, and predicting disease progression seems to be a tall order. Instead, a combination of different methodologies in the discovery of biomarkers specific for each described aspect of the disease seems to be a more viable approach. Although application of personalized medicine in diagnosis and treatment of neurodegenerative diseases may seem far off, some recent developments, such as utilizing specific biological therapies in multiple sclerosis, microRNA profiling as a source of novel biomarkers in Parkinson’s disease, or combination of neuroimaging and proteomic analyses in diagnosis of Alzheimer’s disease patients, already point to the way clinical neurology may integrate new achievements in everyday practice. Combination of genomic, proteomic, glycomic, and metabolomic approaches may yield novel insights into molecular mechanisms of disease pathophysiology, which could then be integrated and translated into clinical neurology. Based on the developments during the past decade, it is feasible to predict that a personalized approach to treating neurological disorders will become more widely applicable in the coming years.

  17. Personality is reflected in the brain's intrinsic functional architecture.

    Directory of Open Access Journals (Sweden)

    Jonathan S Adelstein

    Full Text Available Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective 'hubs' in the brain--the anterior cingulate and precuneus--each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses.

  18. LSD-induced entropic brain activity predicts subsequent personality change.

    Science.gov (United States)

    Lebedev, A V; Kaelen, M; Lövdén, M; Nilsson, J; Feilding, A; Nutt, D J; Carhart-Harris, R L

    2016-09-01

    Personality is known to be relatively stable throughout adulthood. Nevertheless, it has been shown that major life events with high personal significance, including experiences engendered by psychedelic drugs, can have an enduring impact on some core facets of personality. In the present, balanced-order, placebo-controlled study, we investigated biological predictors of post-lysergic acid diethylamide (LSD) changes in personality. Nineteen healthy adults underwent resting state functional MRI scans under LSD (75µg, I.V.) and placebo (saline I.V.). The Revised NEO Personality Inventory (NEO-PI-R) was completed at screening and 2 weeks after LSD/placebo. Scanning sessions consisted of three 7.5-min eyes-closed resting-state scans, one of which involved music listening. A standardized preprocessing pipeline was used to extract measures of sample entropy, which characterizes the predictability of an fMRI time-series. Mixed-effects models were used to evaluate drug-induced shifts in brain entropy and their relationship with the observed increases in the personality trait openness at the 2-week follow-up. Overall, LSD had a pronounced global effect on brain entropy, increasing it in both sensory and hierarchically higher networks across multiple time scales. These shifts predicted enduring increases in trait openness. Moreover, the predictive power of the entropy increases was greatest for the music-listening scans and when "ego-dissolution" was reported during the acute experience. These results shed new light on how LSD-induced shifts in brain dynamics and concomitant subjective experience can be predictive of lasting changes in personality. Hum Brain Mapp 37:3203-3213, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Noninvasive Brain Stimulation and Personal Identity: Ethical Considerations.

    Science.gov (United States)

    Iwry, Jonathan; Yaden, David B; Newberg, Andrew B

    2017-01-01

    As noninvasive brain stimulation (NIBS) technology advances, these methods may become increasingly capable of influencing complex networks of mental functioning. We suggest that these might include cognitive and affective processes underlying personality and belief systems, which would raise important questions concerning personal identity and autonomy. We give particular attention to the relationship between personal identity and belief, emphasizing the importance of respecting users' personal values. We posit that research participants and patients should be encouraged to take an active approach to considering the personal implications of altering their own cognition, particularly in cases of neurocognitive "enhancement." We suggest that efforts to encourage careful consideration through the informed consent process would contribute usefully to studies and treatments that use NIBS.

  20. Personality Is Reflected in the Brain's Intrinsic Functional Architecture

    Science.gov (United States)

    Adelstein, Jonathan S.; Shehzad, Zarrar; Mennes, Maarten; DeYoung, Colin G.; Zuo, Xi-Nian; Kelly, Clare; Margulies, Daniel S.; Bloomfield, Aaron; Gray, Jeremy R.; Castellanos, F. Xavier; Milham, Michael P.

    2011-01-01

    Personality describes persistent human behavioral responses to broad classes of environmental stimuli. Investigating how personality traits are reflected in the brain's functional architecture is challenging, in part due to the difficulty of designing appropriate task probes. Resting-state functional connectivity (RSFC) can detect intrinsic activation patterns without relying on any specific task. Here we use RSFC to investigate the neural correlates of the five-factor personality domains. Based on seed regions placed within two cognitive and affective ‘hubs’ in the brain—the anterior cingulate and precuneus—each domain of personality predicted RSFC with a unique pattern of brain regions. These patterns corresponded with functional subdivisions responsible for cognitive and affective processing such as motivation, empathy and future-oriented thinking. Neuroticism and Extraversion, the two most widely studied of the five constructs, predicted connectivity between seed regions and the dorsomedial prefrontal cortex and lateral paralimbic regions, respectively. These areas are associated with emotional regulation, self-evaluation and reward, consistent with the trait qualities. Personality traits were mostly associated with functional connections that were inconsistently present across participants. This suggests that although a fundamental, core functional architecture is preserved across individuals, variable connections outside of that core encompass the inter-individual differences in personality that motivate diverse responses. PMID:22140453

  1. Infectious diseases of the brain: imaging and differential diagnosis; Infektioese Hirnerkrankungen: Bildgebung und differenzialdiagnostische Aspekte

    Energy Technology Data Exchange (ETDEWEB)

    Haehnel, S.; Seitz, A. [Abt. Neuroradiologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany); Storch-Hagenlocher, B. [Abt. Neurologie, Neurologische Klinik, Universitaetsklinikum Heidelberg (Germany)

    2006-09-15

    Infectious diseases of the central nervous system have to be considered in differential diagnosis particularly in immunocompromised persons. Neuro-imaging, specifically advanced techniques such as diffusion weighted MRI and perfusion MRI contribute much to the differentiation of brain infections and for differentiating brain infections from other, for instance, neoplastic diseases. In this review we present the imaging criteria of the most important brains infections in adults and in pediatric patients and discuss differential diagnostic aspects in detail. (orig.)

  2. Alzheimer's disease camouflaged by histrionic personality disorder.

    Science.gov (United States)

    Hellwig, Sabine; Dykierek, Petra; Hellwig, Bernhard; Zwernemann, Stefan; Meyer, Philipp T

    2012-02-01

    A common condition in Alzheimer's disease (AD) is unawareness of deficits. Different concepts try to elucidate the nature of this symptom. An essential question relates to the interaction of organic and psychogenic factors. Here we present a patient who displayed her cognitive deficits as attention-seeking behaviour. There was a history of histrionic personality disorder according to ICD-10 criteria. Unexpectedly, the final diagnosis after extensive diagnostic work-up was AD. The unusual coincidence of AD and a histrionic personality disorder hampered the clinical process of diagnosing dementia. We discuss unawareness as a complex concept incorporating neuroanatomical, psychiatric, and psychosocial aspects.

  3. Personality influences temporal discounting preferences: behavioral and brain evidence.

    Science.gov (United States)

    Manning, Joshua; Hedden, Trey; Wickens, Nina; Whitfield-Gabrieli, Susan; Prelec, Drazen; Gabrieli, John D E

    2014-09-01

    Personality traits are stable predictors of many life outcomes that are associated with important decisions that involve tradeoffs over time. Therefore, a fundamental question is how tradeoffs over time vary from person to person in relation to stable personality traits. We investigated the influence of personality, as measured by the Five-Factor Model, on time preferences and on neural activity engaged by intertemporal choice. During functional magnetic resonance imaging (fMRI), participants made choices between smaller-sooner and larger-later monetary rewards. For each participant, we estimated a constant-sensitivity discount function that dissociates impatience (devaluation of future consequences) from time sensitivity (consistency with rational, exponential discounting). Overall, higher neuroticism was associated with a relatively greater preference for immediate rewards and higher conscientiousness with a relatively greater preference for delayed rewards. Specifically, higher conscientiousness correlated positively with lower short-term impatience and more exponential time preferences, whereas higher neuroticism (lower emotional stability) correlated positively with higher short-term impatience and less exponential time preferences. Cognitive-control and reward brain regions were more activated when higher conscientiousness participants selected a smaller-sooner reward and, conversely, when higher neuroticism participants selected a larger-later reward. The greater activations that occurred when choosing rewards that contradicted personality predispositions may reflect the greater recruitment of mental resources needed to override those predispositions. These findings reveal that stable personality traits fundamentally influence how rewards are chosen over time. Copyright © 2014 Elsevier Inc. All rights reserved.

  4. An online database for brain disease research

    Directory of Open Access Journals (Sweden)

    Richman Sam

    2006-04-01

    Full Text Available Abstract Background The Stanley Medical Research Institute online genomics database (SMRIDB is a comprehensive web-based system for understanding the genetic effects of human brain disease (i.e. bipolar, schizophrenia, and depression. This database contains fully annotated clinical metadata and gene expression patterns generated within 12 controlled studies across 6 different microarray platforms. Description A thorough collection of gene expression summaries are provided, inclusive of patient demographics, disease subclasses, regulated biological pathways, and functional classifications. Conclusion The combination of database content, structure, and query speed offers researchers an efficient tool for data mining of brain disease complete with information such as: cross-platform comparisons, biomarkers elucidation for target discovery, and lifestyle/demographic associations to brain diseases.

  5. The brain's emotional foundations of human personality and the Affective Neuroscience Personality Scales.

    Science.gov (United States)

    Davis, Kenneth L; Panksepp, Jaak

    2011-10-01

    Six of the primary-process subcortical brain emotion systems - SEEKING, RAGE, FEAR, CARE, GRIEF and PLAY - are presented as foundational for human personality development, and hence as a potentially novel template for personality assessment as in the Affective Neurosciences Personality Scales (ANPS), described here. The ANPS was conceptualized as a potential clinical research tool, which would help experimentalists and clinicians situate subjects and clients in primary-process affective space. These emotion systems are reviewed in the context of a multi-tiered framing of consciousness spanning from primary affect, which encodes biological valences, to higher level tertiary (thought mediated) processing. Supporting neuroscience research is presented along with comparisons to Cloninger's Temperament and Character Inventory and the Five Factor Model (FFM). Suggestions are made for grounding the internal structure of the FFM on the primal emotional systems recognized in affective neuroscience, which may promote substantive dialog between human and animal research traditions. Personality is viewed in the context of Darwinian "continuity" with the inherited subcortical brain emotion systems being foundational, providing major forces for personality development in both humans and animals, and providing an affective infrastructure for an expanded five factor descriptive model applying to normal and clinical human populations as well as mammals generally. Links with ontogenetic and epigenetic models of personality development are also presented. Potential novel clinical applications of the CARE maternal-nurturance system and the PLAY system are also discussed.

  6. Human brain disease recreated in mice

    Energy Technology Data Exchange (ETDEWEB)

    Marx, J.

    1990-12-14

    In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.

  7. Psychopathology of Time in Brain Disease and Schizophrenia

    Directory of Open Access Journals (Sweden)

    John Cutting

    1990-01-01

    Full Text Available The literature on disturbance of time-sense in brain disease and schizophrenia is reviewed and the subjective experience of altered time-sense reported by 45 out of 350 personally interviewed schizophrenics is analyzed. A review of the literature on the effect of brain damage revealed that some phenomena (déjà vu, reduplication of time, altered tempo to events were linked with right hemisphere dysfunction, one phenomenon (incorrect sequencing of events was linked with left anterior brain damage, and others (disrupted “biological clock”, disturbed serise of rate of flow of current or past events could arise from subcortical as well as focal cortical damage. The sparse literature on disturbed time-sense in schizophrenia suggested that there was a shared psychopathology in this respect with right hemisphere dysfunction. The phenomena encountered in the 45 schizophrenics are described and classified.

  8. Taking Crohn’s Disease Personally

    Directory of Open Access Journals (Sweden)

    Yehuda Chowers

    2013-04-01

    Full Text Available Crohn’s disease (CD is a heterogeneous disorder that can involve any segment of the gastrointestinal tract. The pathogenesis of CD is unknown but is thought to involve an uncontrolled immune response triggered by an environmental factor in a genetically susceptible host. The heterogeneity of disease pathogenesis and clinical course, combined with the variable response to treatment and its associated side effects, creates an environment of complex therapeutic decisions. Despite this complexity, significant progress has been made which allows physicians to start and predict disease behavior and natural course, response to therapy, and factors associated with significant side effects. In this manuscript the data pertaining to these variables including clinical, endoscopic and the various biological and genetic markers are reviewed, and the possibility of tailoring personal treatment is discussed.

  9. Touch and personality: extraversion predicts somatosensory brain response.

    Science.gov (United States)

    Schaefer, Michael; Heinze, Hans-Jochen; Rotte, Michael

    2012-08-01

    The Five-Factor-Model describes human personality in five core dimensions (extraversion, neuroticism, agreeableness, conscientiousness, and openness). These factors are supposed to have different neural substrates. For example, it has been suggested that behavioral differences between introverts and extraverts can be explained by the fact that introverts exhibit an inherent drive to compensate for overactive cortical activity in reticulo-thalamo-cortical pathways. The current study examined if responses in somatosensory cortices due to tactile stimulation are affected by personality traits. Based on previous studies and theoretical models we hypothesized a relationship of extraversion with somatosensory responses in primary somatosensory cortex (SI). In order to test this hypothesis we applied nonpainful tactile stimulation on the fingers of both hands of 23 healthy young participants (mean 25 years, standard deviation ± 2.8 years). Personality traits were assessed according to the Five-Factor-Model (NEO-FFI). Neuromagnetic source imaging revealed that the cortical activity (dipole strengths) for sources in SI were closely associated with the personality trait extraversion. Thus, the less extraverted the participants were, the higher was the cortical activity in SI. This relationship was in particular valid for the right hemisphere. We conclude that personality seems to depend on primary cortex activity. Furthermore, our results provide further evidence for an inter-hemispheric asymmetry of the social brain.

  10. Personality and complex brain networks: The role of openness to experience in default network efficiency.

    Science.gov (United States)

    Beaty, Roger E; Kaufman, Scott Barry; Benedek, Mathias; Jung, Rex E; Kenett, Yoed N; Jauk, Emanuel; Neubauer, Aljoscha C; Silvia, Paul J

    2016-02-01

    The brain's default network (DN) has been a topic of considerable empirical interest. In fMRI research, DN activity is associated with spontaneous and self-generated cognition, such as mind-wandering, episodic memory retrieval, future thinking, mental simulation, theory of mind reasoning, and creative cognition. Despite large literatures on developmental and disease-related influences on the DN, surprisingly little is known about the factors that impact normal variation in DN functioning. Using structural equation modeling and graph theoretical analysis of resting-state fMRI data, we provide evidence that Openness to Experience-a normally distributed personality trait reflecting a tendency to engage in imaginative, creative, and abstract cognitive processes-underlies efficiency of information processing within the DN. Across two studies, Openness predicted the global efficiency of a functional network comprised of DN nodes and corresponding edges. In Study 2, Openness remained a robust predictor-even after controlling for intelligence, age, gender, and other personality variables-explaining 18% of the variance in DN functioning. These findings point to a biological basis of Openness to Experience, and suggest that normally distributed personality traits affect the intrinsic architecture of large-scale brain systems. Hum Brain Mapp 37:773-779, 2016. © 2015 Wiley Periodicals, Inc. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  11. Artificial selection on relative brain size reveals a positive genetic correlation between brain size and proactive personality in the guppy.

    Science.gov (United States)

    Kotrschal, Alexander; Lievens, Eva J P; Dahlbom, Josefin; Bundsen, Andreas; Semenova, Svetlana; Sundvik, Maria; Maklakov, Alexei A; Winberg, Svante; Panula, Pertti; Kolm, Niclas

    2014-04-01

    Animal personalities range from individuals that are shy, cautious, and easily stressed (a "reactive" personality type) to individuals that are bold, innovative, and quick to learn novel tasks, but also prone to routine formation (a "proactive" personality type). Although personality differences should have important consequences for fitness, their underlying mechanisms remain poorly understood. Here, we investigated how genetic variation in brain size affects personality. We put selection lines of large- and small-brained guppies (Poecilia reticulata), with known differences in cognitive ability, through three standard personality assays. First, we found that large-brained animals were faster to habituate to, and more exploratory in, open field tests. Large-brained females were also bolder. Second, large-brained animals excreted less cortisol in a stressful situation (confinement). Third, large-brained animals were slower to feed from a novel food source, which we interpret as being caused by reduced behavioral flexibility rather than lack of innovation in the large-brained lines. Overall, the results point toward a more proactive personality type in large-brained animals. Thus, this study provides the first experimental evidence linking brain size and personality, an interaction that may affect important fitness-related aspects of ecology such as dispersal and niche exploration.

  12. Structural brain lesions in inflammatory bowel disease

    Institute of Scientific and Technical Information of China (English)

    Can; Dolapcioglu; Hatice; Dolapcioglu

    2015-01-01

    Central nervous system(CNS) complications or manifes-tations of inflammatory bowel disease deserve particular attention because symptomatic conditions can require early diagnosis and treatment, whereas unexplained manifestations might be linked with pathogenic me-chanisms. This review focuses on both symptomatic and asymptomatic brain lesions detectable on imaging studies, as well as their frequency and potential mecha-nisms. A direct causal relationship between inflammatory bowel disease(IBD) and asymptomatic structural brain changes has not been demonstrated, but several possible explanations, including vasculitis, thromboembolism and malnutrition, have been proposed. IBD is associated with a tendency for thromboembolisms; therefore, cerebro-vascular thromboembolism represents the most frequent and grave CNS complication. Vasculitis, demyelinating conditions and CNS infections are among the other CNS manifestations of the disease. Biological agents also represent a risk factor, particularly for demyelination. Identification of the nature and potential mechanisms of brain lesions detectable on imaging studies would shed further light on the disease process and could improve patient care through early diagnosis and treatment.

  13. Brain mechanisms for representing what another person sees.

    Science.gov (United States)

    Heyda, Ratha D; Green, Steven R; Vander Wyk, Brent C; Morris, James P; Pelphrey, Kevin A

    2010-04-01

    We used functional magnetic resonance imaging (fMRI) and a naturalistic joint attention scenario to evaluate two, alternative hypotheses concerning the social brain. The first, Content Specific Attribution hypothesis, was that core regions previously identified as being involved in social cognition also participate in representing the contents of another mind. The second, Dual Role hypothesis, was that extrastriate, category-specific visual regions respond to a visible stimulus of a specific category and to the same stimulus occluded, but when it appears to be the focus of another person's visual attention. Participants viewed category-specific stimuli (Place and Body images) to localize the extrastriate body area (EBA) and parahippocampal place area (PPA). Then, they observed a computerized character viewing each stimulus category, occluded from the participant's view. In support of the Content Specific Attribution hypothesis, whole-brain analyses revealed that viewing someone else looking at an occluded picture of a body activated brain regions previously associated with components of social cognition more than viewing someone else looking at an occluded picture of a place. Counter to the Dual Role hypothesis, functional region of interest (ROI) analyses revealed that the EBA and PPA were not clearly involved in representing what the character was seeing.

  14. Deep Brain Stimulation: In Search of Reliable Instruments for Assessing Complex Personality-Related Changes

    Directory of Open Access Journals (Sweden)

    Christian Ineichen

    2016-09-01

    Full Text Available During the last 25 years, more than 100,000 patients have been treated with Deep Brain Stimulation (DBS. While human clinical and animal preclinical research has shed light on the complex brain-signaling disturbances that underpin e.g., Parkinson’s disease (PD, less information is available when it comes to complex psychosocial changes following DBS interventions. In this contribution, we propose to more thoroughly investigate complex personality-related changes following deep brain stimulation through refined and reliable instruments in order to help patients and their relatives in the post-surgery phase. By pursuing this goal, we first outline the clinical importance DBS has attained followed by discussing problematic and undesired non-motor problems that accompany some DBS interventions. After providing a brief definition of complex changes, we move on by outlining the measurement problem complex changes relating to non-motor symptoms currently are associated with. The latter circumstance substantiates the need for refined instruments that are able to validly assess personality-related changes. After providing a brief paragraph with regard to conceptions of personality, we argue that the latter is significantly influenced by certain competencies which themselves currently play only a tangential role in the clinical DBS-discourse. Increasing awareness of the latter circumstance is crucial in the context of DBS because it could illuminate a link between competencies and the emergence of personality-related changes, such as new-onset impulse control disorders that have relevance for patients and their relatives. Finally, we elaborate on the field of application of instruments that are able to measure personality-related changes.

  15. Osteoporotic fractures: a brain or bone disease?

    Science.gov (United States)

    Birge, Stanley J

    2008-06-01

    Osteoporosis is a skeletal disorder that predisposes individuals to increased risk of fracture. However, most osteoporotic fractures occur in women who do not meet criteria for osteoporosis. Hence, bone density, by itself, is a relatively poor predictor of fracture. Age and age-related factors are now recognized as increasingly important in determining fracture risk. Osteoporotic fractures are associated with increased disability and mortality, suggesting that osteoporosis may be a clinical manifestation of an underlying disease process affecting multiple systems. The systems affected, the musculo-skeletal system and the central nervous system, are shared in many respects with the frailty syndrome. Vitamin D deficiency is a major contributor to the frailty syndrome, osteoporosis, and osteoporotic fractures. Its effects are mediated by the development of cerebrovascular disease, postural instability, muscle weakness, and bone fragility. Thus, osteoporotic fractures result from both a bone and brain disease.

  16. ADDICTION IS NOT A BRAIN DISEASE

    Directory of Open Access Journals (Sweden)

    Elisardo Becoña

    2016-05-01

    Full Text Available The idea that addiction is a “brain disease” has gradually been consolidated in the medical-psychiatric field over the last years, as it appears in the current DSM-5. In this paper we analyse the way this idea has arisen and been consolidated, as well as the criticisms that it has received, the professional consequences if this model becomes hegemonic, and the underlying interests. The conclusion defends the need to show, as psychologists, our clear contributions to the field of addictions, and the psychological variables that are necessary in order to understand and prevent addictions, as well as the central role of psychological treatment due to its effectiveness. We must also denounce the reductionism that the model of brain disease represents in comparison with a biopsychosocial model of addiction.

  17. Gender-specific impact of personal health parameters on individual brain aging in cognitively unimpaired elderly subjects

    Directory of Open Access Journals (Sweden)

    Katja eFranke

    2014-05-01

    Full Text Available Aging alters brain structure and function. Personal health markers and modifiable lifestyle factors are related to individual brain aging as well as to the risk of developing Alzheimer’s disease (AD. This study uses a novel magnetic resonance imaging (MRI-based biomarker to assess the effects of 17 health markers on individual brain aging in cognitively unimpaired elderly subjects. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for developing AD. Within this cross-sectional, multi-center study 228 cognitively unimpaired elderly subjects (118 males completed an MRI at 1.5T, physiological and blood parameter assessments. The multivariate regression model combining all measured parameters was capable of explaining 39% of BrainAGE variance in males (p < 0.001 and 32% in females (p < 0.01. Furthermore, markers of the metabolic syndrome as well as markers of liver and kidney functions were profoundly related to BrainAGE scores in males (p < 0.05. In females, markers of liver and kidney functions as well as supply of vitamin B12 were significantly related to BrainAGE (p < 0.05. In conclusion, in cognitively unimpaired elderly subjects several clinical markers of poor health were associated with subtle structural changes in the brain that reflect accelerated aging, whereas protective effects on brain aging were observed for markers of good health. Additionally, the relations between individual brain aging and miscellaneous health markers show gender-specific patterns. The BrainAGE approach may thus serve as a clinically relevant biomarker for the detection of subtly abnormal patterns of brain aging probably preceding cognitive decline and development of AD.

  18. 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.

  19. [Personality Change due to Brain Trauma Caused by Traffic Accidents and Its Assessment of Psychiatric Impairment].

    Science.gov (United States)

    Fan, Hui-yu; Zhang, Qin-ting; Tang, Tao; Cai, Wei-xiong

    2016-04-01

    To explore the main performance of personality change in people with mild psychiatric impairments which due to the brain trauma caused by traffic accidents and its value in assessment of psychiatric impairment. The condition of personality change of patients with traumatic brain injury caused by traffic accident was evaluated by the Scale of Personality Change Post-traumatic Brain Injury (SPCPTBI). Furthermore, the correlation between the personality change and the degrees of traumatic brain injury and psychiatric impairment were explored. Results In 271 samples, 239 (88.2%) with personality changes. Among these 239 samples, 178 (65.7%), 46 (17.0%), 15 (5.5%) with mild, moderate and severe personality changes, respectively. The ratio based on the extent of personality changes to the degree of brain trauma was not significant (P > 0.05), but the total score difference between the groups was significant (P traffic accident was high. Correlations exist between the personality change and the degree of psychiatric impairment. Personality change due to brain trauma caused by traffic accident can be assessed effectively by means of SPCPTBI, and the correlation between the total score and the extent of traumatic brain injury can be found.

  20. Early complement components in Alzheimer's disease brains.

    Science.gov (United States)

    Veerhuis, R; Janssen, I; Hack, C E; Eikelenboom, P

    1996-01-01

    Activation products of the early complement components C1, C4 and C3 can be found colocalized with diffuse and fibrillar beta-amyloid (beta/A4) deposits in Alzheimer's disease (AD) brains. Immunohistochemically, C1-esterase inhibitor (C1-Inh) and the C1 subcomponents C1s and C1r can not, or only occasionally, be detected in plaques or in astrocytes. The present finding that C1q, C1s and C1-Inh mRNA are present in both AD and control brains suggests that the variable immunohistochemical staining results for C1r, C1s and C1-Inh are due to a rapid consumption, and that the inability to detect C1s, C1r or C1-Inh is probably due to the dissociation of C1s-C1-Inh and C1r-C1-Inh complexes from the activator-bound C1q into the fluid phase. Employing monoclonal antibodies specific for different forms of C1-Inh, no complexed C1-Inh could be found, whereas inactivated C1-Inh seems to be present in astrocytes surrounding beta/A4 plaques in AD brains. These findings, together with our finding (using reverse transcriptase-polymerase chain reaction) that C1-Inh is locally produced in the brain, suggest that in the brain complement activation at the C1 level is regulated by C1-Inh. Immunohistochemically, no evidence for the presence of the late complement components C5, C7 and C9, or of the membrane attack complex (MAC), was found in beta/A4 plaques. In contrast to the mRNA encoding the early components, that of the late complement components appears to be hardly detectable (C7) or absent (C9). Thus, without blood-brain-barrier impairment, the late complement components are probably present at too low a concentration to allow the formation of the MAC, which is generally believed to be responsible for at least some of the neurodegenerative effects observed in AD. Therefore, the present findings support the idea that in AD, complement does not function as an inflammatory mediator through MAC formation, but through the action of early component activation products.

  1. Time-invariant person-specific frequency templates in human brain activity

    CERN Document Server

    Doron, I; Baruchi, I; Towle, V L; Ben-Jacob, E; Doron, Itai; Hulata, Eyal; Baruchi, Itay; Towle, Vernon L.; Ben-Jacob, Eshel

    2006-01-01

    The various human brain tasks are performed at different locations and time scales. Yet, we discovered the existence of time-invariant (above an essential time scale) partitioning of the brain activity into person-specific frequency bands. For that, we perform temporal and ensemble averaging of best wavelet packet bases from multi-electrode EEG recordings. These personal frequency-bands provide new templates for quantitative analyses of brain function, e.g., normal vs. epileptic activity.

  2. Personalized Medicine in Respiratory Disease: Role of Proteomics.

    Science.gov (United States)

    Priyadharshini, V S; Teran, Luis M

    2016-01-01

    Respiratory diseases affect humanity globally, with chronic lung diseases (e.g., asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, among others) and lung cancer causing extensive morbidity and mortality. These conditions are highly heterogeneous and require an early diagnosis. However, initial symptoms are nonspecific, and the clinical diagnosis is made late frequently. Over the last few years, personalized medicine has emerged as a medical care approach that uses novel technology aiming to personalize treatments according to the particular patient's medical needs. This review highlights the contributions of proteomics toward the understanding of personalized medicine in respiratory disease and its potential applications in the clinic.

  3. Personality changes in dementia: are they disease specific and universal?

    Science.gov (United States)

    Torrente, Fernando; Pose, Mariángeles; Gleichgerrcht, Ezequiel; Torralva, Teresa; López, Pablo; Cetkovich-Bakmas, Marcelo; Manes, Facundo

    2014-01-01

    Previous studies about personality changes in dementia suggest that they may be due to the disruption of the biological basis of personality traits, and hence, that they are disease specific and universal. However, evidence about its specificity is still limited and scarce regarding culturally diverse populations. Accordingly, our aim was to compare personality changes in Argentinean patients with Alzheimer disease, behavioral variant of frontotemporal dementia, and primary progressive aphasia. The closest living relatives of patients diagnosed with Alzheimer disease (n=19), behavioral variant of frontotemporal dementia (n=16), and primary progressive aphasia (n=15) were asked to complete 2 versions of the personality inventory NEO Personality Inventory-Revised, one for assessing patients' premorbid personality traits, and the other for assessing current traits. All groups showed changes in several domains and facets of the NEO Personality Inventory-Revised. Globally, the observed pattern of changes was fairly consistent with previous studies based on the same model of personality. Nevertheless, our results regarding disease-specificity were less conclusive. Even if there were some indicators of specific differences between groups, most traits varied similarly across the 3 groups, revealing a pattern of generalized changes in personality expression after illness onset. More studies are needed that help to distinguish real personality changes from other affective or cognitive symptoms that accompany dementia, as well as further data from culturally diverse populations.

  4. Brain Basics

    Medline Plus

    Full Text Available ... they can cause tremors or symptoms found in Parkinson's disease. Serotonin —helps control many functions, such as ... brain. Problems in producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability ...

  5. Personality in Parkinson's disease: Clinical, behavioural and cognitive correlates.

    Science.gov (United States)

    Santangelo, Gabriella; Piscopo, Fausta; Barone, Paolo; Vitale, Carmine

    2017-03-15

    Affective disorders and personality changes have long been considered pre-motor aspects of Parkinson's disease (PD). Many authors have used the term "premorbid personality" to define distinctive features of PD patients' personality characterized by reduced exploration of new environmental stimuli or potential reward sources ("novelty seeking") and avoidance behaviour ("harm avoidance") present before motor features. The functional correlates underlying the personality changes described in PD, implicate dysfunction of meso-cortico-limbic and striatal circuits. As disease progresses, the imbalance of neurotransmitter systems secondary to degenerative processes, along with dopamine replacement therapy, can produce a reversal of behaviours and an increase in reward seeking, laying the foundations for the emergence of the impulse control disorders. Personality disorders can be interpreted, therefore, as the result of individual susceptibility arising from intrinsic degenerative processes and individual personality features, in combination with extrinsic factors such as lifestyle, PD motor dysfunction and drug treatment. For a better understanding of personality disorders observed in PD and their relationship with the prodromal stage of the disease, prospective clinical studies are needed that correlate different personality profiles with other disease progression markers. Here, we review previous studies investigating the clinical, cognitive and behavioural correlates of personality traits in PD patients. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Prion diseases of the brain; Prionenerkrankung des Gehirns

    Energy Technology Data Exchange (ETDEWEB)

    Lutz, Kira; Urbach, Horst [Universitaetsklinik Freiburg (Germany). Klinik fuer Neuroradiologie

    2015-09-15

    The prion diseases of the brain, especially Creutzfeldt-Jakob disease, are rare fatal neurodegenerative disorders. A definitive CJD diagnosis is currently only possible by a brain biopsy or post mortem autopsy. The diagnosis of Creutzfeldt-Jakob disease is based on clinical signs, pathognomonic EEG, on typical MRI findings and the examination of the cerebrospinal fluid. Using the MRI the diagnosis Creutzfeldt-Jakob disease can be confirmed or excluded with high certainty. The MRI examination should contain diffusion-weighted and FLAIR imaging sequences. This review article provides an overview of the prion diseases of the brain with the corresponding imaging findings.

  7. Parkinson's disease biomarkers program brain imaging repository.

    Science.gov (United States)

    Ofori, Edward; Du, Guangwei; Babcock, Debra; Huang, Xuemei; Vaillancourt, David E

    2016-01-01

    The Parkinson's Disease Biomarkers Program (PDBP) is a multi-site study designed to identify Parkinson's disease (PD) biomarkers that can be used to improve the understanding of PD pathophysiology and to develop tools that provide novel measures to evaluate PD clinical trials. The PDBP consortium comprises numerous individual projects of which two are specifically geared to the development of brain imaging markers for diagnosis, progression, and prognosis of PD or related disorders. All study data from PD patients, atypical Parkinsonian patients, patients with essential tremor, and healthy controls collected from the sites are integrated in the PDBP database and will be publically available. All subjects are asked to submit blood samples, and undergo a battery of clinical evaluations that cover motor, cognitive, and other background information. In addition, a subset of subjects contributed cerebrospinal fluid samples. A restricted access, web-based Data Management Resource facilitates rapid sharing of data and biosamples across the entire PD research community. The PDBP consortium is a useful resource for research and collaboration aimed at the discovery of biomarkers and their use in understanding the pathophysiology of PD.

  8. Reversible "brain atrophy" in patients with Cushing's disease

    OpenAIRE

    Gnjidić, Živko; Sajko, Tomislav; Kudelić, Nenad; Malenica, Maša; Vizner, Branka; Vrkljan, Milan; Hat, Josip; Rumboldt, Zoran

    2008-01-01

    During the past 25 years, we came across 60 patients with corticotroph pituitary adenomas and Cushing’s disease. Neuroradiological examination showed prominent volume loss of the brain parenchyma, unexpected for the patient’s age. This »brain atrophy« appeared to regress after surgical removal of pituitary adenoma and normalization of cortisol level. Observed difference between degree of »brain atrophy« in the Cushing’s disease group and in the control group was statistically sign...

  9. Typical Cerebral Metabolic Patterns in Neurodegenerative Brain Diseases

    NARCIS (Netherlands)

    Teune, Laura K.; Bartels, Anna L.; de Jong, Bauke M.; Willemsen, Antoon T. M.; Eshuis, Silvia A.; de Vries, Jeroen J.; van Oostrom, Joost C. H.; Leenders, Klaus L.

    2010-01-01

    The differential diagnosis of neurodegenerative brain diseases on clinical grounds is difficult, especially at an early disease stage. Several studies have found specific regional differences of brain metabolism applying [F-18]-fluoro-deoxyglucose positron emission tomography (FDG-PET), suggesting t

  10. 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.

  11. Brain imaging changes associated with risk factors for cardiovascular and cerebrovascular disease in asymptomatic patients.

    Science.gov (United States)

    Friedman, Joseph I; Tang, Cheuk Y; de Haas, Hans J; Changchien, Lisa; Goliasch, Georg; Dabas, Puneet; Wang, Victoria; Fayad, Zahi A; Fuster, Valentin; Narula, Jagat

    2014-10-01

    Reviews of imaging studies assessing the brain effects of vascular risk factors typically include a substantial number of studies with subjects with a history of symptomatic cardiovascular or cerebrovascular disease and/or events, limiting our ability to disentangle the primary brain effects of vascular risk factors from those of resulting brain and cardiac damage. The objective of this study was to perform a systematic review of brain changes from imaging studies in patients with vascular risk factors but without clinically manifest cardiovascular or cerebrovascular disease or events. The 77 studies included in this review demonstrate that in persons without symptomatic cardiovascular, cerebrovascular, or peripheral vascular disease, the vascular risk factors of hypertension, diabetes mellitus, obesity, hyperlipidemia, and smoking are all independently associated with brain imaging changes before the clinical manifestation of cardiovascular or cerebrovascular disease. We conclude that the identification of brain changes associated with vascular risk factors, before the manifestation of clinically significant cerebrovascular damage, presents a window of opportunity wherein adequate treatment of these modifiable vascular risk factors may prevent the development of irreversible deleterious brain changes and potentially alter patients' clinical course.

  12. Blood-brain barrier transport of drugs for the treatment of brain diseases.

    Science.gov (United States)

    Gabathuler, Reinhard

    2009-06-01

    The central nervous system is a sanctuary protected by barriers that regulate brain homeostasis and control the transport of endogenous compounds into the brain. The blood-brain barrier, formed by endothelial cells of the brain capillaries, restricts access to brain cells allowing entry only to amino acids, glucose and hormones needed for normal brain cell function and metabolism. This very tight regulation of brain cell access is essential for the survival of neurons which do not have a significant capacity to regenerate, but also prevents therapeutic compounds, small and large, from reaching the brain. As a result, various strategies are being developed to enhance access of drugs to the brain parenchyma at therapeutically meaningful concentrations to effectively manage disease.

  13. Person-centered Health Promotion in Chronic Disease

    Science.gov (United States)

    Cloninger, C. Robert

    2015-01-01

    Health promotion must be person-centered, not organ- or disease-centered, in order to be effective because physical, mental, social, and spiritual aspects of human functioning are inextricably intertwined. Chronic medical disorders, such as heart disease, chronic obstructive pulmonary disease, diabetes, cancer, asthma, and arthritis, are strongly associated with immature personality, emotional instability, and social dysfunction. All indicators of physical, mental, and social well-being are strongly related to the level of maturity and integration of personality, so personality is a useful focus for the promotion of well-being. Assessment of personality also facilitates the awareness of the clinician and the patient about the patient’s strengths, weaknesses, and goals, thereby contributing to an effective therapeutic alliance. Health, well-being, resilience, and recovery of function all involve increasing levels of the character traits of Self-directedness, Cooperativeness, and Self-transcendence. Person-centered programs that enhance self-regulation of functioning to achieve personally valued goals improve compliance with medical treatment and quality of life in people with chronic disease. Effective therapeutic approaches to health promotion activate a complex adaptive system of feedback interactions among functioning, plasticity, and virtuous ways of thinking and acting. The probability of personality change can be predicted by high levels of Self-transcendence, which give rise to an outlook of unity and connectedness, particularly when combined with the temperament traits of high Novelty Seeking and high Persistence. In summary, person-centered psychobiological treatments that facilitate the development of well-being and personality development are crucial in the prevention, treatment, and rehabilitation of chronic medical diseases. PMID:26339469

  14. Similar or disparate brain patterns? The intra-personal EEG variability of three women with multiple personality disorder.

    Science.gov (United States)

    Lapointe, A R; Crayton, J W; DeVito, R; Fichtner, C G; Konopka, L M

    2006-07-01

    Quantitative EEG was used to assess the intra-personal variability of brain electrical activity for 3 women diagnosed with Multiple Personality Disorder (MPD). Two separate control groups (within-subject and between-subject) were used to test the hypothesis that the intra-personal EEG variability between 2 alters would be less than the interpersonal EEG variability between 2 controls, and similar to the intra-personal EEG variability of a single personality. This hypothesis was partially supported. In general, the 2 EEG records of a MPD subject (alter 1 vs. alter 2) were more different from one another than the 2 EEG records of a single control, but less different from one another than the EEG records of 2 separate controls. Most of the EEG variability between alters involved beta activity in the frontal and temporal lobes.

  15. Therapeutic Noninvasive Brain Stimulation in Alzheimer's Disease.

    Science.gov (United States)

    Gonsalvez, Irene; Baror, Roey; Fried, Peter; Santarnecchi, Emiliano; Pascual-Leone, Alvaro

    2017-01-01

    Alzheimer's disease (AD) is a looming public health crisis that currently lacks an effective treatment. Noninvasive Brain Stimulation (NBS), particularly transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS), offers a promising alternative approach to pharmacological interventions for an increasing number of neurological and psychiatric conditions. The aim of this review is summarize data from therapeutic trials of NBS in AD and other dementing illnesses. Despite the potential of NBS, there is limited theoretical framework and a lack of guidelines for its applications to AD. Several published clinical trials failed to report key parameters of the interventions thus limiting the utility of the study to assess efficacy and safety. Our review concludes with some suggestions for future studies aimed to advance research into NBS as a potential treatment for the symptoms and disabilities caused by AD and to enable comparison of results across trials. Ultimately, appropriately powered, and controlled, multi-site randomized clinical trials will be needed to evaluate the therapeutic potential of NBS in AD.

  16. The Extreme Male Brain Theory and Gender Role Behaviour in Persons with an Autism Spectrum Condition

    Science.gov (United States)

    Stauder, J. E. A.; Cornet, L. J. M.; Ponds, R. W. H. M.

    2011-01-01

    According to the Extreme Male Brain theory persons with autism possess masculinised cognitive traits. In this study masculinisation of gender role behaviour is evaluated in 25 persons with an autism spectrum condition (ASC) and matched controls with gender role behaviour as part of a shortened version of the Minnesota Multiphasic Personality…

  17. The Extreme Male Brain Theory and Gender Role Behaviour in Persons with an Autism Spectrum Condition

    Science.gov (United States)

    Stauder, J. E. A.; Cornet, L. J. M.; Ponds, R. W. H. M.

    2011-01-01

    According to the Extreme Male Brain theory persons with autism possess masculinised cognitive traits. In this study masculinisation of gender role behaviour is evaluated in 25 persons with an autism spectrum condition (ASC) and matched controls with gender role behaviour as part of a shortened version of the Minnesota Multiphasic Personality…

  18. Cardiovascular disease in persons with depressive and anxiety disorders

    NARCIS (Netherlands)

    Vogelzangs, Nicole; Seldenrijk, Adrie; Beekman, Aartjan T. F.; van Hout, Hein P. J.; de Jonge, Peter; Penninx, Brenda W. J. H.

    2010-01-01

    Background: Associations between depression, and possibly anxiety, with cardiovascular disease have been established in the general population and among heart patients. This study examined whether cardiovascular disease was more prevalent among a large cohort of depressed and/or anxious persons. In

  19. Cardiovascular disease in persons with depressive and anxiety disorders

    NARCIS (Netherlands)

    Vogelzangs, Nicole; Seldenrijk, Adrie; Beekman, Aartjan T. F.; van Hout, Hein P. J.; de Jonge, Peter; Penninx, Brenda W. J. H.

    Background: Associations between depression, and possibly anxiety, with cardiovascular disease have been established in the general population and among heart patients. This study examined whether cardiovascular disease was more prevalent among a large cohort of depressed and/or anxious persons. In

  20. Brain, mind and machine: what are the implications of deep brain stimulation for perceptions of personal identity, agency and free will?

    Science.gov (United States)

    Lipsman, Nir; Glannon, Walter

    2013-11-01

    Brain implants, such as Deep Brain Stimulation (DBS), which are designed to improve motor, mood and behavioural pathology, present unique challenges to our understanding of identity, agency and free will. This is because these devices can have visible effects on persons' physical and psychological properties yet are essentially undetectable when operating correctly. They can supplement and compensate for one's inherent abilities and faculties when they are compromised by neuropsychiatric disorders. Further, unlike talk therapy or pharmacological treatments, patients need not 'do' anything for the treatment to take effect. If one accepts, as we argue here, that brain implants are unique among implantable types of devices, then this can have significant implications for what it means to persist as the same person and be the source of one's thoughts and actions. By examining two of the most common indications for DBS in current use, namely in the motor (Parkinson's Disease) and psychiatric (Major Depression) domains, we further argue that although DBS, as it is currently applied, does not necessarily represent a unique threat to personal identity and agency per se, it introduces an unprecedented 'third party' into the debate on these concepts. In this way, DBS can be used as a tool to begin probing, both conceptually and empirically, some of philosophy's most perennial metaphysical questions.

  1. Inflammatory bowel disease, to personalized nutrition

    Directory of Open Access Journals (Sweden)

    Sandra Ortiz-Suárez

    2014-04-01

    Full Text Available The incidence of inflammatory bowel disease (IBD is increasing in countries that acquire a Western lifestyle. Its pathogenesis is not well defined but is associated with multifactorial causes. In genetically predisposed people, different environmental factors trigger alterations in the immune response; as a result, tolerance is lost towards commensal gut microbiota, with tissues damage and chronic inflammation. Among the environmental risk factors identified is diet. Diets high in sucrose, refined carbohydrates, omega-6 polyunsaturated fatty acids, and low in fruit, vegetables, and fiber are associated with an increased risk of IBD, particularly Crohn disease (CD. Nutritional recommendations in IBD cannot be generalized because patients respond differently. The emergence of disciplines such as nutrigenetics, nutrigenomics and epigenetics allow a greater understanding of the pathogenesis of the disease, and at the same time, it opens up the possibility to an individualized approach from the nutritional standpoint. An example of this is found in carriers of the polymorphism 857C/T in the gene TNF (Tumor Necrosis Factor, in which a diet high in saturated and monounsaturated fatty acids is harmful and is associated with a more active disease phenotype. This paper reviews the latest scientific articles in these disciplines in relation to IBD and nutritional potential therapeutic applications, like antioxidants application or the ratio of polyunsaturated fatty acids v-6/v-3. It was used the database of the National Center for Biotechnology Information (NCBI to search for articles, including selecting the most interest from 2007 to 2012.

  2. Increased brain-predicted aging in treated HIV disease

    Science.gov (United States)

    Underwood, Jonathan; Caan, Matthan W.A.; De Francesco, Davide; van Zoest, Rosan A.; Leech, Robert; Wit, Ferdinand W.N.M.; Portegies, Peter; Geurtsen, Gert J.; Schmand, Ben A.; Schim van der Loeff, Maarten F.; Franceschi, Claudio; Sabin, Caroline A.; Majoie, Charles B.L.M.; Winston, Alan; Reiss, Peter; Sharp, David J.

    2017-01-01

    Objective: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. Methods: A large sample of virologically suppressed HIV-positive adults (n = 162, age 45–82 years) and highly comparable HIV-negative controls (n = 105) were recruited as part of the Comorbidity in Relation to AIDS (COBRA) collaboration. Using T1-weighted MRI scans, a machine-learning model of healthy brain aging was defined in an independent cohort (n = 2,001, aged 18–90 years). Neuroimaging data from HIV-positive and HIV-negative individuals were then used to estimate brain-predicted age; then brain-predicted age difference (brain-PAD = brain-predicted brain age − chronological age) scores were calculated. Neuropsychological and clinical assessments were also carried out. Results: HIV-positive individuals had greater brain-PAD score (mean ± SD 2.15 ± 7.79 years) compared to HIV-negative individuals (−0.87 ± 8.40 years; b = 3.48, p < 0.01). Increased brain-PAD score was associated with decreased performance in multiple cognitive domains (information processing speed, executive function, memory) and general cognitive performance across all participants. Brain-PAD score was not associated with age, duration of HIV infection, or other HIV-related measures. Conclusion: Increased apparent brain aging, predicted using neuroimaging, was observed in HIV-positive adults, despite effective viral suppression. Furthermore, the magnitude of increased apparent brain aging related to cognitive deficits. However, predicted brain age difference did not correlate with chronological age or duration of HIV infection, suggesting that HIV disease may accentuate rather than accelerate brain aging. PMID:28258081

  3. Variation within the Huntington's disease gene influences normal brain structure.

    Directory of Open Access Journals (Sweden)

    Mark Mühlau

    Full Text Available Genetics of the variability of normal and diseased brain structure largely remains to be elucidated. Expansions of certain trinucleotide repeats cause neurodegenerative disorders of which Huntington's disease constitutes the most common example. Here, we test the hypothesis that variation within the IT15 gene on chromosome 4, whose expansion causes Huntington's disease, influences normal human brain structure. In 278 normal subjects, we determined CAG repeat length within the IT15 gene on chromosome 4 and analyzed high-resolution T1-weighted magnetic resonance images by the use of voxel-based morphometry. We found an increase of GM with increasing long CAG repeat and its interaction with age within the pallidum, which is involved in Huntington's disease. Our study demonstrates that a certain trinucleotide repeat influences normal brain structure in humans. This result may have important implications for the understanding of both the healthy and diseased brain.

  4. Evidence for a membrane defect in Alzheimer disease brain

    Science.gov (United States)

    Nitsch, R. M.; Blusztajn, J. K.; Pittas, A. G.; Slack, B. E.; Growdon, J. H.; Wurtman, R. J.

    1992-01-01

    To determine whether neurodegeneration in Alzheimer disease brain is associated with degradation of structural cell membrane molecules, we measured tissue levels of the major membrane phospholipids and their metabolites in three cortical areas from postmortem brains of Alzheimer disease patients and matched controls. Among phospholipids, there was a significant (P less than 0.05) decrease in phosphatidylcholine and phosphatidylethanolamine. There were significant (P less than 0.05) decreases in the initial phospholipid precursors choline and ethanolamine and increases in the phospholipid deacylation product glycerophosphocholine. The ratios of glycerophosphocholine to choline and glycerophosphoethanolamine to ethanolamine were significantly increased in all examined Alzheimer disease brain regions. The activity of the glycerophosphocholine-degrading enzyme glycerophosphocholine choline-phosphodiesterase was normal in Alzheimer disease brain. There was a near stoichiometric relationship between the decrease in phospholipids and the increase of phospholipid catabolites. These data are consistent with increased membrane phospholipid degradation in Alzheimer disease brain. Similar phospholipid abnormalities were not detected in brains of patients with Huntington disease, Parkinson disease, or Down syndrome. We conclude that the phospholipid abnormalities described here are not an epiphenomenon of neurodegeneration and that they may be specific for the pathomechanism of Alzheimer disease.

  5. Small vessel ischemic disease of the brain and brain metastases in lung cancer patients.

    Directory of Open Access Journals (Sweden)

    Peter J Mazzone

    Full Text Available BACKGROUND: Brain metastases occur commonly in patients with lung cancer. Small vessel ischemic disease is frequently found when imaging the brain to detect metastases. We aimed to determine if the presence of small vessel ischemic disease (SVID of the brain is protective against the development of brain metastases in lung cancer patients. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective cohort of 523 patients with biopsy confirmed lung cancer who had received magnetic resonance imaging of the brain as part of their standard initial staging evaluation was reviewed. Information collected included demographics, comorbidities, details of the lung cancer, and the presence of SVID of the brain. A portion of the cohort had the degree of SVID graded. The primary outcome measure was the portion of study subjects with and without SVID of the brain who had evidence of brain metastases at the time of initial staging of their lung cancer.109 patients (20.8% had evidence of brain metastases at presentation and 345 (66.0% had evidence of SVID. 13.9% of those with SVID and 34.3% of those without SVID presented with brain metastases (p<0.0001. In a model including age, diabetes mellitus, hypertension, hyperlipidemia, and tobacco use, SVID of the brain was found to be the only protective factor against the development of brain metastases, with an OR of 0.31 (0.20, 0.48; p<0.001. The grade of SVID was higher in those without brain metastases. CONCLUSIONS/SIGNIFICANCE: These findings suggest that vascular changes in the brain are protective against the development of brain metastases in lung cancer patients.

  6. New progress in brain aging and its related neurological diseases

    Directory of Open Access Journals (Sweden)

    Ming-wei ZHU

    2014-03-01

    Full Text Available Brain aging-related neurological diseases including Alzheimer's disease (AD, Parkinson's disease (PD and cerebral amyloid angiopathy (CAA have become one of the major diseases endangering the health of old people in China. Although the mechanism of brain aging and pathogenesis of its related neurodegenerative diseases remain unclear, protein pathological studies such as tau, α-synuclein (α-Syn, TDP-43 and amyloid-β protein (Aβ based on brain tissue bank and case registration database are opening the door to solve the mystery in the brain aging process and unlock pathogenesis of aging-related neurodegenerative diseases. Research on functional neuroimaging including 11C-PIB PET and 18F-FDDNP PET in Alzheimer's disease and 18F-FDG PET in Parkinson's disease, and biomarkers such as total-tau, phosphorylated-tau, and the 42 amino acid fragment of β-amyloid in cerebrospinal fluid (CSF in the preclinical stages of Alzheimer's disease now become hot topics in the field of elderly dementia and movement disorders. Clinicopathological correlation research of Alzheimer's disease, Parkinson's disease and cerebral amyloid angiopathy is also one of focuses in the geriatric neurological diseases. doi: 10.3969/j.issn.1672-6731.2014.03.004

  7. Validation of Parkinsonian Disease-Related Metabolic Brain Patterns

    NARCIS (Netherlands)

    Teune, Laura K.; Renken, Remco J.; Mudali, Deborah; De Jong, Bauke M.; Dierckx, Rudi A.; Roerdink, Jos B.T.M.; Leenders, Klaus L.

    2013-01-01

    Background: The objective of this study was to validate disease-related metabolic brain patterns for Parkinson’s disease, multiple system atrophy, and progressive supranuclear palsy. Methods: The study included 20 patients with Parkinson’s disease, 21 with multiple system atrophy, and 17 with progre

  8. Lipidomics of human brain aging and Alzheimer's disease pathology.

    Science.gov (United States)

    Naudí, Alba; Cabré, Rosanna; Jové, Mariona; Ayala, Victoria; Gonzalo, Hugo; Portero-Otín, Manuel; Ferrer, Isidre; Pamplona, Reinald

    2015-01-01

    Lipids stimulated and favored the evolution of the brain. Adult human brain contains a large amount of lipids, and the largest diversity of lipid classes and lipid molecular species. Lipidomics is defined as "the full characterization of lipid molecular species and of their biological roles with respect to expression of proteins involved in lipid metabolism and function, including gene regulation." Therefore, the study of brain lipidomics can help to unravel the diversity and to disclose the specificity of these lipid traits and its alterations in neural (neurons and glial) cells, groups of neural cells, brain, and fluids such as cerebrospinal fluid and plasma, thus helping to uncover potential biomarkers of human brain aging and Alzheimer disease. This review will discuss the lipid composition of the adult human brain. We first consider a brief approach to lipid definition, classification, and tools for analysis from the new point of view that has emerged with lipidomics, and then turn to the lipid profiles in human brain and how lipids affect brain function. Finally, we focus on the current status of lipidomics findings in human brain aging and Alzheimer's disease pathology. Neurolipidomics will increase knowledge about physiological and pathological functions of brain cells and will place the concept of selective neuronal vulnerability in a lipid context. © 2015 Elsevier Inc. All rights reserved.

  9. Brain damage in patients with manifest arterial disease

    NARCIS (Netherlands)

    Raamt, Anne Fleur van

    2006-01-01

    In this thesis we assessed whether the risk factors known to affect markers of brain damage in the general population, also effectuate brain damage in patients who already have symptomatic arterial disease. We found that elevated levels of homocysteine were related to slightly lower global cogniti

  10. Increased brain-predicted aging in treated HIV disease

    NARCIS (Netherlands)

    Cole, James H; Underwood, Jonathan; Caan, Matthan W A; De Francesco, Davide; van Zoest, Rosan A; Leech, Robert; Wit, Ferdinand W N M; Portegies, Peter; Geurtsen, Gert J; Schmand, Ben A; Schim van der Loeff, Maarten F; Franceschi, Claudio; Sabin, Caroline A; Majoie, Charles B L M; Winston, Alan; Reiss, Peter; Sharp, David J; Kalsbeek, A.

    2017-01-01

    OBJECTIVE: To establish whether HIV disease is associated with abnormal levels of age-related brain atrophy, by estimating apparent brain age using neuroimaging and exploring whether these estimates related to HIV status, age, cognitive performance, and HIV-related clinical parameters. METHODS: A la

  11. Bilateral adaptive deep brain stimulation is effective in Parkinson's disease

    NARCIS (Netherlands)

    Little, Simon; Beudel, Martijn; Zrinzo, Ludvic; Foltynie, Thomas; Limousin, Patricia; Hariz, Marwan; Neal, Spencer; Cheeran, Binith; Cagnan, Hayriye; Gratwicke, James; Aziz, Tipu Z.; Pogosyan, Alex; Brown, Peter

    2016-01-01

    Introduction & objectives Adaptive deep brain stimulation (aDBS) uses feedback from brain signals to guide stimulation. A recent acute trial of unilateral aDBS showed that aDBS can lead to substantial improvements in contralateral hemibody Unified Parkinson's Disease Rating Scale (UPDRS) motor score

  12. Relation of cerebral small-vessel disease and brain atrophy to mild Parkinsonism in the elderly.

    Science.gov (United States)

    Reitz, Christiane; Trenkwalder, Claudia; Kretzschmar, Konrad; Roesler, Andreas; V Eckardstein, Arnold; Berger, Klaus

    2006-11-01

    The association between cerebral small-vessel disease, brain atrophy, and the risk and severity of mild parkinsonian signs (MPS) remains unclear. The objective of this study is to examine the effect of lacunar brain infarcts, cerebral white matter lesions (WMLs), and cortical atrophy on the risk and severity of MPS. This study is a cross-sectional community-based cohort study comprising 268 subjects, 65 to 83 years of age, residing in the Augsburg region of southern Germany, and without contraindications for magnetic resonance imaging (MRI) of the brain. Main outcome measures. Subcortical and periventricular WMLs, lacunar brain infarcts, and cortical atrophy determined using a standardized MRI protocol developed for the Rotterdam Scan Study and an established rating scale. MPS, assessed in a standardized neurological examination and based on the Unified Parkinson's Disease Rating Scale motor scale. Lacunar brain infarcts and large subcortical white matter lesions were associated with an elevated risk of resting tremor. More severe cortical atrophy was related to an increased risk of rigidity and bradykinesia. In a linear regression analysis relating each individual MRI measurement with the severity of MPS, the number of lacunar brain infarcts and the degree of brain atrophy were correlated with the severity of resting tremor, whereas the size of subcortical and periventricular WMLs was correlated with the severity of rigidity. A higher degree of brain atrophy was associated with increased severity of either cardinal sign. In our study, presence and volume of lacunar brain infarcts, cerebral WMLs, and cortical atrophy were associated with the risk as well as severity of MPS. Determining the presence of these brain changes using brain imaging might contribute to identify persons at risk for MPS.

  13. PSYCHIATRIC CO - MORBIDITY IN PERSONS WITH HANSEN’S DISEASE

    Directory of Open Access Journals (Sweden)

    Anita

    2015-05-01

    Full Text Available OBJECTIVE: To estimate prevalence of psychiatric co - morbidity and its effect on quality of life in persons with Hansen’s disease. METHOD: The study was conducted on around 80 persons above 18 year age with Hansen’s disease in out - patient department dermatology and i n leprosy home. Participants were diagnosed cases of Hansen’s disease, selected randomly and were evaluated with socio demographic questionnaire, Duke’s general health questionnaire, DSM - 5 self rated level 1 cross cutting symptom measure – adult and WHO - QO L - BREF. The period of data collection was from October 2014 to March 2015. RESULTS: The assessment showed that prevalence of at least one psychiatric co morbidity was 83.75% (67/80 patients and of these 67 patients 18(26.86% have one diagnosis, 26(38.80% have two diagnoses and 23(34.32% have 3 or more psychiatric diagnoses. Among all depression was most prevalent (28.35% mental disorder; followed by anxiety disorder (23.88%. Quality of life was significantly impaired in almost all persons with Hansen’ s disease. CONCLUSION: Persons with Hansen’s disease have significantly high prevalence of mental disorders which have much impact on their quality of life which were under diagnosed and thus remained untreated

  14. Is art therapy a reliable tool for rehabilitating people suffering from brain/mental diseases?

    Science.gov (United States)

    Mirabella, Giovanni

    2015-04-01

    Whether art therapy can be an effective rehabilitative treatment for people with brain or mental diseases (e.g., dementia, Alzheimer's disease, Parkinson's disease, autism, schizophrenia) is a long-standing and highly debated issue. On the one hand, several observational studies and anecdotal evidence enthusiastically support the effectiveness of arts-based therapy. On the other hand, few rigorous clinical investigations have been performed, and there is too little empirical evidence to allow a full assessment of the risks and benefits of this intervention. Nevertheless, there is a progressively increasing demand for the development of appropriate complementary therapies to improve the personal and social lives of patients with neurodegenerative diseases. This is because conventional medical treatments are aimed at alleviating symptoms but cannot arrest or reverse the degenerative process. Thus, as disease progresses and adverse effects emerge, patients' quality of life dramatically decreases; when this occurs patients seek different forms of intervention. Art therapy is a potentially appealing treatment because of its more holistic approach to healthcare. However, as with any medicine, its effects must be tested by using standard, rigorous scientific approaches. This report describes the current state of research into art therapy and outlines many key factors that future research should consider, all of which are directly or indirectly related to the neural mechanism underlying behavioral changes: brain plasticity. Artistic performance could promote some form of brain plasticity that, to some extent, might compensate for the brain damage caused by the disease.

  15. Personalized Medicine in Veterans with Traumatic Brain Injuries

    Science.gov (United States)

    2012-05-01

    prepared a manuscript entitled “Select non-coding RNA in blood components provide novel clinically accessible biological surrogates for improved...Dooley C, Abbi B, Lange G. (2012). Select non-coding RNA in blood components provide novel clinically accessible biological surrogates for improved...in blood components provide novel clinically accessible biological surrogates for improved identification of traumatic brain injury in OEF/OIF

  16. Aluminium in brain tissue in familial Alzheimer's disease.

    Science.gov (United States)

    Mirza, Ambreen; King, Andrew; Troakes, Claire; Exley, Christopher

    2017-03-01

    The genetic predispositions which describe a diagnosis of familial Alzheimer's disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer's disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and aluminium has been shown to be present in brain tissue in sporadic Alzheimer's disease. We have made the first ever measurements of aluminium in brain tissue from 12 donors diagnosed with familial Alzheimer's disease. The concentrations of aluminium were extremely high, for example, there were values in excess of 10μg/g tissue dry wt. in 5 of the 12 individuals. Overall, the concentrations were higher than all previous measurements of brain aluminium except cases of known aluminium-induced encephalopathy. We have supported our quantitative analyses using a novel method of aluminium-selective fluorescence microscopy to visualise aluminium in all lobes of every brain investigated. The unique quantitative data and the stunning images of aluminium in familial Alzheimer's disease brain tissue raise the spectre of aluminium's role in this devastating disease. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  17. Expression of Alzheimer's disease risk genes in ischemic brain degeneration.

    Science.gov (United States)

    Ułamek-Kozioł, Marzena; Pluta, Ryszard; Januszewski, Sławomir; Kocki, Janusz; Bogucka-Kocka, Anna; Czuczwar, Stanisław J

    2016-12-01

    We review the Alzheimer-related expression of genes following brain ischemia as risk factors for late-onset of sporadic Alzheimer's disease and their role in Alzheimer's disease ischemia-reperfusion pathogenesis. More recent advances in understanding ischemic etiology of Alzheimer's disease have revealed dysregulation of Alzheimer-associated genes including amyloid protein precursor, β-secretase, presenilin 1 and 2, autophagy, mitophagy and apoptosis. We review the relationship between these genes dysregulated by brain ischemia and the cellular and neuropathological characteristics of Alzheimer's disease. Here we summarize the latest studies supporting the theory that Alzheimer-related genes play an important role in ischemic brain injury and that ischemia is a needful and leading supplier to the onset and progression of sporadic Alzheimer's disease. Although the exact molecular mechanisms of ischemic dependent neurodegenerative disease and neuronal susceptibility finally are unknown, a downregulated expression of neuronal defense genes like alfa-secretase in the ischemic brain makes the neurons less able to resist injury. The recent challenge is to find ways to raise the adaptive reserve of the brain to overcome such ischemic-associated deficits and support and/or promote neuronal survival. Understanding the mechanisms underlying the association of these genes with risk for Alzheimer's disease will provide the most meaningful targets for therapeutic development to date. Copyright © 2016 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  18. Hostility, Type A Personality and Coronary Heart Disease

    Directory of Open Access Journals (Sweden)

    A. Heidari Pahlavian

    2009-01-01

    Full Text Available Introduction & Objective: In modern medicine, researches in behavioural sciences have described link between psychosocial characteristic, specific personality traits, and development of coronary artery disease. The aim of present study was to investigate the relationship between " hostility" and "type A" personality with acute myocardial infarction. Materials & Methods: In this case-control study 102 patients suffering from acute myocardial infarction and 162 no patents individuals after matching by age, gender, education level, marital status and occupation were studied and compared with regard psychological conditions by type A Najarian questionnaire and SCL – 90 – R. Results: Our study found evidence in support of the hypothesis that hostility may predict heart disease more than type A personality.Conclusion: Our study has some practical meaning for prediction and prevention of CHD. This finding suggests that mental health providers should continue to look at the effectiveness of providing psychological intervention for those individuals with high hostility levels.

  19. Challenges of Work: Voices of Persons with HIV Disease

    Science.gov (United States)

    Maguire, Colleen P.; McNally, Christopher J.; Britton, Paula J.; Werth, James L., Jr.; Borges, Nicole J.

    2008-01-01

    Because of recent advances in medications and treatment regimens, persons with HIV disease are maintaining better health status and living longer. Thus, greater opportunities exist for these individuals to either continue their current employment or return to the world of work. The purpose of this qualitative study was to provide in-depth…

  20. Imaging the structure of the human anxious brain: a review of findings from neuroscientific personality psychology.

    Science.gov (United States)

    Montag, Christian; Reuter, Martin; Jurkiewicz, Magdalena; Markett, Sebastian; Panksepp, Jaak

    2013-01-01

    The emotion of anxiety represents one of the most studied topics in the neurosciences, in part due to its relevance for understanding the evolutionary development of the human brain and its role in the pathogenesis of psychopathological conditions. Structural magnetic resonance imaging (sMRI) has enabled mapping of the anxious human brain and has contributed substantially to the understanding of anxiety. Alongside the fields of clinical psychology/psychiatry, personality psychology aims to support the research endeavor of mapping the anxious brain and has found that individual differences in anxiety-related personality dimensions such as Neuroticism or Harm Avoidance (measured by self-report) are correlated with gray and white matter volumes in different areas of the human brain. This review reveals that structures including parts of the frontal cortex (e.g., the orbitofrontal cortex) and the temporal lobe (e.g., the hippocampus) are often associated with trait anxiety, and it points out the inconsistencies that exist in the personality-sMRI literature on human anxiety. Consequently, we suggest new research strategies to overcome the inconsistencies. This review outlines how results from animal research can guide scientists in developing testable hypotheses in search of the anxious brain. Moreover, genetic imaging is presented as an interesting approach to mapping the anxious brain.

  1. Brain Injury with Sickle Cell Disease

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2003-11-01

    Full Text Available The relationship between brain injury and vasculopathy in 146 sickle cell (SCD patients with hemoglobin SS, the most serious form of SCD, was evaluated by MRI and MRA at St Jude Children’s Research Hospital, Memphis, TN.

  2. Alois Alzheimer and vascular brain disease: Arteriosclerotic atrophy of the brain

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available Alois Alzheimer is best known for his description of neurofibrillary changes in brain neurons of a demented patient, identifying a novel disease, soon named after him by Kraepelin. However, the range of his studies was broad, including vascular brain diseases, published between 1894 and 1902. Alzheimer described the clinical picture of Arteriosclerotic atrophy of the brain, differentiating it from other similar disorders. He stated that autopsy allowed pathological distinction between arteriosclerosis and syphilis, thereby achieving some of his objectives of segregating disorders and separating them from syphilis. His studies contributed greatly to establishing the key information on vascular brain diseases, predating the present state of knowledge on the issue, while providing early descriptions of what would be later regarded as the dimensional presentation of the now called "Vascular cognitive impairment", constituted by a spectrum that includes a stage of "Vascular cognitive impairment not dementia" and another of "Vascular dementia".

  3. Brain aging in normal Egyptians: cognition, education, personality, genetic and immunological study.

    Science.gov (United States)

    Elwan, Osamah; Madkour, Obsis; Elwan, Fadia; Mostafa, Mervat; Abbas Helmy, Azza; Abdel-Naseer, Maged; Abdel Shafy, Sanaa; El Faiuomy, Nervana

    2003-07-15

    Studying the cognitive and immunological changes that occur in old age as well as genetic function have been considered an important subject to differentiate between normal brain aging and early dementia especially Alzheimer's disease. The aim of this study is to stress on age-related neuropsychological and electrophysiological (P(300)) changes in normal Egyptian subjects, to throw light on the value of genetic (Apo-E(4) genotype) and immunological markers [interleukin-6 (IL-6) and intercellular adhesion molecules (ICAM-1) in the serum] as tools used in early detection of cognitive decline in cerebral aging. Ninety-four normal Egyptian subjects (below and above 60 years) were submitted to the following: (1) neuropsychological tests for testing memory, perception, psychomotor performance and attention, (2) Eysenck Personality Questionnaire (EPQ) for personality traits, (3) event-related potential study (P(300), latency and amplitude), (4) genetic test for detection of Apolipoprotein E genotype and (5) immunological studies including detection of the level of IL-6 and ICAM-1 in serum. There was a significant impairment of memory, psychomotor performance and perception in elderly subjects particularly males and subjects with low level of education. Regarding personality, significantly high scores were obtained in neuroticism scale of EPQ in elderly subjects. Apo-E(3)/E(3) was the most common genotype encountered in Egyptian subjects (49.1%). It was found that subjects with Apo-E(4) genotype did significantly worse in scores of intentional memory test (sensory memory) when compared with other genotypes. Statistically significant impairment in attention and sensory memory was found in subjects with high IL-6 level. This could not be detected in subjects with high ICAM-1 level. In conclusion, advancing age and lower levels of education are considered risk factors for cognitive decline in normal brain aging. Neuropsychological tests remain as the highly sensitive tools

  4. Neuromolecular imaging, a nanobiotechnology for Parkinson's disease: advancing pharmacotherapy for personalized medicine.

    Science.gov (United States)

    Broderick, P A; Wenning, L; Li, Y-S

    2017-01-01

    Evaluating each patient and animal as its own control achieves personalized medicine, which honors the hippocratic philosophy, explaining that "it is far more important to know what person has the disease than what disease the person has." Similarly, individualizing molecular signaling directly from the patient's brain in real time is essential for providing prompt, patient-based treatment as dictated by the point of care. Fortunately, nanotechnology effectively treats many neurodegenerative diseases. In particular, the new medicinal frontier for the discovery of therapy for Parkinson's disease is nanotechnology and nanobiotechnology. Indeed, the unique nanotechnology of neuromolecular imaging combined with the series of nanobiosensors enables continuous videotracking of molecular neurotransmitters in both the normal physiologic and disease states with long-term electrochemical operational stability. This nanobiotechnology is able to track a signal in real time with excellent temporal and spatial resolution directly from each patient's brain to a computer as subjects are behaving during movement, normal and/or dysfunctional including prion-like Parkinson's behavioral biometrics. Moreover, the molecular signaling performed by these nanobiosensors live streams directly online and originates from precise neuroanatomic brain sites such as, in this case, the dorsal striatum in basal ganglia. Thus, the nanobiotechnology studies discussed herein imaged neuromolecules with and without L-3,4-dihydroxyphenylalanine (L-DOPA) in dorsal striatal basal ganglia neurons. Parkinsonian and non-Parkinsonian animals were video-tracked, and images were readily seen on a laptop via a potentiostat using a semiderivative electrical circuit. Administered L-DOPA doses were 50 and 100 mg/kg intraperitoneally (ip); the same experimental paradigm was used to image and then contrast data. Results showed that the baseline release of biogenic amine molecules was significantly above detection

  5. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression

    OpenAIRE

    Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

    2015-01-01

    Background Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. Methods In this cross...

  6. A new treatment method for brain diseases. Stereotactic radiosurgery

    Energy Technology Data Exchange (ETDEWEB)

    Shirato, Hiroki (Hokkaido Univ., Sapporo (Japan). School of Medicine)

    1994-01-01

    This paper deals with stereotactic radiosurgery, a novel medical treatment technique for brain diseases. It is the most sophisticated modality that allows the functional preservation. Recently, CT scan and MRI scan have dramatically changed the diagnostic accuracy of tumor localization in the brain. A device named stereotactic head fixation system makes it possible to localize deep-seated brain diseases with an accuracy of 1-1.5 mm. Using multiple convergent narrow beams of high-energy X-ray, a stereotactic head frame, and a three dimensional computer graphics of CT images, patients with deep-seated nidus can be treated without any complications. Normal tissues would not receive large doses but the center of the nidus is irradiated heavily because of the convergence of X-ray beams. Thus stereotactic radiosurgery is more accurate, effective, and less toxic than conventional radiotherapy and is safer and more effective than surgery for many brain diseases. Small arteriovenous malformation in the brain, which is a fetal disease, and small acoustic neurinomas, in which surgery often causes facial nerve palsy and hearing loss, are presented as good candidates for radiosurgery. For metastatic brain tumors, stereotactic radiosurgery makes such patients free from neurological symptoms, such as difficulty in walking and speaking, in a few days. (N.K.).

  7. Relationship between regional brain glucose metabolism and temperament factor of personality

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

  8. Automatic detection of the hippocampal region associated with Alzheimer's disease from microscopic images of mice brain

    Science.gov (United States)

    Albaidhani, Tahseen; Hawkes, Cheryl; Jassim, Sabah; Al-Assam, Hisham

    2016-05-01

    The hippocampus is the region of the brain that is primarily associated with memory and spatial navigation. It is one of the first brain regions to be damaged when a person suffers from Alzheimer's disease. Recent research in this field has focussed on the assessment of damage to different blood vessels within the hippocampal region from a high throughput brain microscopic images. The ultimate aim of our research is the creation of an automatic system to count and classify different blood vessels such as capillaries, veins, and arteries in the hippocampus region. This work should provide biologists with efficient and accurate tools in their investigation of the causes of Alzheimer's disease. Locating the boundary of the Region of Interest in the hippocampus from microscopic images of mice brain is the first essential stage towards developing such a system. This task benefits from the variation in colour channels and texture between the two sides of the hippocampus and the boundary region. Accordingly, the developed initial step of our research to locating the hippocampus edge uses a colour-based segmentation of the brain image followed by Hough transforms on the colour channel that isolate the hippocampus region. The output is then used to split the brain image into two sides of the detected section of the boundary: the inside region and the outside region. Experimental results on a sufficiently number of microscopic images demonstrate the effectiveness of the developed solution.

  9. Brain hydrogen sulfide is severely decreased in Alzheimer's disease.

    Science.gov (United States)

    Eto, Ko; Asada, Takashi; Arima, Kunimasa; Makifuchi, Takao; Kimura, Hideo

    2002-05-24

    Although hydrogen sulfide (H2S) is generally thought of in terms of a poisonous gas, it is endogenously produced in the brain from cysteine by cystathionine beta-synthase (CBS). H2S functions as a neuromodulator as well as a smooth muscle relaxant. Here we show that the levels of H2S are severely decreased in the brains of Alzheimer's disease (AD) patients compared with the brains of the age matched normal individuals. In addition to H2S production CBS also catalyzes another metabolic pathway in which cystathionine is produced from the substrate homocysteine. Previous findings, which showed that S-adenosyl-l-methionine (SAM), a CBS activator, is much reduced in AD brain and that homocysteine accumulates in the serum of AD patients, were confirmed. These observations suggest that CBS activity is reduced in AD brains and the decrease in H2S may be involved in some aspects of the cognitive decline in AD.

  10. Outbreaks of infectious intestinal disease associated with person to person spread in hotels and restaurants.

    LENUS (Irish Health Repository)

    McDonnell, R J

    1995-09-15

    Twenty-eight outbreaks of infectious intestinal disease, reported as being transmitted mainly by the person to person route, were identified in association with retail catering premises, such as hotels, restaurants, and public houses, in England and Wales between 1992 and 1994. Five thousand and forty-eight people were at risk in these outbreaks and 1234 were affected. Most of the outbreaks (over 90%) occurred in hotels. Small round structured viruses were the most commonly detected pathogens. Diarrhoea and vomiting were common symptoms and most of the outbreaks occurred in the summer months. Control measures to contain infectious individuals and improved hygiene measures are necessary to contain such outbreaks.

  11. Neuroimaging of Cerebrovascular Disease in the Aging Brain

    OpenAIRE

    Gupta, Ajay; Nair, Sreejit; Andrew D Schweitzer; Kishore, Sirish; Johnson, Carl E.; Comunale, Joseph P.; Tsiouris, Apostolos J; Sanelli, Pina C.

    2012-01-01

    Cerebrovascular disease remains a significant public health burden with its greatest impact on the elderly population. Advances in neuroimaging techniques allow detailed and sophisticated evaluation of many manifestations of cerebrovascular disease in the brain parenchyma as well as in the intracranial and extracranial vasculature. These tools continue to contribute to our understanding of the multifactorial processes that occur in the age-dependent development of cerebrovascular disease. Str...

  12. Coexistence of reactive plasticity and neurodegeneration in Alzheimer diseased brains

    OpenAIRE

    J. Guevara; Dilhuydy, H.; Espinosa, B.; Delacourte, A; Quirion, R; Mena, R.; Joanette, Y.; Zenteno, E; Robitaille, Y

    2004-01-01

    Alzheimer’s disease (AD) is a pathological process characterized by neuron degeneration and, as recently suggested, brain plasticity. In this work, we compared the reactive plasticity in AD brains associated to O-glycosydically linked glycans, recognized by lectins from Amaranthus leucocarpus (ALL) and Macrobrachium rosenbergii (MRL), and the tau neuritic degeneration. The neuritic degenerative process was evaluated by the quantification of aggregated neuritic ...

  13. Brain MRI changes in chronic liver disease

    Energy Technology Data Exchange (ETDEWEB)

    Skehan, S. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Norris, S. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Hegarty, J. [Liver Unit, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); Owens, A. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland); MacErlaine, D. [Department of Diagnostic Imaging, St. Vincent`s Hospital, Elm Park, Dublin 4 (Ireland)

    1997-08-01

    Cirrhotic patients are known to have abnormally high signal principally in the globus pallidus on non-contrast T1-weighted MRI. The purpose of this study was to relate MR changes to clinical and pathological features of chronic liver disease. We confirmed abnormally high signal in the globus pallidus on T1-weighted images in 25 of 28 patients with chronic liver disease, showing that it also occurs in patients who have not yet progressed to cirrhosis. Changes were seen in patients both with and without clinical portosystemic shunting. This abnormality is not responsible for hepatic encephalopathy. Cholestatic disease was more likely to produce marked changes than non-cholestatic disease. No statistically significant correlation was demonstrated between the severity of liver disease and the degree of MR abnormality. However, marked improvement in MR appearances was seen after successful liver transplantation. (orig.). With 3 figs., 4 tabs.

  14. Family Resiliency, Family Needs, and Community Reintegration in Persons with Brain Injury

    Science.gov (United States)

    Frain, Julianne; Dillahunt-Aspillaga, Tina; Frain, Michael; Ehkle, Sarah

    2014-01-01

    Purpose: The purpose of the study was to measure predictors of community reintegration and empirically test the resiliency model of family stress, adjustment, and adaptation in persons with traumatic brain injury (TBI). The study also aimed to measure family needs by surveying caregiving family members through the use of the Family Needs…

  15. EP 35. Influence of gender on personality-brain structure relationships

    NARCIS (Netherlands)

    Nostro, A.; Mü ller, V.I.; Reid, A.T.; Eickhoff, S.B.

    2016-01-01

    Previous studies have shown that males and females differ in personality. In particular, gender differences have been reported for neuroticism and agreeableness (Costa et al., 2001), with women scoring higher on these two traits than men. Although gender has also been shown to influence brain struct

  16. Imagine all the people: how the brain creates and uses personality models to predict behavior.

    Science.gov (United States)

    Hassabis, Demis; Spreng, R Nathan; Rusu, Andrei A; Robbins, Clifford A; Mar, Raymond A; Schacter, Daniel L

    2014-08-01

    The behaviors of other people are often central to envisioning the future. The ability to accurately predict the thoughts and actions of others is essential for successful social interactions, with far-reaching consequences. Despite its importance, little is known about how the brain represents people in order to predict behavior. In this functional magnetic resonance imaging study, participants learned the unique personality of 4 protagonists and imagined how each would behave in different scenarios. The protagonists' personalities were composed of 2 traits: Agreeableness and Extraversion. Which protagonist was being imagined was accurately inferred based solely on activity patterns in the medial prefrontal cortex using multivariate pattern classification, providing novel evidence that brain activity can reveal whom someone is thinking about. Lateral temporal and posterior cingulate cortex discriminated between different degrees of agreeableness and extraversion, respectively. Functional connectivity analysis confirmed that regions associated with trait-processing and individual identities were functionally coupled. Activity during the imagination task, and revealed by functional connectivity, was consistent with the default network. Our results suggest that distinct regions code for personality traits, and that the brain combines these traits to represent individuals. The brain then uses this "personality model" to predict the behavior of others in novel situations.

  17. Family Resiliency, Family Needs, and Community Reintegration in Persons with Brain Injury

    Science.gov (United States)

    Frain, Julianne; Dillahunt-Aspillaga, Tina; Frain, Michael; Ehkle, Sarah

    2014-01-01

    Purpose: The purpose of the study was to measure predictors of community reintegration and empirically test the resiliency model of family stress, adjustment, and adaptation in persons with traumatic brain injury (TBI). The study also aimed to measure family needs by surveying caregiving family members through the use of the Family Needs…

  18. Brain Emotion Systems, Personality, Hopelessness, Self/Other Perception, and Gambling Cognition: A Structural Equation Model.

    Science.gov (United States)

    Iliceto, Paolo; D'Antuono, Laura; Bowden-Jones, Henrietta; Giovani, Eleni; Giacolini, Teodosio; Candilera, Gabriella; Sabatello, Ugo; Panksepp, Jaak

    2016-03-01

    The aim of this study was to explore the relations between gambling, brain emotion systems, personality, self/other perception, and hopelessness in an Italian community. Dimensions of gambling, positive and negative emotions, self/other perception, personality and hopelessness were assessed in a community sample of 235 adults aged 19-59 years. Two structural models were tested. We found a significant correlation between problem gambling and impulsivity, which in association with aggressivity and negative personality dimensions may help explain the psychopathology factor, i.e. a latent variable involving neurotic personality, hopelessness, high sensation seeking, low metacognitive responsiveness, and disorganized patterns of interpersonal relationships. These results contribute to develop a theoretical framework of gambling in relation with personality factors and provide a new approach for clinical intervention of problem gambling that relies on a solid multidimensional perspective.

  19. Alzheimer and vascular brain diseases: Focal and diffuse subforms

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available Alois Alzheimer is best known for his description of the pre-senile neurodegenerative disease named after him. However, his previous interest in vascular brain diseases, underlying cognitive and behavioral changes, was very strong. Besides describing the Arteriosclerotic atrophy of the brain and the arteriosclerotic subtype of Senile dementia which he viewed as main forms of vascular brain diseases, he also identified and described a series of conditions he considered subforms. These may be divided, as suggested by the authors of the present paper, into 3 groups: gliosis and sclerosis, subcortical atrophies, and apoplectic. The subforms of the three groups present characteristic neuropathological features and clinical, cognitive and behavioral manifestations. These provide the basis, together with part of the main forms, for the contemporary condition known as Vascular Cognitive Impairment.

  20. Cholesterol in brain disease: sometimes determinant and frequently implicated

    Science.gov (United States)

    Martín, Mauricio G; Pfrieger, Frank; Dotti, Carlos G

    2014-01-01

    Cholesterol is essential for neuronal physiology, both during development and in the adult life: as a major component of cell membranes and precursor of steroid hormones, it contributes to the regulation of ion permeability, cell shape, cell–cell interaction, and transmembrane signaling. Consistently, hereditary diseases with mutations in cholesterol-related genes result in impaired brain function during early life. In addition, defects in brain cholesterol metabolism may contribute to neurological syndromes, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD), and even to the cognitive deficits typical of the old age. In these cases, brain cholesterol defects may be secondary to disease-causing elements and contribute to the functional deficits by altering synaptic functions. In the first part of this review, we will describe hereditary and non-hereditary causes of cholesterol dyshomeostasis and the relationship to brain diseases. In the second part, we will focus on the mechanisms by which perturbation of cholesterol metabolism can affect synaptic function. PMID:25223281

  1. [Computerized tomography of the brain in diagnosis of neuroinfections--personal observations].

    Science.gov (United States)

    Kepa, L

    An analysis of CT-scans of the brain in 55 patients with suspected neuroinfections is presented. All patients were treated at the I Department of Infectious Diseases of the Silesian Academy of Medicine in 1983-1992. Patients were divided into 3 groups. The first group included patients with suppurative meningitis and encephalitis, the second--with aseptic meningitis, and the third group--patients with other CNS diseases. An analysis has shown that CT-scans of the brain are very useful in an early detection of neuroinfections complications and sequelae, especially brain abscess. The author suggests that CT-scans of the brain may also play an important role in differential diagnosis of neuroinfections and other CNS diseases together with clinical symptoms.

  2. Drosophila melanogaster as a Model Organism of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Werner Paulus

    2009-02-01

    Full Text Available Drosophila melanogaster has been utilized to model human brain diseases. In most of these invertebrate transgenic models, some aspects of human disease are reproduced. Although investigation of rodent models has been of significant impact, invertebrate models offer a wide variety of experimental tools that can potentially address some of the outstanding questions underlying neurological disease. This review considers what has been gleaned from invertebrate models of neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, metabolic diseases such as Leigh disease, Niemann-Pick disease and ceroid lipofuscinoses, tumor syndromes such as neurofibromatosis and tuberous sclerosis, epilepsy as well as CNS injury. It is to be expected that genetic tools in Drosophila will reveal new pathways and interactions, which hopefully will result in molecular based therapy approaches.

  3. Cognitive and Brain Reserve in Prodromal Huntington Disease

    Science.gov (United States)

    Bonner-Jackson, Aaron; Long, Jeffrey D.; Westervelt, Holly; Tremont, Geoffrey; Aylward, Elizabeth; Paulsen, Jane S.

    2013-01-01

    Background Huntington disease (HD) is associated with decline in cognition and progressive morphological changes in brain structures. Cognitive reserve may represent a mechanism by which disease-related decline may be delayed or slowed. The current study examined the relationship between cognitive reserve and longitudinal change in cognitive functioning and brain volumes among prodromal (gene expansion-positive) HD individuals. Methods Participants were genetically-confirmed individuals with prodromal HD enrolled in the PREDICT-HD study. Cognitive reserve was computed as the composite of performance on a lexical task estimating premorbid intellectual level, occupational status, and years of education. Linear mixed effects regression (LMER) was used to examine longitudinal changes on 4 cognitive measures and 3 brain volumes over approximately 6 years. Results Higher cognitive reserve was significantly associated with a slower rate of change on one cognitive measure (Trail Making Test, Part B) and slower rate of volume loss in two brain structures (caudate, putamen) for those estimated to be closest to motor disease onset. This relationship was not observed among those estimated to be further from motor disease onset. Conclusions Our findings demonstrate a relationship between cognitive reserve and both a measure of executive functioning and integrity of certain brain structures in prodromal HD individuals. PMID:23702309

  4. Approaching neurological diseases to reduce mobility limitations in older persons.

    Science.gov (United States)

    Lauretani, Fulvio; Ceda, Gian Paolo; Pelliccioni, Pio; Ruffini, Livia; Nardelli, Anna; Cherubini, Antonio; Maggio, Marcello

    2014-01-01

    The rapidly increasing elderly population poses a major challenge for future health-care systems. Neurological diseases in older persons are particularly common and coexist with other clinical conditions. This is not surprising given that, for example, even patients with Alzheimer Disease (AD) could have relevant extrapyramidal signs at the moment of the diagnosis with motor signs having more negative prognostic value. Longitudinal studies conducted on Parkinson Disease (PD) showed that, after 20 years, dementia is not only present in almost all survivors but is also the main factor influencing nursing home admission. Recently, it has been reported the importance of Comprehensive Geriatric Assessment (CGA: comprehensive evaluation of cognition, depressive symptoms, mobility and functional assessment) as a tool reducing morbidity in frail older patients admitted to any acute hospital unit. The CGA should be considered as a technological device, for physicians who take care of older persons affected by overlapping neurological diseases. CGA is an extraordinary and cost effective instrument even in patients with advanced neurological diseases where allows to collect valuable information for an effective plan of management.

  5. Overview of impaired facial affect recognition in persons with traumatic brain injury.

    Science.gov (United States)

    Radice-Neumann, Dawn; Zupan, Barbra; Babbage, Duncan R; Willer, Barry

    2007-07-01

    To review the literature of affect recognition for persons with traumatic brain injury (TBI). It is suggested that impairment of affect recognition could be a significant problem for the TBI population and treatment strategies are recommended based on research for persons with autism. Research demonstrates that persons with TBI often have difficulty determining emotion from facial expressions. Studies show that poor interpersonal skills, which are associated with impaired affect recognition, are linked to a variety of negative outcomes. Theories suggest that facial affect recognition is achieved by interpreting important facial features and processing one's own emotions. These skills are often affected by TBI, depending on the areas damaged. Affect recognition impairments have also been identified in persons with autism. Successful interventions have already been developed for the autism population. Comparable neuroanatomical and behavioural findings between TBI and autism suggest that treatment approaches for autism may also benefit those with TBI. Impaired facial affect recognition appears to be a significant problem for persons with TBI. Theories of affect recognition, strategies used in autism and teaching techniques commonly used in TBI need to be considered when developing treatments to improve affect recognition in persons with brain injury.

  6. Neuroprotective Effect against Alzheimer's Disease of Porcine Brain Extract

    Directory of Open Access Journals (Sweden)

    Wipawee Thukham-Mee

    2012-01-01

    Full Text Available Problem statement: Despite the increasing importance of Alzheimer’s disease, no effective therapeutic strategy is available. Therefore, neuroprotective strategy is still required. Recent findings show that numerous substances possessing antioxidant can improve neurodegeneration and memory impairment. Based on the antioxidant effect and its reputation to serve as brain tonic in traditional folklore, we hypothesized that porcine brain extract could mitigate neurodegeneration and memory impairment. Therefore, this study was set up to determine the effect of porcine brain extract on memory impairment and neurodegeneration in animal models of Alzheimer’s disease. Approach: Male Wistar rats (180-220 g had been orally given porcine brain extract at doses of 0.5 and 2.5 mg kg-1 BW for a period of 4 weeks before and 1 week after the induction of cognitive deficit condition as those found in early phase of Alzheimer’s disease via the intraventricular injection of AF64A, a cholinotoxin. Rats were assessed the spatial memory using Morris water maze test. Then, they were determined neuron density in hippocampus using histological techniques. Moreover, the assessment of acetylcholinesterase (AChE activity and malondialdehyde (MDA level in hippocampus were also performed. Results: It was found that both doses of porcine brain extract could enhance memory, neuron and cholinergic neuron density in all subregions of hippocampus. In addition, the decreased AChE and MDA were also observed. Therefore, our results suggested that the possible underlying mechanism of the extract might occur partly via the decrease in oxidative stress marker, MDA and AChE. Conclusion: This study clearly demonstrates that porcine brain extract can protect against memory impairment and neurodegeneration in animal model of Alzheimer’s disease. Therefore, it should be serve as the potential food supplement or adjuvant therapy against Alzheimer’s disease and other age-related cognitive

  7. Regional brain stiffness changes across the Alzheimer's disease spectrum.

    Science.gov (United States)

    Murphy, Matthew C; Jones, David T; Jack, Clifford R; Glaser, Kevin J; Senjem, Matthew L; Manduca, Armando; Felmlee, Joel P; Carter, Rickey E; Ehman, Richard L; Huston, John

    2016-01-01

    Magnetic resonance elastography (MRE) is an MRI-based technique to noninvasively measure tissue stiffness. Currently well established for clinical use in the liver, MRE is increasingly being investigated to measure brain stiffness as a novel biomarker of a variety of neurological diseases. The purpose of this work was to apply a recently developed MRE pipeline to measure regional brain stiffness changes in human subjects across the Alzheimer's disease (AD) spectrum, and to gain insights into the biological processes underlying those stiffness changes by correlating stiffness with existing biomarkers of AD. The results indicate that stiffness changes occur mostly in the frontal, parietal and temporal lobes, in accordance with the known topography of AD pathology. Furthermore, stiffness in those areas correlates with existing imaging biomarkers of AD including hippocampal volumes and amyloid PET. Additional analysis revealed preliminary but significant evidence that the relationship between brain stiffness and AD severity is nonlinear and non-monotonic. Given that similar relationships have been observed in functional MRI experiments, we used task-free fMRI data to test the hypothesis that brain stiffness was sensitive to structural changes associated with altered functional connectivity. The analysis revealed that brain stiffness is significantly and positively correlated with default mode network connectivity. Therefore, brain stiffness as measured by MRE has potential to provide new and essential insights into the temporal dynamics of AD, as well as the relationship between functional and structural plasticity as it relates to AD pathophysiology.

  8. DUF1220 domains, cognitive disease, and human brain evolution.

    Science.gov (United States)

    Dumas, L; Sikela, J M

    2009-01-01

    We have established that human genome sequences encoding a novel protein domain, DUF1220, show a dramatically elevated copy number in the human lineage (>200 copies in humans vs. 1 in mouse/rat) and may be important to human evolutionary adaptation. Copy-number variations (CNVs) in the 1q21.1 region, where most DUF1220 sequences map, have now been implicated in numerous diseases associated with cognitive dysfunction, including autism, autism spectrum disorder, mental retardation, schizophrenia, microcephaly, and macrocephaly. We report here that these disease-related 1q21.1 CNVs either encompass or are directly flanked by DUF1220 sequences and exhibit a dosage-related correlation with human brain size. Microcephaly-producing 1q21.1 CNVs are deletions, whereas macrocephaly-producing 1q21.1 CNVs are duplications. Similarly, 1q21.1 deletions and smaller brain size are linked with schizophrenia, whereas 1q21.1 duplications and larger brain size are associated with autism. Interestingly, these two diseases are thought to be phenotypic opposites. These data suggest a model which proposes that (1) DUF1220 domain copy number may be involved in influencing human brain size and (2) the evolutionary advantage of rapidly increasing DUF1220 copy number in the human lineage has resulted in favoring retention of the high genomic instability of the 1q21.1 region, which, in turn, has precipitated a spectrum of recurrent human brain and developmental disorders.

  9. Huntington's disease : quantifying structural brain changes

    NARCIS (Netherlands)

    Bogaard, Simon Johannes Adrianus van den

    2012-01-01

    The aim of this thesis was to find potential MRI biomarkers for Huntington’s disease (HD). Therefore, after an overview of the current literature on MRI biomarkers, followed by examinations of volumetric MRI, magnetization transfer imaging (MTI), diffusion tensor imaging (DTI) and magnetic resonance

  10. The metabolic syndrome: a brain disease?

    NARCIS (Netherlands)

    Buijs, R.M.; Kreier, F.

    2006-01-01

    The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia--the metabolic syndrome--is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each

  11. Towards Personalized Intervention for Alzheimer’s Disease

    Institute of Scientific and Technical Information of China (English)

    Xing Peng; Peiqi Xing; Xiuhui Li; Ying Qian; Fuhai Song; Zhouxian Bai; Guangchun Han; Hongxing Lei

    2016-01-01

    Alzheimer’s disease (AD) remains to be a grand challenge for the international commu-nity despite over a century of exploration. A key factor likely accounting for such a situation is the vast heterogeneity in the disease etiology, which involves very complex and divergent pathways. Therefore, intervention strategies shall be tailored for subgroups of AD patients. Both demographic and in-depth information is needed for patient stratification. The demographic information includes primarily APOE genotype, age, gender, education, environmental exposure, life style, and medical history, whereas in-depth information stems from genome sequencing, brain imaging, peripheral biomarkers, and even functional assays on neurons derived from patient-specific induced pluripo-tent cells (iPSCs). Comprehensive information collection, better understanding of the disease mech-anisms, and diversified strategies of drug development would help with more effective intervention in the foreseeable future.

  12. Theory of feedback controlled brain stimulations for Parkinson's disease

    Science.gov (United States)

    Sanzeni, A.; Celani, A.; Tiana, G.; Vergassola, M.

    2016-01-01

    Limb tremor and other debilitating symptoms caused by the neurodegenerative Parkinson's disease are currently treated by administering drugs and by fixed-frequency deep brain stimulation. The latter interferes directly with the brain dynamics by delivering electrical impulses to neurons in the subthalamic nucleus. While deep brain stimulation has shown therapeutic benefits in many instances, its mechanism is still unclear. Since its understanding could lead to improved protocols of stimulation and feedback control, we have studied a mathematical model of the many-body neural network dynamics controlling the dynamics of the basal ganglia. On the basis of the results obtained from the model, we propose a new procedure of active stimulation, that depends on the feedback of the network and that respects the constraints imposed by existing technology. We show by numerical simulations that the new protocol outperforms the standard ones for deep brain stimulation and we suggest future experiments that could further improve the feedback procedure.

  13. [Functional imaging of deep brain stimulation in idiopathic Parkinson's disease].

    Science.gov (United States)

    Hilker, R

    2010-10-01

    Functional brain imaging allows the effects of deep brain stimulation (DBS) on the living human brain to be investigated. In patients with advanced Parkinson's disease (PD), positron emission tomography (PET) studies were undertaken at rest as well as under motor, cognitive or behavioral activation. DBS leads to a reduction of abnormal PD-related network activity in the motor system, which partly correlates with the improvement of motor symptoms. The local increase of energy consumption within the direct target area suggests a predominant excitatory influence of the stimulation current on neuronal tissue. Remote effects of DBS of the subthalamic nucleus (STN) on frontal association cortices indicate an interference of stimulation energy with associative and limbic basal ganglia loops. Taken together, functional brain imaging provides very valuable data for advancement of the DBS technique in PD therapy.

  14. Testing predictions from personality neuroscience. Brain structure and the big five.

    Science.gov (United States)

    DeYoung, Colin G; Hirsh, Jacob B; Shane, Matthew S; Papademetris, Xenophon; Rajeevan, Nallakkandi; Gray, Jeremy R

    2010-06-01

    We used a new theory of the biological basis of the Big Five personality traits to generate hypotheses about the association of each trait with the volume of different brain regions. Controlling for age, sex, and whole-brain volume, results from structural magnetic resonance imaging of 116 healthy adults supported our hypotheses for four of the five traits: Extraversion, Neuroticism, Agreeableness, and Conscientiousness. Extraversion covaried with volume of medial orbitofrontal cortex, a brain region involved in processing reward information. Neuroticism covaried with volume of brain regions associated with threat, punishment, and negative affect. Agreeableness covaried with volume in regions that process information about the intentions and mental states of other individuals. Conscientiousness covaried with volume in lateral prefrontal cortex, a region involved in planning and the voluntary control of behavior. These findings support our biologically based, explanatory model of the Big Five and demonstrate the potential of personality neuroscience (i.e., the systematic study of individual differences in personality using neuroscience methods) as a discipline.

  15. Network structure of brain atrophy in de novo Parkinson's disease.

    Science.gov (United States)

    Zeighami, Yashar; Ulla, Miguel; Iturria-Medina, Yasser; Dadar, Mahsa; Zhang, Yu; Larcher, Kevin Michel-Herve; Fonov, Vladimir; Evans, Alan C; Collins, D Louis; Dagher, Alain

    2015-09-07

    We mapped the distribution of atrophy in Parkinson's disease (PD) using magnetic resonance imaging (MRI) and clinical data from 232 PD patients and 117 controls from the Parkinson's Progression Markers Initiative. Deformation-based morphometry and independent component analysis identified PD-specific atrophy in the midbrain, basal ganglia, basal forebrain, medial temporal lobe, and discrete cortical regions. The degree of atrophy reflected clinical measures of disease severity. The spatial pattern of atrophy demonstrated overlap with intrinsic networks present in healthy brain, as derived from functional MRI. Moreover, the degree of atrophy in each brain region reflected its functional and anatomical proximity to a presumed disease epicenter in the substantia nigra, compatible with a trans-neuronal spread of the disease. These results support a network-spread mechanism in PD. Finally, the atrophy pattern in PD was also seen in healthy aging, where it also correlated with the loss of striatal dopaminergic innervation.

  16. Genetic control of human brain transcript expression in Alzheimer disease.

    Science.gov (United States)

    Webster, Jennifer A; Gibbs, J Raphael; Clarke, Jennifer; Ray, Monika; Zhang, Weixiong; Holmans, Peter; Rohrer, Kristen; Zhao, Alice; Marlowe, Lauren; Kaleem, Mona; McCorquodale, Donald S; Cuello, Cindy; Leung, Doris; Bryden, Leslie; Nath, Priti; Zismann, Victoria L; Joshipura, Keta; Huentelman, Matthew J; Hu-Lince, Diane; Coon, Keith D; Craig, David W; Pearson, John V; Heward, Christopher B; Reiman, Eric M; Stephan, Dietrich; Hardy, John; Myers, Amanda J

    2009-04-01

    We recently surveyed the relationship between the human brain transcriptome and genome in a series of neuropathologically normal postmortem samples. We have now analyzed additional samples with a confirmed pathologic diagnosis of late-onset Alzheimer disease (LOAD; final n = 188 controls, 176 cases). Nine percent of the cortical transcripts that we analyzed had expression profiles correlated with their genotypes in the combined cohort, and approximately 5% of transcripts had SNP-transcript relationships that could distinguish LOAD samples. Two of these transcripts have been previously implicated in LOAD candidate-gene SNP-expression screens. This study shows how the relationship between common inherited genetic variants and brain transcript expression can be used in the study of human brain disorders. We suggest that studying the transcriptome as a quantitative endo-phenotype has greater power for discovering risk SNPs influencing expression than the use of discrete diagnostic categories such as presence or absence of disease.

  17. Parkinson’s Disease Biomarkers Program Brain Imaging Repository

    OpenAIRE

    Ofori, Edward; Du, Guangwei; Babcock, Debra; Huang, Xuemei; Vaillancourt, David E.

    2015-01-01

    The Parkinson’s Disease Biomarkers Program (PDBP) is a multi-site study designed to identify Parkinson’s Disease (PD) biomarkers that can be used to improve the understanding of PD pathophysiology and to develop tools that provide novel measures to evaluate PD clinical trials. The PDBP consortium comprises numerous individual projects of which two are specifically geared to the development of brain imaging markers for diagnosis, progression, and prognosis of PD or related disorders. All study...

  18. Loss of functional GABAA receptors in the Alzheimer diseased brain

    Science.gov (United States)

    Limon, Agenor; Reyes-Ruiz, Jorge Mauricio; Miledi, Ricardo

    2012-01-01

    The cholinergic and glutamatergic neurotransmission systems are known to be severely disrupted in Alzheimer's disease (AD). GABAergic neurotransmission, in contrast, is generally thought to be well preserved. Evidence from animal models and human postmortem tissue suggest GABAergic remodeling in the AD brain. Nevertheless, there is no information on changes, if any, in the electrophysiological properties of human native GABA receptors as a consequence of AD. To gain such information, we have microtransplanted cell membranes, isolated from temporal cortices of control and AD brains, into Xenopus oocytes, and recorded the electrophysiological activity of the transplanted GABA receptors. We found an age-dependent reduction of GABA currents in the AD brain. This reduction was larger when the AD membranes were obtained from younger subjects. We also found that GABA currents from AD brains have a faster rate of desensitization than those from non-AD brains. Furthermore, GABA receptors from AD brains were slightly, but significantly, less sensitive to GABA than receptors from non-AD brains. The reduction of GABA currents in AD was associated with reductions of mRNA and protein of the principal GABA receptor subunits normally present in the temporal cortex. Pairwise analysis of the transcripts within control and AD groups and analyses of the proportion of GABA receptor subunits revealed down-regulation of α1 and γ2 subunits in AD. In contrast, the proportions of α2, β1, and γ1 transcripts were up-regulated in the AD brains. Our data support a functional remodeling of GABAergic neurotransmission in the human AD brain. PMID:22691495

  19. Does Parkinson's disease affect judgement about another person's action?

    Science.gov (United States)

    Poliakoff, E; Galpin, A J; Dick, J P R; Tipper, S P

    2010-07-01

    The observer's motor system has been shown to be involved in observing the actions of another person. Recent findings suggest that people with Parkinson's disease do not show the same motor facilitatory effects when observing the actions of another person. We studied whether Parkinson's patients were able to make unspeeded judgements about another person's action. Participants were asked to watch video clips of an actor lifting a box containing different weights (100, 200, 300 or 400 g) and to guess the weight that was being lifted on a 9-point scale. We compared the performance of 16 patients with PD with 16 healthy age-matched controls. Both groups were able to do the task, showing a significant relationship between the real weight and the guessed weight, albeit with a tendency to overestimate the lowest weight and underestimate the heaviest weight. The PD patients, however, showed a reduced slope value. These results show that despite their own motor deficits, PD patients are still able to judge the weight being lifted by another person, albeit with a slight reduction in accuracy. Further research will be required to determine whether PD patients use a motor simulation or a visual compensatory strategy to achieve this.

  20. The metabolic syndrome: a brain disease?

    Science.gov (United States)

    Buijs, Ruud M; Kreier, Felix

    2006-09-01

    The incidence of obesity with, as consequence, a rise in associated diseases such as diabetes, hypertension and dyslipidemia--the metabolic syndrome--is reaching epidemic proportions in industrialized countries. Here, we provide a hypothesis that the biological clock which normally prepares us each morning for the coming activity period is altered due to a modern life style of low activity during the day and late-night food intake. Furthermore, we review the anatomical evidence supporting the proposal that an unbalanced autonomic nervous system output may lead to the simultaneous occurrence of diabetes type 2, dyslipidemia, hypertension and visceral obesity.

  1. Physical Activity, Brain Plasticity, and Alzheimer’s Disease

    Science.gov (United States)

    Erickson, Kirk I; Weinstein, Andrea M; Lopez, Oscar L

    2013-01-01

    In this review we summarize the epidemiological, cross-sectional, and interventional studies examining the association between physical activity and brain volume, function, and risk for Alzheimer’s disease. The epidemiological literature provides compelling evidence that greater amounts of physical activity are associated with a reduced risk of dementia in late life. In addition, randomized interventions using neuroimaging tools have reported that participation in physical activity increases the size of prefrontal and hippocampal brain areas, which may lead to a reduction in memory impairments. Consistent with these findings, longitudinal studies using neuroimaging tools also find that the volume of prefrontal and hippocampal brain areas are larger in individuals who engaged in more physical activity earlier in life. We conclude from this review that there is convincing evidence that physical activity has a consistent and robust association with brain regions implicated in age-related cognitive decline and Alzheimer’s disease. In addition to summarizing this literature we provide recommendations for future research on physical activity and brain health. PMID:23085449

  2. Clearance systems in the brain-implications for Alzheimer disease.

    Science.gov (United States)

    Tarasoff-Conway, Jenna M; Carare, Roxana O; Osorio, Ricardo S; Glodzik, Lidia; Butler, Tracy; Fieremans, Els; Axel, Leon; Rusinek, Henry; Nicholson, Charles; Zlokovic, Berislav V; Frangione, Blas; Blennow, Kaj; Ménard, Joël; Zetterberg, Henrik; Wisniewski, Thomas; de Leon, Mony J

    2015-08-01

    Accumulation of toxic protein aggregates-amyloid-β (Aβ) plaques and hyperphosphorylated tau tangles-is the pathological hallmark of Alzheimer disease (AD). Aβ accumulation has been hypothesized to result from an imbalance between Aβ production and clearance; indeed, Aβ clearance seems to be impaired in both early and late forms of AD. To develop efficient strategies to slow down or halt AD, it is critical to understand how Aβ is cleared from the brain. Extracellular Aβ deposits can be removed from the brain by various clearance systems, most importantly, transport across the blood-brain barrier. Findings from the past few years suggest that astroglial-mediated interstitial fluid (ISF) bulk flow, known as the glymphatic system, might contribute to a larger portion of extracellular Aβ (eAβ) clearance than previously thought. The meningeal lymphatic vessels, discovered in 2015, might provide another clearance route. Because these clearance systems act together to drive eAβ from the brain, any alteration to their function could contribute to AD. An understanding of Aβ clearance might provide strategies to reduce excess Aβ deposits and delay, or even prevent, disease onset. In this Review, we describe the clearance systems of the brain as they relate to proteins implicated in AD pathology, with the main focus on Aβ.

  3. Putative periodontopathogens in "diseased" and "non-diseased" persons exhibiting poor oral hygiene.

    Science.gov (United States)

    Dahlén, G; Manji, F; Baelum, V; Fejerskov, O

    1992-01-01

    The aim of the study was to assess the occurrence of some putative periodonto-pathogens in "test" and "control" sites in "diseased" and "non-diseased" persons, respectively, from an adult rural Kenyan population exhibiting poor oral hygiene and widespread loss of attachment (LA). 14 persons (less than 35 years) were assigned to a "diseased" category on the basis of at least 4 sites with LA greater than or equal to 4 mm; at least 5 mm LA and a pocket greater than or equal to 4 mm interproximally in a lower incisor ("test" site): and less than 2 mm LA and no pocket greater than or equal to 4 mm distal to a lower canine or mesial to a lower first premolar ("control" site). Age-matched "non-diseased" persons were identified on the basis of no sites with LA greater than 2 mm and no pockets greater than or equal to 4 mm associated with LA. Paperpoint samples from test and control sites as well as a scraping sample from the dorsum of tongue were examined for presence of Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides intermedius, B. melaninogenicus group, Capnocytophaga, Selenomonas spp., and Wolinella recta. P. gingivalis was found in 79% of test sites and 36% of control sites in "diseased" persons, and in 18% and 35% of test and control sites, respectively, in "non-diseased" persons. "No other bacterial group discriminated significantly between test and control sites or between diseased and non-diseased subjects. The surprisingly high occurrence of P. gingivalis in non-diseased subjects, both subgingivally and on tongue, indicates that deep periodontal pockets are not prerequisite ecological environments for P. gingivalis establishment.

  4. Impaired brain creatine kinase activity in Huntington's disease.

    Science.gov (United States)

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

    2011-01-01

    Huntington's disease (HD) is associated with impaired energy metabolism in the brain. Creatine kinase (CK) catalyzes ATP-dependent phosphorylation of creatine (Cr) into phosphocreatine (PCr), thereby serving as readily available high-capacity spatial and temporal ATP buffering. Substantial evidence supports a specific role of the Cr/PCr system in neurodegenerative diseases. In the brain, the Cr/PCr ATP-buffering system is established by a concerted operation of the brain-specific cytosolic enzyme BB-CK and ubiquitous mitochondrial uMt-CK. It is not yet established whether the activity of these CK isoenzymes is impaired in HD. We measured PCr, Cr, ATP and ADP in brain extracts of 3 mouse models of HD - R6/2 mice, N171-82Q and HdhQ(111) mice - and the activity of CK in cytosolic and mitochondrial brain fractions from the same mice. The PCr was significantly increased in mouse HD brain extracts as compared to nontransgenic littermates. We also found an approximately 27% decrease in CK activity in both cytosolic and mitochondrial fractions of R6/2 and N171-82Q mice, and an approximately 25% decrease in the mitochondria from HdhQ(111) mice. Moreover, uMt-CK and BB-CK activities were approximately 63% lower in HD human brain samples as compared to nondiseased controls. Our findings lend strong support to the role of impaired energy metabolism in HD, and point out the potential importance of impairment of the CK-catalyzed ATP-buffering system in the etiology of HD. Copyright © 2010 S. Karger AG, Basel.

  5. Brain imaging of mild cognitive impairment and Alzheimer's disease

    Institute of Scientific and Technical Information of China (English)

    Changhao Yin; Siou Li; Weina Zhao; Jiachun Feng

    2013-01-01

    The rapidly increasing prevalence of cognitive impairment and Alzheimer's disease has the potential to create a major worldwide healthcare crisis. Structural MRI studies in patients with Alzheimer's disease and mild cognitive impairment are currently attracting considerable interest. It is extremely important to study early structural and metabolic changes, such as those in the hippocampus, entorhinal cortex, and gray matter structures in the medial temporal lobe, to allow the early detection of mild cognitive impairment and Alzheimer's disease. The microstructural integrity of white matter can be studied with diffusion tensor imaging. Increased mean diffusivity and decreased fractional anisotropy are found in subjects with white matter damage. Functional imaging studies with positron emission tomography tracer compounds enable detection of amyloid plaques in the living brain in patients with Alzheimer's disease. In this review, we will focus on key findings from brain imaging studies in mild cognitive impairment and Alzheimer's disease, including structural brain changes studied with MRI and white matter changes seen with diffusion tensor imaging, and other specific imaging methodologies will also be discussed.

  6. Diamox-enhanced brain SPECT in cerebrovascular diseases

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Yun Young [College of Medicine, Hanyang University, Seoul (Korea, Republic of)

    2007-04-15

    Acute event in cerebrovascular disease is the second most common cause of death in Korea following cancer, and it can also cause serious neurologic deficits. Understanding of perfusion status is important for clinical applications in management of patients with cerebrovascular diseases, and then the attacks of ischemic neurologic symptoms and the risk of acute events can be reduced. Therefore, the normal vascular anatomy of brain, various clinical applications of acetazolamide-enhanced brain perfusion SPECT, including meaning and role of assessment of vascular reserve in carotid stenosis before procedure, in pediatric Moyamoya disease before and after operation, in prediction of development of hyperperfusion syndrome before procedure, and in prediction of vasospasm and of prognosis in subarachnoid hemorrhage were reviewed in this paper.

  7. Endogenously Nitrated Proteins in Mouse Brain: Links To Neurodegenerative Disease

    Energy Technology Data Exchange (ETDEWEB)

    Sacksteder, Colette A.; Qian, Weijun; Knyushko, Tanya V.; Wang, Haixing H.; Chin, Mark H.; Lacan, Goran; Melega, William P.; Camp, David G.; Smith, Richard D.; Smith, Desmond J.; Squier, Thomas C.; Bigelow, Diana J.

    2006-07-04

    Increased nitrotyrosine modification of proteins has been documented in multiple pathologies in a variety of tissue types; emerging evidence suggests its additional role in redox regulation of normal metabolism. In order to identify proteins sensitive to nitrating conditions in vivo, a comprehensive proteomic dataset identifying 7,792 proteins from whole mouse brain, generated by LC/LC-MS/MS analyses, was used to identify nitrated proteins. This analysis resulted in identification of 31 unique nitrotyrosine sites within 29 different proteins. Over half of the nitrated proteins identified have been reported to be involved in Parkinson's disease, Alzheimer's disease, or other neurodegenerative disorders. Similarly, nitrotyrosine immunoblots of whole brain homogenates show that treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an experimental model of Parkinson's disease, induces increased nitration of the same protein bands observed to be nitrated in brains of untreated animals. Comparing sequences and available high resolution structures around nitrated tyrosines with those of unmodified sites indicates a preference of nitration in vivo for surface accessible tyrosines in loops, characteristics consistent with peroxynitrite-induced tyrosine modification. More striking is the five-fold greater nitration of tyrosines having nearby basic sidechains, suggesting electrostatic attraction of basic groups with the negative charge of peroxynitrite. Together, these results suggest that elevated peroxynitrite generation plays a role in neurodegenerative changes in the brain and provides a predictive tool of functionally important sites of nitration.

  8. Dock protein family in brain development and neurological disease.

    Science.gov (United States)

    Shi, Lei

    2013-11-01

    The family of dedicator of cytokinesis (Dock), a protein family that belongs to the atypical Rho guanine nucleotide exchange factors (GEFs) for Rac and/or Cdc42 GTPases, plays pivotal roles in various processes of brain development. To date, 11 members of Docks have been identified in the mammalian system. Emerging evidence has suggested that members of the Dock family are associated with several neurodegenerative and neuropsychiatric diseases, including Alzheimer disease and autism spectrum disorders. This review summarizes recent advances on the understanding of the roles of the Dock protein family in normal and diseased processes in the nervous system. Furthermore, interacting proteins and the molecular regulation of Docks are discussed.

  9. Brain Plasticity and Disease: A Matter of Inhibition

    Directory of Open Access Journals (Sweden)

    Laura Baroncelli

    2011-01-01

    Full Text Available One major goal in Neuroscience is the development of strategies promoting neural plasticity in the adult central nervous system, when functional recovery from brain disease and injury is limited. New evidence has underscored a pivotal role for cortical inhibitory circuitries in regulating plasticity both during development and in adulthood. This paper summarizes recent findings showing that the inhibition-excitation balance controls adult brain plasticity and is at the core of the pathogenesis of neurodevelopmental disorders like autism, Down syndrome, and Rett syndrome.

  10. Personality Trait and Facial Expression Filter-Based Brain-Computer Interface

    OpenAIRE

    Seongah Chin; Chung-Yeon Lee

    2013-01-01

    In this paper, we present technical approaches that bridge the gap in the research related to the use of brain‐computer interfaces for entertainment and facial expressions. Such facial expressions that reflect an individual’s personal traits can be used to better realize artificial facial expressions in a gaming environment based on a brain‐computer interface. First, an emotion extraction filter is introduced in order to classify emotions on the basis of the users’ brain signals in real time....

  11. Using 3D Printing to Create Personalized Brain Models for Neurosurgical Training and Preoperative Planning.

    Science.gov (United States)

    Ploch, Caitlin C; Mansi, Chris S S A; Jayamohan, Jayaratnam; Kuhl, Ellen

    2016-06-01

    Three-dimensional (3D) printing holds promise for a wide variety of biomedical applications, from surgical planning, practicing, and teaching to creating implantable devices. The growth of this cheap and easy additive manufacturing technology in orthopedic, plastic, and vascular surgery has been explosive; however, its potential in the field of neurosurgery remains underexplored. A major limitation is that current technologies are unable to directly print ultrasoft materials like human brain tissue. In this technical note, the authors present a new technology to create deformable, personalized models of the human brain. The method combines 3D printing, molding, and casting to create a physiologically, anatomically, and tactilely realistic model based on magnetic resonance images. Created from soft gelatin, the model is easy to produce, cost-efficient, durable, and orders of magnitude softer than conventionally printed 3D models. The personalized brain model cost $50, and its fabrication took 24 hours. In mechanical tests, the model stiffness (E = 25.29 ± 2.68 kPa) was 5 orders of magnitude softer than common 3D printed materials, and less than an order of magnitude stiffer than mammalian brain tissue (E = 2.64 ± 0.40 kPa). In a multicenter surgical survey, model size (100.00%), visual appearance (83.33%), and surgical anatomy (81.25%) were perceived as very realistic. The model was perceived as very useful for patient illustration (85.00%), teaching (94.44%), learning (100.00%), surgical training (95.00%), and preoperative planning (95.00%). With minor refinements, personalized, deformable brain models created via 3D printing will improve surgical training and preoperative planning with the ultimate goal to provide accurate, customized, high-precision treatment. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Addiction postulates and legal causation, or who's in charge, person or brain?

    Science.gov (United States)

    Wallace, David L

    2013-01-01

    In this article, I address the persistent confusion over the meaning of a medical diagnosis of drug addiction or substance dependence in the courtroom, specifically in regard to legal judgments about the reasonable legal person, causation, and individual responsibility in civil actions. Using the example of the Engle tobacco litigation in Florida, where the plaintiffs have reduced mind to brain and claimed that the clinical status of addiction excuses or mitigates the smoker's responsibility for the health consequences of smoking based on brain processes, I examine the conceptual difficulties presented by use of biomedical models of behavior in a legal system predicated on different assumptions altogether. For legal purposes, the biological system in question is the human organism as a whole, not a brain per se, and there is a functional identity between a smoker and his motivational states for purposes of responsibility attribution.

  13. Nanoparticle-mediated brain drug delivery: Overcoming blood-brain barrier to treat neurodegenerative diseases.

    Science.gov (United States)

    Saraiva, Cláudia; Praça, Catarina; Ferreira, Raquel; Santos, Tiago; Ferreira, Lino; Bernardino, Liliana

    2016-08-10

    The blood-brain barrier (BBB) is a vital boundary between neural tissue and circulating blood. The BBB's unique and protective features control brain homeostasis as well as ion and molecule movement. Failure in maintaining any of these components results in the breakdown of this specialized multicellular structure and consequently promotes neuroinflammation and neurodegeneration. In several high incidence pathologies such as stroke, Alzheimer's (AD) and Parkinson's disease (PD) the BBB is impaired. However, even a damaged and more permeable BBB can pose serious challenges to drug delivery into the brain. The use of nanoparticle (NP) formulations able to encapsulate molecules with therapeutic value, while targeting specific transport processes in the brain vasculature, may enhance drug transport through the BBB in neurodegenerative/ischemic disorders and target relevant regions in the brain for regenerative processes. In this review, we will discuss BBB composition and characteristics and how these features are altered in pathology, namely in stroke, AD and PD. Additionally, factors influencing an efficient intravenous delivery of polymeric and inorganic NPs into the brain as well as NP-related delivery systems with the most promising functional outcomes will also be discussed.

  14. In vivo calcium imaging of the aging and diseased brain

    Energy Technology Data Exchange (ETDEWEB)

    Eichhoff, Gerhard; Busche, Marc A.; Garaschuk, Olga [Technical University of Munich, Institute of Neuroscience, Munich (Germany)

    2008-03-15

    Over the last decade, in vivo calcium imaging became a powerful tool for studying brain function. With the use of two-photon microscopy and modern labelling techniques, it allows functional studies of individual living cells, their processes and their interactions within neuronal networks. In vivo calcium imaging is even more important for studying the aged brain, which is hard to investigate in situ due to the fragility of neuronal tissue. In this article, we give a brief overview of the techniques applicable to image aged rodent brain at cellular resolution. We use multicolor imaging to visualize specific cell types (neurons, astrocytes, microglia) as well as the autofluorescence of the ''aging pigment'' lipofuscin. Further, we illustrate an approach for simultaneous imaging of cortical cells and senile plaques in mouse models of Alzheimer's disease. (orig.)

  15. Gluten-induced cognitive impairment ("brain fog") in coeliac disease.

    Science.gov (United States)

    Yelland, Gregory W

    2017-03-01

    Much is known about the serious neurological effects of gluten ingestion in coeliac disease patients, such as sporadic ataxia and peripheral neuropathy, although the causal links to gluten are still under debate. However, such disorders are observed in only a small percentage of coeliac patients. Much less is known about the transient cognitive impairments to memory, attention, executive function, and the speed of cognitive processing reported by the majority of patients with coeliac disease. These mild degradations of cognitive functions, referred to as "brain fog," are yet to be formally recognized as a medical or psychological condition. However, subtle tests of cognitive function are measurable in untreated patients with coeliac disease and improve over the first 12 months' therapy with a gluten-free diet. Such deficits also occur in patients with Crohn's disease, particularly in association with systemic inflammatory activity. Thus, cognitive impairments associated with brain fog are psychologically and neurologically real and improve with adherence to a gluten-free diet. There is not yet sufficient evidence to provide a definitive account of the mechanism by which gluten ingestion causes the impairments to cognitive function associated with brain fog, but current evidence suggests that it is more likely that the causal factor is not directly related to exposure to gluten. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  16. Personality changes and return to work after severe traumatic brain injury: a prospective study.

    Science.gov (United States)

    Diaz, Alexandre P; Schwarzbold, Marcelo L; Thais, Maria E; Cavallazzi, Gisele G; Schmoeller, Roseli; Nunes, Jean C; Hohl, Alexandre; Guarnieri, Ricardo; Linhares, Marcelo N; Walz, Roger

    2014-09-01

    To evaluate predictors of non-return to work (nRTW) among social, demographic, clinical, and psychiatric variables after severe traumatic brain injury (TBI) in a cohort of Brazilian patients. Prospective study. Forty-three community-dwelling individuals treated at a Level I trauma center at the time of TBI were evaluated 18 months after trauma. Measures included DSM-IV-TR criteria for personality changes after TBI and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) to assess psychiatric diagnosis. Hospitalization variables included Glasgow Coma Scale scores, pupil examination findings, associated limb trauma, Marshall computed tomography classification, and blood glucose levels. After multiple logistic regression analysis, only the diagnosis of personality changes was found to be independently associated with nRTW, with an adjusted odds ratio of 10.92 (p = 0.02, 95% confidence interval 1.41-84.28). In this study, personality changes were an independent predictor of nRTW after severe TBI. Ways to predict risk factors associated with personality changes after severe brain injury could aid in identification of early and effective interventions that might ease the burden associated with this condition.

  17. Personality changes and return to work after severe traumatic brain injury: a prospective study

    Directory of Open Access Journals (Sweden)

    Alexandre P. Diaz

    2014-09-01

    Full Text Available Objective: To evaluate predictors of non-return to work (nRTW among social, demographic, clinical, and psychiatric variables after severe traumatic brain injury (TBI in a cohort of Brazilian patients. Methods: Prospective study. Forty-three community-dwelling individuals treated at a Level I trauma center at the time of TBI were evaluated 18 months after trauma. Measures included DSM-IV-TR criteria for personality changes after TBI and Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I to assess psychiatric diagnosis. Hospitalization variables included Glasgow Coma Scale scores, pupil examination findings, associated limb trauma, Marshall computed tomography classification, and blood glucose levels. Results: After multiple logistic regression analysis, only the diagnosis of personality changes was found to be independently associated with nRTW, with an adjusted odds ratio of 10.92 (p = 0.02, 95% confidence interval 1.41-84.28. Conclusions: In this study, personality changes were an independent predictor of nRTW after severe TBI. Ways to predict risk factors associated with personality changes after severe brain injury could aid in identification of early and effective interventions that might ease the burden associated with this condition.

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

    Directory of Open Access Journals (Sweden)

    Martin Göttlich

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

  19. Community-based training and employment: an effective program for persons with traumatic brain injury.

    Science.gov (United States)

    Wall, J R; Niemczura, J G; Rosenthal, M

    1998-01-01

    Occupational entry is an important issue for persons with disabilities, as many become or remain unemployed after their injury. After traumatic brain injury (TBI), individuals exhibit high unemployment rates, especially those persons with injuries of greater severity, a limited premorbid work history and/or persons from economically disadvantaged backgrounds. Vocational rehabilitation programs have been developed to improve employability. Traditional vocational rehabilitation approaches, based on integrating work skills with cognitive rehabilitation models have proven only minimally effective with TBI. The supported employment model has been demonstrated to be much more effective with this group, as has an approach that combines vocational and psychosocial skills training along with job support. Even with these generally successful approaches, the literature on vocational rehabilitation in clients from economically disadvantaged environments who are diagnosed with TBI is limited. An approach for the economically disadvantaged, which combines work skills training in a real work community along with supported employment is presented.

  20. Healthy aging persons and their brains: promoting resilience through creative engagement.

    Science.gov (United States)

    McFadden, Susan H; Basting, Anne D

    2010-02-01

    Creative engagement, as an expression of and a support for resilience, may have a neuroprotective effect among older adults, contributing to retention of cognitive capacity. Recent research on creative activities shows that they strengthen social networks and give persons a sense of control; both outcomes have been associated with brain health. The authors cite evidence suggesting that positive social interactions can nurture resilience and creative engagement among older persons, including those living with dementia. The motivational, attentional, affective, and social components of creative activities combine to offer older persons meaningful opportunities to express and strengthen their resilience, regardless of their cognitive status, despite the biopsychosocial challenges of aging. The article addresses implications for future research, clinical practice, and public policy, and suggests how gaps in current research on resilience and creativity might be addressed.

  1. Genetic mouse models of brain ageing and Alzheimer's disease.

    Science.gov (United States)

    Bilkei-Gorzo, Andras

    2014-05-01

    Progression of brain ageing is influenced by a complex interaction of genetic and environmental factors. Analysis of genetically modified animals with uniform genetic backgrounds in a standardised, controlled environment enables the dissection of critical determinants of brain ageing on a molecular level. Human and animal studies suggest that increased load of damaged macromolecules, efficacy of DNA maintenance, mitochondrial activity, and cellular stress defences are critical determinants of brain ageing. Surprisingly, mouse lines with genetic impairment of anti-oxidative capacity generally did not show enhanced cognitive ageing but rather an increased sensitivity to oxidative challenge. Mouse lines with impaired mitochondrial activity had critically short life spans or severe and rapidly progressing neurodegeneration. Strains with impaired clearance in damaged macromolecules or defects in the regulation of cellular stress defences showed alterations in the onset and progression of cognitive decline. Importantly, reduced insulin/insulin-like growth factor signalling generally increased life span but impaired cognitive functions revealing a complex interaction between ageing of the brain and of the body. Brain ageing is accompanied by an increased risk of developing Alzheimer's disease. Transgenic mouse models expressing high levels of mutant human amyloid precursor protein showed a number of symptoms and pathophysiological processes typical for early phase of Alzheimer's disease. Generally, therapeutic strategies effective against Alzheimer's disease in humans were also active in the Tg2576, APP23, APP/PS1 and 5xFAD lines, but a large number of false positive findings were also reported. The 3xtg AD model likely has the highest face and construct validity but further studies are needed. Copyright © 2013 Elsevier Inc. All rights reserved.

  2. Circulating exosomes as new biomarkers for brain disease and injury

    Science.gov (United States)

    Graner, Michael W.; Epple, Laura M.; Dusto, Nathaniel L.; Lencioni, Alex M.; Nega, Meheret; Herring, Matthew; Winston, Ben; Madsen, Helen; Bemis, Lynne T.; Anchordoquy, Thomas J.

    2013-05-01

    Brain diseases such as cancers, neurodegenerative disorders, or trauma are frequently diagnosed with imaging modalities and sometimes with intracranial biopsies. Treatment response is similarly monitored, along with clinical indications. While these technologies provide important windows into the disease state, they fail to provide us a detailed molecular portrait of the disease and of the changes taking place during therapy. Exosomes are virus-sized nanovesicles derived from the endosomal system and are released extracellularly from essentially all cell types. Exosomes contain intracellular entities (proteins, nucleic acids, metabolites), membrane proteins and lipids, and even extracellular proteins bound to them. Exosomes may be considered as mini-surrogates of their cells of origin, with some content common to all cells/exosomes, but some of the content would be cell-specific. These vesicles are found in all biofluids in humans, and are thus accessible to "liquid biopsy" with harvest of vesicles from such fluids. Current challenges are to identify disease-related markers or panels of markers to distinguish the disease state. Here we will show examples of brain tumor markers found in/on exosomes from cell culture and patient sera, and we will suggest that aspects of the biology of disease may have a relevant place in the search for biomarkers.

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

    Science.gov (United States)

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

    2015-02-24

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

  4. Inflammatory bowel diseases: a dysfunction of brain-gut interactions?

    Science.gov (United States)

    Bonaz, B

    2013-09-01

    The gut has the capacity to function as an autonomous organ. However, in normal conditions, the gut and the central nervous system talk to each other through the autonomic nervous system (ANS), represented by the sympathetic (i.e. the splanchnic nerves) and the parasympathetic nervous system (i.e. the vagus nerve and the sacral parasympathetic pelvic nerves). The brain is able to integrate inputs coming from the digestive tract inside a central autonomic network organized around the hypothalamus, limbic system and cerebral cortex and in return to modify the ANS and the hypothalamic pituitary adrenal axis (HPA axis). An abnormal functioning of these brain-gut interactions has been described in irritable bowel syndrome (IBS) classically considered as a biopsychosocial model where stress plays a promoting role. Inflammatory bowel diseases (IBD) result from an inappropriate inflammatory response to intestinal microbes in a genetically susceptible host. In this article we review the current knowledge on the possible involvement of a dysfunction of brain-gut interactions in the pathogeny of IBD as represented by a dysfunction of the ANS, an abnormal HPA axis and cholinergic anti-inflammatory pathway, a deleterious effect of stress and depression as well as an abnormal coupling of the prefrontal cortex-amygdala complex and an abnormal relation between the microbiota and the brain as pro-inflammatory factors. Therapeutic approaches with the aim to restore an equilibrium of these brain-gut interactions are of interest.

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

    Science.gov (United States)

    Mulak, Agata; Bonaz, Bruno

    2015-10-07

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

  6. Brain imaging of neurovascular dysfunction in Alzheimer's disease.

    Science.gov (United States)

    Montagne, Axel; Nation, Daniel A; Pa, Judy; Sweeney, Melanie D; Toga, Arthur W; Zlokovic, Berislav V

    2016-05-01

    Neurovascular dysfunction, including blood-brain barrier (BBB) breakdown and cerebral blood flow (CBF) dysregulation and reduction, are increasingly recognized to contribute to Alzheimer's disease (AD). The spatial and temporal relationships between different pathophysiological events during preclinical stages of AD, including cerebrovascular dysfunction and pathology, amyloid and tau pathology, and brain structural and functional changes remain, however, still unclear. Recent advances in neuroimaging techniques, i.e., magnetic resonance imaging (MRI) and positron emission tomography (PET), offer new possibilities to understand how the human brain works in health and disease. This includes methods to detect subtle regional changes in the cerebrovascular system integrity. Here, we focus on the neurovascular imaging techniques to evaluate regional BBB permeability (dynamic contrast-enhanced MRI), regional CBF changes (arterial spin labeling- and functional-MRI), vascular pathology (structural MRI), and cerebral metabolism (PET) in the living human brain, and examine how they can inform about neurovascular dysfunction and vascular pathophysiology in dementia and AD. Altogether, these neuroimaging approaches will continue to elucidate the spatio-temporal progression of vascular and neurodegenerative processes in dementia and AD and how they relate to each other.

  7. [The blood-brain barrier and neurodegenerative lysosomal storage diseases].

    Science.gov (United States)

    Urayama, Akihiko

    2013-02-01

    Enzyme replacement therapy has been a very effective treatment for several lysosomal storage diseases. However, correcting central nervous system (CNS) storage has been challenging due to the presence of the blood-brain barrier (BBB), which hampers the entry of circulating lysosomal enzymes into the brain. In our previous studies, we discovered that luminally expressed cation-independent mannose 6-phosphate (M6P) receptor is a universal transporter for lysosomal enzymes that contain M6P moieties on the enzyme molecule. This receptor-mediated transport of lysosomal enzymes showed developmental down-regulation that resulted in a failure of delivery of lysosomal enzymes across the BBB in the adult brain. Conceptually, if one can re-induce M6P receptor-mediated transport of lysosomal enzymes in adult BBB, this could provide a novel brain targeting approach for treating abnormal storage in the CNS, regardless of the age of subjects. We found that systemic adrenergic stimuli restored functional transport of β-glucuronidase across the adult BBB. The concept of manipulating BBB transport activity by endogenous characteristics has also been demonstrated by another group who showed effective treatment in a Pompe disease model animal in vivo. It is intriguing that lysosomal enzymes utilize multiple mechanisms for their transport across the BBB. This review explores pharmacological manipulations for the delivery of lysosomal enzymes into the CNS, and the mechanisms of their transport across the BBB, based on existing evidence from studies of β-glucuronidase, sulfamidase, acid α-glucosidase, and arylsulfatase A.

  8. Personal health technology: A new era in cardiovascular disease prevention.

    Science.gov (United States)

    Franklin, Nina C; Lavie, Carl J; Arena, Ross A

    2015-03-01

    Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide yet the majority of related risk factors are largely preventable (primary prevention [PP]) and effectively treatable (secondary prevention [SP]) with healthy lifestyle behaviors. The use of information and communication technology (ICT) offers a unique approach to personal health and CVD prevention, as these mediums are relatively affordable, approachable, and accessible. The purpose of this review is to provide an overview of ICT-driven personal health technologies and their potential role in promoting and supporting self-care behaviors for PP and SP of CVD. In this review, we focus on technological interventions that have been successful at supporting positive behavior change in order to determine which tools, resources, and methods are most appropriate for delivering interventions geared towards CVD prevention. We conducted a literature search from a range of sources including scholarly, peer-reviewed journal articles indexed in PubMed and CINAHL, gray literature, and reputable websites and other Internet-based media. A synthesis of existing literature indicates that the overall efficacy of ICT-driven personal health technologies is largely determined by: 1) the educational resources provided and the extent to which the relayed information is customized or individually tailored; and 2) the degree of self-monitoring and levels of personalized feedback or other interactions (e.g. interpersonal communications). We conclude that virtually all the technological tools and resources identified (e.g. Internet-based communications including websites, weblogs and wikis, mobile devices and applications, social media, and wearable monitors) can be strategically leveraged to enhance self-care behaviors for CVD risk reduction and SP but further research is needed to evaluate their efficacy, cost-effectiveness, and long-term maintainability.

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

    Science.gov (United States)

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

    2017-02-14

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

  10. Striatal blood–brain barrier permeability in Parkinson's disease

    OpenAIRE

    Gray , Madison T.; Woulfe, John M.

    2015-01-01

    In vivo studies have shown that blood–brain barrier (BBB) dysfunction is involved in the course of Parkinson's disease (PD). However, these have lacked either anatomic definition or the ability to recognize minute changes in BBB integrity. Here, using histologic markers of serum protein, iron, and erythrocyte extravasation, we have shown significantly increased permeability of the BBB in the postcommissural putamen of PD patients. The dense innervation of the striatum by PD-affected regions a...

  11. NEUROPSYCHOLOGICAL CHANGES ASSOCIATED WITH DEEP BRAIN STIMULATION OF PARKINSON DISEASE: THEORETICAL REVIEW

    Directory of Open Access Journals (Sweden)

    Oscar M. Aguilar

    2011-12-01

    Full Text Available Parkinson’s disease is a neurodegenerative disorder attributable to midbrain dopaminergiccell loss within the substantia nigra. This causes a dysfunction of thebasal ganglia manifested by motor symptoms such as tremor, rigidity, bradykinesiaamong others. With Deep Brain Stimulation (DBS, neurosurgery has emergedas a therapeutic option, being the subthalamic nucleus its main target area. Studiesshow significant improvement in motor deficits, but there is no knowledge on theneuropsychological changes in patients after DBS. A review of several studies thathave researched the cognitive, emotional and behavioral changes concluded thatmost cognitive skills are either maintained or improved after DBS, but there may beadverse emotional and behavioral changes that are related to the core brain wherethe electrode is implanted and with its premorbid personality characteristics.

  12. Differential effects of ischemic vascular disease and Alzheimer's disease on brain atrophy and cognition.

    Science.gov (United States)

    Zheng, Ling; Vinters, Harry V; Mack, Wendy J; Weiner, Michael W; Chui, Helena C

    2016-01-01

    We previously reported that pathologic measures of arteriosclerosis (AS), cerebral infarction, and Alzheimer’s disease (AD) are independently correlated with cortical gray matter (CGM) atrophy measured by in vivo magnetic resonance imaging (MRI). Here, we use path analyses to model the associations between these three pathology measures and cognitive impairment, as mediated by CGM atrophy, after controlling for age and education. In this sample of 116 elderly persons followed longitudinally to autopsy (ischemic vascular disease (IVD) program project), differential patterns were observed between AS and atrophy/cognition versus AD and atrophy/cognition. The total effect of AD pathology on global cognition (β = -0.61, s.e. = 0.06) was four times stronger than that of AS (β = -0.15, s.e. = 0.08). The effect of AS on cognition appears to occur through cerebral infarction and CGM atrophy (β = -0.13, s.e. = 0.04). In contrast, the effects of AD pathology on global cognition (β = -0.50, s.e. = 0.07) occur through a direct pathway that is five times stronger than the indirect pathway acting through CGM atrophy (β = -0.09, s.e. = 0.03). The strength of this direct AD pathway was not significantly mitigated by adding hippocampal volume to the model. AD pathology affects cognition not only through brain atrophy, but also via an unmeasured pathway that could be related to synaptic dysfunction before the development of cortical atrophy.

  13. How does your own knowledge influence the perception of another person's action in the human brain?

    Science.gov (United States)

    Ramsey, Richard; Hamilton, Antonia F de C

    2012-02-01

    When you see someone reach into a cookie jar, their goal remains obvious even if you know that the last cookie has already been eaten. Thus, it is possible to infer the goal of an action even if you know that the goal cannot be achieved. Previous research has identified distinct brain networks for processing information about object locations, actions and mental-state inferences. However, the relationship between brain networks for action understanding in social contexts remains unclear. Using functional magnetic resonance imaging, this study assesses the role of these networks in understanding another person searching for hidden objects. Participants watched movie clips depicting a toy animal hiding and an actor, who was ignorant of the hiding place, searching in the filled or empty location. When the toy animal hid in the same location repeatedly, the blood oxygen level-dependent (BOLD) response was suppressed in occipital, posterior temporal and posterior parietal brain regions, consistent with processing object properties and spatial attention. When the actor searched in the same location repeatedly, the BOLD signal was suppressed in the inferior frontal gyrus, consistent with the observation of hand actions. In contrast, searches towards the filled location compared to the empty location were associated with a greater response in the medial prefrontal cortex and right temporal pole, which are both associated with mental state inference. These findings show that when observing another person search for a hidden object, brain networks for processing information about object properties, actions and mental state inferences work together in a complementary fashion. This supports the hypothesis that brain regions within and beyond the putative human mirror neuron system are involved in action comprehension within social contexts.

  14. Deep brain stimulation in Huntington's disease: assessment of potential targets.

    Science.gov (United States)

    Sharma, Mayur; Deogaonkar, Milind

    2015-05-01

    Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder that has very few effective therapeutic interventions. Since the disease has a defined neural circuitry abnormality, neuromodulation could be an option. Case reports, original research, and animal model studies were selected from the databases of Medline and PubMed. All related studies published up to July 2014 were included in this review. The following search terms were used: "Deep brain stimulation," "DBS," "thalamotomy," "pallidal stimulation," and "Huntington's Disease," "HD," "chorea," or "hyperkinetic movement disorders." This review examines potential nodes in the HD circuitry that could be modulated using deep brain stimulation (DBS) therapy. With rapid evolution of imaging and ability to reach difficult targets in the brain with refined DBS technology, some phenotypes of HD could potentially be treated with DBS in the near future. Further clinical studies are warranted to validate the efficacy of neuromodulation and to determine the most optimal target for HD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Amino Acid Catabolism in Alzheimer's Disease Brain: Friend or Foe?

    Science.gov (United States)

    2017-01-01

    There is a dire need to discover new targets for Alzheimer's disease (AD) drug development. Decreased neuronal glucose metabolism that occurs in AD brain could play a central role in disease progression. Little is known about the compensatory neuronal changes that occur to attempt to maintain energy homeostasis. In this review using the PubMed literature database, we summarize evidence that amino acid oxidation can temporarily compensate for the decreased glucose metabolism, but eventually altered amino acid and amino acid catabolite levels likely lead to toxicities contributing to AD progression. Because amino acids are involved in so many cellular metabolic and signaling pathways, the effects of altered amino acid metabolism in AD brain are far-reaching. Possible pathological results from changes in the levels of several important amino acids are discussed. Urea cycle function may be induced in endothelial cells of AD patient brains, possibly to remove excess ammonia produced from increased amino acid catabolism. Studying AD from a metabolic perspective provides new insights into AD pathogenesis and may lead to the discovery of dietary metabolite supplements that can partially compensate for alterations of enzymatic function to delay AD or alleviate some of the suffering caused by the disease. PMID:28261376

  16. Me, Myself and My Brain Implant: Deep Brain Stimulation Raises Questions of Personal Authenticity and Alienation.

    Science.gov (United States)

    Kraemer, Felicitas

    2013-01-01

    In this article, I explore select case studies of Parkinson patients treated with deep brain stimulation (DBS) in light of the notions of alienation and authenticity. While the literature on DBS has so far neglected the issues of authenticity and alienation, I argue that interpreting these cases in terms of these concepts raises new issues for not only the philosophical discussion of neuro-ethics of DBS, but also for the psychological and medical approach to patients under DBS. In particular, I suggest that the experience of alienation and authenticity varies from patient to patient with DBS. For some, alienation can be brought about by neurointerventions because patients no longer feel like themselves. But, on the other hand, it seems alienation can also be cured by DBS as other patients experience their state of mind as authentic under treatment and retrospectively regard their former lives without stimulation as alienated. I argue that we must do further research on the relevance of authenticity and alienation to patients treated with DBS in order to gain a deeper philosophical understanding, and to develop the best evaluative criterion for the behavior of DBS patients.

  17. Brain connectivity in neurodegenerative diseases--from phenotype to proteinopathy.

    Science.gov (United States)

    Pievani, Michela; Filippini, Nicola; van den Heuvel, Martijn P; Cappa, Stefano F; Frisoni, Giovanni B

    2014-11-01

    Functional and structural connectivity measures, as assessed by means of functional and diffusion MRI, are emerging as potential intermediate biomarkers for Alzheimer disease (AD) and other disorders. This Review aims to summarize current evidence that connectivity biomarkers are associated with upstream and downstream disease processes (molecular pathology and clinical symptoms, respectively) in the major neurodegenerative diseases. The vast majority of studies have addressed functional and structural connectivity correlates of clinical phenotypes, confirming the predictable correlation with topography and disease severity in AD and frontotemporal dementia. In neurodegenerative diseases with motor symptoms, structural--but, to date, not functional--connectivity has been consistently found to be associated with clinical phenotype and disease severity. In the latest studies, the focus has moved towards the investigation of connectivity correlates of molecular pathology. Studies in cognitively healthy individuals with brain amyloidosis or genetic risk factors for AD have shown functional connectivity abnormalities in preclinical disease stages that are reminiscent of abnormalities observed in symptomatic AD. This shift in approach is promising, and may aid identification of early disease markers, establish a paradigm for other neurodegenerative disorders, shed light on the molecular neurobiology of connectivity disruption and, ultimately, clarify the pathophysiology of neurodegenerative diseases.

  18. [Does acidosis in brain play a role in Alzheimer's disease?].

    Science.gov (United States)

    Pirchl, Michael; Humpel, Christian

    2009-01-01

    Alzheimer's disease is characterized by beta-amyloid plaques, tau pathology, cell death of cholinergic neurons, inflammatory processes and cerebrovascular damage. The reasons for the development of this chronic disease are not known yet. We hypothesize that chronic long lasting mild damage of the cerebrovascular brain capillaries cause hypoperfusion, acidosis and neurodegeneration, and induces a cell death cascade with beta-amyloid dysfunction and tau-pathology and inflammation. Vascular risk factors, such as hyperhomocysteinemia or hypercholesterolemia, may play a role in this process. The accumulation of chronic silent strokes may cause cognitive defects as seen in vascular dementia and Alzheimer's disease. This summary tries to link the different events, which occur in Alzheimer's disease, focusing on the cerebrovascular hypothesis.

  19. The rationale for deep brain stimulation in Alzheimer's disease.

    Science.gov (United States)

    Mirzadeh, Zaman; Bari, Ausaf; Lozano, Andres M

    2016-07-01

    Alzheimer's disease is a major worldwide health problem with no effective therapy. Deep brain stimulation (DBS) has emerged as a useful therapy for certain movement disorders and is increasingly being investigated for treatment of other neural circuit disorders. Here we review the rationale for investigating DBS as a therapy for Alzheimer's disease. Phase I clinical trials of DBS targeting memory circuits in Alzheimer's disease patients have shown promising results in clinical assessments of cognitive function, neurophysiological tests of cortical glucose metabolism, and neuroanatomical volumetric measurements showing reduced rates of atrophy. These findings have been supported by animal studies, where electrical stimulation of multiple nodes within the memory circuit have shown neuroplasticity through stimulation-enhanced hippocampal neurogenesis and improved performance in memory tasks. The precise mechanisms by which DBS may enhance memory and cognitive functions in Alzheimer's disease patients and the degree of its clinical efficacy continue to be examined in ongoing clinical trials.

  20. Brain correlates of pro-social personality traits: a voxel-based morphometry study.

    Science.gov (United States)

    Coutinho, Joana F; Sampaio, Adriana; Ferreira, Miguel; Soares, José M; Gonçalves, Oscar F

    2013-09-01

    Of the five personality dimensions described by the Big Five Personality Model (Costa and McCrae 1992), Extraversion and Agreeableness are the traits most commonly associated with a pro-social orientation. In this study we tested whether a pro-social orientation, as expressed in terms of Extraversion and Agreeableness, is associated with a specific grey matter phenotype. Fifty-two healthy participants underwent magnetic resonance imaging (MRI) and completed the NEO-Five Factor Inventory (NEO-FFI), a self-report measure of the Big Five personality traits. Voxel-based morphometry (VBM) was used to investigate the correlation between brain structure and the personality traits of Agreeableness and Extraversion. We found that Extraversion was negatively correlated with grey matter density in the middle frontal and orbitofrontal gyri while Agreeableness was negatively correlated with grey matter density in the inferior parietal, middle occipital and posterior cingulate gyri. No positive correlations were found. These results suggest that pro-social personality traits seem to be associated with decreases in grey matter density in more frontal regions for Extraversion, and more posterior regions for Agreeableness.

  1. The association of type D personality with quality of life in patients with Parkinson's disease

    NARCIS (Netherlands)

    Dubayova, Tatiana; Nagyova, Iveta; Havlikova, Eva; Rosenberger, Jaroslav; Gdovinova, Zuzana; Middel, Berrie; van Dijk, Jitse P.; Groothoff, Johan W.

    2009-01-01

    Objectives: Personality traits appear as determinants of quality of life (QoL) in most chronic diseases. Type D personality is characterized by ineffective coping strategies that reduce QoL in patients with coronary heart disease. The aim of this study was to evaluate whether Type D personality also

  2. The association of type D personality with quality of life in patients with Parkinson's disease

    NARCIS (Netherlands)

    Dubayova, Tatiana; Nagyova, Iveta; Havlikova, Eva; Rosenberger, Jaroslav; Gdovinova, Zuzana; Middel, Berrie; van Dijk, Jitse P.; Groothoff, Johan W.

    2009-01-01

    Objectives: Personality traits appear as determinants of quality of life (QoL) in most chronic diseases. Type D personality is characterized by ineffective coping strategies that reduce QoL in patients with coronary heart disease. The aim of this study was to evaluate whether Type D personality also

  3. I know how you feel: the warm-altruistic personality profile and the empathic brain.

    Science.gov (United States)

    Haas, Brian W; Brook, Michael; Remillard, Laura; Ishak, Alexandra; Anderson, Ian W; Filkowski, Megan M

    2015-01-01

    The ability to empathize with other people is a critical component of human social relationships. Empathic processing varies across the human population, however it is currently unclear how personality traits are associated with empathic processing. This study was designed to test the hypothesis that specific personality traits are associated with behavioral and biological indicators of improved empathy. Extraversion and Agreeableness are personality traits designed to measure individual differences in social-cognitive functioning, however each trait-dimension includes elements that represent interpersonal social functioning and elements that do not represent interpersonal social functioning. We tested the prediction that interpersonal elements of Extraversion (Warmth) and Agreeableness (Altruism) are associated with empathy and non-interpersonal elements of Extraversion and Agreeableness are not associated with empathy. We quantified empathic processing behaviorally (empathic accuracy task using video vignettes) and within the brain (fMRI and an emotional perspective taking task) in 50 healthy subjects. Converging evidence shows that highly warm and altruistic people are well skilled in recognizing the emotional states of other people and exhibit greater activity in brain regions important for empathy (temporoparietal junction and medial prefrontal cortex) during emotional perspective taking. A mediation analysis further supported the association between warm-altruistic personality and empathic processing; indicating that one reason why highly warm-altruistic individuals may be skilled empathizers is that they engage the temporoparietal junction and medial prefrontal cortex more. Together, these findings advance the way the behavioral and neural basis of empathy is understood and demonstrates the efficacy of personality scales to measure individual differences in interpersonal social function.

  4. I know how you feel: the warm-altruistic personality profile and the empathic brain.

    Directory of Open Access Journals (Sweden)

    Brian W Haas

    Full Text Available The ability to empathize with other people is a critical component of human social relationships. Empathic processing varies across the human population, however it is currently unclear how personality traits are associated with empathic processing. This study was designed to test the hypothesis that specific personality traits are associated with behavioral and biological indicators of improved empathy. Extraversion and Agreeableness are personality traits designed to measure individual differences in social-cognitive functioning, however each trait-dimension includes elements that represent interpersonal social functioning and elements that do not represent interpersonal social functioning. We tested the prediction that interpersonal elements of Extraversion (Warmth and Agreeableness (Altruism are associated with empathy and non-interpersonal elements of Extraversion and Agreeableness are not associated with empathy. We quantified empathic processing behaviorally (empathic accuracy task using video vignettes and within the brain (fMRI and an emotional perspective taking task in 50 healthy subjects. Converging evidence shows that highly warm and altruistic people are well skilled in recognizing the emotional states of other people and exhibit greater activity in brain regions important for empathy (temporoparietal junction and medial prefrontal cortex during emotional perspective taking. A mediation analysis further supported the association between warm-altruistic personality and empathic processing; indicating that one reason why highly warm-altruistic individuals may be skilled empathizers is that they engage the temporoparietal junction and medial prefrontal cortex more. Together, these findings advance the way the behavioral and neural basis of empathy is understood and demonstrates the efficacy of personality scales to measure individual differences in interpersonal social function.

  5. Role of brain-derived neurotrophic factor in Huntington's disease.

    Science.gov (United States)

    Zuccato, Chiara; Cattaneo, Elena

    2007-04-01

    Neurotrophic factors are essential contributors to the survival of peripheral and central nervous system (CNS) neurons, and demonstration of their reduced availability in diseased brains indicates that they play a role in various neurological disorders. This paper will concentrate on the role of brain-derived neurotrophic factor (BDNF) in the survival and activity of the neurons that die in Huntington's disease (HD) by reviewing the evidence indicating that it involves profound changes in BDNF levels and that attempts to restore these levels are therapeutically interesting. BDNF is a small dimeric protein that is widely expressed in adult mammalian brain and has been shown to promote the survival of all major neuronal types affected in Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, cortical BDNF production is required for the correct activity of the corticostriatal synapse and the survival of the GABA-ergic medium-sized spiny striatal neurons that die in HD. We will highlight the available data concerning changes in BDNF levels in HD cells, mice and human postmortem samples, describe the molecular evidence underlying this alteration, and review the data concerning the impact of the experimental manipulation of BDNF levels on HD progression. Such studies have revealed a major loss of BDNF protein in the striatum of HD patients which may contribute to the clinical manifestations of the disease. They have also opened up a molecular window into the underlying pathogenic mechanism and new therapeutic perspectives by raising the possibility that one of the mechanisms triggering the reduction in BDNF in HD may also affect the activity of many other neuronal proteins.

  6. 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.

  7. Alexithymia and personality traits of patients with inflammatory bowel disease

    Science.gov (United States)

    La Barbera, D.; Bonanno, B.; Rumeo, M. V.; Alabastro, V.; Frenda, M.; Massihnia, E.; Morgante, M. C.; Sideli, L.; Craxì, A.; Cappello, M.; Tumminello, M.; Miccichè, S.; Nastri, L.

    2017-01-01

    Psychological factors, specific lifestyles and environmental stressors may influence etiopathogenesis and evolution of chronic diseases. We investigate the association between Chronic Inflammatory Bowel Diseases (IBD) and psychological dimensions such as personality traits, defence mechanisms, and Alexithymia, i.e. deficits of emotional awareness with inability to give a name to emotional states. We analyzed a survey of 100 patients with IBD and a control group of 66 healthy individuals. The survey involved filling out clinical and anamnestic forms and administering five psychological tests. These were then analyzed by using a network representation of the system by considering it as a bipartite network in which elements of one set are the 166 individuals, while the elements of the other set are the outcome of the survey. We then run an unsupervised community detection algorithm providing a partition of the 166 participants into clusters. That allowed us to determine a statistically significant association between psychological factors and IBD. We find clusters of patients characterized by high neuroticism, alexithymia, impulsivity and severe physical conditions and being of female gender. We therefore hypothesize that in a population of alexithymic patients, females are inclined to develop psychosomatic diseases like IBD while males might eventually develop behavioral disorders. PMID:28150800

  8. Endogenously nitrated proteins in mouse brain: links to neurodegenerative disease.

    Science.gov (United States)

    Sacksteder, Colette A; Qian, Wei-Jun; Knyushko, Tatyana V; Wang, Haixing; Chin, Mark H; Lacan, Goran; Melega, William P; Camp, David G; Smith, Richard D; Smith, Desmond J; Squier, Thomas C; Bigelow, Diana J

    2006-07-04

    Increased abundance of nitrotyrosine modifications of proteins have been documented in multiple pathologies in a variety of tissue types and play a role in the redox regulation of normal metabolism. To identify proteins sensitive to nitrating conditions in vivo, a comprehensive proteomic data set identifying 7792 proteins from a whole mouse brain, generated by LC/LC-MS/MS analyses, was used to identify nitrated proteins. This analysis resulted in the identification of 31 unique nitrotyrosine sites within 29 different proteins. More than half of the nitrated proteins that have been identified are involved in Parkinson's disease, Alzheimer's disease, or other neurodegenerative disorders. Similarly, nitrotyrosine immunoblots of whole brain homogenates show that treatment of mice with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), an experimental model of Parkinson's disease, induces an increased level of nitration of the same protein bands observed to be nitrated in brains of untreated animals. Comparing sequences and available high-resolution structures around nitrated tyrosines with those of unmodified sites indicates a preference of nitration in vivo for surface accessible tyrosines in loops, a characteristic consistent with peroxynitrite-induced tyrosine modification. In addition, most sequences contain cysteines or methionines proximal to nitrotyrosines, contrary to suggestions that these amino acid side chains prevent tyrosine nitration. More striking is the presence of a positively charged moiety near the sites of nitration, which is not observed for non-nitrated tyrosines. Together, these observations suggest a predictive tool of functionally important sites of nitration and that cellular nitrating conditions play a role in neurodegenerative changes in the brain.

  9. Sticking with the nice guy: trait warmth information impairs learning and modulates person perception brain network activity.

    Science.gov (United States)

    Lee, Victoria K; Harris, Lasana T

    2014-12-01

    Social learning requires inferring social information about another person, as well as evaluating outcomes. Previous research shows that prior social information biases decision making and reduces reliance on striatal activity during learning (Delgado, Frank, & Phelps, Nature Neuroscience 8 (11): 1611-1618, 2005). A rich literature in social psychology on person perception demonstrates that people spontaneously infer social information when viewing another person (Fiske & Taylor, 2013) and engage a network of brain regions, including the medial prefrontal cortex, temporal parietal junction, superior temporal sulcus, and precuneus (Amodio & Frith, Nature Reviews Neuroscience, 7(4), 268-277, 2006; Haxby, Gobbini, & Montgomery, 2004; van Overwalle Human Brain Mapping, 30, 829-858, 2009). We investigate the role of these brain regions during social learning about well-established dimensions of person perception-trait warmth and trait competence. We test the hypothesis that activity in person perception brain regions interacts with learning structures during social learning. Participants play an investment game where they must choose an agent to invest on their behalf. This choice is guided by cues signaling trait warmth or trait competence based on framing of monetary returns. Trait warmth information impairs learning about human but not computer agents, while trait competence information produces similar learning rates for human and computer agents. We see increased activation to warmth information about human agents in person perception brain regions. Interestingly, activity in person perception brain regions during the decision phase negatively predicts activity in the striatum during feedback for trait competence inferences about humans. These results suggest that social learning may engage additional processing within person perception brain regions that hampers learning in economic contexts.

  10. Brain Imaging of Nicotinic Receptors in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Jin Wu

    2010-01-01

    Full Text Available Neuronal nicotinic acetylcholine receptors (nAChRs are a family of ligand-gated ion channels which are widely distributed in the human brain. Several lines of evidence suggest that two major subtypes (α4β2 and α7 of nAChRs play an important role in the pathophysiology of Alzheimer's disease (AD. Postmortem studies demonstrated alterations in the density of these subtypes of nAChRs in the brain of patients with AD. Currently, nAChRs are one of the most attractive therapeutic targets for AD. Therefore, several researchers have made an effort to develop novel radioligands that can be used to study quantitatively the distribution of these two subtypes in the human brain with positron emission tomography (PET and single-photon emission computed tomography (SPECT. In this paper, we discuss the current topics on in vivo imaging of two subtypes of nAChRs in the brain of patients with AD.

  11. Increased caveolin-1 expression in Alzheimer's disease brain.

    Science.gov (United States)

    Gaudreault, Sophie B; Dea, Doris; Poirier, Judes

    2004-07-01

    Increasing evidence suggests that cholesterol plays a central role in the pathophysiology of Alzheimer's disease (AD). Caveolin is a cholesterol-binding membrane protein involved in cellular cholesterol transport. We investigated the changes in the protein amount of hippocampal caveolin of autopsy-confirmed AD and aged-matched control subjects. Our results demonstrate that caveolin protein levels in the hippocampus and caveolin mRNA in the frontal cortex are up-regulated in AD by approximately two-fold, compared to control brains. These results suggest a relationship between caveolin-1 expression levels and a dysregulation of cholesterol homeostasis at the plasma membrane of brain cells. In support of this hypothesis, a significant increase in caveolin protein levels has also been observed in hippocampal tissue from ApoE-deficient (knockout) and aged wild-type mice; two situations associated with modifications of transbilayer distribution of cholesterol in brain synaptic plasma membranes. These results indicate that caveolin over-expression is linked to alterations of cholesterol distribution in the plasma membrane of brain cells and are consistent with the notion of a deterioration of cholesterol homeostasis in AD.

  12. Predictors of loneliness in caregivers of persons with Parkinson's disease.

    Science.gov (United States)

    McRae, Cynthia; Fazio, Emily; Hartsock, Gina; Kelley, Livia; Urbanski, Shawna; Russell, Dan

    2009-09-01

    This study examined loneliness among caregivers of individuals with Parkinson's disease (PD). The sample included 70 caregivers (74% female; 96% spouses) who were currently living with the patient. A postal survey was sent to caregivers of persons with PD on the mailing list of a regional Parkinson association; response rate was 39%. Assessment instruments included the UCLA Loneliness Scale, Social Provisions Scale, Hoehn and Yahr (caregiver version), a perceived Self-Efficacy Scale developed previously for use with PD caregivers, and questions related to both patient and caregiver characteristics. Caregivers reported more loneliness than all similar normative groups except Alzheimer caregivers (Ploneliness. Results indicated that patient variables accounted for only 12% of the variance in loneliness, whereas caregiver variables accounted for an additional 46% of the variance (Ploneliness were less education, lower perceived self-efficacy (both Ploneliness (Ploneliness was significantly predicted by caregiver rather than patient variables, it is possible that strategic interventions for caregivers could ameliorate loneliness.

  13. Music and the brain. Lessons from brain diseases and some reflections on the "emotional" brain.

    Science.gov (United States)

    Wieser, Heinz Gregor

    2003-11-01

    Studies are reviewed from the perspective of a neurologist and epileptologist interested in "music and the brain." At the neurocognitive level, deficits in pitch discrimination of patients with brain lesions and those during the intracarotid amobarbital test are outlined, because they show that the temporal lobe and, in particular, the right acoustic cortex are crucial. Hallucinations of music during epileptic seizures as well as the analysis of musicogenic epilepsy point to the same gross localization and lateralization. At the esthetic level, music theoretical concepts on the consonance-dissonance dichotomy and related EEG examinations are reported, which illustrate the importance of mesiolimbic temporal lobe structures for the pleasure that we might experience when listening to music. The complex interaction of many neuronal circuits and assemblies of both hemispheres in musical perception and performance is illustrated by musical analysis of a recording by an organ player who experienced a right temporal lobe seizure. This analysis revealed that the seizure-induced errors of the left hand were compensated with the right hand in a musically meaningful way.

  14. Similarity-based disease risk assessment for personal genomes: proof of concept.

    Science.gov (United States)

    Woo, Jung Hoon; Lai, Albert M; Chung, Wendy K; Weng, Chunhua

    2011-01-01

    The increasing availability of personal genome data has led to escalating needs by consumers to understand the implications of their gene sequences. At present, poorly integrated genetic knowledge has not met these needs. This proof-of-concept study proposes a similarity-based approach to assess the disease risk predisposition for personal genomes. We hypothesize that the semantic similarity between a personal genome and a disease can indicate the disease risks in the person. We developed a knowledge network that integrates existing knowledge of genes, diseases, and symptoms from six sources using the Semantic Web standard, Resource Description Framework (RDF). We then used latent relationships between genes and diseases derived from our knowledge network to measure the semantic similarity between a personal genome and a genetic disease. For demonstration, we showed the feasibility of assessing the disease risks in one personal genome and discussed related methodology issues.

  15. Cognitive Interventions in Older Persons: Do They Change the Functioning of the Brain?

    Directory of Open Access Journals (Sweden)

    Yindee van Os

    2015-01-01

    Full Text Available Background. Cognitive interventions for older persons that may diminish the burden of cognitive problems and could delay conversion to dementia are of great importance. The underlying mechanisms of such interventions might be psychological compensation and neuronal plasticity. This review provides an overview of the literature concerning the evidence that cognitive interventions cause brain activation changes, even in damaged neural systems. Method. A systematic search of the literature was conducted in several international databases, Medline, Embase, Cinahl, Cochrane, and Psychinfo. The methodological quality was assessed according to the guidelines of the Dutch Institute for Health Care Improvement (CBO. Results. Nineteen relevant articles were included with varied methodological quality. All studies were conducted in diverse populations from healthy elderly to patients with dementia and show changes in brain activation after intervention. Conclusions. The results thus far show that cognitive interventions cause changes in brain activation patterns. The exact interpretation of these neurobiological changes remains unclear. More study is needed to understand the extent to which cognitive interventions are effective to delay conversion to dementia. Future studies should more explicitly try to relate clinically significant improvement to changes in brain activation. Long-term follow-up data are necessary to evaluate the stability of the effects.

  16. Outcomes of a multicomponent intervention on occupational performance in persons with unilateral acquired brain injury

    Science.gov (United States)

    Hoyas, Elisabet Huertas; Pérez, Eduardo José Pedrero; Águila Maturana, Ana M.; Mota, Gloria Rojo; Piédrola, Rosa Martínez; de Heredia Torres, Marta Pérez

    2016-01-01

    Summary Complications after unilateral acquired brain injury (ABI) can affect various areas of expertise causing (depending on the location of the lesion) impairment in occupational performance. The aim of this study was to analyze and compare the concepts of occupational performance and functional independence, both before and after a multicomponent intervention including occupational therapy, in persons with unilateral brain damage. This was a longitudinal quasi-experimental pretest post-test study in a sample of 58 patients with unilateral brain injury (28 with traumatic brain injury and 30 with ischemic stroke). The patients’ level of independence was measured using the short version of the International Classification of Functioning, Disability and Health. We also measured quality of performance using the Assessment of Motor and Process Skills. The findings of this study showed that patients with injury in the right hemisphere improved more than those with left hemisphere damage (p<0.001). All the patients with ABI, especially those with right-sided injury, derived benefit from the multicomponent intervention, except in the area of motor skills. More research is needed on the specific techniques that might address such skills. PMID:27358224

  17. Brain Basics

    Medline Plus

    Full Text Available ... they can cause tremors or symptoms found in Parkinson's disease. Serotonin —helps control many functions, such as mood, ... brain. Problems in producing dopamine can result in Parkinson's disease, a disorder that affects a person's ability to ...

  18. Astrocytic modulation of blood brain barrier: perspectives on Parkinson's disease.

    Science.gov (United States)

    Cabezas, Ricardo; Avila, Marcos; Gonzalez, Janneth; El-Bachá, Ramon Santos; Báez, Eliana; García-Segura, Luis Miguel; Jurado Coronel, Juan Camilo; Capani, Francisco; Cardona-Gomez, Gloria Patricia; Barreto, George E

    2014-01-01

    The blood-brain barrier (BBB) is a tightly regulated interface in the Central Nervous System (CNS) that regulates the exchange of molecules in and out from the brain thus maintaining the CNS homeostasis. It is mainly composed of endothelial cells (ECs), pericytes and astrocytes that create a neurovascular unit (NVU) with the adjacent neurons. Astrocytes are essential for the formation and maintenance of the BBB by providing secreted factors that lead to the adequate association between the cells of the BBB and the formation of strong tight junctions. Under neurological disorders, such as chronic cerebral ischemia, brain trauma, Epilepsy, Alzheimer and Parkinson's Diseases, a disruption of the BBB takes place, involving a lost in the permeability of the barrier and phenotypical changes in both the ECs and astrocytes. In this aspect, it has been established that the process of reactive gliosis is a common feature of astrocytes during BBB disruption, which has a detrimental effect on the barrier function and a subsequent damage in neuronal survival. In this review we discuss the implications of astrocyte functions in the protection of the BBB, and in the development of Parkinson's disease (PD) and related disorders. Additionally, we highlight the current and future strategies in astrocyte protection aimed at the development of restorative therapies for the BBB in pathological conditions.

  19. Disease progresses more quickly in introverts. Shy, inhibited personalities may fare worse.

    Science.gov (United States)

    2004-03-01

    Los Angeles researchers recently have discovered clinical evidence that HIV-positive people with shy and introverted personalities tend to have a faster disease progression and less optimal outcomes under antiretroviral treatment than do people with extroverted personalities.

  20. Objective and Personalized Longitudinal Assessment of a Pregnant Patient with Post Severe Brain Trauma

    Directory of Open Access Journals (Sweden)

    Elizabeth B Torres

    2015-03-01

    Full Text Available Background: Following severe trauma to the brain (whether internally generated by seizures, tumors or externally caused by collision with or penetration of objects individuals may experience initial coma state followed by slow recovery and rehabilitation treatment. At present there is no objective biometric to track the daily progression of the person for extended periods of time.Objective: We introduce new analytical techniques to process data from physically wearable sensors and help track the longitudinal progression of motions and physiological states upon the brain trauma. Settings and Participant: The data used to illustrate the methods were collected at the hospital settings from a pregnant patient in coma state. The patient had brain trauma from a large debilitating seizure due to a large tumor in the right pre-frontal lobe.Main Measures: We registered the wrist motions and the surface-skin-temperature across several daily sessions in four consecutive months. A new statistical technique is introduced for personalized analyses of the rates of change of the stochastic signatures of these patterns.Results: We detected asymmetries in the wrists’ data that identified in the dominant limb critical points of change in physiological and motor control states. These patterns could blindly identify the time preceding the baby’s delivery by C-section when the patient systematically brought her dominant hand to her abdominal area. Changes in temperature were sharp and accompanied by systematic changes in the statistics of the motions that rendered her dominant wrist’s micro-movements more systematically reliable and predictable than those of the non-dominant wrist.Conclusions: The new analytics paired with wearable sensing technology may help track the day-by-day individual progression of a patient with post brain trauma in clinical settings and in the home environment.

  1. Profile analyses of the Personality Assessment Inventory following military-related traumatic brain injury.

    Science.gov (United States)

    Kennedy, Jan E; Cooper, Douglas B; Reid, Matthew W; Tate, David F; Lange, Rael T

    2015-05-01

    Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service members (SMs) following mild-severe traumatic brain injury (TBI). Participants who sustained a mild TBI had significantly higher PAI scores than those with moderate-severe TBI on eight of the nine clinical scales examined. A two-step cluster analysis identified four PAI profiles, heuristically labeled "High Distress", "Moderate Distress", "Somatic Distress," and "No Distress". Postconcussive and posttraumatic stress symptom severity was highest for the High Distress group, followed by the Somatic and Moderate Distress groups, and the No Distress group. Profile groups differed in age, ethnicity, rank, and TBI severity. Findings indicate that meaningful patterns of behavioral and personality characteristics can be detected in active duty military SMs following TBI, which may prove useful in selecting the most efficacious rehabilitation strategies.

  2. Profile Analyses of the Personality Assessment Inventory Following Military-Related Traumatic Brain Injury

    Science.gov (United States)

    Kennedy, Jan E.; Cooper, Douglas B.; Reid, Matthew W.; Tate, David F.; Lange, Rael T.

    2015-01-01

    Personality Assessment Inventory (PAI) profiles were examined in 160 U.S. service members (SMs) following mild–severe traumatic brain injury (TBI). Participants who sustained a mild TBI had significantly higher PAI scores than those with moderate–severe TBI on eight of the nine clinical scales examined. A two-step cluster analysis identified four PAI profiles, heuristically labeled “High Distress”, “Moderate Distress”, “Somatic Distress,” and “No Distress”. Postconcussive and posttraumatic stress symptom severity was highest for the High Distress group, followed by the Somatic and Moderate Distress groups, and the No Distress group. Profile groups differed in age, ethnicity, rank, and TBI severity. Findings indicate that meaningful patterns of behavioral and personality characteristics can be detected in active duty military SMs following TBI, which may prove useful in selecting the most efficacious rehabilitation strategies. PMID:25857403

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

    Science.gov (United States)

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

    2015-10-01

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

  4. Microglia emerge as central players in brain disease.

    Science.gov (United States)

    Salter, Michael W; Stevens, Beth

    2017-09-08

    There has been an explosion of new findings recently giving us insights into the involvement of microglia in central nervous system (CNS) disorders. A host of new molecular tools and mouse models of disease are increasingly implicating this enigmatic type of nervous system cell as a key player in conditions ranging from neurodevelopmental disorders such as autism to neurodegenerative disorders such as Alzheimer's disease and chronic pain. Contemporaneously, diverse roles are emerging for microglia in the healthy brain, from sculpting developing neuronal circuits to guiding learning-associated plasticity. Understanding the physiological functions of these cells is crucial to determining their roles in disease. Here we focus on recent developments in our rapidly expanding understanding of the function, as well as the dysfunction, of microglia in disorders of the CNS.

  5. MicroRNAs in neural cell development and brain diseases.

    Science.gov (United States)

    Feng, Wei; Feng, Yue

    2011-12-01

    MicroRNAs play important roles in post-transcriptional regulation of gene expression by inhibiting protein translation and/or promoting mRNA degradation. Importantly, biogenesis of microRNAs displays specific temporal and spatial profiles in distinct cell and tissue types and hence affects a broad spectrum of biological functions in normal cell growth and tumor development. Recent discoveries have revealed sophisticated mechanisms that control microRNA production and homeostasis in response to developmental and extracellular signals. Moreover, a link between dysregulation of microRNAs and human brain disorders has become increasingly evident. In this review, we focus on recent advances in understanding the regulation of microRNA biogenesis and function in neuronal and glial development in the mammalian brain, and dysregulation of the microRNA pathway in neurodevelopmental and neurodegenerative diseases.

  6. [Non-invasive brain stimulation for Parkinson's disease].

    Science.gov (United States)

    Gajo, Gianandrea; Pollak, Pierre; Lüscher, Christian; Benninger, David

    2015-04-29

    Parkinson's disease (PD) is a major socio-economic burden increasing with the aging population. In advanced PD, the emergence of symptoms refractory to conventional therapy poses a therapeutic challenge. The success of deep brain stimulation (DBS) and advances in the understanding of the pathophysiology of PD have raised interest in non-invasive brain stimulation (NIBS) as an alternative therapeutic tool. NIBS could offer an alternative approach for patients at risk who are excluded from surgery and/or to treat refractory symptoms. The treatment of the freezing of gait, a major cause of disability and falls in PD patients, could be enhanced by transcranial direct current stimulation (tDCS). A therapeutic study is currently performed at the Department of Neurology at the CHUV.

  7. Hyponatremia in acute brain disease: the cerebral salt wasting syndrome.

    Science.gov (United States)

    Betjes, Michiel G.H.

    2002-02-01

    Hyponatremia in acute brain disease is a common occurrence, especially after an aneurysmal subarachnoid hemorrhage. Originally, excessive natriuresis, called cerebral salt wasting, and later the syndrome of inappropriate antidiuretic hormone secretion (SIADH), were considered to be the causes of hyponatremia. In recent years, it has become clear that most of these patients are volume-depleted and have a negative sodium balance, consistent with the original description of cerebral salt wasting. Elevated plasma concentrations of atrial or brain natriuretic peptide have been identified as the putative natriuretic factor. Hyponatremia and volume depletion may aggravate neurological symptoms, and timely treatment with adequate replacement of water and NaCl is essential. The use of fludrocortisone to increase sodium reabsorption by the renal tubules may be an alternative approach.

  8. Functional connectivity in the resting brain as biological correlate of the Affective Neuroscience Personality Scales.

    Science.gov (United States)

    Deris, Nadja; Montag, Christian; Reuter, Martin; Weber, Bernd; Markett, Sebastian

    2017-02-15

    According to Jaak Panksepp's Affective Neuroscience Theory and the derived self-report measure, the Affective Neuroscience Personality Scales (ANPS), differences in the responsiveness of primary emotional systems form the basis of human personality. In order to investigate neuronal correlates of personality, the underlying neuronal circuits of the primary emotional systems were analyzed in the present fMRI-study by associating the ANPS to functional connectivity in the resting brain. N=120 healthy participants were invited for the present study. The results were reinvestigated in an independent, smaller sample of N=52 participants. A seed-based whole brain approach was conducted with seed-regions bilaterally in the basolateral and superficial amygdalae. The selection of seed-regions was based on meta-analytic data on affective processing and the Juelich histological atlas. Multiple regression analyses on the functional connectivity maps revealed associations with the SADNESS-scale in both samples. Functional resting-state connectivity between the left basolateral amygdala and a cluster in the postcentral gyrus, and between the right basolateral amygdala and clusters in the superior parietal lobe and subgyral in the parietal lobe was associated with SADNESS. No other ANPS-scale revealed replicable results. The present findings give first insights into the neuronal basis of the SADNESS-scale of the ANPS and support the idea of underlying neuronal circuits. In combination with previous research on genetic associations of the ANPS functional resting-state connectivity is discussed as a possible endophenotype of personality. Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Assessment of brain reference genes for RT-qPCR studies in neurodegenerative diseases

    DEFF Research Database (Denmark)

    Rydbirk, Rasmus; Folke, Jonas; Winge, Kristian

    2016-01-01

    . This is especially important in relation to neurodegenerative diseases where disease-related structural changes may affect the most commonly used RGs. We analysed 15 candidate RGs in 98 brain samples from two brain regions from Alzheimer's disease (AD), Parkinson's disease (PD), Multiple System Atrophy...

  10. Personalized nutrition and cardiovascular disease prevention: From Framingham to PREDIMED.

    Science.gov (United States)

    Konstantinidou, Valentini; Daimiel, Lidia; Ruiz, Lidia Angeles Daimiel; Ordovás, Jose M

    2014-05-01

    Diet is considered the cornerstone for the prevention of age-related diseases, and a low-fat diet has been considered for decades as the most suitable alternative to achieve this goal. However, mounting evidence supports the efficacy of other alternatives, such as the Mediterranean diet. Nevertheless, it is well known that people present a dramatic range of responses to similar environmental challenges, and it has been shown that some of this variability is rooted in the genome. In fact, this knowledge is driving the field of nutrigenetics. The finding of interactions between diet and genetic variants has led to intense research and debate about the effectiveness of personalized nutrition as a more suitable tool for the prevention of chronic diseases than the traditional 1-size-fits-all recommendations. Here, we provide some of our own examples that illustrate the progression of nutrigenetics through the years, from the initial studies within the Framingham Heart Study, to the most recent use of large consortia, such as the Cohorts for Heart and Aging Research in Genomic Epidemiology, and ending up with large dietary intervention studies, such as the PREDIMED (Prevención con Dieta Mediterránea) study. These recent approaches are providing more robust and clinically relevant gene-diet interactions. Therefore, although the current evidence level of applying genomic information to tailoring is at its early stages, the prospect of widespread incorporation of nutrigenetics to the clinical practice is encouraging.

  11. Evaluating Voting Competence in Persons with Alzheimer Disease

    Directory of Open Access Journals (Sweden)

    Pietro Tiraboschi

    2011-01-01

    Full Text Available Voting by persons with dementia raises questions about their decision-making capacity. Methods specifically addressing voting capacity of demented people have been proposed in the US, but never tested elsewhere. We translated and adapted the US Competence Assessment Tool for Voting (CAT-V to the Italian context, using it before 2006 elections for Prime Minister. Consisting of a brief questionnaire, this tool evaluates the following decision-making abilities: understanding nature and effect of voting, expressing a choice, and reasoning about voting choices. Subjects' performance was examined in relation to dementia severity. Of 38 subjects with Alzheimer's disease (AD enrolled in the study, only three scored the maximum on all CAT-V items. MMSE and CAT-V scores correlated only moderately (=0.59; <0.0001 with one another, reflecting the variability of subjects' performance at any disease stage. Most participants (90%, although performing poorly on understanding and reasoning items, scored the maximum on the choice measure. Our results imply that voting capacity in AD is only roughly predicted by MMSE scores and may more accurately be measured by a structured questionnaire, such as the CAT-V. Among the decision-making abilities evaluated by the CAT-V, expressing a choice was by far the least affected by the dementing process.

  12. Molecular imaging of brain tumors personal experience and review of the literature.

    Science.gov (United States)

    Schaller, Bernhard J; Cornelius, Jan F; Sandu, Nora; Buchfelder, Michael

    2008-12-01

    Non-invasive energy metabolism measurements in brain tumors in vivo are now performed widely as molecular imaging by positron emission tomography. This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. Apart from precise anatomical localization and quantification, the most intriguing advantage of such imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, molecular imaging represents a key-technology in translational research, helping to develop experimental protocols that may later be applied to human patients. Common clinical indications for molecular imaging of primary brain tumors therefore contain (i) primary brain tumor diagnosis, (ii) identification of the metabolically most active brain tumor reactions (differentiation of viable tumor tissue from necrosis), and (iii) prediction of treatment response by measurement of tumor perfusion, or ischemia. The key-question remains whether the magnitude of biochemical alterations demonstrated by molecular imaging reveals prognostic value with respect to survival. Molecular imaging may identify early disease and differentiate benign from malignant lesions. Moreover, an early identification of treatment effectiveness could influence patient management by providing objective criteria for evaluation of therapeutic strategies for primary brain tumors. Specially, its novel potential to visualize metabolism and signal transduction to gene expression is used in reporter gene assays to trace the location and temporal level of expression of therapeutic and endogenous genes. The authors present here illustrative data of PET imaging: the thymidine kinase gene expression in experimentally transplanted F98 gliomas in cat brain indicates, that [(18)F]FHBG visualizes cells expressing TK-GFP gene in transduced gliomas as well as quantities and localizes transduced

  13. Current Topics in Deep Brain Stimulation for Parkinson Disease

    Science.gov (United States)

    UMEMURA, Atsushi; OYAMA, Genko; SHIMO, Yasushi; NAKAJIMA, Madoka; NAKAJIMA, Asuka; JO, Takayuki; SEKIMOTO, Satoko; ITO, Masanobu; MITSUHASHI, Takumi; HATTORI, Nobutaka; ARAI, Hajime

    2016-01-01

    There is a long history of surgical treatment for Parkinson disease (PD). After pioneering trials and errors, the current primary surgical treatment for PD is deep brain stimulation (DBS). DBS is a promising treatment option for patients with medically refractory PD. However, there are still many problems and controversies associated with DBS. In this review, we discuss current issues in DBS for PD, including patient selection, clinical outcomes, complications, target selection, long-term outcomes, management of axial symptoms, timing of surgery, surgical procedures, cost-effectiveness, and new technology. PMID:27349658

  14. Striatal blood-brain barrier permeability in Parkinson's disease.

    Science.gov (United States)

    Gray, Madison T; Woulfe, John M

    2015-05-01

    In vivo studies have shown that blood-brain barrier (BBB) dysfunction is involved in the course of Parkinson's disease (PD). However, these have lacked either anatomic definition or the ability to recognize minute changes in BBB integrity. Here, using histologic markers of serum protein, iron, and erythrocyte extravasation, we have shown significantly increased permeability of the BBB in the postcommissural putamen of PD patients. The dense innervation of the striatum by PD-affected regions allows for exploitation of this permeability for therapeutic goals. These results are also discussed in the context of the retrograde trans-synaptic hypothesis of PD spread.

  15. Nearly All Autopsied NFL Players Show Trauma-Linked Brain Disease

    Science.gov (United States)

    ... gov/news/fullstory_167405.html Nearly All Autopsied NFL Players Show Trauma-Linked Brain Disease No position ... 2017 (HealthDay News) -- Ninety-nine percent of former NFL players who donated their brain to science turned ...

  16. Tau protein in normal and Alzheimer's disease brain: an update.

    Science.gov (United States)

    Johnson, G V; Hartigan, J A

    1999-11-01

    Tau is a microtubule-associated protein that, in a hyperphosphorylated form, comprises the main component of the paired helical filaments and neurofibrillary tangles found in Alzheimer's Disease (AD) brain. It is therefore important to understand the normal functioning and processing of tau protein, and the abnormal posttranslational processing of tau in AD pathology. In 1996, Johnson and Jenkins reviewed the literature on the biochemistry, function, and phosphorylation of tau in normal and AD brain. Since that time, numerous publications have come out further elucidating the properties of tau. The present review updates the topics originally covered in the 1996 review, as well as presents a number of new topics. For example, mutations in the tau gene have been found in several non-AD, autosomal dominant neurodegenerative disorders that exhibit extensive neurofibrillary pathology. In addition, there is increasing evidence that tau may be involved in signal transduction, organelle transport, and cell growth, independent of its microtubule-binding functions. Taken together, the research reviewed here demonstrates that tau is a very complex protein with various functions that are intricately regulated. It is clear that more research is required to completely understand the functions and regulation of tau in normal and AD brain.

  17. Coexistence of reactive plasticity and neurodegeneration in Alzheimer diseased brains.

    Science.gov (United States)

    Guevara, J; Dilhuydy, H; Espinosa, B; Delacourte, A; Quirion, R; Mena, R; Joanette, Y; Zenteno, E; Robitaille, Y

    2004-10-01

    Alzheimer's disease (AD) is a pathological process characterized by neuron degeneration and, as recently suggested, brain plasticity. In this work, we compared the reactive plasticity in AD brains associated to O-glycosydically linked glycans, recognized by lectins from Amaranthus leucocarpus (ALL) and Macrobrachium rosenbergii (MRL), and the tau neuritic degeneration. The neuritic degenerative process was evaluated by the quantification of aggregated neuritic structures. Lesions were determined using antibodies against hyperphosphorylated-tau (AD2), amyloid-beta, and synaptophysin. In these conditions, we classified and quantified three pathological structures associated to the neuritic degenerative process: 1) Amyloid-beta deposits (AbetaDs), 2) Classic neuritic plaques (NPs), and 3) Dystrophic neurites clusters (DNCs) lacking amyloid-beta deposits. Reactive plasticity structures were constituted by meganeuritic clusters (MCs) and peri-neuronal sprouting in neurons of the CA4 region of the hippocampus, immunoreactive to synaptophysin (exclusively in AD brains) and GAP-43. Besides, MCs were associated to sialylated O-glycosydically linked glycans as determined by positive labeling with ALL and MRL. Considering that these lectins are specific for the synaptic sprouting process in AD, our results suggest the co-occurrence of of several areas of reactive plasticity and neuron degeneration in AD.

  18. Identifying with fictive characters: structural brain correlates of the personality trait 'fantasy'.

    Science.gov (United States)

    Cheetham, Marcus; Hänggi, Jürgen; Jancke, Lutz

    2014-11-01

    The perception of oneself as absorbed in the thoughts, feelings and happenings of a fictive character (e.g. in a novel or film) as if the character's experiences were one's own is referred to as identification. We investigated whether individual variation in the personality trait of identification is associated with individual variation in the structure of specific brain regions, using surface and volume-based morphometry. The hypothesized regions of interest were selected on the basis of their functional role in subserving the cognitive processing domains considered important for identification (i.e. mental imagery, empathy, theory of mind and merging) and for the immersive experience called 'presence'. Controlling for age, sex, whole-brain volume and other traits, identification covaried significantly with the left hippocampal volume, cortical thickness in the right anterior insula and the left dorsal medial prefrontal cortex, and with gray matter volume in the dorsolateral prefrontal cortex. These findings show that trait identification is associated with structural variation in specific brain regions. The findings are discussed in relation to the potential functional contribution of these regions to identification.

  19. Personality Change Due to Traumatic Brain Injury in Children and Adolescents: Neurocognitive Correlates.

    Science.gov (United States)

    Max, Jeffrey E; Wilde, Elisabeth A; Bigler, Erin D; Hanten, Gerri; Dennis, Maureen; Schachar, Russell J; Saunders, Ann E; Ewing-Cobbs, Linda; Chapman, Sandra B; Thompson, Wesley K; Yang, Tony T; Levin, Harvey S

    2015-01-01

    Personality change due to traumatic brain injury (PC) in children is an important psychiatric complication of injury and is a form of severe affective dysregulation. This study aimed to examine neurocognitive correlates of PC. The sample included 177 children 5-14 years old with traumatic brain injury who were enrolled from consecutive admissions to five trauma centers. Patients were followed up prospectively at baseline and at 6 months, and they were assessed with semistructured psychiatric interviews. Injury severity, socioeconomic status, and neurocognitive function (measures of attention, processing speed, verbal memory, IQ, verbal working memory, executive function, naming/reading, expressive language, motor speed, and motor inhibition) were assessed with standardized instruments. Unremitted PC was present in 26 (18%) of 141 participants assessed at 6 months postinjury. Attention, processing speed, verbal memory, IQ, and executive function were significantly associated with PC even after socioeconomic status, injury severity, and preinjury attention deficit hyperactivity disorder were controlled. These findings are a first step in characterizing concomitant cognitive impairments associated with PC. The results have implications beyond brain injury to potentially elucidate the neurocognitive symptom complex associated with mood instability regardless of etiology.

  20. 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

  1. Does excessive play of violent first-person-shooter-video-games dampen brain activity in response to emotional stimuli?

    Science.gov (United States)

    Montag, Christian; Weber, Bernd; Trautner, Peter; Newport, Beate; Markett, Sebastian; Walter, Nora T; Felten, Andrea; Reuter, Martin

    2012-01-01

    The present case-control study investigated the processing of emotional pictures in excessive first-person-shooter-video-players and control persons. All participants of the fMRI experiment were confronted with pictures from four categories including pleasant, unpleasant, neutral content and pictures from the first-person-shooter-video-game 'Counterstrike'. Compared to controls, gamers showed a significantly lower activation of the left lateral medial frontal lobe while processing negative emotions. Another interesting finding of the study represents the higher activation of frontal and temporal brain areas in gamers when processing screen-shots from the first-person-shooter-video-game 'Counterstrike'. Higher brain activity in the lateral prefrontal cortex could represent a protection mechanism against experiencing negative emotions by down-regulating limbic brain activity. Due to a frequent confrontation with violent scenes, the first-person-shooter-video-gamers might have habituated to the effects of unpleasant stimuli resulting in lower brain activation. Individual differences in brain activations of the contrast Counterstrike>neutral pictures potentially resemble the activation of action-scripts related to the video-game. Copyright © 2011 Elsevier B.V. All rights reserved.

  2. Abnormal regional brain function in Parkinson's disease: truth or fiction?

    Science.gov (United States)

    Ma, Yilong; Tang, Chengke; Moeller, James R; Eidelberg, David

    2009-04-01

    Normalization of regional measurements by the global mean is commonly employed to minimize inter-subject variability in functional imaging studies. This practice is based on the assumption that global values do not substantially differ between patient and control groups. In this issue of NeuroImage, Borghammer and colleagues challenge the validity of this assumption. They focus on Parkinson's disease (PD) and use computer simulations to show that lower global values can produce spurious increases in subcortical brain regions. The authors speculate that the increased signal observed in these areas in PD is artefactual and unrelated to localized changes in brain function. In this commentary, we summarize what is currently known of the relationship between regional and global metabolic activity in PD and experimental parkinsonism. We found that early stage PD patients exhibit global values that are virtually identical to those of age-matched healthy subjects. SPM analysis revealed increased normalized metabolic activity in a discrete set of biologically relevant subcortical brain regions. Because of their higher variability, the corresponding absolute regional measures did not differ across the two groups. Longitudinal imaging studies in this population showed that the subcortical elevations in normalized metabolism appeared earlier and progressed faster than did focal cortical or global metabolic reductions. The observed increases in subcortical activity, but not the global changes, correlated with independent clinical measures of disease progression. Multivariate analysis with SSM/PCA further confirmed that the abnormal spatial covariance structure of early PD is dominated by these subcortical increases as opposed to network-related reductions in cortical metabolic activity or global changes. Thus, increased subcortical activity in PD cannot be regarded as a simple artefact of global normalization. Moreover, stability of the normalized measurements, particularly at

  3. Genetic biomarkers for brain hemisphere differentiation in Parkinson's Disease

    Science.gov (United States)

    Hourani, Mou'ath; Mendes, Alexandre; Berretta, Regina; Moscato, Pablo

    2007-11-01

    This work presents a study on the genetic profile of the left and right hemispheres of the brain of a mouse model of Parkinson's disease (PD). The goal is to characterize, in a genetic basis, PD as a disease that affects these two brain regions in different ways. Using the same whole-genome microarray expression data introduced by Brown et al. (2002) [1], we could find significant differences in the expression of some key genes, well-known to be involved in the mechanisms of dopamine production control and PD. The problem of selecting such genes was modeled as the MIN (α,β)—FEATURE SET problem [2]; a similar approach to that employed previously to find biomarkers for different types of cancer using gene expression microarray data [3]. The Feature Selection method produced a series of genetic signatures for PD, with distinct expression profiles in the Parkinson's model and control mice experiments. In addition, a close examination of the genes composing those signatures shows that many of them belong to genetic pathways or have ontology annotations considered to be involved in the onset and development of PD. Such elements could provide new clues on which mechanisms are implicated in hemisphere differentiation in PD.

  4. Alzheimer's disease gene signature says: beware of brain viral infections

    Directory of Open Access Journals (Sweden)

    Ianni Manuela

    2010-12-01

    Full Text Available Abstract Background Recent findings from a genome wide association investigation in a large cohort of patients with Alzheimer's disease (AD and non demented controls (CTR showed that a limited set of genes was in a strong association (p > l0-5 with the disease. Presentation of the hypothesis In this report we suggest that the polymorphism association in 8 of these genes is consistent with a non conventional interpretation of AD etiology. Nectin-2 (NC-2, apolipoprotein E (APOE, glycoprotein carcinoembryonic antigen related cell adhesion molecule- 16 (CEACAM-16, B-cell lymphoma-3 (Bcl-3, translocase of outer mitochondrial membrane 40 homolog (T0MM-40, complement receptor-1 (CR-l, APOJ or clusterin and C-type lectin domain A family-16 member (CLEC-16A result in a genetic signature that might affect individual brain susceptibility to infection by herpes virus family during aging, leading to neuronal loss, inflammation and amyloid deposition. Implications of the hypothesis We hypothesized that such genetic trait may predispose to AD via complex and diverse mechanisms each contributing to an increase of individual susceptibility to brain viral infections

  5. Personality Trait and Facial Expression Filter-Based Brain-Computer Interface

    Directory of Open Access Journals (Sweden)

    Seongah Chin

    2013-02-01

    Full Text Available In this paper, we present technical approaches that bridge the gap in the research related to the use of brain‐computer interfaces for entertainment and facial expressions. Such facial expressions that reflect an individual’s personal traits can be used to better realize artificial facial expressions in a gaming environment based on a brain‐computer interface. First, an emotion extraction filter is introduced in order to classify emotions on the basis of the users’ brain signals in real time. Next, a personality trait filter is defined to classify extrovert and introvert types, which manifest as five traits: very extrovert, extrovert, medium, introvert and very introvert. In addition, facial expressions derived from expression rates are obtained by an extrovert‐introvert fuzzy model through its defuzzification process. Finally, we confirm this validation via an analysis of the variance of the personality trait filter, a k‐fold cross validation of the emotion extraction filter, an accuracy analysis, a user study of facial synthesis and a test case game.

  6. Serum brain-derived neurotrophic factor levels and personality traits in patients with major depression.

    Science.gov (United States)

    Nomoto, Hiroshi; Baba, Hajime; Satomura, Emi; Maeshima, Hitoshi; Takebayashi, Naoko; Namekawa, Yuki; Suzuki, Toshihito; Arai, Heii

    2015-03-04

    Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family of growth factors. Previous studies have demonstrated lower serum BDNF levels in patients with major depressive disorder (MDD) and reported an association between BDNF levels and depression-related personality traits in healthy subjects. The aim of the present study was to explore for a possible association between peripheral BDNF levels and personality traits in patients with MDD. In this cross-sectional study, a total of 123 inpatients with MDD (Diagnostic and Statistical Manual for Mental Disorders, 4th edition) at the Juntendo University Koshigaya Hospital were recruited. Serum levels of BDNF were measured. Personality traits were assessed using the 125-item short version of the Temperament and Character Inventory (TCI). Multiple regression analysis adjusted for age, sex, body mass index, dose of antidepressant, and depression severity showed that TCI Self-Directedness (SD) scores were negatively associated with serum BDNF levels (β = -0.23, p = 0.026). MDD patients who have low SD did not show the reduction in serum BDNF levels that is normally associated with depressive state. Our findings suggest that depression-related biological changes may not occur in these individuals.

  7. Narrative discourse impairments in Persian-speaking persons with traumatic brain injury: a pilot study.

    Science.gov (United States)

    Ghayoumi Anaraki, Zahra; Marini, Andrea; Yadegari, Fariba; Mahmoodi Bakhtiari, Behrooz; Fakharian, Esmaeil; Rahgozar, Mehdi; Rassouli, Maryam

    2014-01-01

    Studies have shown the presence of narrative discourse difficulties in persons with traumatic brain injury (TBI), even in those who do not suffer from aphasia. Yet, there still exist inconsistencies between the results of different studies, in particular at the microlinguistic level. Moreover, a limited number of languages have been studied in this regard. Therefore, this study aimed at examining these skills in Persian-speaking individuals with TBI. The purpose of this pilot study was to analyse the microlinguistic and macrolinguistic skills of these individuals to determine impaired linguistic measures at different levels of narrative discourse. Fourteen non-aphasic Persian-speaking persons with TBI (9 with severe TBI and 5 with moderate TBI), aged 19-40 years (mean = 25.84, SD = 5.69), and 61 age-matched healthy adults completed a narrative task. Measures of language productivity, clause density, verbal error ratio, and cohesion ratio were calculated. Also, test-retest and inter-rater reliability coefficients were analysed. The TBI group was impaired in some microlinguistic and all macrolinguistic measures compared to their control peers. The results of this study suggest that multi-level narrative discourse analyses of Persian-speaking individuals with TBI may be useful for speech/language pathologists wishing to evaluate communication disorders in persons with TBI. © 2015 S. Karger AG, Basel.

  8. Monoaminergic and histaminergic strategies and treatments in brain diseases

    Directory of Open Access Journals (Sweden)

    Giuseppe Di Giovanni

    2016-11-01

    Full Text Available The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson’s disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable treatments for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity, the identification of monoamines in the diseases processes (Parkinson’s disease, addiction and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer’s disease, stroke. In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in

  9. Monoaminergic and Histaminergic Strategies and Treatments in Brain Diseases

    Science.gov (United States)

    Di Giovanni, Giuseppe; Svob Strac, Dubravka; Sole, Montse; Unzeta, Mercedes; Tipton, Keith F.; Mück-Šeler, Dorotea; Bolea, Irene; Della Corte, Laura; Nikolac Perkovic, Matea; Pivac, Nela; Smolders, Ilse J.; Stasiak, Anna; Fogel, Wieslawa A.; De Deurwaerdère, Philippe

    2016-01-01

    The monoaminergic systems are the target of several drugs for the treatment of mood, motor and cognitive disorders as well as neurological conditions. In most cases, advances have occurred through serendipity, except for Parkinson's disease where the pathophysiology led almost immediately to the introduction of dopamine restoring agents. Extensive neuropharmacological studies first showed that the primary target of antipsychotics, antidepressants, and anxiolytic drugs were specific components of the monoaminergic systems. Later, some dramatic side effects associated with older medicines were shown to disappear with new chemical compounds targeting the origin of the therapeutic benefit more specifically. The increased knowledge regarding the function and interaction of the monoaminergic systems in the brain resulting from in vivo neurochemical and neurophysiological studies indicated new monoaminergic targets that could achieve the efficacy of the older medicines with fewer side-effects. Yet, this accumulated knowledge regarding monoamines did not produce valuable strategies for diseases where no monoaminergic drug has been shown to be effective. Here, we emphasize the new therapeutic and monoaminergic-based strategies for the treatment of psychiatric diseases. We will consider three main groups of diseases, based on the evidence of monoamines involvement (schizophrenia, depression, obesity), the identification of monoamines in the diseases processes (Parkinson's disease, addiction) and the prospect of the involvement of monoaminergic mechanisms (epilepsy, Alzheimer's disease, stroke). In most cases, the clinically available monoaminergic drugs induce widespread modifications of amine tone or excitability through neurobiological networks and exemplify the overlap between therapeutic approaches to psychiatric and neurological conditions. More recent developments that have resulted in improved drug specificity and responses will be discussed in this review. PMID

  10. Rehabilitation of Older Persons Disabled by Cancer, Stroke, and Heart Disease.

    Science.gov (United States)

    Finnerty-Fried, Pamela; And Others

    1986-01-01

    Rehabilitation of older persons disabled by cancer, stroke, or heart disease is discussed. Aspects of each disability are described, and the importance of timely and appropriate intervention with older persons is emphasized. Barriers generally faced by older disabled persons are briefly outlined. (Author)

  11. Evaluation of proinflammatory cytokines and brain natriuretic peptide in patients with rheumatic heart diseases and coronary heart disease complicated by chronic heart insufficiency

    OpenAIRE

    2005-01-01

    Objective. To study proinflammatory cytokines and brain natriuretic peptide (BNP) in patients with rheumatic heart diseases (RHD) and coronary heart disease (CHD) complicated by chronic heart insufficiency (CHI). Material and methods. 54 pts with CHI (among them 16 with RHD and 38 with CHD with signs of CHI ofll-IV functional class according to NYHA that correspond to 11A-III stage according to N.D. Strazesko-V.H. \\frsilenko classification) and 30 healthy persons of control group were examine...

  12. Importance of the brain Angiotensin system in Parkinson's disease.

    Science.gov (United States)

    Wright, John W; Harding, Joseph W

    2012-01-01

    Parkinson's disease (PD) has become a major health problem affecting 1.5% of the world's population over 65 years of age. As life expectancy has increased so has the occurrence of PD. The primary direct consequence of this disease is the loss of dopaminergic (DA) neurons in the substantia nigra and striatum. As the intensity of motor dysfunction increases, the symptomatic triad of bradykinesia, tremors-at-rest, and rigidity occur. Progressive neurodegeneration may also impact non-DA neurotransmitter systems including cholinergic, noradrenergic, and serotonergic, often leading to the development of depression, sleep disturbances, dementia, and autonomic nervous system failure. L-DOPA is the most efficacious oral delivery treatment for controlling motor symptoms; however, this approach is ineffective regarding nonmotor symptoms. New treatment strategies are needed designed to provide neuroprotection and encourage neurogenesis and synaptogenesis to slow or reverse this disease process. The hepatocyte growth factor (HGF)/c-Met receptor system is a member of the growth factor family and has been shown to protect against degeneration of DA neurons in animal models. Recently, small angiotensin-based blood-brain barrier penetrant mimetics have been developed that activate this HGF/c-Met system. These compounds may offer a new and novel approach to the treatment of Parkinson's disease.

  13. Identification of Personal Factors in Motor Neurone Disease: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Louisa Ng

    2011-01-01

    Full Text Available Motor neurone disease (MND is a devastating condition. This preliminary study aims to identify relevant personal factors affecting the experience of living with MND from the perspective of persons with MND (pwMND in an Australian cohort. A prospective cross-sectional survey of pwMND (=44 using an open-ended questionnaire identified personal factors that were categorised thematically. Standardised questionnaires assessed disease severity: depression, anxiety, and stress and coping strategies. Personal factors identified included demographic factors (socioeconomic status, emotional states (depression, anxiety, and fear, coping strategies (problem-based coping and denial, personality, beliefs (religious and personal values, attitudes (of the patient, and others (such as perceived support. An understanding of personal factors by treating clinicians is essential in the provision of optimal care in MND. This study may assist in the development of personal factors within the International Classification of Functioning, Disability, and Health for improved consensus of care and communication amongst treating clinicians.

  14. Indicators for root caries in Danish persons with recently diagnosed Alzheimer's disease

    DEFF Research Database (Denmark)

    Ellefsen, Birita; Morse, Douglas E; Waldemar, Gunhild;

    2012-01-01

    doi: 10.1111/j.1741-2358.2011.00560.x Indicators for root caries in Danish persons with recently diagnosed Alzheimer's disease Objective:  To identify indicators of root caries among persons with newly diagnosed Alzheimer's disease (AD). Background:  Few studies have investigated dental caries...

  15. The predictor status of personality variables : Etiological significance and their role in the course of disease

    NARCIS (Netherlands)

    Sanderman, R; Ranchor, AV

    1997-01-01

    In this paper the role of personality in the onset and course of coronary heart disease (CHD) and cancer is described. When the role of personality as an etiologic factor in the onset of disease is considered, the overall conclusion is that the evidence supporting this notion is generally weak. Only

  16. [Recovery of walk in persons with stroke and heart disease].

    Science.gov (United States)

    Kapidzić-Duraković, Suada; Karabegović, Azra; Zonić-Imamović, Majda

    2006-01-01

    The goal of this research is to analyze the differences in recovery of walk of two groups of patients who have suffered the stroke--those who have and have not suffered from heart disease prior to the stroke. Test group consisted of patients who have suffered the stroke, and have been rehabilitated in the Clinic for physical medicine and rehabilitation in Tuzla, in 2003. Patients who have had a heart disease before suffering the stroke and have been treated by a cardiologist comprised the first test group (Group I, N=48), while patients without previous heart disease comprised the second test group (Group II, N=69). In relation to their ability to walk, patients have been divided into three groups: those who are able to walk without help, those who are not able to walk and those who are able to walk with a walking aid. Therapies used include kinesiotherapy, paraffin, criotherapy, and electro procedures. Total number of those rehabilitated in the hospital after the stroke is 117, out of which 45 (38.5 %) were women and 72 (61.5 %) men, with average of 68 +/- 9,2 years of age. According to the kind of stroke suffered, 105 patients have had ischemia (89.7 %) and 12 have had hemorrhagia (10.3 %). The highest number of patients have had paralysis of the left side of the body--48 (41.0 %), then paralysis of the right side--43 (36.8 %) and both sides--15 (12.8 %). In relation to the localization of the changes in the brain detected in the CT, the highest number of patients have had multiply lacunar changes--41 (35,0 %), then changes in parietal area--33 (28.2 %) and temporoparietal area--22 (18.8 %), and a bit less had changes in capsula interna--15 (12.8 %), occipital--3 (2.6 %) and cerebellum--3 (2.6 %). In relation to the heart diseases, most of the patients have had compensated weakness of the heart--20 (41.7 %), suffered infarctus myocardii--8 (16.7 %) and atrial fibrillation--8 (16.7 %), with angina pectoris 6 (12,5 %), with arrhitmia--3 (6.3 %) and heart surgery--3

  17. Familial Alzheimer's disease: genetic analysis related to disease heterogeneity, Down syndrome and human brain evolution.

    Science.gov (United States)

    Schapiro, M B; Rapoport, S I

    1989-01-01

    Etiologically heterogeneous subgroups of patients with Alzheimer's disease (AD) exist and need to be distinguished so as to better identify genetic causes of familial cases. Furthermore, the presence of AD neuropathology in Down syndrome (trisomy 21) subjects older than 35 years suggests that AD in some cases is caused by dysregulation of expression of genes on chromosome 21. Cerebral metabolic abnormalities in life, and the distribution of AD neuropathology in the post-mortem brain, indicate that AD involves the association neocortices and subcortical regions with which they evolved during evolution of the human brain. Accordingly, understanding the molecular basis of this evolution should elucidate the genetic basis of AD, whereas knowing the genetics of AD should be informative about the genomic changes which promoted brain evolution.

  18. Using Personality Traits to Construct Linear Growth Models of Mental Health in Family Members of Individuals With Severe Brain Injury

    DEFF Research Database (Denmark)

    Trujillo, Michael; Perrin, Paul B; Doser, Karoline

    2016-01-01

    Objective: No studies have examined the impact of personality traits on mental health among caregivers of individuals with severe brain injury. Therefore, the purpose of the current study was to construct linear growth models to examine whether the personality traits of family members of individu......Objective: No studies have examined the impact of personality traits on mental health among caregivers of individuals with severe brain injury. Therefore, the purpose of the current study was to construct linear growth models to examine whether the personality traits of family members...... of individuals with severe brain injury could predict the trajectories of their own mental health-related quality of life (HRQoL), anxiety, and depression beginning in a neurointensive care unit through 1 year after injury. Method: Danish family members of individuals with severe brain injury (n = 52) completed...... the Short Form-36 assessing mental HRQoL (vitality, social functioning, role limitations-emotional, mental health), anxiety, and depression across 5 time points during the 1st year after injury. The measure of personality was administered 3 months after the patients' discharge. Results: All mental HRQo...

  19. Parkinson's disease rigidity: relation to brain connectivity and motor performance

    Directory of Open Access Journals (Sweden)

    Nazanin eBaradaran

    2013-06-01

    Full Text Available Objective: 1 To determine the brain connectivity pattern associated with clinical rigidity scores in Parkinson's disease (PD and 2 to determine the relation between clinically-assessed rigidity and quantitative metrics of motor performance.Background: Rigidity, the resistance to passive movement, is exacerbated in PD by asking the subject to move the contralateral limb, implying that rigidity involves a distributed brain network. Rigidity mainly affects subjects when they attempt to move; yet the relation between clinical rigidity scores and quantitative aspects of motor performance are unknown.Methods: Ten clinically diagnosed PD patients (off medication and ten controls were recruited to perform an fMRI squeeze-bulb tracking task that included both visually guided and internally guided features. The direct functional connectivity between anatomically defined regions of interest was assessed with Dynamic Bayesian Networks (DBNs. Tracking performance was assessed by fitting Linear Dynamical System (LDS models to the motor performance, and was compared to the clinical rigidity scores. A cross-validated Least Absolute Shrinkage and Selection Operator (LASSO regression method was used to determine the brain connectivity network that best predicted clinical rigidity scores.Results: The damping ratio of the LDS models significantly correlated with clinical rigidity scores (p < 10-4. An fMRI connectivity network in subcortical and primary and premotor cortical regions accurately predicted clinical rigidity scores (p < 10-5. Conclusions: A widely distributed cortical/subcortical network is associated with rigidity observed in PD patients, which reinforces the importance of altered functional connectivity in the pathophysiology of PD. PD subjects with higher rigidity scores tend to have less overshoot in their tracking performance, and damping ratio may represent a robust, quantitative marker of the motoric effects of increasing rigidity.

  20. Progressive Multifocal Leukoencephalopathy: Endemic Viruses and Lethal Brain Disease.

    Science.gov (United States)

    Haley, Sheila A; Atwood, Walter J

    2017-06-21

    In 1971, the first human polyomavirus was isolated from the brain of a patient who died from a rapidly progressing demyelinating disease known as progressive multifocal leukoencephalopathy. The virus was named JC virus after the initials of the patient. In that same year a second human polyomavirus was discovered in the urine of a kidney transplant patient and named BK virus. In the intervening years it became clear that both viruses were widespread in the human population but only rarely caused disease. The past decade has witnessed the discovery of eleven new human polyomaviruses, two of which cause unusual and rare cancers. We present an overview of the history of these viruses and the evolution of JC polyomavirus-induced progressive multifocal leukoencephalopathy over three different epochs.Wereview what is currently known about JC polyomavirus, what is suspected, and what remains to be done to understand the biology of how this mostly harmless endemic virus gives rise to lethal disease. Expected final online publication date for the Annual Review of Virology Volume 4 is September 29, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  1. Copper pathology in vulnerable brain regions in Parkinson's disease.

    Science.gov (United States)

    Davies, Katherine M; Bohic, Sylvain; Carmona, Asunción; Ortega, Richard; Cottam, Veronica; Hare, Dominic J; Finberg, John P M; Reyes, Stefanie; Halliday, Glenda M; Mercer, Julian F B; Double, Kay L

    2014-04-01

    Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving neurons in the SN and LC. Specific activity of the cuproprotein superoxide dismutase 1 was unchanged in the SN in PD but was enhanced in the parkinsonian anterior cingulate cortex, a region with α-synuclein pathology, normal Cu, and limited cell loss. These data suggest that regions affected by α-synuclein pathology may display enhanced vulnerability and cell loss if Cu-dependent protective mechanisms are compromised. Additional investigation of copper pathology in PD may identify novel targets for the development of protective therapies for this disorder. Copyright © 2014 Elsevier Inc. All rights reserved.

  2. Coping mediates the influence of personality on life satisfaction in patients with rheumatic diseases.

    Science.gov (United States)

    Vollmann, Manja; Pukrop, Jörg; Salewski, Christel

    2016-04-01

    A rheumatic disease can severely impair a person's quality of life. The degree of impairment, however, is not closely related to objective indicators of disease severity. This study investigated the influence and the interplay of core psychological factors, i.e., personality and coping, on life satisfaction in patients with rheumatic diseases. Particularly, it was tested whether coping mediates the effects of personality on life satisfaction. In a cross-sectional design, 158 patients diagnosed with a rheumatic disease completed questionnaires assessing the Big 5 personality traits (BFI-10), several disease-related coping strategies (EFK) and life satisfaction (HSWBS). Data were analyzed using a complex multiple mediation analysis with the Big 5 personality traits as predictors, coping strategies as mediators and life satisfaction as outcome. All personality traits and seven of the nine coping strategies were associated with life satisfaction (rs > |0.16|, ps ≤ 0.05). The mediation analysis revealed that personality traits had no direct, but rather indirect effects on life satisfaction through coping. Neuroticism had a negative indirect effect on life satisfaction through less active problem solving and more depressive coping (indirect effects > -0.03, ps satisfaction through more active problem solving, less depressive coping and/or a more active search for social support (indirect effects > 0.06, ps < 0.05). Personality and coping play a role in adjustment to rheumatic diseases. The interplay of these variables should be considered in psychological interventions for patients with rheumatic diseases.

  3. Improving brain injury cognitive rehabilitation by personalized telerehabilitation services: Guttmann neuropersonal trainer.

    Science.gov (United States)

    Solana, Javier; Cáceres, César; García-Molina, Alberto; Opisso, Eloy; Roig, Teresa; Tormos, José M; Gómez, Enrique J

    2015-01-01

    Cognitive rehabilitation aims to remediate or alleviate the cognitive deficits appearing after an episode of acquired brain injury (ABI). The purpose of this work is to describe the telerehabilitation platform called Guttmann Neuropersonal Trainer (GNPT) which provides new strategies for cognitive rehabilitation, improving efficiency and access to treatments, and to increase knowledge generation from the process. A cognitive rehabilitation process has been modeled to design and develop the system, which allows neuropsychologists to configure and schedule rehabilitation sessions, consisting of set of personalized computerized cognitive exercises grounded on neuroscience and plasticity principles. It provides remote continuous monitoring of patient's performance, by an asynchronous communication strategy. An automatic knowledge extraction method has been used to implement a decision support system, improving treatment customization. GNPT has been implemented in 27 rehabilitation centers and in 83 patients' homes, facilitating the access to the treatment. In total, 1660 patients have been treated. Usability and cost analysis methodologies have been applied to measure the efficiency in real clinical environments. The usability evaluation reveals a system usability score higher than 70 for all target users. The cost efficiency study results show a relation of 1-20 compared to face-to-face rehabilitation. GNPT enables brain-damaged patients to continue and further extend rehabilitation beyond the hospital, improving the efficiency of the rehabilitation process. It allows customized therapeutic plans, providing information to further development of clinical practice guidelines.

  4. [Brain hemorrhage in a patient with Kawasaki disease].

    Science.gov (United States)

    Yamazaki-Nakashimada, Marco Antonio; Rivas-Larrauri, Francisco; Alcántara-Salinas, Adriana; Hernández-Bautista, Victor; Rodríguez-Lozano, Ana Luisa

    2013-01-01

    Kawasaki disease is an acute, self-limiting vasculitis of unknown origin, characterized by fever, palms and soles edema, cervical lymphadenopathy, strawberry tongue, and non-exudative conjunctivitis. It is a multisystemic vasculitis that affects predominantly infants and young children. The most feared complication is the development of coronary aneurysms that occurs up to 25% of untreated patients; however there are reports of extra coronary involvement. Herein we present the case of a 2 year-old girl who had a severe symptomatology and persistent fever despite intravenous gammaglobulin. Two years later she presented right hemiparesia and headache, with data from CAT and MRI suggestive of brain mass and deviation of the midline, secondary to left frontoparietal haemorrhage that was treated with a craniotomy. She was discharged on prednisone, ASA and rehabilitation.

  5. Satisfaction with Cognitive Rehabilitation Delivered via the Internet in Persons with Acquired Brain Injury

    Directory of Open Access Journals (Sweden)

    Thomas F. Bergquist

    2015-01-01

    Full Text Available We examined the level of satisfaction with cognitive rehabilitation delivered via the Internet in persons with moderate to severe acquired brain injury (ABI. Fifteen adults with moderate to severe ABI were randomized to 30 days of Internet-based active treatment (AT or to a wait list (WL group, and crossed over to the opposite condition after 30 sessions. Both caregivers and participants were assessed at three time points during the study. This study focused on participant satisfaction with receiving treatment in this manner. Though the results of this study showed no significant treatment effect, the vast majority of participants (>87% were satisfied with treatment. Treatment satisfaction accounted for 25% of additional variance in predicting lower family ratings of mood difficulties after final assessment (p<.03. Greater satisfaction with treatment was positively correlated with greater employment rate after treatment (r=.63, p=.02, as well as lower family ratings of memory and mood difficulties after final assessment (r=-.59, p=.03; r=-.58, p=.03,. Results suggest that treatment satisfaction in persons with ABI is related to less activity limitations, and maintaining employment after cognitive rehabilitation delivered via the Internet.  

  6. PREVALENCE OF TYPE D PERSONALITY AND ITS ASSOCIATION WITH CARDIOVASCULAR DISEASES AND THEIR RISK FACTORS ACCORDING TO THE ESSE STUDY CONDUCTED IN KEMEROVO REGION

    Directory of Open Access Journals (Sweden)

    A. N. Sumin

    2015-01-01

    Full Text Available Aim. To study the prevalence of type D personality and its association with cardiovascular diseases and their risk factors in Russia’s population.Material and methods. The research was conducted within the framework of multicentre epidemiological study ESSE-RF. The total sample size was 1610 patients (men and women aged 25-64 years. The type D personality was assessed using questionnaire DS-14. The patients were divided into two groups: patients with the presence of type D personality (n=231 and patients without type D personality (n=1379. Arterial hypertension, smoking, diabetes, hypercholesterolemia and obesity were accepted as major cardiovascular risk factors that are well studied and used in the most of the known cardiovascular risk assessment models.Results. Type D personality was detected in 231 (14.3% patients. Among patients with the type D personality as compared with those without one arterial hypertension (r=0.033, ischemic heart disease (r=0.053, vascular diseases of a brain (r=0.041 were revealed more often. Type D personality was associated with such risk factors as diabetes, smoking duration, low physical activity, overweight and obesity.Conclusion. The study results can be useful in the development and carrying out programs of primary and secondary prevention of cardiovascular diseases.

  7. Use of the WHOQOL-BREF for evaluating persons with traumatic brain injury.

    Science.gov (United States)

    Chiu, Wen-Ta; Huang, Sheng-Jean; Hwang, Hei-Fen; Tsauo, Jau-Yih; Chen, Chun-Fu; Tsai, Shin-Han; Lin, Mau-Roung

    2006-11-01

    This study examined psychometric properties of a brief version of the World Health Organization Quality of Life questionnaire (WHOQOL-BREF) among persons with traumatic brain injury (TBI) and the relations of the WHOQOL-BREF domains, including physical capacity, psychological wellbeing, social relationships, and environment, to different indicators of TBI severity. Of the 354 eligible and available subjects from 22 hospitals in northern Taiwan over a 6-month period, 199 completed telephone interviews during data collection. Three indicators of TBI severity were used: the Glasgow Coma Scale, the presence of post-traumatic amnesia, and the abbreviated injury scale to the head. All domain scores of the WHOQOL-BREF had nearly symmetrical distributions: low percentages of ceiling and floor values (0-3%), low missing rates (0-0.5%) for all but one item (43.2%), and very good internal consistency (0.75-0.89) and test-retest reliability (0.74-0.95). The WHOQOL-BREF also exhibited excellent known-groups validity, as well as very good responsiveness and convergent validity with regard to employment, independence in daily life activities, social support, and depression. After adjustment for potential confounders, almost none of the domain scores of the WHOQOL-BREF significantly differed in the severity levels of the three severity indicators. In conclusion, the WHOQOL-BREF is an appropriate health-related quality of life (HRQL) instrument for persons with TBI. Furthermore, the initial severity of the TBI might not be suitable for predicting levels of HRQL in persons with TBI.

  8. Clinical, genetic, and brain sonographic features related to Parkinson's disease in Gaucher disease.

    Science.gov (United States)

    Böttcher, Tobias; Rolfs, Arndt; Meyer, Bianca; Grossmann, Annette; Berg, Daniela; Kropp, Peter; Benecke, Reiner; Walter, Uwe

    2013-10-01

    Homozygous or compound heterozygous mutations in the glucocerebrosidase gene cause Gaucher disease. Moreover, heterozygous glucocerebrosidase gene mutations represent the most common genetic risk factor for Parkinson's disease (PD) known so far. Substantia nigra (SN) hyperechogenicity, a sonographic feature thought to reflect iron accumulation, has been described in both PD and Gaucher disease patients. Here we studied how clinical, genetic, and brain sonographic findings relate to the occurrence of PD in Gaucher disease. Sixteen Gaucher disease patients, 12 PD patients, and 32 control subjects were enrolled. The glucocerebrosidase genotypes were identified by DNA sequencing. All subjects underwent transcranial ultrasound, and eight Gaucher disease patients additionally MRI for comparison with SN ultrasound findings. SN hyperechogenicity and reduced echogenicity of brainstem raphe were more frequent in Gaucher disease patients (62, 37 %) than in controls (12, 12 %; p Gaucher disease patients was unrelated to type or severity of glucocerebrosidase gene mutation, but correlated with iron-sensitive MRI-T2 hypointensity of SN pars compacta, and with age at start of enzyme replacement therapy. While none of the five Gaucher disease patients with signs of PD (definite PD, n = 4; early PD, n = 1) had severe glucocerebrosidase gene mutations known to cause neuronopathic Gaucher disease, all carried a N370S allele, previously reported to predict non-neuronopathic Gaucher disease. Hyposmia, higher non-motor symptoms score (constipation, depression, executive dysfunction), and SN hyperechogenicity were characteristic features of Gaucher disease-related PD. We conclude that the combined clinical, genetic, and transcranial sonographic assessment may improve the PD risk evaluation in Gaucher disease.

  9. Transfer effects of errorless Goal Management Training on cognitive function and quality of life in brain-injured persons

    NARCIS (Netherlands)

    Bertens, D.; Kessels, R.P.C.; Boelen, D.H.; Fasotti, L.

    2016-01-01

    BACKGROUND: Previous findings had shown that the addition of errorless learning to traditional Goal Management Training (GMT) resulted in superior results when training everyday tasks in persons with executive deficits after brain injury. OBJECTIVE: To investigate the additional effects of an

  10. Stroke and brain atrophy in chronic Chagas disease patients: A new theory proposition

    Directory of Open Access Journals (Sweden)

    Jamary Oliveira-Filho

    Full Text Available Abstract Chagas disease (CD remains a major cause of cardiomyopathy and stroke in developing countries. Brain damage in CD has been attributed exclusively to the effects of structural heart disease on the brain, including cardioembolism and low cardiac output symptoms. However, CD patients also develop stroke and brain atrophy independently of cardiac disease severity. Chronic inflammation directed against T. cruzi may act as a trigger for endothelial damage, platelet activation, acceleration of atherosclerosis and apoptosis, all of which lead to stroke and brain atrophy. In the present article, evidence supporting this new theory is presented, along with considerations towards mechanistically-based targeted treatment.

  11. Brain derived neurotrophic factor gene (BDNF) and personality traits: the modifying effect of season of birth and sex.

    Science.gov (United States)

    Kazantseva, A; Gaysina, D; Kutlumbetova, Yu; Kanzafarova, R; Malykh, S; Lobaskova, M; Khusnutdinova, E

    2015-01-02

    Personality traits are complex phenotypes influenced by interactions of multiple genetic variants of small effect and environmental factors. It has been suggested that the brain derived neurotrophic factor gene (BDNF) is involved in personality traits. Season of birth (SOB) has also been shown to affect personality traits due to its influences on brain development during prenatal and early postnatal periods. The present study aimed to investigate the effects of BDNF on personality traits; and the modifying effects of SOB and sex on associations between BDNF and personality traits. A sample of 1018 young adults (68% women; age range 17-25years) of Caucasian origin from the Russian Federation was assessed on personality traits (Novelty Seeking, Harm Avoidance, Reward Dependence, Persistence, Self-directedness, Cooperativeness, Self-transcendence) with the Temperament and Character Inventory-125 (TCI-125). Associations between personality traits and 12 BDNF SNPs were tested using linear regression models. The present study demonstrated the effect of rs11030102 on Persistence in females only (PFDR=0.043; r(2)=1.3%). There were significant interaction effects between Val66Met (rs6265) and SOB (PFDR=0.048, r(2)=1.4%), and between rs2030323 and SOB (PFDR=0.042, r(2)=1.3%), on Harm Avoidance. Our findings provide evidence for the modifying effect of SOB on the association between BDNF and Harm Avoidance, and for the modifying effect of sex on the association between BDNF and Persistence.

  12. The motivational hierarchy between the personal self and close others in the Chinese brain: an ERP study

    Directory of Open Access Journals (Sweden)

    Xiangru Zhu

    2016-09-01

    Full Text Available People base their decisions not only on their own self-interest but also on the interests of close others. Generally, the personal self has primacy in the motivational hierarchy in the Western culture. A recent study found that friends have the same motivational hierarchy as the personal self in the Eastern collectivist culture. Remaining unknown is whether the motivational hierarchy of the personal self and close others can be manifested in the collectivist brain. In the present study, we asked participants to gamble for the personal self, close others (i.e., mother, father, and close friend, and strangers. The positive-going deflection of event-related potentials (ERPs in response to positive feedback showed the following pattern: personal self = mother = father > friend > stranger. In the loss condition, no significant beneficiary effect was observed. The present results indicate that the personal self and parents are intertwined in the motivational system in the Chinese undergraduate student brain, supporting the view that the personal self and parents have the same motivational primacy at the electrocortical level.

  13. The Motivational Hierarchy between the Personal Self and Close Others in the Chinese Brain: an ERP Study.

    Science.gov (United States)

    Zhu, Xiangru; Wang, Lili; Yang, Suyong; Gu, Ruolei; Wu, Haiyan; Luo, Yuejia

    2016-01-01

    People base their decisions not only on their own self-interest but also on the interests of close others. Generally, the personal self has primacy in the motivational hierarchy in the Western culture. A recent study found that friends have the same motivational hierarchy as the personal self in the Eastern collectivist culture. Remaining unknown is whether the motivational hierarchy of the personal self and close others can be manifested in the collectivist brain. In the present study, we asked participants to gamble for the personal self, close others (i.e., mother, father, and close friend), and strangers. The positive-going deflection of event-related potentials (ERPs) in response to positive feedback showed the following pattern: personal self = mother = father > friend > stranger. In the loss condition, no significant beneficiary effect was observed. The present results indicate that the personal self and parents are intertwined in the motivational system in the Chinese undergraduate student brain, supporting the view that the personal self and parents have the same motivational primacy at the electrocortical level.

  14. Symptoms of fatigue and depression in ischemic heart disease are driven by personality characteristics rather than disease stage

    DEFF Research Database (Denmark)

    Smith, Otto R F; Pedersen, Susanne S.; Van Domburg, Ron T;

    2008-01-01

    Symptoms of fatigue and depression are prevalent across stages of ischemic heart disease (IHD). We examined (i) the effect of both the IHD stage and type-D personality on fatigue and depressive symptoms at 12-month follow-up, and (ii) whether the effect of type-D personality on these symptoms...

  15. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    Science.gov (United States)

    Liu, He; Song, Ni

    2016-01-01

    Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and brain tumors. PMID:27375363

  16. [Theoretic basis on the same therapeutic program for different degenerative brain diseases in terms of the Governor Vessel: Alzheimer's disease and Parkinson's disease].

    Science.gov (United States)

    Wu, Junyan; Wang, Jie; Zhang, Junlong

    2015-05-01

    Through the consultation of TCM ancient classical theory, the relationship of kidney essence, marrow and brain is analyzed. It is discovered that the degenerative brain diseases, represented by Alzheimer's disease (AD) and Parkinson's disease (PD) share the same etiological basis as "kidney essence deficiency and brain marrow emptiness" and have the mutual pathological outcomes as yang qi declining. The Governor Vessel gathers yang qi of the whole body and maintains the normal functional activity of zangfu organs in the human body through the storage, regulation and invigoration of yang qi. It is viewed that the theory of the Governor Vessel is applied to treat the different degenerative brain diseases, which provides the theoretic support and practice guide for the thought of TCM as the same therapeutic program for the different diseases. As a result, the degenerative brain diseases can be retarded and the approach is provided to the effective prevention and treatment of degenerative diseases in central nerve system:

  17. Dyslipidemia and Blood-Brain Barrier Integrity in Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Gene L. Bowman

    2012-01-01

    Full Text Available Background. Blood-brain barrier (BBB dysfunction may have a significant role in the pathogenesis of Alzheimer's disease (AD. Modifiable factors associated with BBB function may have therapeutic implication. This study tested the hypothesis that dyslipidemia is associated with BBB impairment in mild-to-moderate AD. Methods. Thirty-six subjects with AD were followed for 1 year. Fasting CSF and plasma were collected with clinical assessments at baseline and 12 months. BBB impairment was defined as CSF albumin index ≥9. Independent t-tests and linear regression assessed the relationship between plasma lipoproteins and BBB integrity. Results. Dyslipidemia was prevalent in 47% of the population, and in 75% of those with BBB impairment. Subjects with BBB impairment had significantly higher mean plasma triglyceride and lower HDL cholesterol (TG, P=0.007; HDL, P=0.043. Plasma triglycerides explained 22% of the variance in BBB integrity and remained significant after controlling for age, gender, ApoE-4 genotype, blood pressure, and statin use. Conclusion. Dyslipidemia is more prevalent in AD subjects with BBB impairment. Plasma triglyceride and HDL cholesterol may have a role in maintaining BBB integrity in mild-to-moderate Alzheimer's disease.

  18. 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.

  19. Regional and cellular gene expression changes in human Huntington's disease brain

    OpenAIRE

    2006-01-01

    Huntington's disease (HD) pathology is well understood at a histological level but a comprehensive molecular analysis of the effect of the disease in the human brain has not previously been available. To elucidate the molecular phenotype of HD on a genome-wide scale, we compared mRNA profiles from 44 human HD brains with those from 36 unaffected controls using microarray analysis. Four brain regions were analyzed: caudate nucleus, cerebellum, prefrontal association cortex [Brodmann's area 9 (...

  20. Systems pharmacology and blood-brain barrier functionality in Parkinson's disease

    NARCIS (Netherlands)

    Ravenstijn, Paulien Gerarda Maria

    2009-01-01

    Parkinson’s disease is a progressive neurodegenerative disease, which is composed of many components, each caused by interplay of a number of genetic and nongenetic causes. As the blood-brain barrier (BBB) is a key player in the relationship between plasma and brain pharmacokinetics, the influences

  1. Systems pharmacology and blood-brain barrier functionality in Parkinson's disease

    NARCIS (Netherlands)

    Ravenstijn, Paulien Gerarda Maria

    2009-01-01

    Parkinson’s disease is a progressive neurodegenerative disease, which is composed of many components, each caused by interplay of a number of genetic and nongenetic causes. As the blood-brain barrier (BBB) is a key player in the relationship between plasma and brain pharmacokinetics, the influences

  2. MRI/MRA evaluation of sickle cell disease of the brain

    Energy Technology Data Exchange (ETDEWEB)

    Zimmerman, Robert A. [Childrens Hospital, Department of Radiology, Philadelphia, PA (United States)

    2005-03-01

    Sickle cell disease is a major cause of pediatric stroke. Understanding the disease that affects the brain as infarctions, both clinically apparent and silent, requires an understanding of how the blood vessels are affected, the way in which both the brain and the blood vessels are imaged by MRI and MRA and the mechanism of injury. (orig.)

  3. More Years Playing Football, Greater Risk of Brain Disease

    Science.gov (United States)

    ... and Human Services. More Health News on: Concussion Sports Injuries Traumatic Brain Injury Recent Health News Related MedlinePlus Health Topics Concussion Sports Injuries Traumatic Brain Injury About MedlinePlus Site Map FAQs Customer Support ...

  4. Type D personality and health status in cardiovascular disease populations

    DEFF Research Database (Denmark)

    Versteeg, Henneke; Spek, Viola; Pedersen, Susanne S.

    2012-01-01

    in patient-reported physical and mental health status among cardiovascular patients. Methods: A computerized search of the literature through PUBMED and PsychINFO (from 1995 to May 2011) was performed and prospective studies were selected that analysed the association between Type D personality and health...... status in cardiovascular patients. Two separate meta-analyses were performed for the association of Type D personality with physical and mental health status, respectively. Results: Of all identified studies, ten studies met the selection criteria. The meta-analyses showed that Type D was associated......: Type D personality was shown to be an independent correlate of impaired patient-reported physical and mental health status in various cardiovascular patient groups. Clinicians should be aware of the association between chronic psychological distress and poor patient-reported outcomes....

  5. Badness, madness and the brain - the late 19th-century controversy on immoral persons and their malfunctioning brains

    NARCIS (Netherlands)

    Schirmann, Felix

    2013-01-01

    In the second half of the 19th-century, a group of psychiatric experts discussed the relation between brain malfunction and moral misconduct. In the ensuing debates, scientific discourses on immorality merged with those on insanity and the brain. This yielded a specific definition of what it means t

  6. Brain white matter volume abnormalities in Lesch-Nyhan disease and its variants.

    Science.gov (United States)

    Schretlen, David J; Varvaris, Mark; Vannorsdall, Tracy D; Gordon, Barry; Harris, James C; Jinnah, H A

    2015-01-13

    We sought to examine brain white matter abnormalities based on MRI in adults with Lesch-Nyhan disease (LND) or an attenuated variant (LNV) of this rare, X-linked neurodevelopmental disorder of purine metabolism. In this observational study, we compared 21 adults with LND, 17 with LNV, and 33 age-, sex-, and race-matched healthy controls using voxel-based morphometry and analysis of covariance to identify white matter volume abnormalities in both patient groups. Patients with classic LND showed larger reductions of white (26%) than gray (17%) matter volume relative to healthy controls. Those with LNV showed comparable reductions of white (14%) and gray (15%) matter volume. Both patient groups demonstrated reduced volume in medial inferior white matter regions. Compared with LNV, the LND group showed larger reductions in inferior frontal white matter adjoining limbic and temporal regions and the motor cortex. These regions likely include such long association fibers as the superior longitudinal and uncinate fasciculi. Despite earlier reports that LND primarily involves the basal ganglia, this study reveals substantial white matter volume abnormalities. Moreover, white matter deficits are more severe than gray matter deficits in classic LND, and also characterize persons with LNV. The brain images acquired for these analyses cannot precisely localize white matter abnormalities or determine whether they involve changes in tract orientation or anisotropy. However, clusters of reduced white matter volume identified here affect regions that are consistent with the neurobehavioral phenotype. © 2014 American Academy of Neurology.

  7. Brain Na+, K+-ATPase Activity In Aging and Disease

    Science.gov (United States)

    de Lores Arnaiz, Georgina Rodríguez; Ordieres, María Graciela López

    2014-01-01

    , enzyme changes in diverse neurological diseases as well as during aging, have been summarized. Issues refer mainly to Na+, K+-ATPase studies in ischemia, brain injury, depression and mood disorders, mania, stress, Alzheimer´s disease, learning and memory, and neuronal hyperexcitability and epilepsy. PMID:25018677

  8. Disclosure Decisions: HIV-Positive Persons Coping With Disease-Related Stressors

    DEFF Research Database (Denmark)

    Rodkjaer, Lotte; Sodemann, Morten; Østergaard, Lars Jørgen;

    2011-01-01

    The purpose of this grounded theory study was to investigate how Danish HIV-positive persons live with their disease, focusing on HIV-related stressors. Using the Glaserian method, we analyzed textual data from in-depth interviews with 16 HIV-positive persons. Decisions about disclosure appeared...... and plans, and offers a theoretical basis for interventions designed to assist persons living with HIV to make the best possible individual decisions regarding disclosure, and thereby reduce HIV-related stress....

  9. Interactive 3D visualization of structural changes in the brain of a person with corticobasal syndrome

    Directory of Open Access Journals (Sweden)

    Claudia eHänel

    2014-05-01

    Full Text Available The visualization of the progression of brain tissue loss, which occurs in neurodegenerative diseases like corticobasal syndrome (CBS, is an important prerequisite to understand the course and the causes of this neurodegenerative disorder. Common workflows for visual analysis are often based on single 2D sections since in 3D visualizations more internally situated structures may be occluded by structures near the surface. The reduction of dimensions from 3D to 2D allows for an holistic view onto internal and external structures, but results in a loss of spatial information. Here, we present an application with two 3D visualization designs to resolve these challenges. First, in addition to the volume changes, the semi-transparent anatomy is displayed with an anatomical section and cortical areas for spatial orientation. Second, the principle of importance-driven volume rendering is adapted to give an unrestricted line-of-sight to relevant structures by means of a frustum-like cutout. To strengthen the benefits of the 3D visualization, we decided to provide the application next to standard desktop environments in immersive virtual environments with stereoscopic viewing as well. This improves the depth perception in general and in particular for the second design. Thus, the application presented in this work allows for aneasily comprehensible visual analysis of the extent of brain degeneration and the corresponding affected regions.

  10. Premorbid Personality Characteristics in Alzheimer’s Disease: An Exploratory Case–Control Study

    Directory of Open Access Journals (Sweden)

    M. Malinchoc

    1997-01-01

    Full Text Available Linking data from a case–control study of Alzheimer’s disease with data from a Minnesota Multiphasic Personality Inventory (MMPI outpatient study, we identified 13 Alzheimer's disease cases and 16 controls for case–control comparison. The mean time between personality testing and onset of Alzheimer's disease (or corresponding age for controls was 13 years in cases and 14 years in controls. Alzheimer's disease cases, but not the controls, had scores significantly greater than the normative reference on MMPI scales measuring Social Introversion (p = 0.05, and Pessimism (p = 0.01. When compared to controls, Alzheimer's disease cases had significantly greater scores on the Social Introversion scale (p = 0.03. Despite the small sample size and some design limitations of this exploratory study, our findings may suggest that subjects who score higher on these personality scales have a greater risk of Alzheimer's disease.

  11. The oral microbiome in health and disease and the potential impact on personalized dental medicine.

    Science.gov (United States)

    Zarco, M F; Vess, T J; Ginsburg, G S

    2012-03-01

    Every human body contains a personalized microbiome that is essential to maintaining health but capable of eliciting disease. The oral microbiome is particularly imperative to health because it can cause both oral and systemic disease. The oral microbiome rests within biofilms throughout the oral cavity, forming an ecosystem that maintains health when in equilibrium. However, certain ecological shifts in the microbiome allow pathogens to manifest and cause disease. Severe forms of oral disease may result in systemic disease at different body sites. Microbiomics and metagenomics are two fields of research that have emerged to identify the presence of specific microbes in the body and understand the nature of the microbiome activity during both health and disease. The analysis of the microbiome and its genomes will pave the way for more effective therapeutic and diagnostic techniques and, ultimately, contribute to the development of personalized medicine and personalized dental medicine.

  12. Personality.

    Science.gov (United States)

    Funder, D C

    2001-01-01

    Personality psychology is as active today as at any point in its history. The classic psychoanalytic and trait paradigms are active areas of research, the behaviorist paradigm has evolved into a new social-cognitive paradigm, and the humanistic paradigm is a basis of current work on cross-cultural psychology. Biology and evolutionary theory have also attained the status of new paradigms for personality. Three challenges for the next generation of research are to integrate these disparate approaches to personality (particularly the trait and social-cognitive paradigms), to remedy the imbalance in the person-situation-behavior triad by conceptualizing the basic properties of situations and behaviors, and to add to personality psychology's thin inventory of basic facts concerning the relations between personality and behavior.

  13. Functional brain imaging of gastrointestinal sensation in health and disease

    Institute of Scientific and Technical Information of China (English)

    Lukas Van Oudenhove; Steven J Coen; Qasim Aziz

    2007-01-01

    It has since long been known, from everyday experience as well as from animal and human studies, that psychological processes-both affective and cognitiveexert an influence on gastrointestinal sensorimotor function. More specifically, a link between psychological factors and visceral hypersensitivity has been suggested,mainly based on research in functional gastrointestinal disorder patients. However, until recently, the exact nature of this putative relationship remained unclear,mainly due to a lack of non-invasive methods to study the (neurobiological) mechanisms underlying this relationship in non-sleeping humans. As functional brain imaging, introduced in visceral sensory neuroscience some 10 years ago, does provide a method for in vivo study of brain-gut interactions, insight into the neurobiological mechanisms underlying visceral sensation in general and the influence of psychological factors more particularly,has rapidly grown. In this article, an overview of brain imaging evidence on gastrointestinal sensation will be given, with special emphasis on the brain mechanisms underlying the interaction between affective & cognitive processes and visceral sensation. First, the reciprocal neural pathways between the brain and the gut (braingut axis) will be briefly outlined, including brain imaging evidence in healthy volunteers. Second, functional brain imaging studies assessing the influence of psychological factors on brain processing of visceral sensation in healthy humans will be discussed in more detail.Finally, brain imaging work investigating differences in brain responses to visceral distension between healthy volunteers and functional gastrointestinal disorder patients will be highlighted.

  14. Subthalamic nucleus deep brain stimulation in early stage Parkinson's disease.

    Science.gov (United States)

    Charles, David; Konrad, Peter E; Neimat, Joseph S; Molinari, Anna L; Tramontana, Michael G; Finder, Stuart G; Gill, Chandler E; Bliton, Mark J; Kao, Chris; Phibbs, Fenna T; Hedera, Peter; Salomon, Ronald M; Cannard, Kevin R; Wang, Lily; Song, Yanna; Davis, Thomas L

    2014-07-01

    Deep brain stimulation (DBS) is an effective and approved therapy for advanced Parkinson's disease (PD), and a recent study suggests efficacy in mid-stage disease. This manuscript reports the results of a pilot trial investigating preliminary safety and tolerability of DBS in early PD. Thirty subjects with idiopathic PD (Hoehn & Yahr Stage II off medication), age 50-75, on medication ≥6 months but ≤4 years, and without motor fluctuations or dyskinesias were randomized to optimal drug therapy (ODT) (n = 15) or DBS + ODT (n = 15). Co-primary endpoints were the time to reach a 4-point worsening from baseline in the UPDRS-III off therapy and the change in levodopa equivalent daily dose from baseline to 24 months. As hypothesized, the mean UPDRS total and part III scores were not significantly different on or off therapy at 24 months. Medication requirements in the DBS + ODT group were lower at all time points with a maximal difference at 18 months. With a few exceptions, differences in neuropsychological functioning were not significant. Two subjects in the DBS + ODT group suffered serious adverse events; remaining adverse events were mild or transient. This study demonstrates that subjects with early stage PD will enroll in and complete trials testing invasive therapies and provides preliminary evidence that DBS is well tolerated in early PD. The results of this trial provide the data necessary to design a large, phase III, double-blind, multicenter trial investigating the safety and efficacy of DBS in early PD. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Clinical outcome of deep brain stimulation for Parkinson's disease.

    Science.gov (United States)

    Deuschl, Günther; Paschen, Steffen; Witt, Karsten

    2013-01-01

    Deep brain stimulation is one of the most effective treatments of Parkinson's disease (PD). This report summarizes the state of the art as at January 2013. Stimulation of the subthalamic nucleus is the most commonly used approach. It improves the core motor symptoms better than medication in patients with advanced disease. It also improves the majority of nonmotor symptoms, such as mood, impulse control disorders, sleep, and some autonomic dysfunctions. Quality of life (QoL) is improved significantly more than with medication. Long-term data show that the treatment is effective for up to 10 years, but the late appearance of l-dopa-resistant symptoms is seemingly not influenced. Internal globus pallidus (GPi) stimulation is less well studied but seems to have similar short-term efficacy. Importantly l-dopa use cannot be reduced with GPi DBS, which is a major disadvantage for patients suffering from medication side-effects, although gait may be influenced more positively. Although short-term QoL improvement seems to be similar to that for subthalamic nucleus (STN) DBS - gait and speech may be better improved - long-term data are rare for GPi DBS. Thalamic stimulation in the ventral intermediate nucleus (VIM) is applied only in tremor-dominant elderly patients. The treatment improves the dopa-sensitive symptoms and effectively reduces fluctuations leading to an overall QoL improvement. Although most of the controlled studies have been on advanced PD, the recently published EARLYSTIM study suggests that even patients with a very short duration of their fluctuations and dyskinesia are doing significantly better with neurostimulation in terms of QoL and all major motor outcome parameters.

  16. Review: Role of developmental inflammation and blood-brain barrier dysfunction in neurodevelopmental and neurodegenerative diseases.

    Science.gov (United States)

    Stolp, H B; Dziegielewska, K M

    2009-04-01

    The causes of most neurological disorders are not fully understood. Inflammation and blood-brain barrier dysfunction appear to play major roles in the pathology of these diseases. Inflammatory insults that occur during brain development may have widespread effects later in life for a spectrum of neurological disorders. In this review, a new hypothesis suggesting a mechanistic link between inflammation and blood-brain barrier function (integrity), which is universally important in both neurodevelopmental and neurodegenerative diseases, is proposed. The role of inflammation and the blood-brain barrier will be discussed in cerebral palsy, schizophrenia, Parkinson's disease, Alzheimer's disease and multiple sclerosis, conditions where both inflammation and blood-brain barrier dysfunction occur either during initiation and/or progression of the disease. We suggest that breakdown of normal blood-brain barrier function resulting in a short-lasting influx of blood-born molecules, in particular plasma proteins, may cause local damage, such as reduction of brain white matter observed in some newborn babies, but may also be the mechanism behind some neurodegenerative diseases related to underlying brain damage and long-term changes in barrier properties.

  17. Blood-brain barrier P-glycoprotein function in neurodegenerative disease.

    Science.gov (United States)

    Bartels, A L

    2011-01-01

    Protection of the brain is strengthened by active transport and ABC transporters. P-glycoprotein (P-gp) at the blood-brain barrier (BBB) functions as an active efflux pump by extruding a substrate from the brain, which is important for maintaining loco-regional homeostasis in the brain and protection against toxic compounds. Importantly, dysfunctional BBB P-gp transport is postulated as an important factor contributing to accumulation of aggregated protein in neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Furthermore, P-gp is a major factor in mediating resistance to brain entry of numerous exogenous compounds, including toxins that can be involved in PD pathogenesis. This review highlights the role of altered P-gp function in the pathogenesis and progression of neurodegenerative disease. Also the implications of alterations in P-gp function for the treatment of these diseases are discussed.

  18. The real-time link between person perception and action: brain potential evidence for dynamic continuity.

    Science.gov (United States)

    Freeman, Jonathan B; Ambady, Nalini; Midgley, Katherine J; Holcomb, Phillip J

    2011-01-01

    Using event-related potentials, we investigated how the brain extracts information from another's face and translates it into relevant action in real time. In Study 1, participants made between-hand sex categorizations of sex-typical and sex-atypical faces. Sex-atypical faces evoked negativity between 250 and 550 ms (N300/N400 effects), reflecting the integration of accumulating sex-category knowledge into a coherent sex-category interpretation. Additionally, the lateralized readiness potential revealed that the motor cortex began preparing for a correct hand response while social category knowledge was still gradually evolving in parallel. In Study 2, participants made between-hand eye-color categorizations as part of go/no-go trials that were contingent on a target's sex. On no-go trials, although the hand did not actually move, information about eye color partially prepared the motor cortex to move the hand before perception of sex had finalized. Together, these findings demonstrate the dynamic continuity between person perception and action, such that ongoing results from face processing are immediately and continuously cascaded into the motor system over time. The preparation of action begins based on tentative perceptions of another's face before perceivers have finished interpreting what they just saw.

  19. Blood-brain interfaces and bilirubin-induced neurological diseases.

    Science.gov (United States)

    Ghersi-Egea, J F; Gazzin, S; Strazielle, N

    2009-01-01

    The endothelium of the brain microvessels and the choroid plexus epithelium form highly specialized cellular barriers referred to as blood-brain interfaces through which molecular exchanges take place between the blood and the neuropil or the cerebrospinal fluid, respectively. Within the brain, the ependyma and the pia-glia limitans modulate exchanges between the neuropil and the cerebrospinal fluid. All these interfaces are key elements of neuroprotection and fulfill trophic functions; both properties are critical to harmonious brain development and maturation. By analogy to hepatic bilirubin detoxification pathways, we review the transport and metabolic mechanisms which in all these interfaces may participate in the regulation of bilirubin cerebral bioavailability in physiologic conditions, both in adult and in developing brain. We specifically address the role of ABC and OATP transporters, glutathione-S-transferases, and the potential involvement of glucuronoconjugation and oxidative metabolic pathways. Regulatory mechanisms are explored which are involved in the induction of these pathways and represent potential pharmacological targets to prevent bilirubin accumulation into the brain. We then review the possible alteration of the neuroprotective and trophic barrier functions in the course of bilirubin-induced neurological dysfunctions resulting from hyperbilirubinemia. Finally, we highlight the role of the blood-brain and blood-CSF barriers in regulating the brain biodisposition of candidate drugs for the treatment or prevention of bilirubin-induced brain injury.

  20. Vascular and Alzheimer's disease markers independently predict brain atrophy rate in Alzheimer's Disease Neuroimaging Initiative controls.

    Science.gov (United States)

    Barnes, Josephine; Carmichael, Owen T; Leung, Kelvin K; Schwarz, Christopher; Ridgway, Gerard R; Bartlett, Jonathan W; Malone, Ian B; Schott, Jonathan M; Rossor, Martin N; Biessels, Geert Jan; DeCarli, Charlie; Fox, Nick C

    2013-08-01

    This study assessed relationships among white matter hyperintensities (WMH), cerebrospinal fluid (CSF), Alzheimer's disease (AD) pathology markers, and brain volume loss. Subjects included 197 controls, 331 individuals with mild cognitive impairment (MCI), and 146 individuals with AD with serial volumetric 1.5-T MRI. CSF Aβ1-42 (n = 351) and tau (n = 346) were measured. Brain volume change was quantified using the boundary shift integral (BSI). We assessed the association between baseline WMH volume and annualized BSI, adjusting for intracranial volume. We also performed multiple regression analyses in the CSF subset, assessing the relationships of WMH and Aβ1-42 and/or tau with BSI. WMH burden was positively associated with BSI in controls (p = 0.02) but not MCI or AD. In multivariable models, WMH (p = 0.003) and Aβ1-42 (p = 0.001) were independently associated with BSI in controls; in MCI Aβ1-42 (p brain atrophy in the context of AD pathology in pre-dementia stages.

  1. Brain volumes predict neurodevelopment in adolescents after surgery for congenital heart disease.

    Science.gov (United States)

    von Rhein, Michael; Buchmann, Andreas; Hagmann, Cornelia; Huber, Reto; Klaver, Peter; Knirsch, Walter; Latal, Beatrice

    2014-01-01

    Patients with complex congenital heart disease are at risk for neurodevelopmental impairments. Evidence suggests that brain maturation can be delayed and pre- and postoperative brain injury may occur, and there is limited information on the long-term effect of congenital heart disease on brain development and function in adolescent patients. At a mean age of 13.8 years, 39 adolescent survivors of childhood cardiopulmonary bypass surgery with no structural brain lesions evident through conventional cerebral magnetic resonance imaging and 32 healthy control subjects underwent extensive neurodevelopmental assessment and cerebral magnetic resonance imaging. Cerebral scans were analysed quantitatively using surface-based and voxel-based morphometry. Compared with control subjects, patients had lower total brain (P = 0.003), white matter (P = 0.004) and cortical grey matter (P = 0.005) volumes, whereas cerebrospinal fluid volumes were not different. Regional brain volume reduction ranged from 5.3% (cortical grey matter) to 11% (corpus callosum). Adolescents with cyanotic heart disease showed more brain volume loss than those with acyanotic heart disease, particularly in the white matter, thalami, hippocampi and corpus callosum (all P-values Brain volume reduction correlated significantly with cognitive, motor and executive functions (grey matter: P < 0.05, white matter: P < 0.01). Our findings suggest that there are long-lasting cerebral changes in adolescent survivors of cardiopulmonary bypass surgery for congenital heart disease and that these changes are associated with functional outcome.

  2. An abnormal resting-state functional brain network indicates progression towards Alzheimer’s disease*****

    Institute of Scientific and Technical Information of China (English)

    Jie Xiang; Hao Guo; Rui Cao; Hong Liang; Junjie Chen

    2013-01-01

    Brain structure and cognitive function change in the temporal lobe, hippocampus, and prefrontal cortex of patients with mild cognitive impairment and Alzheimer’s disease, and brain network-connection strength, network efficiency, and nodal attributes are abnormal. However, existing research has only analyzed the differences between these patients and normal controls. In this study, we constructed brain networks using resting-state functional MRI data that was extracted from four populations mal controls, patients with early mild cognitive impairment, patients with late mild cognitive impairment, and patients with Alzheimer’s disease) using the Alzheimer’s Disease Neuroimaging Initiative data set. The aim was to analyze the characteristics of resting-state functional neural networks, and to observe mild cognitive impairment at different stages before the transformation to Alzheimer’s disease. Results showed that as cognitive deficits increased across the four groups, the shortest path in the rest-ing-state functional network gradual y increased, while clustering coefficients gradual y decreased. This evidence indicates that dementia is associated with a decline of brain network efficiency. In tion, the changes in functional networks revealed the progressive deterioration of network function across brain regions from healthy elderly adults to those with mild cognitive impairment and Alzhei-mer’s disease. The alterations of node attributes in brain regions may reflect the cognitive functions in brain regions, and we speculate that early impairments in memory, hearing, and language function can eventual y lead to diffuse brain injury and other cognitive impairments.

  3. Personal Experience in Acupuncture Treatment of Mental Diseases

    Institute of Scientific and Technical Information of China (English)

    丁德正

    2001-01-01

    @@ Under the guidance of family veteran Chinese physicians, the author has been pursuing the research and treatment of mental diseases with Chinese herbal medicine supplemented by acupuncture and moxibustion with satisfactory therapeutic effects which is introduced as follows.

  4. The role of disease characteristics in the ethical debate on personal genome testing

    Directory of Open Access Journals (Sweden)

    Bunnik Eline M

    2012-01-01

    Full Text Available Abstract Background Companies are currently marketing personal genome tests directly-to-consumer that provide genetic susceptibility testing for a range of multifactorial diseases simultaneously. As these tests comprise multiple risk analyses for multiple diseases, they may be difficult to evaluate. Insight into morally relevant differences between diseases will assist researchers, healthcare professionals, policy-makers and other stakeholders in the ethical evaluation of personal genome tests. Discussion In this paper, we identify and discuss four disease characteristics - severity, actionability, age of onset, and the somatic/psychiatric nature of disease - and show how these lead to specific ethical issues. By way of illustration, we apply this framework to genetic susceptibility testing for three diseases: type 2 diabetes, age-related macular degeneration and clinical depression. For these three diseases, we point out the ethical issues that are relevant to the question whether it is morally justifiable to offer genetic susceptibility testing to adults or to children or minors, and on what conditions. Summary We conclude that the ethical evaluation of personal genome tests is challenging, for the ethical issues differ with the diseases tested for. An understanding of the ethical significance of disease characteristics will improve the ethical, legal and societal debate on personal genome testing.

  5. Exercise Regulation of Cognitive Function and Neuroplasticity in the Healthy and Diseased Brain.

    Science.gov (United States)

    Hamilton, Gilian F; Rhodes, Justin S

    2015-01-01

    Regular exercise broadly enhances physical and mental health throughout the lifespan. Animal models have provided us with the tools to gain a better understanding of the underlying biochemical, physiological, and morphological mechanisms through which exercise exerts its beneficial cognitive effects. One brain region in particular, the hippocampus, is especially responsive to exercise. It is critically involved in learning and memory and is one of two regions in the mammalian brain that continues to generate new neurons throughout life. Exercise prevents the decline of the hippocampus from aging and ameliorates many neurodegenerative diseases, in part by increasing adult hippocampal neurogenesis but also by activating a multitude of molecular mechanisms that promote brain health. In this chapter, we first describe some rodent models used to study effects of exercise on the brain. Then we review the rodent work focusing on the mechanisms behind which exercise improves cognition and brain health in both the normal and the diseased brain, with emphasis on the hippocampus.

  6. Stress and the brain: from adaptation to disease

    NARCIS (Netherlands)

    de Kloet, E.R.; Joëls, M.; Holsboer, F.

    2005-01-01

    In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many ge

  7. Using induced pluripotent stem cells derived neurons to model brain diseases

    Directory of Open Access Journals (Sweden)

    Cindy E McKinney

    2017-01-01

    Full Text Available The ability to use induced pluripotent stem cells (iPSC to model brain diseases is a powerful tool for unraveling mechanistic alterations in these disorders. Rodent models of brain diseases have spurred understanding of pathology but the concern arises that they may not recapitulate the full spectrum of neuron disruptions associated with human neuropathology. iPSC derived neurons, or other neural cell types, provide the ability to access pathology in cells derived directly from a patient's blood sample or skin biopsy where availability of brain tissue is limiting. Thus, utilization of iPSC to study brain diseases provides an unlimited resource for disease modelling but may also be used for drug screening for effective therapies and may potentially be used to regenerate aged or damaged cells in the future. Many brain diseases across the spectrum of neurodevelopment, neurodegenerative and neuropsychiatric are being approached by iPSC models. The goal of an iPSC based disease model is to identify a cellular phenotype that discriminates the disease-bearing cells from the control cells. In this mini-review, the importance of iPSC cell models validated for pluripotency, germline competency and function assessments is discussed. Selected examples for the variety of brain diseases that are being approached by iPSC technology to discover or establish the molecular basis of the neuropathology are discussed.

  8. Low brain ascorbic acid increases susceptibility to seizures in mouse models of decreased brain ascorbic acid transport and Alzheimer's disease.

    Science.gov (United States)

    Warner, Timothy A; Kang, Jing-Qiong; Kennard, John A; Harrison, Fiona E

    2015-02-01

    Seizures are a known co-occurring symptom of Alzheimer's disease, and they can accelerate cognitive and neuropathological dysfunction. Sub-optimal vitamin C (ascorbic acid) deficiency, that is low levels that do not lead the sufferer to present with clinical signs of scurvy (e.g. lethargy, hemorrhage, hyperkeratosis), are easily obtainable with insufficient dietary intake, and may contribute to the oxidative stress environment of both Alzheimer's disease and epilepsy. The purpose of this study was to test whether mice that have diminished brain ascorbic acid in addition to carrying human Alzheimer's disease mutations in the amyloid precursor protein (APP) and presenilin 1 (PSEN1) genes, had altered electrical activity in the brain (electroencephalography; EEG), and were more susceptible to pharmacologically induced seizures. Brain ascorbic acid was decreased in APP/PSEN1 mice by crossing them with sodium vitamin C transporter 2 (SVCT2) heterozygous knockout mice. These mice have an approximately 30% decrease in brain ascorbic acid due to lower levels of SVCT2 that supplies the brain with ASC. SVCT2+/-APP/PSEN1 mice had decreased ascorbic acid and increased oxidative stress in brain, increased mortality, faster seizure onset latency following treatment with kainic acid (10 mg/kg i.p.), and more ictal events following pentylenetetrazol (50 mg/kg i.p.) treatment. Furthermore, we report the entirely novel phenomenon that ascorbic acid deficiency alone increased the severity of kainic acid- and pentylenetetrazol-induced seizures. These data suggest that avoiding ascorbic acid deficiency may be particularly important in populations at increased risk for epilepsy and seizures, such as Alzheimer's disease.

  9. [Critical review of instruments to assess pain in the non communicative brain injured persons in intensive care].

    Science.gov (United States)

    Roulin, Marie-José; Goulet, Céline; Ramelet, Anne-Sylvie

    2011-03-01

    The purpose of this review is to critically appraise the pain assessment tools for non communicative persons in intensive care available in the literature and to determine their relevance for those with brain injury. Nursing and medical electronic databases were searched to identify pain tools, with a description of psychometric proprieties, in English and French. Seven of the ten tools were considered relevant and systematically evaluated according to the criteria and the indicators in the following five areas: conceptualisation, target population, feasibility and clinical utility, reliability and validity. Results indicate a number of well designed pain tools, but additional work is necessary to establish their accuracy and adequacy for the brain injured non communicative person in intensive care. Recommendations are made to choose the best tool for clinical practice and for research.

  10. Are abnormal premorbid personality traits associated with Alzheimer's disease? - A case-control study.

    Science.gov (United States)

    Nicholas, Helen; Moran, Paul; Foy, Catherine; Brown, Richard G; Lovestone, Simon; Bryant, Stephanie; Boothby, Harry

    2010-04-01

    To examine the association between premorbid personality traits, social networks and AD, using a case-control design, and two informant-based retrospective assessments of premorbid personality. Cases consisted of 217 Subjects diagnosed with probable late onset Alzheimer's disease (160 females and 57 males). Recruitment was from both community and nursing home settings. Controls consisted of 76 unaffected siblings (44 females and 32 males) of patients with AD. Both cases and controls received informant ratings of premorbid personality. A selection of abnormal personality traits were over represented in the AD group. AD was particularly associated with Cluster A personality disorder traits (Paranoid, Schizoid, Schizotypal). AD cases had correspondingly sparser social networks. There is an association between abnormal personality traits and AD. Individuals with AD also appear to have had lower levels of social interactivity.

  11. A derangement of the brain wound healing process may cause some cases of Alzheimer's disease.

    Science.gov (United States)

    Lehrer, Steven; Rheinstein, Peter H

    2016-08-01

    A derangement of brain wound healing may cause some cases of Alzheimer's disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer's disease. Our hypothesis -- Alzheimer's disease is brain wound healing gone awry at least in some cases -- could be tested by measuring progression with biomarkers for the four stages of wound healing in humans or appropriate animal models. Autopsy studies might be done. Chronic traumatic encephalopathy might also result from the brain wound healing process.

  12. Aluminum and Alzheimer's disease, a personal perspective after 25 years.

    Science.gov (United States)

    Perl, Daniel P; Moalem, Sharon

    2006-01-01

    It is now 25 years since the publication of our original paper investigating the association aluminum with Alzheimer's disease. This publication reported on the results of scanning electron microscopy coupled x-ray spectrometry microprobe elemental studies of both neurofibrillary tangle-bearing and tangle-free neurons in the hippocampus of cases of Alzheimer's disease and controls. Peaks related to the presence of aluminum were consistently detected within the tangle-bearing neurons. This paper supported the association of aluminum and Alzheimer's disease on the cellular level of resolution and caused considerable interest and discussion. Subsequent work demonstrated prominent evidence of aluminum accumulation in the tangle-bearing neurons of cases of amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam. This latter observation has now been replicated using five different forms of microanalysis. Finally, using laser microprobe mass analysis, we demonstrated that the abnormally high aluminum-related signal which we originally detected was actually located within the neurofibrillary tangle, itself, and was accompanied by excess concentrations of iron. Although it is unlikely that aluminum represents an etiologic cause of Alzheimer's disease, we believe that this highly reactive element, known to cross-link hyperphosphorylated proteins, may play an active role in the pathogenesis of critical neuropathologic lesion in Alzheimer's disease and other related disorders.

  13. Transcranial brain sonography in Parkinson's disease with restless legs syndrome.

    Science.gov (United States)

    Kwon, Do-Young; Seo, Woo-Keun; Yoon, Ho-Kyoung; Park, Moon-Ho; Koh, Seong-Beom; Park, Kun-Woo

    2010-07-30

    Substantia nigra (SN) hyperechogenicity assessed by transcranial brain sonography (TCS) is a characteristic finding in idiopathic Parkinson's disease (PD). In contrast, SN hypoechogenicity on TCS has been recently demonstrated in restless legs syndrome (RLS). RLS is one of the most common sleep problems in PD, but the pathophysiologic relationship between these two disorders has not been thoroughly elucidated. We compared the SN echogenicities of PD patients with and without RLS to investigate whether comorbid RLS in PD affects SN echogenicity and to explain the echogenic differences between idiopathic RLS (iRLS) and secondary PD-related RLS (pRLS). Sixty-three PD patients (median age 64.6 +/- 10.6 years), 40 iRLS patients (53.1 +/- 11.7 years), and 40 healthy controls (69.1 +/- 2.3 years) were enrolled in our study. All subjects answered a sleep questionnaire and underwent TCS. PD patients were subdivided into two groups, PD with RLS (PD+RLS, n = 26) and PD without RLS (PD-RLS, n = 37), and the sonographic findings of each group were compared. Although significant hyperechogenicity was detected in both the SN and SN/midbrain ratios in both PD subgroups compared with the controls and the iRLS group (P hypoechogenicity. In conclusion, comorbid RLS in PD did not have an impact on the sonographic SN findings. These results suggest that the pathogenesis of pRLS and iRLS involve different mechanisms. Further study will be required to clarify the association between RLS and PD.

  14. Coping mediates the influence of personality on life satisfaction in patients with rheumatic diseases

    NARCIS (Netherlands)

    Vollmann, M.; Pukrop, Jörg; Salewski, Christel

    2016-01-01

    A rheumatic disease can severely impair a person’s quality of life. The degree of impairment, however, is not closely related to objective indicators of disease severity. This study investigated the influence and the interplay of core psychological factors, i.e., personality and coping, on life sati

  15. The burden of disease in personality disorders: Diagnosis-specific quality of life

    NARCIS (Netherlands)

    D.I. Soeteman (Djora); R. Verheul (Roel); J.J.V. Bussehbaeh (Jan J.)

    2008-01-01

    textabstractA generic quality of life measure was used to investigate the burden of disease in a large sample of patients with personality disorders. The 1,708 subjects included in this study were recruited from six different mental health care institutes in the Netherlands. The burden of disease wa

  16. The role of disease characteristics in the ethical debate on personal genome testing

    NARCIS (Netherlands)

    E.M. Bunnik (Eline); M.H.N. Schermer (Maartje); A.C.J.W. Janssens (Cécile)

    2012-01-01

    textabstractBackground: Companies are currently marketing personal genome tests directly-to-consumer that provide genetic susceptibility testing for a range of multifactorial diseases simultaneously. As these tests comprise multiple risk analyses for multiple diseases, they may be difficult to evalu

  17. Is type D personality here to stay? Emerging evidence across cardiovascular disease patient groups

    NARCIS (Netherlands)

    S.S. Pedersen (Susanne); J. Denollet (Johan)

    2006-01-01

    textabstractThe distressed personality (Type D) is an emerging risk factor in cardiovascular disease (CVD) that incurs a risk on par with left ventricular dysfunction in patients with ischemic heart disease. Type D is defined as the co-occurring tendencies to experience increased negative emotions a

  18. The burden of disease in personality disorders: Diagnosis-specific quality of life

    NARCIS (Netherlands)

    Soeteman, D.I.; Verheul, R.; Busschbach, J.J.V.

    2008-01-01

    A generic quality of life measure was used to investigate the burden of disease in a large sample of patients with personality disorders. The 1,708 subjects included in this study were recruited from six different mental health care institutes in the Netherlands. The burden of disease was measured u

  19. Physiological Correlates of Intellectual Function in Children with Sickle Cell Disease: Hypoxaemia, Hyperaemia and Brain Infarction

    Science.gov (United States)

    Hogan, Alexandra M.; Pit-ten Cate, Ineke M.; Vargha-Khadem, Faraneh; Prengler, Mara; Kirkham, Fenella J.

    2006-01-01

    Lowered intelligence relative to controls is evident by mid-childhood in children with sickle cell disease. There is consensus that brain infarct contributes to this deficit, but the subtle lowering of IQ in children with normal MRI scans might be accounted for by chronic systemic complications leading to insufficient oxygen delivery to the brain.…

  20. Neuroinflammation in the Aging Down Syndrome Brain; Lessons from Alzheimer's Disease

    Directory of Open Access Journals (Sweden)

    Donna M. Wilcock

    2012-01-01

    Full Text Available Down syndrome (DS is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50–70% of DS patients showing dementia by 60–70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation in the DS brain and how the genetics of DS may alter this inflammatory response and change the course of disease in the DS brain. The goal of this review is to highlight our current understanding of inflammation in Alzheimer's disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21.

  1. Neuroinflammation in the aging down syndrome brain; lessons from Alzheimer's disease.

    Science.gov (United States)

    Wilcock, Donna M

    2012-01-01

    Down syndrome (DS) is the most genetic cause of mental retardation and is caused by the triplication of chromosome 21. In addition to the disabilities caused early in life, DS is also noted as causing Alzheimer's-disease-like pathological changes in the brain, leading to 50-70% of DS patients showing dementia by 60-70 years of age. Inflammation is a complex process that has a key role to play in the pathogenesis of Alzheimer's disease. There is relatively little understood about inflammation in the DS brain and how the genetics of DS may alter this inflammatory response and change the course of disease in the DS brain. The goal of this review is to highlight our current understanding of inflammation in Alzheimer's disease and predict how inflammation may affect the pathology of the DS brain based on this information and the known genetic changes that occur due to triplication of chromosome 21.

  2. Genetics Home Reference: COL4A1-related brain small-vessel disease

    Science.gov (United States)

    ... hemorrhage Johns Hopkins Medicine Department of Neurology and Neurosurgery: Intracerebral Hemorrhage Johns Hopkins Medicine Department of Neurology and Neurosurgery: Stroke MalaCards: col4a1-related brain small-vessel disease ...

  3. Personal significance is encoded automatically by the human brain: an event-related potential study with ringtones.

    Science.gov (United States)

    Roye, Anja; Jacobsen, Thomas; Schröger, Erich

    2007-08-01

    In this human event-related brain potential (ERP) study, we have used one's personal--relative to another person's--ringtone presented in a two-deviant passive oddball paradigm to investigate the long-term memory effects of self-selected personal significance of a sound on the automatic deviance detection and involuntary attention system. Our findings extend the knowledge of long-term effects usually reported in group-approaches in the domains of speech, music and environmental sounds. In addition to the usual mismatch negativity (MMN) and P3a component elicited by deviants in contrast to standard stimuli, we observed a posterior ERP deflection directly following the MMN for the personally significant deviant only. This specific impact of personal significance started around 200 ms after sound onset and involved neural generators that were different from the mere physical deviance detection mechanism. Whereas the early part of the P3a component was unaffected by personal significance, the late P3a was enhanced for the ERPs to the personal significant deviant suggesting that this stimulus was more powerful in attracting attention involuntarily. Following the involuntary attention switch, the personally significant stimulus elicited a widely-distributed negative deflection, probably reflecting further analysis of the significant sound involving evaluation of relevance or reorienting to the primary task. Our data show, that the personal significance of mobile phone and text message technology, which have developed as a major medium of communication in our modern world, prompts the formation of individual memory representations, which affect the processing of sounds that are not in the focus of attention.

  4. Characterizing the role of brain derived neurotrophic factor genetic variation in Alzheimer's disease neurodegeneration.

    Directory of Open Access Journals (Sweden)

    Robyn A Honea

    Full Text Available There is accumulating evidence that neurotrophins, like brain-derived neurotrophic factor (BDNF, may impact aging and Alzheimer's Disease. However, traditional genetic association studies have not found a clear relationship between BDNF and AD. Our goal was to test whether BDNF single nucleotide polymorphisms (SNPs impact Alzheimer's Disease-related brain imaging and cognitive markers of disease. We completed an imaging genetics study on 645 Alzheimer's Disease Neuroimaging Initiative participants (ND=175, MCI=316, AD=154 who had cognitive, brain imaging, and genetics data at baseline and a subset of those with brain imaging data at two years. Samples were genotyped using the Illumina Human610-Quad BeadChip. 13 SNPs in BDNF were identified in the dataset following quality control measures (rs6265(Val66Met, rs12273363, rs11030094, rs925946, rs1050187, rs2203877, rs11030104, rs11030108, rs10835211, rs7934165, rs908867, rs1491850, rs1157459. We analyzed a subgroup of 8 SNPs that were in low linkage disequilibrium with each other. Automated brain morphometric measures were available through ADNI investigators, and we analyzed baseline cognitive scores, hippocampal and whole brain volumes, and rates of hippocampal and whole brain atrophy and rates of change in the ADAS-Cog over one and two years. Three out of eight BDNF SNPs analyzed were significantly associated with measures of cognitive decline (rs1157659, rs11030094, rs11030108. No SNPs were significantly associated with baseline brain volume measures, however six SNPs were significantly associated with hippocampal and/or whole brain atrophy over two years (rs908867, rs11030094, rs6265, rs10501087, rs1157659, rs1491850. We also found an interaction between the BDNF Val66Met SNP and age with whole brain volume. Our imaging-genetics analysis in a large dataset suggests that while BDNF genetic variation is not specifically associated with a diagnosis of AD, it appears to play a role in AD

  5. The modulatory effect of adaptive deep brain stimulation on beta bursts in Parkinson's disease.

    Science.gov (United States)

    Tinkhauser, Gerd; Pogosyan, Alek; Little, Simon; Beudel, Martijn; Herz, Damian M; Tan, Huiling; Brown, Peter

    2017-02-13

    Adaptive deep brain stimulation uses feedback about the state of neural circuits to control stimulation rather than delivering fixed stimulation all the time, as currently performed. In patients with Parkinson's disease, elevations in beta activity (13-35 Hz) in the subthalamic nucleus have been demonstrated to correlate with clinical impairment and have provided the basis for feedback control in trials of adaptive deep brain stimulation. These pilot studies have suggested that adaptive deep brain stimulation may potentially be more effective, efficient and selective than conventional deep brain stimulation, implying mechanistic differences between the two approaches. Here we test the hypothesis that such differences arise through differential effects on the temporal dynamics of beta activity. The latter is not constantly increased in Parkinson's disease, but comes in bursts of different durations and amplitudes. We demonstrate that the amplitude of beta activity in the subthalamic nucleus increases in proportion to burst duration, consistent with progressively increasing synchronization. Effective adaptive deep brain stimulation truncated long beta bursts shifting the distribution of burst duration away from long duration with large amplitude towards short duration, lower amplitude bursts. Critically, bursts with shorter duration are negatively and bursts with longer duration positively correlated with the motor impairment off stimulation. Conventional deep brain stimulation did not change the distribution of burst durations. Although both adaptive and conventional deep brain stimulation suppressed mean beta activity amplitude compared to the unstimulated state, this was achieved by a selective effect on burst duration during adaptive deep brain stimulation, whereas conventional deep brain stimulation globally suppressed beta activity. We posit that the relatively selective effect of adaptive deep brain stimulation provides a rationale for why this approach could

  6. Concise review: Patient-derived olfactory stem cells: new models for brain diseases.

    Science.gov (United States)

    Mackay-Sim, Alan

    2012-11-01

    Traditional models of brain diseases have had limited success in driving candidate drugs into successful clinical translation. This has resulted in large international pharmaceutical companies moving out of neuroscience research. Cells are not brains, obviously, but new patient-derived stem models have the potential to elucidate cell biological aspects of brain diseases that are not present in worm, fly, or rodent models, the work horses of disease investigations and drug discovery. Neural stem cells are present in the olfactory mucosa, the organ of smell in the nose. Patient-derived olfactory mucosa has demonstrated disease-associated differences in a variety of brain diseases and recently olfactory mucosa stem cells have been generated from patients with schizophrenia, Parkinson's disease, and familial dysautonomia. By comparison with cells from healthy controls, patient-derived olfactory mucosa stem cells show disease-specific alterations in gene expression and cell functions including: a shorter cell cycle and faster proliferation in schizophrenia, oxidative stress in Parkinson's disease, and altered cell migration in familial dysautonomia. Olfactory stem cell cultures thus reveal patient-control differences, even in complex genetic diseases such as schizophrenia and Parkinson's disease, indicating that multiple genes of small effect can converge on shared cell signaling pathways to present as a disease-specific cellular phenotype. Olfactory mucosa stem cells can be maintained in homogeneous cultures that allow robust and repeatable multiwell assays suitable for screening libraries of drug candidate molecules. Copyright © 2012 AlphaMed Press.

  7. Corpus callosum thickness on mid-sagittal MRI as a marker of brain volume: a pilot study in children with HIV-related brain disease and controls

    Energy Technology Data Exchange (ETDEWEB)

    Andronikou, Savvas [University of the Witwatersrand, Department of Radiology, Faculty of Health Sciences, Cape Town (South Africa); Ackermann, Christelle [University of Stellenbosch, Department of Radiology, Stellenbosch (South Africa); Laughton, Barbara; Cotton, Mark [Stellenbosch University and Tygerberg Children' s Hospital, Children' s Infectious Diseases Research Unit, Stellenbosch (South Africa); Tomazos, Nicollette [University of Cape Town, Faculty of Commerce, Department of Management Studies, Cape Town (South Africa); Spottiswoode, Bruce [University of Cape Town, MRC/UCT Medical Imaging Research Unit, Department of Human Biology, Cape Town (South Africa); Mauff, Katya [University of Cape Town, Department of Statistical Sciences, Cape Town (South Africa); Pettifor, John M. [University of the Witwatersrand, MRC/Wits Developmental Pathways for Health Research Unit, Department of Paediatrics, Faculty of Health Sciences, Witwatersrand (South Africa)

    2015-07-15

    Corpus callosum thickness measurement on mid-sagittal MRI may be a surrogate marker of brain volume. This is important for evaluation of diseases causing brain volume gain or loss, such as HIV-related brain disease and HIV encephalopathy. To determine if thickness of the corpus callosum on mid-sagittal MRI is a surrogate marker of brain volume in children with HIV-related brain disease and in controls without HIV. A retrospective MRI analysis in children (<5 years old) with HIV-related brain disease and controls used a custom-developed semi-automated tool, which divided the midline corpus callosum and measured its thickness in multiple locations. Brain volume was determined using volumetric analysis. Overall corpus callosum thickness and thickness of segments of the corpus callosum were correlated with overall and segmented (grey and white matter) brain volume. Forty-four children (33 HIV-infected patients and 11 controls) were included. Significant correlations included overall corpus callosum (mean) and total brain volume (P = 0.05); prefrontal corpus callosum maximum with white matter volume (P = 0.02); premotor corpus callosum mean with total brain volume (P = 0.04) and white matter volume (P = 0.02), premotor corpus callosum maximum with white matter volume (P = 0.02) and sensory corpus callosum mean with total brain volume (P = 0.02). Corpus callosum thickness correlates with brain volume both in HIV-infected patients and controls. (orig.)

  8. Symptom Status Predicts Patient Outcomes in Persons with HIV and Comorbid Liver Disease

    Directory of Open Access Journals (Sweden)

    Wendy A. Henderson

    2012-01-01

    Full Text Available Persons living with human immunodeficiency virus (HIV are living longer; therefore, they are more likely to suffer significant morbidity due to potentially treatable liver diseases. Clinical evidence suggests that the growing number of individuals living with HIV and liver disease may have a poorer health-related quality of life (HRQOL than persons living with HIV who do not have comorbid liver disease. Thus, this study examined the multiple components of HRQOL by testing Wilson and Cleary’s model in a sample of 532 individuals (305 persons with HIV and 227 persons living with HIV and liver disease using structural equation modeling. The model components include biological/physiological factors (HIV viral load, CD4 counts, symptom status (Beck Depression Inventory II and the Medical Outcomes Study HIV Health Survey (MOS-HIV mental function, functional status (missed appointments and MOS-HIV physical function, general health perceptions (perceived burden visual analogue scale and MOS-HIV health transition, and overall quality of life (QOL (Satisfaction with Life Scale and MOS-HIV overall QOL. The Wilson and Cleary model was found to be useful in linking clinical indicators to patient-related outcomes. The findings provide the foundation for development and future testing of targeted biobehavioral nursing interventions to improve HRQOL in persons living with HIV and liver disease.

  9. Up-Regulated Production and Activation of the Complement System in Alzheimer’s Disease Brain

    OpenAIRE

    Yasojima, Koji; Schwab, Claudia; McGeer, Edith G.; McGeer, Patrick L.

    1999-01-01

    We used reverse transcriptase-polymerase chain reaction and Western blotting techniques to measure the levels of complement mRNAs and their protein products in Alzheimer’s disease (AD) brain compared with non-AD brain. mRNAs for C1q, C1r, C1s, C2, C3, C4, C5, C6, C7, C8, and C9 were detected in the 11 regions of brain that were investigated. The mRNA levels were markedly up-regulated in affected areas of AD brain. In the entorhinal cortex, hippocampus, and midtemporal gyrus, which had dense a...

  10. Disease-Specific Regions Outperform Whole-Brain Approaches in Identifying Progressive Supranuclear Palsy: A Multicentric MRI Study

    Science.gov (United States)

    Mueller, Karsten; Jech, Robert; Bonnet, Cecilia; Tintěra, Jaroslav; Hanuška, Jaromir; Möller, Harald E.; Fassbender, Klaus; Ludolph, Albert; Kassubek, Jan; Otto, Markus; Růžička, Evžen; Schroeter, Matthias L.

    2017-01-01

    To identify progressive supranuclear palsy (PSP), we combined voxel-based morphometry (VBM) and support vector machine (SVM) classification using disease-specific features in multicentric magnetic resonance imaging (MRI) data. Structural brain differences were investigated at four centers between 20 patients with PSP and 20 age-matched healthy controls with T1-weighted MRI at 3T. To pave the way for future application in personalized medicine, we applied SVM classification to identify PSP on an individual level besides group analyses based on VBM. We found a major decline in gray matter density in the brainstem, insula, and striatum, and also in frontomedian regions, which is in line with current literature. Moreover, SVM classification yielded high accuracy rates above 80% for disease identification in imaging data. Focusing analyses on disease-specific regions-of-interest (ROI) led to higher accuracy rates compared to a whole-brain approach. Using a polynomial kernel (instead of a linear kernel) led to an increased sensitivity and a higher specificity of disease detection. Our study supports the application of MRI for individual diagnosis of PSP, if combined with SVM approaches. We demonstrate that SVM classification provides high accuracy rates in multicentric data—a prerequisite for potential application in diagnostic routine. PMID:28326008

  11. The balance between cognitive reserve and brain imaging biomarkers of cerebrovascular and Alzheimer's diseases.

    Science.gov (United States)

    Murray, Alison D; Staff, Roger T; McNeil, Christopher J; Salarirad, Sima; Ahearn, Trevor S; Mustafa, Nazahah; Whalley, Lawrence J

    2011-12-01

    The cognitive reserve hypothesis explains the disparity between clinical and pathological phenotypes and why, in two individuals with the same extent of neuropathology, one may be demented while the other remains cognitively intact. We examined the balance between brain magnetic resonance imaging measures of the two most common pathologies associated with brain ageing, cerebrovascular disease and Alzheimer's disease, and parameters of cerebral reserve in well-characterized participants born in 1936, for whom childhood intelligence is known. Brain magnetic resonance imaging was carried out at 1.5T using fluid attenuation inversion recovery and T(1)-weighted volumetric sequences in 249 participants. Cerebrovascular disease was quantified by measuring brain white matter hyperintensities on fluid attenuation inversion recovery images using Scheltens' scale and Alzheimer's disease was measured from volumetric data using FreeSurfer to extract whole brain volume and hippocampal volumes in turn. The effect of these measures of brain burden on life-long cognitive ageing from the age of 11 to 68 years was compared with the effect of educational attainment and occupational grade using structural equation modelling. Complete brain burden and reserve data were available in 224 participants. We found that educational attainment, but not occupation, has a measurable and positive effect, with a standardized regression weight of +0.23, on late life cognitive ability in people without cognitive impairment aged 68 years, allowing for the influence of childhood intelligence and the two most common subclinical brain pathological burdens in the ageing brain. In addition, we demonstrate that the magnitude of the contribution of education is greater than the negative impact of either neuropathological burden alone, with standardized regression weights of -0.14 for white matter hyperintensities and -0.20 for hippocampal atrophy. This study illustrates how education counteracts the

  12. Locus of control, depression and quality of life among persons with sickle cell disease in Jamaica.

    Science.gov (United States)

    Gibson, Roger C; Morgan, Kai A D; Abel, Wendel D; Sewell, Clayton A; Martin, Jacqueline S; Lowe, Gillian A; Haye, Winston De La; Edwards, Christopher L; O'Garo, Keisha N; Reid, Marvin E; Asnani, Monika R

    2013-01-01

    This study explored how locus of control (LOC), depression and quality of life (QOL) interplay in patients with sickle cell disease. One hundred and forty-three sickle cell clinic patients with consecutive clinic consultations completed the Multidimensional Health Locus of Control and Short Factor 36 (SF-36) scales as well as the Beck Depression Inventory. Participants in this study had higher scores on the "chance", "other people" and "internal" domains of LOC than persons with a number of other chronic illnesses in a previous study. Hierarchical regression analyses showed that high scores on the "internal" domain of LOC were associated with better QOL and fewer symptoms of depression. Depressive symptoms were greater in persons with high scores on the "other people" LOC domain and in younger persons. These findings would suggest that it is possible that interventions which enhance internal LOC and discourage "other people" orientations might improve QOL and ameliorate depression among persons with sickle cell disease.

  13. 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.

  14. Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Elaheh Moradi

    2017-01-01

    Full Text Available Rey's Auditory Verbal Learning Test (RAVLT is a powerful neuropsychological tool for testing episodic memory, which is widely used for the cognitive assessment in dementia and pre-dementia conditions. Several studies have shown that an impairment in RAVLT scores reflect well the underlying pathology caused by Alzheimer's disease (AD, thus making RAVLT an effective early marker to detect AD in persons with memory complaints. We investigated the association between RAVLT scores (RAVLT Immediate and RAVLT Percent Forgetting and the structural brain atrophy caused by AD. The aim was to comprehensively study to what extent the RAVLT scores are predictable based on structural magnetic resonance imaging (MRI data using machine learning approaches as well as to find the most important brain regions for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed approach provided highly significant cross-validated correlation between the estimated and observed RAVLT Immediate (R = 0.50 and RAVLT Percent Forgetting (R = 0.43 in a dataset consisting of 806 AD, mild cognitive impairment (MCI or healthy subjects. In addition, the selected machine learning method provided more accurate estimates of RAVLT scores than the relevance vector regression used earlier for the estimation of RAVLT based on MRI data. The top predictors were medial temporal lobe structures and amygdala for the estimation of RAVLT Immediate and angular gyrus, hippocampus and amygdala for the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy comparable to MRI-based biomarkers.

  15. Rey's Auditory Verbal Learning Test scores can be predicted from whole brain MRI in Alzheimer's disease.

    Science.gov (United States)

    Moradi, Elaheh; Hallikainen, Ilona; Hänninen, Tuomo; Tohka, Jussi

    2017-01-01

    Rey's Auditory Verbal Learning Test (RAVLT) is a powerful neuropsychological tool for testing episodic memory, which is widely used for the cognitive assessment in dementia and pre-dementia conditions. Several studies have shown that an impairment in RAVLT scores reflect well the underlying pathology caused by Alzheimer's disease (AD), thus making RAVLT an effective early marker to detect AD in persons with memory complaints. We investigated the association between RAVLT scores (RAVLT Immediate and RAVLT Percent Forgetting) and the structural brain atrophy caused by AD. The aim was to comprehensively study to what extent the RAVLT scores are predictable based on structural magnetic resonance imaging (MRI) data using machine learning approaches as well as to find the most important brain regions for the estimation of RAVLT scores. For this, we built a predictive model to estimate RAVLT scores from gray matter density via elastic net penalized linear regression model. The proposed approach provided highly significant cross-validated correlation between the estimated and observed RAVLT Immediate (R = 0.50) and RAVLT Percent Forgetting (R = 0.43) in a dataset consisting of 806 AD, mild cognitive impairment (MCI) or healthy subjects. In addition, the selected machine learning method provided more accurate estimates of RAVLT scores than the relevance vector regression used earlier for the estimation of RAVLT based on MRI data. The top predictors were medial temporal lobe structures and amygdala for the estimation of RAVLT Immediate and angular gyrus, hippocampus and amygdala for the estimation of RAVLT Percent Forgetting. Further, the conversion of MCI subjects to AD in 3-years could be predicted based on either observed or estimated RAVLT scores with an accuracy comparable to MRI-based biomarkers.

  16. Do we need personalized recommendations for infants at risk of developing disease?

    Science.gov (United States)

    Hernell, Olle; West, Christina

    2008-01-01

    Current nutrition recommendations, directed towards populations, are based on estimated average nutrient requirements for a target population and intend to meet the needs of most individuals within that population. They also aim at preventing common diseases such as obesity, diabetes and cardiovascular disease. For infants with specific genetic polymorphisms, e.g. some inborn errors of metabolism, adherence to current recommendations will cause disease symptoms and they need personalized nutrition recommendations. Some other monogenic polymorphisms, e.g. adult hypolactasia, are common but with varying prevalence between ethnic groups and within populations. Ages at onset as well as the degree of the resulting lactose intolerance also vary, making population-based as well as personalized recommendations difficult. The tolerable intake is best set by each individual based on symptoms. For polygenetic diseases such as celiac disease, type-1 diabetes and allergic disease, current knowledge is insufficient to suggest personalized recommendations aiming at primary prevention for all high-risk infants, although it may be justified to provide such recommendations on an individual level should the parents ask for them. New technologies such as nutrigenetics and nutrigenomics are promising tools with which current nutrition recommendations can possibly be refined and the potential of individualized nutrition be explored. It seems likely that in the future it will be possible to offer more subgroups within a population personalized recommendations.

  17. Brain Dysplasia Associated with Ciliary Dysfunction in Infants with Congenital Heart Disease.

    Science.gov (United States)

    Panigrahy, Ashok; Lee, Vincent; Ceschin, Rafael; Zuccoli, Giulio; Beluk, Nancy; Khalifa, Omar; Votava-Smith, Jodie K; DeBrunner, Mark; Munoz, Ricardo; Domnina, Yuliya; Morell, Victor; Wearden, Peter; Sanchez De Toledo, Joan; Devine, William; Zahid, Maliha; Lo, Cecilia W

    2016-11-01

    To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) STUDY DESIGN: We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound scan and brain magnetic resonance imaging were obtained pre- and/or postoperatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury but was correlated with increased extraaxial cerebrospinal fluid volume (P dysplasia including the hippocampus (P dysplasia score (P dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. Adolf Hitler's Parkinson's disease and an attempt to analyse his personality structure.

    Science.gov (United States)

    Gerstenbrand, F; Karamat, E

    1999-03-01

    It has been proved that Adolf Hitler suffered from idiopathic Parkinson's disease. No indication for postencephalitic parkinsonism was found in the clinical symptoms or the case history. Professor Max de Crinis established his diagnosis of Parkinson's disease in Hitler early in 1945 and informed the SS leadership, who decided to initiate treatment with a specially prepared 'antiparkinsonian mixture' to be administered by a physician. However, Hitler never received the mixture, this implies that the SS intended to remove the severely diseased 'Leader'. Two different character traits can be analysed in Hitler's personality: on the one hand the typical premorbid personality of parkinsonian patients with uncorrectable mental rigidity, extreme inflexibility and insupportable pedantry. On the other an antisocial personality disorder with lack of ethical and social values, a deeply rooted tendency to betray others and to deceive himself and uncontrollable emotional reactions. This special combination in Hitler's personality resulted in the uncritical conviction of his mission and an enormous driving for recognition. The neuropsychiatric analysis of Hitler's personality could lead to a better explanation of the pathological traits of one of the most conspicuous historical personalities.

  19. Long-term use of psychedelic drugs is associated with differences in brain structure and personality in humans.

    Science.gov (United States)

    Bouso, José Carlos; Palhano-Fontes, Fernanda; Rodríguez-Fornells, Antoni; Ribeiro, Sidarta; Sanches, Rafael; Crippa, José Alexandre S; Hallak, Jaime E C; de Araujo, Draulio B; Riba, Jordi

    2015-04-01

    Psychedelic agents have a long history of use by humans for their capacity to induce profound modifications in perception, emotion and cognitive processes. Despite increasing knowledge of the neural mechanisms involved in the acute effects of these drugs, the impact of sustained psychedelic use on the human brain remains largely unknown. Molecular pharmacology studies have shown that psychedelic 5-hydroxytryptamine (5HT)2A agonists stimulate neurotrophic and transcription factors associated with synaptic plasticity. These data suggest that psychedelics could potentially induce structural changes in brain tissue. Here we looked for differences in cortical thickness (CT) in regular users of psychedelics. We obtained magnetic resonance imaging (MRI) images of the brains of 22 regular users of ayahuasca (a preparation whose active principle is the psychedelic 5HT2A agonist N,N-dimethyltryptamine (DMT)) and 22 controls matched for age, sex, years of education, verbal IQ and fluid IQ. Ayahuasca users showed significant CT differences in midline structures of the brain, with thinning in the posterior cingulate cortex (PCC), a key node of the default mode network. CT values in the PCC were inversely correlated with the intensity and duration of prior use of ayahuasca and with scores on self-transcendence, a personality trait measuring religiousness, transpersonal feelings and spirituality. Although direct causation cannot be established, these data suggest that regular use of psychedelic drugs could potentially lead to structural changes in brain areas supporting attentional processes, self-referential thought, and internal mentation. These changes could underlie the previously reported personality changes in long-term users and highlight the involvement of the PCC in the effects of psychedelics.

  20. The role of gap junctions in the brain in health and disease.

    Science.gov (United States)

    Dere, Ekrem; Zlomuzica, Armin

    2012-01-01

    Gap junctions connect the cytosolic compartments of adjacent cells for direct electrotonic and metabolic cell-to-cell communication. Gap junctions between glial cells or neurons are ubiquitously expressed in the brain and play a role in brain development including cell differentiation, cell migration and survival, tissue homeostasis, as well as in human diseases including hearing loss, skin disease, neuropathies, epilepsy, brain trauma, and cardiovascular disease. Furthermore, gap junctions are involved in the synchronization and rhythmic oscillation of hippocampal and neocotical neuronal ensembles which might be important for memory formation and consolidation. In this review the accumulated evidence from mouse mutant and pharmacological studies using gap junction blockers is summarized and the progress made in dissecting the physiological, pathophysiological and behavioral roles of gap junction mediated intercellular communication in the brain is discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Should Alzheimer's disease be equated with human brain ageing? A maladaptive interaction between brain evolution and senescence.

    Science.gov (United States)

    Neill, David

    2012-01-01

    In this review Alzheimer's disease is seen as a maladaptive interaction between human brain evolution and senescence. It is predicted to occur in everyone although does not necessarily lead to dementia. The pathological process is initiated in relation to a senescence mediated functional down-regulation in the posteromedial cortex (Initiation Phase). This leads to a loss of glutamatergic excitatory input to layer II entorhinal cortex neurons. A human specific maladaptive neuroplastic response is initiated in these neurons leading to neuronal dysfunction, NFT formation and death. This leads to further loss of glutamatergic excitatory input and propagation of the maladaptive response along excitatory pathways linking evolutionary progressed vulnerable neurons (Propagation Phase). Eventually neurons are affected in many brain areas resulting in dementia. Possible therapeutic approaches include enhancing glutamatergic transmission. The theory may have implications with regards to how Alzheimer's disease is classified.

  2. Pharmacogenetics and cardiovascular disease--implications for personalized medicine.

    Science.gov (United States)

    Johnson, Julie A; Cavallari, Larisa H

    2013-07-01

    The past decade has seen tremendous advances in our understanding of the genetic factors influencing response to a variety of drugs, including those targeted at treatment of cardiovascular diseases. In the case of clopidogrel, warfarin, and statins, the literature has become sufficiently strong that guidelines are now available describing the use of genetic information to guide treatment with these therapies, and some health centers are using this information in the care of their patients. There are many challenges in moving from research data to translation to practice; we discuss some of these barriers and the approaches some health systems are taking to overcome them. The body of literature that has led to the clinical implementation of CYP2C19 genotyping for clopidogrel, VKORC1, CYP2C9; and CYP4F2 for warfarin; and SLCO1B1 for statins is comprehensively described. We also provide clarity for other genes that have been extensively studied relative to these drugs, but for which the data are conflicting. Finally, we comment briefly on pharmacogenetics of other cardiovascular drugs and highlight β-blockers as the drug class with strong data that has not yet seen clinical implementation. It is anticipated that genetic information will increasingly be available on patients, and it is important to identify those examples where the evidence is sufficiently robust and predictive to use genetic information to guide clinical decisions. The review herein provides several examples of the accumulation of evidence and eventual clinical translation in cardiovascular pharmacogenetics.

  3. The Alzheimer's Disease-Related Glucose Metabolic Brain Pattern

    NARCIS (Netherlands)

    Teune, Laura K.; Strijkert, Fijanne; Renken, Remco J.; Izaks, Gerbrand J.; de Vries, Jeroen J.; Segbers, Marcel; Roerdink, Jos B. T. M.; Dierckx, Rudi A. J. O.; Leenders, Klaus L.

    2014-01-01

    Purpose: [F-18] fluorodeoxyglucose (FDG) PET imaging of the brain can be used to assist in the differential diagnosis of dementia. Group differences in glucose uptake between patients with dementia and controls are well-known. However, a multivariate analysis technique called scaled subprofile model

  4. The value of personal health records for chronic disease management: what do we know?

    Science.gov (United States)

    Tenforde, Mark; Jain, Anil; Hickner, John

    2011-05-01

    Electronic personal health records (PHRs) allow patients access to their medical records, self-management tools, and new avenues of communication with their health care providers. They will likely become a valuable component of the primary care Patient-centered Medical Home model. Primary care physicians, who manage the majority of chronic disease, will use PHRs to help patients manage their diabetes and other chronic diseases requiring continuity of care and enhanced information flow between patient and physician. In this brief report, we explore the evidence for the value of PHRs in chronic disease management. We used a comprehensive review of MEDLINE articles published in English between January 2000 and September 2010 on personal health records and related search terms. Few published articles have described PHR programs designed for use in chronic disease management or PHR adoption and attitudes in the context of chronic disease management. Only three prospective randomized trials have evaluated the benefit of PHR use in chronic disease management, all in diabetes care. These trials showed small improvements in some but not all diabetes care measures. All three trials involved additional interventions, making it difficult to determine the influence of patient PHR use in improved outcomes. The evidence remains sparse to support the value of PHR use for chronic disease management. With the current policy focus on meaningful use of electronic and personal health records, it is crucial to investigate and learn from new PHR products so as to maximize the clinical value of this tool.

  5. Modern treatment in Parkinson's disease, a personal approach.

    Science.gov (United States)

    Reichmann, Heinz

    2016-01-01

    There are many guidelines available concerning the treatment of Parkinson's disease. Most of these advocate treating young-onset patients with a dopamine agonist and older patients with levodopa. The rationale behind this recommendation has its origins in the side effects associated with each of these drug classes: whilst levodopa leads to dyskinesia, which may not be relevant for patients with a limited life-expectancy, dopamine agonists have a much longer plasma half life which probably leads to more continuous dopamine receptor stimulation and thus decreases the occurrence and severity of dyskinesia. However, the side effects associated with the use of dopamine agonists, such as sleepiness, orthostatic problems, hallucinations and impulse control disorders are a drawback. In this overview, the hypothesis will be put forward that perhaps such a strict distinction is no longer needed. A new idea may be the early combination of levodopa with a dopamine agonist which would provide good clinical efficacy and, because of the relatively low doses involved, would reduce the side effects associated with both substances. MAO-B inhibitors may be a good option for early treatment and especially for patients who experience first motor fluctuations. Similarly, and particularly if a wearing-off symptom is present, COMT inhibitors smoothen and prolong the action of levodopa. More invasive escalation therapy comes into play when patients reach the advanced stages with problems of insufficient motor control, such as bradykinesia, rigidity and resting tremor, combined with on-time dyskinesia. The use of all oral and invasive treatment has to be individualized to gain a good motor and non-motor control and especially a good quality of life.

  6. Prediction of neurodegenerative diseases from functional brain imaging data

    NARCIS (Netherlands)

    Mudali, Deborah

    2016-01-01

    Neurodegenerative diseases are a challenge, especially in the developed society where life expectancy is high. Since these diseases progress slowly, they are not easy to diagnose at an early stage. Moreover, they portray similar disease features, which makes them hard to differentiate. In this thesi

  7. A common brain network links development, aging, and vulnerability to disease.

    Science.gov (United States)

    Douaud, Gwenaëlle; Groves, Adrian R; Tamnes, Christian K; Westlye, Lars Tjelta; Duff, Eugene P; Engvig, Andreas; Walhovd, Kristine B; James, Anthony; Gass, Achim; Monsch, Andreas U; Matthews, Paul M; Fjell, Anders M; Smith, Stephen M; Johansen-Berg, Heidi

    2014-12-09

    Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8-85 y) reveals a largely--but not only--transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer's disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer's disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer's disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.

  8. Disrupted brain network topology in Parkinson's disease: a longitudinal magnetoencephalography study.

    Science.gov (United States)

    Olde Dubbelink, Kim T E; Hillebrand, Arjan; Stoffers, Diederick; Deijen, Jan Berend; Twisk, Jos W R; Stam, Cornelis J; Berendse, Henk W

    2014-01-01

    Although alterations in resting-state functional connectivity between brain regions have previously been reported in Parkinson's disease, the spatial organization of these changes remains largely unknown. Here, we longitudinally studied brain network topology in Parkinson's disease in relation to clinical measures of disease progression, using magnetoencephalography and concepts from graph theory. We characterized whole-brain functional networks by means of a standard graph analysis approach, measuring clustering coefficient and shortest path length, as well as the construction of a minimum spanning tree, a novel approach that allows a unique and unbiased characterization of brain networks. We observed that brain networks in early stage untreated patients displayed lower local clustering with preserved path length in the delta frequency band in comparison to controls. Longitudinal analysis over a 4-year period in a larger group of patients showed a progressive decrease in local clustering in multiple frequency bands together with a decrease in path length in the alpha2 frequency band. In addition, minimum spanning tree analysis revealed a decentralized and less integrated network configuration in early stage, untreated Parkinson's disease that also progressed over time. Moreover, the longitudinal changes in network topology identified with both techniques were associated with deteriorating motor function and cognitive performance. Our results indicate that impaired local efficiency and network decentralization are very early features of Parkinson's disease that continue to progress over time, together with reductions in global efficiency. As these network changes appear to reflect clinically relevant phenomena, they hold promise as markers of disease progression.

  9. Patient-derived xenografts from non-small cell lung cancer brain metastases are valuable translational platforms for the development of personalized targeted therapy.

    Science.gov (United States)

    Lee, Hye Won; Lee, Jung-Il; Lee, Se Jeong; Cho, Hyun Jung; Song, Hye Jin; Jeong, Da Eun; Seo, Yun Jee; Shin, Sang; Joung, Je-Gun; Kwon, Yong-Jun; Choi, Yoon-La; Park, Woong-Yang; Lee, Hyun Moo; Seol, Ho Jun; Shim, Young Mog; Joo, Kyeung Min; Nam, Do-Hyun

    2015-03-01

    The increasing prevalence of distant metastases from non-small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies. We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment. NSCLC brain metastases (n = 34) showed a significantly higher successful PDX establishment rate than primary specimens (n = 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions. Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments. ©2014 American Association for Cancer Research.

  10. Properties of glutamate receptors of Alzheimer's disease brain transplanted to frog oocytes

    Science.gov (United States)

    Bernareggi, Annalisa; Dueñas, Zulma; Reyes-Ruiz, Jorge Mauricio; Ruzzier, Fabio; Miledi, Ricardo

    2007-01-01

    It is known that Alzheimer's disease (AD) is a synaptic disease that involves various neurotransmitter systems, particularly those where synaptic transmission is mediated by acetylcholine or glutamate (Glu). Nevertheless, very little is known about the properties of neurotransmitter receptors of the AD human brain. We have shown previously that cell membranes, carrying neurotransmitter receptors from the human postmortem brain, can be transplanted to frog oocytes, and their receptors will still be functional. Taking advantage of this fact, we have now studied the properties of Glu receptors (GluRs) from the cerebral cortices of AD and non-AD brains and found that oocytes injected with AD membranes acquired GluRs that have essentially the same functional properties as those of oocytes injected with membranes from non-AD brains. However, the amplitudes of the currents elicited by Glu were always smaller in the oocytes injected with membranes from AD brains. Western blot analyses of the same membrane preparations used for the electrophysiological studies showed that AD membranes contained significantly fewer GluR2/3 subunit proteins. Furthermore, the corresponding mRNAs were also diminished in the AD brain. Therefore, the smaller amplitude of membrane currents elicited by Glu in oocytes injected with membranes from an AD brain is a consequence of a reduced number of GluRs in cell membranes transplanted from the AD brain. Thus, using the comparatively simple method of microtransplantation of receptors, it is now possible to determine the properties of neurotransmitter receptors of normal and diseased human brains. That knowledge may help to decipher the etiology of the diseases and also to develop new treatments. PMID:17301224

  11. MicroRNAs and their therapeutic potential for human diseases: aberrant microRNA expression in Alzheimer's disease brains.

    Science.gov (United States)

    Satoh, Jun-ichi

    2010-01-01

    MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate translational repression of multiple target mRNAs. The miRNAs in a whole cell regulate greater than 30% of all protein-coding genes. The vast majority of presently identified miRNAs are expressed in the brain in a spatially and temporally controlled manner. They play a key role in neuronal development, differentiation, and synaptic plasticity. However, at present, the pathological implications of deregulated miRNA expression in neurodegenerative diseases remain largely unknown. This review will briefly summarize recent studies that focus attention on aberrant miRNA expression in Alzheimer's disease brains.

  12. Brain region's relative proximity as marker for Alzheimer's disease based on structural MRI

    DEFF Research Database (Denmark)

    Erleben, Lene Lillemark; Sørensen, Lauge Emil Borch Laurs; Pai, Akshay Sadananda Uppinakudru;

    2014-01-01

    BACKGROUND:Alzheimer's disease (AD) is a progressive, incurable neurodegenerative disease and the most common type of dementia. It cannot be prevented, cured or drastically slowed, even though AD research has increased in the past 5-10 years. Instead of focusing on the brain volume or on the single...

  13. Computer-Aided Diagnosis Systems for Brain Diseases in Magnetic Resonance Images

    Directory of Open Access Journals (Sweden)

    Yasuo Yamashita

    2009-07-01

    Full Text Available This paper reviews the basics and recent researches of computer-aided diagnosis (CAD systems for assisting neuroradiologists in detection of brain diseases, e.g., asymptomatic unruptured aneurysms, Alzheimer's disease, vascular dementia, and multiple sclerosis (MS, in magnetic resonance (MR images. The CAD systems consist of image feature extraction based on image processing techniques and machine learning classifiers such as linear discriminant analysis, artificial neural networks, and support vector machines. We introduce useful examples of the CAD systems in the neuroradiology, and conclude with possibilities in the future of the CAD systems for brain diseases in MR images.

  14. A Personalized Approach to Parkinson’s Disease Patients Based on Founder Mutation Analysis

    Science.gov (United States)

    Giladi, Nir; Mirelman, Anat; Thaler, Avner; Orr-Urtreger, Avi

    2016-01-01

    While the phenotype of Parkinson disease (PD) is heterogeneous, treatment approaches are mostly uniform. Personalized medicine aims to treat diseases with targeted therapies based on cumulative variables, including genotype. We believe that sufficient evidence has accumulated to warrant the initiation of personalized medicine in PD based on subjects genotype and provide examples for our reasoning from observations of GBA and LRRK2 mutations carriers. While PD patients who carry the G2019S mutation in the LRRK2 gene seem to develop relatively mild disease with more frequent postural instability gait disturbance phenotype, carriers of mutations in the GBA gene tend to have an early onset, rapidly deteriorating disease, with more pronounced cognitive and autonomic impairments. These characteristics have significant implications for treatment and outcome and should be addressed from an early stage in the attempt to improve the patient’s quality of life. PMID:27242656

  15. A Personalized Approach to Parkinson's disease patients based on founder mutation analysis

    Directory of Open Access Journals (Sweden)

    Nir eGiladi

    2016-05-01

    Full Text Available While the phenotype of Parkinson disease (PD is heterogeneous, treatment approaches are mostly uniform. Personalized medicine aims to treat diseases with targeted therapies based on cumulative variables including genotype. We believe that sufficient evidence has accumulated to warrant the initiation of personalized medicine in PD based on subjects genotype and provide examples for our reasoning from observations of GBA and LRRK2 mutations carriers. While PD patients who carry the G2019S mutation in the LRRK2 gene seem to develop relatively mild disease with more frequent postural instability gait disturbance phenotype, carriers of mutations in the GBA gene tend to have an early onset, rapidly deteriorating disease, with more pronounced cognitive and autonomic impairments. These characteristics have significant implications for treatment and outcome and should be addressed from an early stage in the attempt to improve the patient's quality of life.

  16. Effect of subthalamic deep brain stimulation on pain in Parkinson's disease.

    Science.gov (United States)

    Dellapina, Estelle; Ory-Magne, Fabienne; Regragui, Wafa; Thalamas, Claire; Lazorthes, Yves; Rascol, Olivier; Payoux, Pierre; Brefel-Courbon, Christine

    2012-11-01

    Painful sensations are common in Parkinson's disease. In many patients, such sensations correspond to neuropathic pain and could be related to central alterations of pain processing. Subthalamic nuclei deep brain stimulation improves motor function in Parkinson's disease. Several structures of the basal ganglia are involved in nociceptive function, and deep brain stimulation could thus also modify pain perception in Parkinson's disease. To test this hypothesis, we compared subjective heat pain thresholds, in deep brain stimulation OFF and ON conditions in 2 groups of Parkinson's disease patients with or without neuropathic pain. We also compared pain-induced cerebral activations during experimental nociceptive stimulations using H(2)(15)O positron emission tomography in both deep brain stimulation OFF and ON conditions. Correlation analyses were performed between clinical and neuroimaging results. Deep brain stimulation significantly increased subjective heat pain threshold (from 40.3 ± 4.2 to 41.6 ± 4.3, P=.03) and reduced pain-induced cerebral activity in the somatosensory cortex (BA 40) in patients with pain, whereas it had no effect in pain-free patients. There was a significant negative correlation in the deep brain stimulation OFF condition between pain threshold and pain-induced activity in the insula of patients who were pain free but not in those who had pain. There was a significant positive correlation between deep brain stimulation-induced changes in pain threshold and in pain-induced cerebral activations in the primary somatosensory cortex and insula of painful patients only. These results suggest that subthalamic nuclei deep brain stimulation raised pain thresholds in Parkinson's disease patients with pain and restored better functioning of the lateral discriminative pain system.

  17. Graph theoretical analysis and application of fMRI-based brain network in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    LIU Xue-na

    2012-08-01

    Full Text Available Alzheimer's disease (AD, a progressive neurodegenerative disease, is clinically characterized by impaired memory and many other cognitive functions. However, the pathophysiological mechanisms underlying the disease are not thoroughly understood. In recent years, using functional magnetic resonance imaging (fMRI as well as advanced graph theory based network analysis approach, several studies of patients with AD suggested abnormal topological organization in both global and regional properties of functional brain networks, specifically, as demonstrated by a loss of small-world network characteristics. These studies provide novel insights into the pathophysiological mechanisms of AD and could be helpful in developing imaging biomarkers for disease diagnosis. In this paper we introduce the essential concepts of complex brain networks theory, and review recent advances of the study on human functional brain networks in AD, especially focusing on the graph theoretical analysis of small-world network based on fMRI. We also propound the existent problems and research orientation.

  18. PIXE analysis of low concentration aluminum in brain tissues of an Alzheimer's disease patient

    Science.gov (United States)

    Ishihara, R.; Hanaichi, T.; Takeuchi, T.; Ektessabi, A. M.

    1999-06-01

    An excess accumulation and presence of metal ions may significantly alter a brain cell's normal functions. There have been increasing efforts in recent years to measure and quantify the density and distribution of excessive accumulations of constituent elements (such as Fe, Zn, Cu, and Ca) in the brain, as well as the presence and distribution of contaminating elements (such as Al). This is particularly important in cases of neuropathological disorders such as Alzheimer's disease, Parkinson's disease and ALS. The aim of this paper was to measure the Al present in the temporal cortex of the brain of an Alzheimer's disease patient. The specimens were taken from an unfixed autopsy brain which has been preserved for a period of 4 years in the deep freezer at -80 °C. Proton Induced X-ray Emission Spectroscopy was used for the measurement of Al concentration in this brain tissue. A tandem accelerator with 2 MeV of energy was also used. In order to increase the sensitivity of the signals in the low energy region of the spectra, the absorbers were removed. The results show that the peak height depends on the measurement site. However, in certain cases an extremely high concentration of Al was observed in the PIXE spectra, with an intensity higher than those in the other major elements of the brain's matrix element. Samples from tissues affected by the same disease were analyzed using the EDX analyzer. The results are quantitatively in very good agreement with those of the PIXE analysis.

  19. Pathological Gambling in Parkinson's disease patients: Dopaminergic medication or personality traits fault?

    Science.gov (United States)

    Brusa, L; Pavino, V; Massimetti, M C; Ceravolo, R; Stefani, S; Stanzione, P

    2016-07-15

    Impulse control disorders (ICDs) are clinically relevant in Parkinson disease (PD) patients, with an established association with PD medication. Aim of our study was to study whether the increased frequency of pathological gambling (PG), reported in subgroups of PD patients, is related to specific personality tracts additional to dopaminergic medications. Thirty-seven PD patients with a personal history of PG where enrolled. Twenty one PD patients, matched for disease and dopaminergic therapy, never experiencing PG, were enrolled as controls. All subjects were tested with the Minnesota Multiphasic Inventory Personality scales (MMPI-2). Our data showed that PD group with PG exhibited significantly higher mean values of the three validity scales in comparison to the non-PG-PD group, demonstrating an higher tendency to lie. Content scales showed a significant increase of cynicism and bizarre ideation scales score in the PG-PD group, not exhibiting pathological values at the validity scales, (p: 0.02) in comparison to non-PG PD patients. According to our results, PG seems to be associated with precise personality tracts. Personality profiles of cluster A personality disturbances - Axys 2 according with DSM-5 TR (paranoid type) at MMPI-2 might be a warning index helpful in selecting dopaminergic treatment, to avoid subsequent ICDs appearance.

  20. Boosting Brain Connectome Classification Accuracy in Alzheimer’s disease using Higher-Order Singular Value Decomposition

    Directory of Open Access Journals (Sweden)

    Liang eZhan

    2015-07-01

    Full Text Available Alzheimer's disease (AD is a progressive brain disease. Accurate detection of AD and its prodromal stage, mild cognitive impairment (MCI, are crucial. There is also a growing interest in identifying brain imaging biomarkers that help to automatically differentiate stages of Alzheimer’s disease. Here, we focused on anatomical brain networks computed from diffusion MRI and proposed a new feature extraction and classification framework based on higher order singular value decomposition and sparse logistic regression. In tests on publicly available data from the Alzheimer’s Disease Neuroimaging Initiative, our proposed framework showed promise in detecting brain network differences that help in classifying different stages of Alzheimer’s disease.

  1. Preventing zoonotic diseases in immunocompromised persons: the role of physicians and veterinarians.

    OpenAIRE

    2000-01-01

    We surveyed physicians and veterinarians in Wisconsin about the risk for and prevention of zoonotic diseases in immunocompromised persons. We found that physicians and veterinarians hold significantly different views about the risks posed by certain infectious agents and species of animals and communicate very little about zoonotic issues; moreover, physicians believe that veterinarians should be involved in many aspects of zoonotic disease prevention, including patient education.

  2. Personality, lifestyle, and risk of cardiovascular disease and cancer: follow-up of population based cohort.

    Science.gov (United States)

    Stürmer, Til; Hasselbach, Petra; Amelang, Manfred

    2006-06-10

    To study the relation between measures of personality and risk of cardiovascular disease and cancer in a large cohort. Follow-up of population based cohort. Heidelberg, Germany. 5114 women and men aged 40-65 in 1992-5. Psychological traits assessed by several standardised personality questionnaires in 1992-5, related to cause of death (to 2002-3) or reported incidence of cardiovascular diseases and cancer (validated by treating doctors). Relative risks (and 95% confidence intervals) for combined morbidity and mortality according to five important personality traits were estimated using multivariable Cox proportional hazards models. During median follow-up of 8.5 years, 257 participants died and 72 were diagnosed with a heart attack, 62 with stroke, and 240 with cancer (morbidity and mortality combined). A high internal locus of control over disease was associated with a decreased risk of myocardial infarction (adjusted relative risk for an increase of 1 SD = 0.75; 95% confidence interval 0.58 to 0.96). An increase of 1 SD in time urgency was associated with a decreased risk of cancer (adjusted relative risk 0.83; 0.73 to 0.95). Other major personality traits--anger control, psychoticism, and symptoms of depression--were not consistently associated with myocardial infarction, stroke, or cancer. Internal locus of control over disease and time urgency seem to be associated with reduced risk for common chronic diseases, probably by affecting unmeasured health related behaviour. The other personality traits assessed had no major impact on cardiovascular disease and cancer.

  3. Oxytocin receptor polymorphism and childhood social experiences shape adult personality, brain structure and neural correlates of mentalizing.

    Science.gov (United States)

    Schneider-Hassloff, H; Straube, B; Jansen, A; Nuscheler, B; Wemken, G; Witt, S H; Rietschel, M; Kircher, T

    2016-07-01

    The oxytocin system is involved in human social behavior and social cognition such as attachment, emotion recognition and mentalizing (i.e. the ability to represent mental states of oneself and others). It is shaped by social experiences in early life, especially by parent-infant interactions. The single nucleotid polymorphism rs53576 in the oxytocin receptor (OXTR) gene has been linked to social behavioral phenotypes. In 195 adult healthy subjects we investigated the interaction of OXTR rs53576 and childhood attachment security (CAS) on the personality traits "adult attachment style" and "alexithymia" (i.e. emotional self-awareness), on brain structure (voxel-based morphometry) and neural activation (fMRI) during an interactive mentalizing paradigm (prisoner's dilemma game; subgroup: n=163). We found that in GG-homozygotes, but not in A-allele carriers, insecure childhood attachment is - in adulthood - associated with a) higher attachment-related anxiety and alexithymia, b) higher brain gray matter volume of left amygdala and lower volumes in right superior parietal lobule (SPL), left temporal pole (TP), and bilateral frontal regions, and c) higher mentalizing-related neural activity in bilateral TP and precunei, and right middle and superior frontal gyri. Interaction effects of genotype and CAS on brain volume and/or function were associated with individual differences in alexithymia and attachment-related anxiety. Interactive effects were in part sexually dimorphic. The interaction of OXTR genotype and CAS modulates adult personality as well as brain structure and function of areas implicated in salience processing and mentalizing. Rs53576 GG-homozygotes are partially more susceptible to childhood attachment experiences than A-allele carriers. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Long-chain polyunsaturated fatty acid (LCPUFA) requirement for brain development: A personal view

    OpenAIRE

    2016-01-01

    Dietary docosahexaenoic acid (DHA) is known to accumulate in the infant brain and clinical trials have established that dietary DHA is associated with improvements in visual and neural function in preterm infants. Thus, an elevated DHA status is considered to be important throughout infancy for brain development. While DHA can be added directly to infant foods, there have been important studies to show that infants can partially meet ...

  5. BrainAGE in Mild Cognitive Impaired Patients: Predicting the Conversion to Alzheimer's Disease.

    Directory of Open Access Journals (Sweden)

    Christian Gaser

    Full Text Available Alzheimer's disease (AD, the most common form of dementia, shares many aspects of abnormal brain aging. We present a novel magnetic resonance imaging (MRI-based biomarker that predicts the individual progression of mild cognitive impairment (MCI to AD on the basis of pathological brain aging patterns. By employing kernel regression methods, the expression of normal brain-aging patterns forms the basis to estimate the brain age of a given new subject. If the estimated age is higher than the chronological age, a positive brain age gap estimation (BrainAGE score indicates accelerated atrophy and is considered a risk factor for conversion to AD. Here, the BrainAGE framework was applied to predict the individual brain ages of 195 subjects with MCI at baseline, of which a total of 133 developed AD during 36 months of follow-up (corresponding to a pre-test probability of 68%. The ability of the BrainAGE framework to correctly identify MCI-converters was compared with the performance of commonly used cognitive scales, hippocampus volume, and state-of-the-art biomarkers derived from cerebrospinal fluid (CSF. With accuracy rates of up to 81%, BrainAGE outperformed all cognitive scales and CSF biomarkers in predicting conversion of MCI to AD within 3 years of follow-up. Each additional year in the BrainAGE score was associated with a 10% greater risk of developing AD (hazard rate: 1.10 [CI: 1.07-1.13]. Furthermore, the post-test probability was increased to 90% when using baseline BrainAGE scores to predict conversion to AD. The presented framework allows an accurate prediction even with multicenter data. Its fast and fully automated nature facilitates the integration into the clinical workflow. It can be exploited as a tool for screening as well as for monitoring treatment options.

  6. Interaction between personality traits and cerebrospinal fluid biomarkers of Alzheimer's disease pathology modulates cognitive performance.

    Science.gov (United States)

    Tautvydaitė, Domilė; Kukreja, Deepti; Antonietti, Jean-Philippe; Henry, Hugues; von Gunten, Armin; Popp, Julius

    2017-02-02

    During adulthood, personality characteristics may contribute to the individual capacity to compensate the impact of developing cerebral Alzheimer's disease (AD) pathology on cognitive impairment in later life. In this study we aimed to investigate whether and how premorbid personality traits interact with cerebrospinal fluid (CSF) markers of AD pathology to predict cognitive performance in subjects with mild cognitive impairment or mild AD dementia and in participants with normal cognition. One hundred and ten subjects, of whom 66 were patients with mild cognitive impairment or mild AD dementia and 44 were healthy controls, had a comprehensive medical and neuropsychological examination as well as lumbar puncture to measure CSF biomarkers of AD pathology (amyloid beta1-42, phosphorylated tau and total-tau). Participants' proxies completed the Revised NEO Personality Inventory, Form R to retrospectively assess subjects' premorbid personality. In hierarchical multivariate regression analyses, including age, gender, education, APOEε4 status and cognitive level, premorbid neuroticism, conscientiousness and agreeableness modulated the effect of CSF biomarkers on cognitive performance. Low premorbid openness independently predicted lower levels of cognitive functioning after controlling for biomarker concentrations. Our findings suggest that specific premorbid personality traits are associated with cerebral AD pathology and modulate its impact on cognitive performance. Considering personality characteristics may help to appraise a person's cognitive reserve and the risk of cognitive decline in later life.

  7. Brain-gut-microbe communication in health and disease.

    Science.gov (United States)

    Grenham, Sue; Clarke, Gerard; Cryan, John F; Dinan, Timothy G

    2011-01-01

    Bidirectional signalling between the gastrointestinal tract and the brain is regulated at neural, hormonal, and immunological levels. This construct is known as the brain-gut axis and is vital for maintaining homeostasis. Bacterial colonization of the intestine plays a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS) signaling. Recent research advances have seen a tremendous improvement in our understanding of the scale, diversity, and importance of the gut microbiome. This has been reflected in the form of a revised nomenclature to the more inclusive brain-gut-enteric microbiota axis and a sustained research effort to establish how communication along this axis contributes to both normal and pathological conditions. In this review, we will briefly discuss the critical components of this axis and the methodological challenges that have been presented in attempts to define what constitutes a normal microbiota and chart its temporal development. Emphasis is placed on the new research narrative that confirms the critical influence of the microbiota on mood and behavior. Mechanistic insights are provided with examples of both neural and humoral routes through which these effects can be mediated. The evidence supporting a role for the enteric flora in brain-gut axis disorders is explored with the spotlight on the clinical relevance for irritable bowel syndrome, a stress-related functional gastrointestinal disorder. We also critically evaluate the therapeutic opportunities arising from this research and consider in particular whether targeting the microbiome might represent a valid strategy for the management of CNS disorders and ponder the pitfalls inherent in such an approach. Despite the considerable challenges that lie ahead, this is an exciting area of research and one that is destined to remain the center of focus for some time to come.

  8. Brain-Gut-Microbe Communication in Health and Disease

    Directory of Open Access Journals (Sweden)

    Sue eGrenham

    2011-12-01

    Full Text Available Bidirectional signalling between the gastrointestinal tract and the brain is regulated at neural, hormonal and immunological levels. This construct is known as the brain-gut axis and is vital for maintaining homeostasis. Bacterial colonisation of the intestine plays a major role in the post-natal development and maturation of the immune and endocrine systems. These processes are key factors underpinning central nervous system (CNS signalling. Recent research advances have seen a tremendous improvement in our understanding of the scale, diversity and importance of the gut microbiome. This has been reflected in the form of a revised nomenclature to the more inclusive brain-gut-enteric microbiota axis and a sustained research effort to establish how communication along this axis contributes to both normal and pathological conditions. In this review, we will briefly discuss the critical components of this axis and the methodological challenges that have been presented in attempts to define what constitutes a normal microbiota and chart its temporal development. Emphasis is placed on the new research narrative that confirms the critical influence of the microbiota on mood and behaviour. Mechanistic insights are provided with examples of both neural and humoral routes through which these effects can be mediated. The evidence supporting a role for the enteric flora in brain-gut axis disorders is explored with the spotlight on the clinical relevance for irritable bowel syndrome (IBS, a stress-related functional gastrointestinal disorder. We also critically evaluate the therapeutic opportunities arising from this research and consider in particular whether targeting the microbiome might represent a valid strategy for the management of CNS disorders and ponder the pitfalls inherent in such an approach. Despite the considerable challenges that lie ahead, this is an exciting area of research and one that is destined to remain the centre of focus for some

  9. Cross-sex hormone treatment in male-to-female transsexual persons reduces serum brain-derived neurotrophic factor (BDNF).

    Science.gov (United States)

    Fuss, Johannes; Hellweg, Rainer; Van Caenegem, Eva; Briken, Peer; Stalla, Günter K; T'Sjoen, Guy; Auer, Matthias K

    2015-01-01

    Serum levels of brain-derived neurotrophic factor (BDNF) are reduced in male-to-female transsexual persons (MtF) compared to male controls. It was hypothesized before that this might reflect either an involvement of BDNF in a biomechanism of transsexualism or to be the result of persistent social stress due to the condition. Here, we demonstrate that 12 month of cross-sex hormone treatment reduces serum BDNF levels in male-to-female transsexual persons independent of anthropometric measures. Participants were acquired through the European Network for the Investigation of Gender Incongruence (ENIGI). Reduced serum BDNF in MtF thus seems to be a result of hormonal treatment rather than a consequence or risk factor of transsexualism.

  10. The effect of a home physiotherapy program for persons with Parkinson's disease

    NARCIS (Netherlands)

    Nieuwboer, A; De Weerdt, W; Dom, R; Truyen, M; Janssens, L; Kamsma, Y

    2001-01-01

    The purpose of this study was to evaluate the effect of a home physiotherapy program for persons with Parkinson's disease. Thirty-three patients took part in the study using a within-subject controlled design. Functional activities including walking and carrying out transfers were measured at home a

  11. Validating the Type D personality construct in Chinese patients with coronary heart disease

    DEFF Research Database (Denmark)

    Yu, Doris S F; Thompson, David R; Yu, Cheuk Man

    2010-01-01

    Type D personality predicts poor prognosis in coronary heart disease (CHD) but little is known about Type D in non-Western cultures. We examined the (a) validity of the Type D construct and its assessment with the DS14 scale in the Chinese culture, (b) prevalence of Type D, and (c) gender vs. Type...

  12. How Persons with a Neuromuscular Disease Perceive Employment Participation : A Qualitative Study

    NARCIS (Netherlands)

    Minis, Marie-Antoinette; Satink, Ton; Kinébanian, Astrid; Engels, Josephine; Heerkens, Yvonne; Engelen, Baziel van

    2014-01-01

    Introduction A qualitative study was carried out to understand how people with a slow progressive adult type neuromuscular disease (NMD) perceive employment participation. Methods 16 paid employed persons with NMD were interviewed in open, in-depth interviews. Data were analyzed using the constant c

  13. The Experience of Care-Giving for a Person with Parkinson's Disease

    Science.gov (United States)

    Bogard, Connie Lynn

    2010-01-01

    As the population continues to become more aged and at risk for chronic illness, there will be a growing need for caregivers. Caregivers to persons with Parkinson's disease (PD) face the challenge of providing care over many years due to the chronic progressive nature of this neurological disorder. The purpose of this study was to understand and…

  14. The Impact of Personalized Risk Feedback on Mexican Americans' Perceived Risk for Heart Disease and Diabetes

    Science.gov (United States)

    Hovick, Shelly R.; Wilkinson, Anna V.; Ashida, Sato; de Heer, Hendrik D.; Koehly, Laura M.

    2014-01-01

    Little is known about the effect of personalized risk information on risk perceptions over time, particularly among ethnically diverse subpopulations. The present study examines Mexican American's (MAs) risk perceptions for heart disease and diabetes at baseline and following receipt of risk feedback based on family health history. Participants…

  15. Somatic chronic diseases and 6-year change in cognitive functioning among older persons

    NARCIS (Netherlands)

    Comijs, H.; Kriegsman, D.M.W.; Dik, M.G.; Deeg, D.J.H.; Jonker, C.; Stalman, W.A.B.

    2009-01-01

    The influence of seven highly prevalent somatic chronic diseases on changes in cognitive functioning is investigated in older persons in a prospective design covering a 6-year follow-up period. The data were collected as part of the Longitudinal Aging Study Amsterdam (LASA). The associations between

  16. End-stage liver disease in persons with hemophilia and transfusion-associated infections

    NARCIS (Netherlands)

    Goedert, JJ; Eyster, ME; Lederman, MM; Mandalaki, T; de Moerloose, P; White, GC; Angiolillo, AL; Luban, NLC; Sherman, KE; Manco-Johnson, M; Preiss, L; Leissinger, C; Kessler, CM; Cohen, AR; DiMichele, D; Hilgartner, MW; Aledort, LM; Kroner, BL; Rosenberg, PS; Hatzakis, A

    2002-01-01

    Many persons with hemophilia were infected with hepatitis C and B viruses (HCV, HBV) and HIV, but the consequences of these transfusion-acquired infections are poorly defined. We estimated the risk of HCV-related end-stage liver disease (ESLD) and the associations of age, HBV, and HIV with that risk

  17. Clinical, psychophysiological and psychological aspects of risk factors of periodontal disease development in clinically healthy persons

    Directory of Open Access Journals (Sweden)

    I.N. Nikulina

    2009-12-01

    Full Text Available The research goal is to determine risk factors of periodontal disease development, psychophysiological personal types and their interrelations in clinically healthy persons. 47 first-year cadets of St.-Petersburg Military School of radio electronics have been examined. This group of respondents has been chosen by presence of such social stressor as change of place of living (97,9% cadets have arrived in St.-Petersburg from other cities and republics of the Russian Federation and strict disciplinary conditions. The research has revealed a low level of oral hygiene, cases of mild gingivitis in most respondents. The general mental state of group under study is characterized by raised level of personal anxiety and low indices of reactive anxiety. The examined group has demonstrated anxiety, tension, indecision and lowered stress stability. Clinically healthy persons are more liable to develop inflammatory and inflammatory-destructive periodontal diseases. It was possible to determine psychophysiological features correlated with physiological parameters of risk degree of periodontal diseases. It may have a great significance in defining of periodontal disease etiology and pathogenesis

  18. The effect of a home physiotherapy program for persons with Parkinson's disease

    NARCIS (Netherlands)

    Nieuwboer, A; De Weerdt, W; Dom, R; Truyen, M; Janssens, L; Kamsma, Y

    2001-01-01

    The purpose of this study was to evaluate the effect of a home physiotherapy program for persons with Parkinson's disease. Thirty-three patients took part in the study using a within-subject controlled design. Functional activities including walking and carrying out transfers were measured at home

  19. Aluminium in brain tissue in familial Alzheimer’s disease

    OpenAIRE

    Mirza, A; King, A.; Troakes, C.; Exley, C

    2016-01-01

    The genetic predispositions which describe a diagnosis of familial Alzheimer’s disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer’s disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to aluminium and a...

  20. Aluminium in brain tissue in familial Alzheimer’s disease

    OpenAIRE

    2016-01-01

    Abstract The genetic predispositions which describe a diagnosis of familial Alzheimer’s disease can be considered as cornerstones of the amyloid cascade hypothesis. Essentially they place the expression and metabolism of the amyloid precursor protein as the main tenet of disease aetiology. However, we do not know the cause of Alzheimer’s disease and environmental factors may yet be shown to contribute towards its onset and progression. One such environmental factor is human exposure to alumin...

  1. Positron Emission Tomography and Magnetic Resonance Imaging of the Brain in Fabry Disease

    DEFF Research Database (Denmark)

    Korsholm, Kirsten; Feldt-Rasmussen, Ulla; Granqvist, Henrik;

    2015-01-01

    risk of cerebrovascular disease at a young age in addition to heart and kidney failure. OBJECTIVE: The objective of this study was to assess brain function and structure in the Danish cohort of patients with Fabry disease in a prospective way using 18-fluoro-deoxyglucose (F-18 FDG) positron emission....... CONCLUSION: Our data indicated that, in patients with Fabry disease, MRI is the preferable clinical modality--if applicable--when monitoring cerebral status, as no additional major brain-pathology was detected with FDG-PET.......BACKGROUND: Fabry disease is a rare metabolic glycosphingolipid storage disease caused by deficiency of the lysosomal enzyme α-galactosidase A--leading to cellular accumulation of globotriasylceramide in different organs, vessels, tissues, and nerves. The disease is associated with an increased...

  2. Periodontal disease associates with higher brain amyloid load in normal elderly.

    Science.gov (United States)

    Kamer, Angela R; Pirraglia, Elizabeth; Tsui, Wai; Rusinek, Henry; Vallabhajosula, Shankar; Mosconi, Lisa; Yi, Li; McHugh, Pauline; Craig, Ronald G; Svetcov, Spencer; Linker, Ross; Shi, Chen; Glodzik, Lidia; Williams, Schantel; Corby, Patricia; Saxena, Deepak; de Leon, Mony J

    2015-02-01

    The accumulation of amyloid-β (Aβ) plaques is a central feature of Alzheimer's disease (AD). First reported in animal models, it remains uncertain if peripheral inflammatory and/or infectious conditions in humans can promote Aβ brain accumulation. Periodontal disease, a common chronic infection, has been previously reported to be associated with AD. Thirty-eight cognitively normal, healthy, and community-residing elderly (mean age, 61 and 68% female) were examined in an Alzheimer's Disease Research Center and a University-Based Dental School. Linear regression models (adjusted for age, apolipoprotein E, and smoking) were used to test the hypothesis that periodontal disease assessed by clinical attachment loss was associated with brain Aβ load using (11)C-Pittsburgh compound B (PIB) positron emission tomography imaging. After adjusting for confounders, clinical attachment loss (≥3 mm), representing a history of periodontal inflammatory/infectious burden, was associated with increased PIB uptake in Aβ vulnerable brain regions (p = 0.002). We show for the first time in humans an association between periodontal disease and brain Aβ load. These data are consistent with the previous animal studies showing that peripheral inflammation/infections are sufficient to produce brain Aβ accumulations.

  3. Microprobe PIXE analysis and EDX analysis on the brain of patients with Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Yumoto, S. [Tokyo Univ. (Japan). Faculty of Medicine; Horino, Y.; Mokuno, Y.; Fujii, K.; Kakimi, S.; Mizutani, T.; Matsushima, H.; Ishikawa, A.

    1996-12-31

    To investigate the cause of Alzheimer`s disease (senile dementia of Alzheimer`s disease type), we examined aluminium (Al) in the brain (hippocampus) of patients with Alzheimer`s disease using heavy ion (5 MeV Si{sup 3+}) microprobe particle-induced X-ray emission (PIXE) analysis. Heavy ion microprobes (3 MeV Si{sup 2+}) have several times higher sensitivity for Al detection than 2 MeV proton microprobes. We also examined Al in the brain of these patients by energy dispersive X-ray spectroscopy (EDX). (1) Al was detected in the cell nuclei isolated from the brain of patients with Alzheimer`s disease using 5 MeV Si{sup 3+} microprobe PIXE analysis, and EDX analysis. (2) EDX analysis demonstrated high levels of Al in the nucleolus of nerve cells in frozen sections prepared from the brain of these patients. Our results support the theory that Alzheimer`s disease is caused by accumulation of Al in the nuclei of brain cells. (author)

  4. Disruption of the blood-brain barrier in Parkinson's disease: curse or route to a cure?

    Science.gov (United States)

    Lee, Heyne; Pienaar, Ilse S

    2014-01-01

    The vertebrate blood-brain barrier (BBB) is critical for ensuring the maintenance of brain homeostasis, whilst protecting the brain against toxic insults. Various pathological events disrupt BBB integrity, holding several important clinical implications. In instances where the normal mechanisms controlling passage of substances into the brain are compromised, these could sensitize or even worsen endogenous pathological conditions. Recognition has grown recently that patients diagnosed with Parkinson's disease (PD) present with concurrent medical problems, including cerebrovascular lesions. However, cerebrovascular disturbances may also result from PD-related disease processes; the pathological mechanisms which could entail interaction between environment-derived and genetic factors. The current review addresses the accumulation of studies aimed at better understanding the series of processes affecting the neurovascular unit in human Parkinsonism, due in part to the BBB presenting as a formidable opponent in the effective delivery of therapeutics that have shown promise as therapeutic strategies for treating aspects of PD when tested in vitro.

  5. [Shh signal and its functional roles in normal and diseased brain].

    Science.gov (United States)

    Ruat, Martial; Angot, Elodie; Traiffort, Elisabeth

    2011-11-01

    The identification of a Sonic Hedgehog (Shh) signaling pathway in the adult vertebrate central nervous system has paved the way to the characterization of the functional roles of Shh signals in normal and diseased brain. This morphogen is proposed to play a key role in the establishment and maintenance of adult neurogenic niches and to modulate the proliferation of neuronal or glial precursors. Consistent with its role during embryogenesis, alteration of Shh signaling is associated with tumorigenesis while its recruitment in damaged neural tissue might be part of the regenerating process. We will discuss the most recent data of the Hedgehog pathway in the adult brain and its relevance as a novel therapeutic approach for brain diseases including brain tumors.

  6. Toward a brain-computer interface for Alzheimer's disease patients by combining classical conditioning and brain state classification.

    Science.gov (United States)

    Liberati, Giulia; Dalboni da Rocha, Josué Luiz; van der Heiden, Linda; Raffone, Antonino; Birbaumer, Niels; Olivetti Belardinelli, Marta; Sitaram, Ranganatha

    2012-01-01

    Brain-computer interfaces (BCIs) provide alternative methods for communicating and acting on the world, since messages or commands are conveyed from the brain to an external device without using the normal output pathways of peripheral nerves and muscles. Alzheimer's disease (AD) patients in the most advanced stages, who have lost the ability to communicate verbally, could benefit from a BCI that may allow them to convey basic thoughts (e.g., "yes" and "no") and emotions. There is currently no report of such research, mostly because the cognitive deficits in AD patients pose serious limitations to the use of traditional BCIs, which are normally based on instrumental learning and require users to self-regulate their brain activation. Recent studies suggest that not only self-regulated brain signals, but also involuntary signals, for instance related to emotional states, may provide useful information about the user, opening up the path for so-called "affective BCIs". These interfaces do not necessarily require users to actively perform a cognitive task, and may therefore be used with patients who are cognitively challenged. In the present hypothesis paper, we propose a paradigm shift from instrumental learning to classical conditioning, with the aim of discriminating "yes" and "no" thoughts after associating them to positive and negative emotional stimuli respectively. This would represent a first step in the development of a BCI that could be used by AD patients, lending a new direction not only for communication, but also for rehabilitation and diagnosis.

  7. Copper pathology in vulnerable brain regions in Parkinson's disease. : Copper pathology in PD

    OpenAIRE

    Davies, Katherine,; Bohic, Sylvain; Carmona, Asunción; Ortega, Richard; Cottam, Veronica; Hare, Dominic; Finberg, John,; Reyes, Stefanie; Halliday, Glenda; Mercer, Julian; Double, Kay,

    2014-01-01

    International audience; Synchrotron-based x-ray fluorescence microscopy, immunofluorescence, and Western blotting were used to investigate changes in copper (Cu) and Cu-associated pathways in the vulnerable substantia nigra (SN) and locus coeruleus (LC) and in nondegenerating brain regions in cases of Parkinson's disease (PD) and appropriate healthy and disease controls. In PD and incidental Lewy body disease, levels of Cu and Cu transporter protein 1, were significantly reduced in surviving ...

  8. Synchrotron FTIR microspectroscopy of Alzheimer's diseased brain tissue at the SRC beamline

    Science.gov (United States)

    Bromberg, Pam S.; Gough, Kathleen M.; Ogg, Mandy; Del Bigio, M. R.; Julian, Robert

    1999-10-01

    Alzheimer's Disease is a neurodegenerative disorder marked by progressive cognitive decline. AD presents with many of the same clinical symptoms as senile dementia, but the diagnosis of AD must be confirmed by post-mortem examination of the morphological and histopathological features of the brain. The two classical lesions found in the cortical and hippocampal regions of the brain are the (beta) -amyloid- bearing neuritic plaques and the intraneuronal neurofibrillary tangles.

  9. Alpha-synuclein in blood and brain from familial Parkinson disease with SNCA locus triplication.

    Science.gov (United States)

    Miller, D W; Hague, S M; Clarimon, J; Baptista, M; Gwinn-Hardy, K; Cookson, M R; Singleton, A B

    2004-05-25

    The authors recently demonstrated that genetic triplication of the SNCA locus causes Parkinson disease. Here it is shown that SNCA triplication results in a doubling in the amount of alpha-synuclein protein in blood. Examination of brain tissue showed a doubling in the level of SNCA message. However, at the protein level in brain, there was a greater effect on deposition of aggregated forms into insoluble fractions than on net expression of soluble alpha-synuclein.

  10. Personality and neurochemicals in the human brain: A preliminary study using 1H MRS

    Institute of Scientific and Technical Information of China (English)

    XU Shiyong; PENG Danling; JIN Zhen; LIU Hongyan; YANG Jie

    2005-01-01

    To investigate the neuro-biological bases of introversion-extraversion personality traits, the concentra- tion of four neurochemicals (Cho, mI, α-Glx and NAA) in anterior cigulate gyrus between normal extroverts and introverts were examined using non-invasive 1H MRS technique. Our study revealed that introverts have significantly higher level of α-Glx, Cho and mI in the anterior cingulate gyrus than extroverts. This result provides new evidence that the anterior cingulate gyrus is related to personality traits partly in support of Eysenck's supposition that introverts have higher arousal level than extroverts. Moreover, this result offers neurochemical data for psychobiological theories of personality.

  11. Brain expression genome-wide association study (eGWAS identifies human disease-associated variants.

    Directory of Open Access Journals (Sweden)

    Fanggeng Zou

    Full Text Available Genetic variants that modify brain gene expression may also influence risk for human diseases. We measured expression levels of 24,526 transcripts in brain samples from the cerebellum and temporal cortex of autopsied subjects with Alzheimer's disease (AD, cerebellar n=197, temporal cortex n=202 and with other brain pathologies (non-AD, cerebellar n=177, temporal cortex n=197. We conducted an expression genome-wide association study (eGWAS using 213,528 cisSNPs within ± 100 kb of the tested transcripts. We identified 2,980 cerebellar cisSNP/transcript level associations (2,596 unique cisSNPs significant in both ADs and non-ADs (q<0.05, p=7.70 × 10(-5-1.67 × 10(-82. Of these, 2,089 were also significant in the temporal cortex (p=1.85 × 10(-5-1.70 × 10(-141. The top cerebellar cisSNPs had 2.4-fold enrichment for human disease-associated variants (p<10(-6. We identified novel cisSNP/transcript associations for human disease-associated variants, including progressive supranuclear palsy SLCO1A2/rs11568563, Parkinson's disease (PD MMRN1/rs6532197, Paget's disease OPTN/rs1561570; and we confirmed others, including PD MAPT/rs242557, systemic lupus erythematosus and ulcerative colitis IRF5/rs4728142, and type 1 diabetes mellitus RPS26/rs1701704. In our eGWAS, there was 2.9-3.3 fold enrichment (p<10(-6 of significant cisSNPs with suggestive AD-risk association (p<10(-3 in the Alzheimer's Disease Genetics Consortium GWAS. These results demonstrate the significant contributions of genetic factors to human brain gene expression, which are reliably detected across different brain regions and pathologies. The significant enrichment of brain cisSNPs among disease-associated variants advocates gene expression changes as a mechanism for many central nervous system (CNS and non-CNS diseases. Combined assessment of expression and disease GWAS may provide complementary information in discovery of human disease variants with functional implications. Our findings

  12. Person-Centered Care in the Home Setting for Parkinson's Disease: Operation House Call Quality of Care Pilot Study.

    Science.gov (United States)

    Hack, Nawaz; Akbar, Umer; Monari, Erin H; Eilers, Amanda; Thompson-Avila, Amanda; Hwynn, Nelson H; Sriram, Ashok; Haq, Ihtsham; Hardwick, Angela; Malaty, Irene A; Okun, Michael S

    2015-01-01

    Objective. (1) To evaluate the feasibility of implementing and evaluating a home visit program for persons with Parkinson's disease (PD) in a rural setting. (2) To have movement disorders fellows coordinate and manage health care delivery. Background. The University of Florida, Center for Movement Disorders and Neurorestoration established Operation House Call to serve patients with PD who could not otherwise afford to travel to an expert center or to pay for medical care. PD is known to lead to significant disability, frequent hospitalization, early nursing home placement, and morbidity. Methods. This was designed as a quality improvement project. Movement disorders fellows travelled to the home(s) of underserved PD patients and coordinated their clinical care. The diagnosis of Parkinson's disease was confirmed using standardized criteria, and the Unified Parkinson's Disease Rating Scale was performed and best treatment practices were delivered. Results. All seven patients have been followed up longitudinally every 3 to 6 months in the home setting, and they remain functional and independent. None of the patients have been hospitalized for PD related complications. Each patient has a new updatable electronic medical record. All Operation House Call cases are presented during video rounds for the interdisciplinary PD team to make recommendations for care (neurology, neurosurgery, neuropsychology, psychiatry, physical therapy, occupational therapy, speech therapy, and social work). One Operation House Call patient has successfully received deep brain stimulation (DBS). Conclusion. This program is a pilot program that has demonstrated that it is possible to provide person-centered care in the home setting for PD patients. This program could provide a proof of concept for the construction of a larger visiting physician or nurse program.

  13. Plasma and Brain Fatty Acid Profiles in Mild Cognitive Impairment and Alzheimer’s Disease

    OpenAIRE

    Cunnane, Stephen C; Schneider, Julie A.; Tangney, Christine; Tremblay-Mercier, Jennifer; Fortier, Mélanie; Bennett, David A; Morris, Martha Clare

    2012-01-01

    Alzheimer’s disease (AD) is generally associated with lower omega-3 fatty acid intake from fish but despite numerous studies, it is still unclear whether there are differences in omega-3 fatty acids in plasma or brain. In matched plasma and brain samples provided by the Memory and Aging Project, fatty acid profiles were quantified in several plasma lipid classes and in three brain cortical regions. Fatty acid data were expressed as % composition and as concentrations (mg/dL for plasma or mg/g...

  14. Insights into brain development and disease from neurogenetic analyses in Drosophila melanogaster

    Indian Academy of Sciences (India)

    Heinrich Reichert

    2014-09-01

    Groundbreaking work by Obaid Siddiqi has contributed to the powerful genetic toolkit that is now available for studying the nervous system of Drosophila. Studies carried out in this powerful neurogenetic model system during the last decade now provide insight into the molecular mechanisms that operate in neural stem cells during normal brain development and during abnormal brain tumorigenesis. These studies also provide strong support for the notion that conserved molecular genetic programs act in brain development and disease in insects and mammals including humans.

  15. Research progress of neuroimaging of blood-brain barrier breakdown in Alzheimer's disease patients

    Directory of Open Access Journals (Sweden)

    Qin XU

    2017-07-01

    Full Text Available Recent studies indicate that blood-brain barrier (BBB breakdown may play an important role in the pathophysiology of cognitive dysfunction and dementia. BBB regulates the homeostasis of brain microenvironment, controls the transfer of required nutrients (e.g., glucose and amino acids, and limits entry of blood - derived products, pathogens and neurotoxins into the brain tissue. Recent advances in neuroimaging techniques offer new possibilities to realize positioning and quantitative detection of BBB disruption. It provides a new insertion point for elucidating the pathogenesis of Alzheimer's disease (AD. DOI: 10.3969/j.issn.1672-6731.2017.06.013

  16. Distribution of PSA-NCAM in normal, Alzheimer's and Parkinson's disease human brain.

    Science.gov (United States)

    Murray, Helen C; Low, Victoria F; Swanson, Molly E V; Dieriks, Birger V; Turner, Clinton; Faull, Richard L M; Curtis, Maurice A

    2016-08-25

    Polysialated neural cell adhesion molecule (PSA-NCAM) is a membrane bound glycoprotein widely expressed during nervous system development. While commonly described in the neurogenic niches of the adult human brain, there is limited evidence of its distribution in other brain regions. PSA-NCAM is an important regulator of cell-cell interactions and facilitates cell migration and plasticity. Recent evidence suggests these functions may be altered in neurodegenerative diseases such as Alzheimer's (AD) and Parkinson's disease (PD). This study provides a detailed description of the PSA-NCAM distribution throughout the human brain and quantitatively compares the staining load in cortical regions and sub-cortical structures between the control, AD and PD brain. Our results provide evidence of widespread, yet specific, PSA-NCAM expression throughout the human brain including regions devoid of PSA-NCAM in the rodent brain such as the caudate nucleus (CN) and cerebellum (CB). We also detected a significant reduction in PSA-NCAM load in the entorhinal cortex (EC) of cases that was inversely correlated with hyperphosphorylated tau load. These results demonstrate that PSA-NCAM-mediated structural plasticity may not be limited to neurogenic niches and is conserved in the aged brain. We also provide evidence that PSA-NCAM is reduced in the EC, a region severely affected by AD pathology. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  17. Huntington's disease accelerates epigenetic aging of human brain and disrupts DNA methylation levels.

    Science.gov (United States)

    Horvath, Steve; Langfelder, Peter; Kwak, Seung; Aaronson, Jeff; Rosinski, Jim; Vogt, Thomas F; Eszes, Marika; Faull, Richard L M; Curtis, Maurice A; Waldvogel, Henry J; Choi, Oi-Wa; Tung, Spencer; Vinters, Harry V; Coppola, Giovanni; Yang, X William

    2016-07-01

    Age of Huntington's disease (HD) motoric onset is strongly related to the number of CAG trinucleotide repeats in the huntingtin gene, suggesting that biological tissue age plays an important role in disease etiology. Recently, a DNA methylation based biomarker of tissue age has been advanced as an epigenetic aging clock. We sought to inquire if HD is associated with an accelerated epigenetic age. DNA methylation data was generated for 475 brain samples from various brain regions of 26 HD cases and 39 controls. Overall, brain regions from HD cases exhibit a significant epigenetic age acceleration effect (p=0.0012). A multivariate model analysis suggests that HD status increases biological age by 3.2 years. Accelerated epigenetic age can be observed in specific brain regions (frontal lobe, parietal lobe, and cingulate gyrus). After excluding controls, we observe a negative correlation (r=-0.41, p=5.5×10-8) between HD gene CAG repeat length and the epigenetic age of HD brain samples. Using correlation network analysis, we identify 11 co-methylation modules with a significant association with HD status across 3 broad cortical regions. In conclusion, HD is associated with an accelerated epigenetic age of specific brain regions and more broadly with substantial changes in brain methylation levels.

  18. Exosomes in the Diseased Brain: First Insights from In vivo Studies

    Science.gov (United States)

    Levy, Efrat

    2017-01-01

    Extracellular vesicles (EVs) are nanoscale size vesicles secreted by cells and are important mediators of intercellular communication and genetic exchange. Exosomes, EVs generated in endosomal multivesicular bodies, have been the focus of numerous publications as they have emerged as clinically valuable markers of disease states. Exosomes have been mostly studied from conditioned culture media and body fluids, with the difficulty of isolating exosomes from tissues having delayed their study in vivo. The implementation of a method designed to isolate exosomes from tissues, however, has yielded the first insights into characteristics of exosomes in the brain. It has been observed that brain exosomes from murine models of neurodegenerative diseases and human postmortem brains tend to mirror the protein content of the cells of origin, and interestingly, they are enriched with toxic proteins. Whether this enrichment with neurotoxic proteins is beneficial by relieving neurons of accumulated toxic material or detrimental to the brain by propagating pathogenicity throughout the brain remains to be answered. Here is summarized the first group of studies describing exosomes isolated from brain, results that demonstrate that exosomes in vivo reflect complex multicellular pathogenic processes in neurodegenerative disorders and the brain's response to injury and damage.

  19. Lymphatic Clearance of the Brain: Perivascular, Paravascular and Significance for Neurodegenerative Diseases.

    Science.gov (United States)

    Bakker, Erik N T P; Bacskai, Brian J; Arbel-Ornath, Michal; Aldea, Roxana; Bedussi, Beatrice; Morris, Alan W J; Weller, Roy O; Carare, Roxana O

    2016-03-01

    The lymphatic clearance pathways of the brain are different compared to the other organs of the body and have been the subject of heated debates. Drainage of brain extracellular fluids, particularly interstitial fluid (ISF) and cerebrospinal fluid (CSF), is not only important for volume regulation, but also for removal of waste products such as amyloid beta (Aβ). CSF plays a special role in clinical medicine, as it is available for analysis of biomarkers for Alzheimer's disease. Despite the lack of a complete anatomical and physiological picture of the communications between the subarachnoid space (SAS) and the brain parenchyma, it is often assumed that Aβ is cleared from the cerebral ISF into the CSF. Recent work suggests that clearance of the brain mainly occurs during sleep, with a specific role for peri- and para-vascular spaces as drainage pathways from the brain parenchyma. However, the direction of flow, the anatomical structures involved and the driving forces remain elusive, with partially conflicting data in literature. The presence of Aβ in the glia limitans in Alzheimer's disease suggests a direct communication of ISF with CSF. Nonetheless, there is also the well-described pathology of cerebral amyloid angiopathy associated with the failure of perivascular drainage of Aβ. Herein, we review the role of the vasculature and the impact of vascular pathology on the peri- and para-vascular clearance pathways of the brain. The different views on the possible routes for ISF drainage of the brain are discussed in the context of pathological significance.

  20. Altered brain iron homeostasis and dopaminergic function in Restless Legs Syndrome (Willis-Ekbom Disease).

    Science.gov (United States)

    Earley, Christopher J; Connor, James; Garcia-Borreguero, Diego; Jenner, Peter; Winkelman, John; Zee, Phyllis C; Allen, Richard

    2014-11-01

    Restless legs syndrome (RLS), also known as Willis-Ekbom Disease (WED), is a sensorimotor disorder for which the exact pathophysiology remains unclear. Brain iron insufficiency and altered dopaminergic function appear to play important roles in the etiology of the disorder. This concept is based partly on extensive research studies using cerebrospinal fluid (CSF), autopsy material, and brain imaging indicating reduced regional brain iron and on the clinical efficacy of dopamine receptor agonists for alleviating RLS symptoms. Finding causal relations, linking low brain iron to altered dopaminergic function in RLS, has required however the use of animal models. These models have provided insights into how alterations in brain iron homeostasis and dopaminergic system may be involved in RLS. The results of animal models of RLS and biochemical, postmortem, and imaging studies in patients with the disease suggest that disruptions in brain iron trafficking lead to disturbances in striatal dopamine neurotransmission for at least some patients with RLS. This review examines the data supporting an iron deficiency-dopamine metabolic theory of RLS by relating the results from animal model investigations of the influence of brain iron deficiency on dopaminergic systems to data from clinical studies in patients with RLS. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Impact of smoking and obesity on rheumatic disease in persons of productive age

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    Lusianawaty Tana

    2016-02-01

    Full Text Available Arthritis is a disease of the joints that causes pain and musculoskeletal stiffness, and may cause limitation of joint movement. Age, obesity, smoking behavior, and occupation are risk factors for rheumatic diseases. The objective of the present study was to evaluate the role of body mass index (BMI, smoking behavior, and occupation on rheumatic disease among persons of productive age in Indonesia. A cross-sectional study was conducted using National Basic Health Research data. The inclusion criterion was age 15-64 years. Rheumatic disease diagnosis was based on interview results and was defined as the presence of a history of rheumatic disease diagnosed by health professionals and/or rheumatic symptoms in the past 12 months. The study sample consisted of 609.097 persons who fulfilled the inclusion criterion. Compared to persons with normal BMI, rheumatic disease was more prevalent in the overweight (OR 1.25; 95%CI 1.21—1.29 and the obese (OR 1.52; 95%CI 1.47—1.56, but less prevalent in the underweight (OR 0.91; 95%CI 0.88—0.93. Compared to non-smokers, rheumatic disease was more prevalent in every day smokers (OR 1.65; 95%CI 1.60—1.70, occasional smokers (OR 1.41; 95%CI 1.35—1.47, and ex-smokers (OR 1.85; 95%CI 1.76—1.95. Measures for prevention of rheumatic disease are needed, e.g. through education to increase knowledge about the impact of smoking and obesity on rheumatic disease.

  2. The thyroid function of Graves' disease patients is aggravated by depressive personality during antithyroid drug treatment

    Directory of Open Access Journals (Sweden)

    Miyauchi Akira

    2011-08-01

    Full Text Available Abstract Background We previously reported that depressive personality (the scores of hypochondriasis, depression and psychasthenia determined by the Minnesota Multiphasic Personality Inventory (MMPI and daily hassles of Graves' disease (GD patients treated long trem with antithyroid drug (ATD were significantly higher in a relapsed group than in a remitted group, even in the euthyroid state. The present study aims to examine the relationship among depressive personality, emotional stresses, thyroid function and the prognosis of hyperthyroidism in newly diagnosed GD patients. Methods Sixty-four untreated GD patients responded to the MMPI for personality traits, the Natsume's Stress Inventory for major life events, and the Hayashi's Daily Life Stress Inventory for daily life stresses before and during ATD treatment. Results In the untreated thyrotoxic state, depressive personality (T-scores of hypochondriasis, depression or psychasthenia greater than 60 points in MMPI were found for 44 patients (69%. For 15 (23% of these patients, the scores decreased to the normal range after treatment. However, depressive personality persisted after treatment in the remaining 29 patients (46%. Normal scores before treatment were found for 20 patients (31%, and the scores were persistently normal for 15 patients (23%. The remaining 5 patients (8% had higher depressive personality after treatment. Such depressive personality was not associated with the severity of hyperthyroidism. Serum TSH receptor antibody activity at three years after treatment was significantly (p = 0.0351 greater in the depression group than in the non- depression group. The remission rate at four years after treatment was significantly (p = 0.0305 lower in the depression group than in the non- depression group (22% vs 52%. Conclusion The data indicate that in GD patients treated with ATD, depressive personality during treatment reflects the effect of emotional stress more than that of

  3. High-Frequency Deep Brain Stimulation of the Putamen Improves Bradykinesia in Parkinson’s Disease

    Science.gov (United States)

    Montgomery, Erwin B.; Huang, He; Walker, Harrison C.; Guthrie, Barton L.; Watts, Ray L.

    2014-01-01

    Deep brain stimulation is effective for a wide range of neurological disorders; however, its mechanisms of action remain unclear. With respect to Parkinson’s disease, the existence of multiple effective targets suggests that putamen stimulation also may be effective and raises questions as to the mechanisms of action. Are there as many mechanisms of action as there are effective targets or some single or small set of mechanisms common to all effective targets? During the course of routine surgery of the globus pallidus interna in patients with Parkinson’s disease, the deep brain stimulation lead was placed in the putamen en route to the globus pallidus interna. Recordings of hand opening and closing during high-frequency and no stimulation were made. Speed of the movements, based on the amplitude and frequency of the repetitive hand movements as well as the decay in amplitude, were studied. Hand speed in 6 subjects was statistically significantly faster during active deep brain stimulation than the no-stimulation condition. There were no statistically significant differences in decay in the amplitude of hand movements. High-frequency deep brain stimulation of the putamen improves bradykinesia in a hand-opening and -closing task in patients with Parkinson’s disease. Consequently, high-frequency deep brain stimulation of virtually every structure in the basal ganglia-thalamic-cortical system improves bradykinesia. These observations, together with microelectrode recordings reported in the literature, argue that deep brain stimulation effects may be system specific and not structure specific. PMID:21714010

  4. 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

  5. Neurodevelopment and brain growth in classic Menkes disease is influenced by age and symptomatology at initiation of copper treatment.

    Science.gov (United States)

    Kaler, Stephen G

    2014-10-01

    Menkes disease is an X-linked recessive disorder of brain copper metabolism caused by mutations in an essential mammalian copper transport gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that usually commence at 6-8 weeks of age. Death by age three years is typical. While provision of working copies of ATP7A to the brain by viral vectors is a promising strategy under development, the only treatment currently available is subcutaneous copper injections. These can normalize circulating blood levels and may replete brain copper depending on the molecular context, e.g., the severity of ATP7A mutation and potential presence of mosaicism. In this paper, we summarize somatic growth and neurodevelopmental outcomes for 60 subjects enrolled in a recently concluded phase I/II clinical trial of copper histidine for Menkes disease (ClinicalTrials.gov Identifier: NCT00001262). Primary outcomes indicate highly statistically significant improvements in gross motor, fine motor/adaptive, personal-social, and language neurodevelopment in the cohort of subjects who received early treatment prior to onset of symptoms (n=35). Correlating with these findings, quantitative parameters of somatic growth indicated statistically significant greater growth in head circumference for the initially asymptomatic group, whereas weight and height/length at age three years (or at time of death) did not differ significantly. Mortality at age 3 was higher (50%) in subjects older and symptomatic when treatment commenced compared to the asymptomatic group (28.6%). We conclude that early copper histidine for Menkes disease is safe and efficacious, with treatment outcomes influenced by the timing of intervention, and ATP7A mutation.

  6. Blood N-terminal Pro-brain Natriuretic Peptide and Interleukin-17 for Distinguishing Incomplete Kawasaki Disease from Infectious Diseases.

    Science.gov (United States)

    Wu, Ling; Chen, Yuanling; Zhong, Shiling; Li, Yunyan; Dai, Xiahua; Di, Yazhen

    2015-06-01

    To explore the diagnostic value of blood N-terminal pro-brain natriuretic peptide (NT-proBNP) and interleukin-17(IL-17) for incomplete Kawasaki disease. Patients with Kawasaki disease, Incomplete Kawasaki disease and unclear infectious fever were included in this retrospective study. Their clinical features, and laboratory test results of blood NT-proBNP and IL-17 were collected and compared. 766 patients with complete clinical information were recruited, consisting of 291 cases of Kawasaki disease, 74 cases of incomplete Kawasaki disease, and 401 cases of unclear infectious diseases. When the consistency with indicator 2 and 3 in Kawasaki disease diagnosis criteria was assessed with blood IL-17 ?11.55 pg/mL and blood NT-proBNP ? 225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases reached 86.5% and 94.8%, respectively. When we chose the consistency with indicator 1 and 2 in Kawasaki disease diagnosis criteria, the appearance of decrustation and/or the BCG erythema, blood IL-17 ?11.55 pg/mL and blood NT-Pro BNP ?225.5 pg/dL as the criteria, the sensitivity and specificity for distinguishing incomplete Kawasaki disease and infectious diseases was 43.2% and 100%, respectively. Blood NT-proBNP and IL-17 are useful laboratory indicators for distinguishing incomplete Kawasaki disease and infectious diseases at the early stage.

  7. Brain correlates of pro-social personality traits: a voxel-based morphometry study

    OpenAIRE

    Coutinho,Joana; Sampaio, Adriana; Ferreira, Miguel; Soares, José Miguel; Gonçalves, Óscar F.

    2013-01-01

    Of the five personality dimensions described by the Big Five Personality Model (Costa and McCrae 1992), Extraversion and Agreeableness are the traits most commonly associated with a pro-social orientation. In this study we tested whether a pro-social orientation, as expressed in terms of Extraversion and Agreeableness, is associated with a specific grey matter phenotype. Fifty-two healthy participants underwent magnetic resonance imaging (MRI) and completed the NEO-Five Factor Inventory (NEO-...

  8. Brain molecular aging, promotion of neurological disease and modulation by sirtuin 5 longevity gene polymorphism.

    Science.gov (United States)

    Glorioso, Christin; Oh, Sunghee; Douillard, Gaelle Guilloux; Sibille, Etienne

    2011-02-01

    Mechanisms determining characteristic age-of-onset for neurological diseases are largely unknown. Normal brain aging associates with robust and progressive transcriptome changes ("molecular aging"), but the intersection with disease pathways is mostly uncharacterized. Here, using cross-cohort microarray analysis of four human brain areas, we show that neurological disease pathways largely overlap with molecular aging and that subjects carrying a newly-characterized low-expressing polymorphism in a putative longevity gene (Sirtuin5; SIRT5(prom2)) have older brain molecular ages. Specifically, molecular aging was remarkably conserved across cohorts and brain areas, and included numerous developmental and transcription-regulator genes. Neurological disease-associated genes were highly overrepresented within age-related genes and changed almost unanimously in pro-disease directions, together suggesting an underlying genetic "program" of aging that progressively promotes disease. To begin testing this putative pathway, we developed and used an age-biosignature to assess five candidate longevity gene polymorphisms' association with molecular aging rates. Most robustly, aging was accelerated in cingulate, but not amygdala, of subjects carrying a SIRT5 promoter polymorphism (+9 years, p=0.004), in concordance with cingulate-specific decreased SIRT5 expression. This effect was driven by a set of core transcripts (+24 years, p=0.0004), many of which were mitochondrial, including Parkinson's disease genes, PINK-1 and DJ-1/PARK7, hence suggesting that SIRT5(prom2) may represent a risk factor for mitochondrial dysfunction-related diseases, including Parkinson's, through accelerated molecular aging of disease-related genes. Based on these results we speculate that a "common mechanism" may underlie age-of-onset across several neurological diseases. Confirming this pathway and its regulation by common genetic variants would provide new strategies for predicting, delaying, and

  9. Microphysiological Human Brain and Neural Systems-on-a-Chip: Potential Alternatives to Small Animal Models and Emerging Platforms for Drug Discovery and Personalized Medicine.

    Science.gov (United States)

    Haring, Alexander P; Sontheimer, Harald; Johnson, Blake N

    2017-06-01

    Translational challenges associated with reductionist modeling approaches, as well as ethical concerns and economic implications of small animal testing, drive the need for developing microphysiological neural systems for modeling human neurological diseases, disorders, and injuries. Here, we provide a comprehensive review of microphysiological brain and neural systems-on-a-chip (NSCs) for modeling higher order trajectories in the human nervous system. Societal, economic, and national security impacts of neurological diseases, disorders, and injuries are highlighted to identify critical NSC application spaces. Hierarchical design and manufacturing of NSCs are discussed with distinction for surface- and bulk-based systems. Three broad NSC classes are identified and reviewed: microfluidic NSCs, compartmentalized NSCs, and hydrogel NSCs. Emerging areas and future directions are highlighted, including the application of 3D printing to design and manufacturing of next-generation NSCs, the use of stem cells for constructing patient-specific NSCs, and the application of human NSCs to 'personalized neurology'. Technical hurdles and remaining challenges are discussed. This review identifies the state-of-the-art design methodologies, manufacturing approaches, and performance capabilities of NSCs. This work suggests NSCs appear poised to revolutionize the modeling of human neurological diseases, disorders, and injuries.

  10. Diffusion tensor imaging analysis of the brain in the canine model of Krabbe disease.

    Science.gov (United States)

    Bradbury, Allison; Peterson, David; Vite, Charles; Chen, Steven; Ellinwood, N Matthew; Provenzale, James

    2016-12-01

    The goal of this study was to compare the diffusion tensor imaging (DTI) metrics from an end-stage canine Krabbe brain evaluated by MR imaging ex vivo to those of a normal dog brain. We hypothesized that the white matter of the canine Krabbe brain would show decreased fractional anisotropy (FA) values and increased apparent diffusion coefficient (ADC) and radial diffusivity (RD) values. An 11-week-old Krabbe dog was euthanized after disease progression. The brain was removed and was placed in a solution of 10% formalin. MR imaging was performed and compared to the brain images of a normal dog that was similarly fixed post-mortem. Both brains were scanned using similar protocols on a 7 T small-animal MRI system. For each brain, maps of ADC, FA, and RD were calculated for 11 white-matter regions and five control gray-matter regions. Large decreases in FA values, increases in ADC values, and increases in RD (consistent with demyelination) values, were seen in white matter of the Krabbe brain but not gray matter. ADC values in gray matter of the Krabbe brain were decreased by approximately 29% but increased by approximately 3.6% in white matter of the Krabbe brain. FA values in gray matter were decreased by approximately 3.3% but decreased by approximately 29% in white matter. RD values were decreased by approximately 27.2% in gray matter but increased by approximately 20% in white matter. We found substantial abnormalities of FA, ADC, and RD values in an ex vivo canine Krabbe brain. © The Author(s) 2016.

  11. Novel retinal findings in an infant with muscle-eye-brain disease.

    Science.gov (United States)

    Khan, Mehnaz; Hamid, Rizwan; Recchia, Franco M

    2012-01-01

    To describe novel retinal findings in an infant with muscle-eye-brain disease and suggest a novel mechanism for congenital retinal detachment. Case report. A 7-week-old, white, female infant presented with total retinal detachment, peripheral retinal avascularity, and neovascularization of the right eye. In the left eye, there was hypoplastic optic nerve, no identifiable foveal avascular zone, and a small area of avascularity in the temporal peripheral retina. Genetic testing ultimately confirmed the diagnosis of muscle-eye-brain disease, a disorder of aberrant neuronal migration. This case describes retinal findings that, to our knowledge, have not been reported in previous cases of muscle-eye-brain disease: peripheral avascularity, leading to retinal detachment in one eye, and foveal dysplasia. It is speculated that aberrant retinal vasculogenesis arose from disordered migration and patterning of retinal neurons.

  12. Acidity and Acid-Sensing Ion Channels in the Normal and Alzheimer's Disease Brain.

    Science.gov (United States)

    Gonzales, Eric B; Sumien, Nathalie

    2017-02-15

    Alzheimer's disease prevalence has reached epidemic proportion with very few treatment options, which are associated with a multitude of side effects. A potential avenue of research for new therapies are protons, and their associated receptor: acid-sensing ion channels (ASIC). Protons are often overlooked neurotransmitters, and proton-gated currents have been identified in the brain. Furthermore, ASICs have been determined to be crucial for proper brain function. While there is more work to be done, this review is intended to highlight protons as neurotransmitters and their role along with the role of ASICs within physiological functioning of the brain. We will also cover the pathophysiological associations between ASICs and modulators of ASICs. Finally, this review will sum up how the studies of protons, ASICs and their modulators may generate new therapeutic molecules for Alzheimer's disease and other neurodegenerative diseases.

  13. LIS1 and DCX: Implications for Brain Development and Human Disease in Relation to Microtubules

    Directory of Open Access Journals (Sweden)

    Orly Reiner

    2013-01-01

    Full Text Available Proper lamination of the cerebral cortex requires the orchestrated motility of neurons from their place of birth to their final destination. Improper neuronal migration may result in a wide range of diseases, including brain malformations, such as lissencephaly, mental retardation, schizophrenia, and autism. Ours and other studies have implicated that microtubules and microtubule-associated proteins play an important role in the regulation of neuronal polarization and neuronal migration. Here, we will review normal processes of brain development and neuronal migration, describe neuronal migration diseases, and will focus on the microtubule-associated functions of LIS1 and DCX, which participate in the regulation of neuronal migration and are involved in the human developmental brain disease, lissencephaly.

  14. An experience of detection brain disease by roentgenographic CT on head

    Energy Technology Data Exchange (ETDEWEB)

    Kobata, Daikichi [Minami Osaka Total Health Screening Center (Japan)

    1996-08-01

    MRI and MRA are recommended today from the standpoint of sensitivity for the detraction of asymptomatic brain disease, and roentgenographic CT on head is not recommended. Under certain circumstances, however, having recently been given an opportunity of detecting brain disease by means of roentgenographic CT on head, we make a report of the diagnostic results. The examinees were the staff members of a non-profit organization consisting of 62 men and 56 women whose age was 48.6 years on the average. Asymptomatic brain disease was found in 6 cases including 1 case of cerebral infarction, 1 case of calcification of cerebral vascular wall and 1 case of cranial osteoma with a suspicion of Gardner syndrome. Incidentally, there were 31 cases with a complaint of headache, 20 cases of hypertension and 3 cases with a past history of head trauma. After such findings were obtained, guidance was provided to each of them. (author)

  15. Brain slices as models for neurodegenerative disease and screening platforms to identify novel therapeutics.

    Science.gov (United States)

    Cho, Seongeun; Wood, Andrew; Bowlby, Mark R

    2007-03-01

    Recent improvements in brain slice technology have made this biological preparation increasingly useful for examining pathophysiology of brain diseases in a tissue context. Brain slices maintain many aspects of in vivo biology, including functional local synaptic circuitry with preserved brain architecture, while allowing good experimental access and precise control of the extracellular environment, making them ideal platforms for dissection of molecular pathways underlying neuronal dysfunction. Importantly, these ex vivo systems permit direct treatment with pharmacological agents modulating these responses and thus provide surrogate therapeutic screening systems without recourse to whole animal studies. Virus or particle mediated transgenic expression can also be accomplished relatively easily to study the function of novel genes in a normal or injured brain tissue context.In this review we will discuss acute brain injury models in organotypic hippocampal and co-culture systems and the effects of pharmacological modulation on neurodegeneration. The review will also cover the evidence of developmental plasticity in these ex vivo models, demonstrating emergence of injury-stimulated neuronal progenitor cells, and neurite sprouting and axonal regeneration following pathway lesioning. Neuro-and axo-genesis are emerging as significant factors contributing to brain repair following many acute and chronic neurodegenerative disorders. Therefore brain slice models may provide a critical contextual experimental system to explore regenerative mechanisms in vitro.

  16. [Research resource network and Parkinson disease brain bank donor registration program in Japan].

    Science.gov (United States)

    Arima, Kunimasa

    2010-10-01

    In spite of the increasing need for brain tissue in biomedical research, overall brain banking activities in Japan has been lagging behind. On the initiative of the National Center of Neurology and Psychiatry, 2 projects have been carried out; the Research Resource Network (RRN) and the Parkinson's Disease Brain Bank (PDBB) donor registration program. RRN is a nation-wide network that links 15 brain repositories, and 1,463 autopsy brains have been registered in this network as of December 2009. The brain donor registration program for PDBB was established in 2006. A donor without cognitive impairment can enroll in this PDBB donor registration program. When the donor dies, the next-of-kin will contact the PDBB coordinators for subsequent autopsy services and brain retention. On obtaining the next-of-kin's consent at the time of donor's death, autopsy will be performed at PDBB collaborating hospitals of National Center of Neurology and Psychiatry, Juntendo University Hospital, and Tokyo Metropolitan Geriatric Hospital. In order to arouse public interest, lecture meetings for citizens have been held on a regular basis. Fifty individuals have registered in the PDBB donor registration program including 27 patients with PD, 4 patient with Parkinson syndrome, 1 patient with progressive supranuclear palsy, and 18 individuals without PD or related disorders as of December 2009. Autopsies have been performed for 2 of these donors. To promote brain banking activities,it is necessary to establish legal and ethical guidelines for the use of autopsied materials in biomedical research.

  17. New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brainrelated diseases

    Institute of Scientific and Technical Information of China (English)

    Naoki; Adachi; Tadahiro; Numakawa; Misty; Richards; Shingo; Nakajima; Hiroshi; Kunugi

    2014-01-01

    Brain-derived neurotrophic factor(BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has beenreported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer’s disease, Huntington’s disease, depression and schizophrenia.

  18. Effect of disease duration on personality type in multiple sclerosis patients and healthy individual

    Directory of Open Access Journals (Sweden)

    Sahar Vesal

    2016-01-01

    Full Text Available Background: Multiple sclerosis may have profound emotional consequences. The relation between psychological and physical factors could lead patients toward unforeseen disease. This study focuses on multiple sclerosis (MS disease duration on personality type A and B in relation to individuals' behaviors. Materials and Methods: This descriptive-analytical study was conducted in Isfahan Alzahra hospital in 2013. Three hundred MS patients and 100 healthy individuals were determined. The distributed questionnaires related to MS patients and considering the descriptive statistics such as demographic variables. Data were analyzed by SPSS software (version 18 based on Chi-square test and independent T-test. Results: Disease duration varied between 1 to 38 years: 30% (1-4 years, 38% (5-10 years, 20% (10-20 years, and 12% (more than 20 years. Significant relationship was observed between disease duration and tendency to type A (higher stress. This relation was positive and significant in Relapsing Remitting MS patients; but negative correlation was seen in Secondary Progressive MS patients. These patients tended to type B (lower stress when disease duration increased. Conclusions: Individuals with disease duration of one year and less than one year tend to type A personality, while patients with increment of disease duration have tendency to type B.

  19. Personalized Medicine: New Perspectives for the Diagnosis and the Treatment of Renal Diseases

    Directory of Open Access Journals (Sweden)

    Anna Gluba-Brzózka

    2017-06-01

    Full Text Available The prevalence of renal diseases is rising and reaching 5–15% of the adult population. Renal damage is associated with disturbances of body homeostasis and the loss of equilibrium between exogenous and endogenous elements including drugs and metabolites. Studies indicate that renal diseases are influenced not only by environmental but also by genetic factors. In some cases the disease is caused by mutation in a single gene and at that time severity depends on the presence of one or two mutated alleles. In other cases, renal disease is associated with the presence of alteration within a gene or genes, but environmental factors are also necessary for the development of disease. Therefore, it seems that the analysis of genetic aspects should be a natural component of clinical and experimental studies. The goal of personalized medicine is to determine the right drug, for the right patient, at the right time. Whole-genome examinations may help to change the approach to the disease and the patient resulting in the creation of “personalized medicine” with new diagnostic and treatment strategies designed on the basis of genetic background of each individual. The identification of high-risk patients in pharmacogenomics analyses will help to avoid many unwarranted side effects while optimizing treatment efficacy for individual patients. Personalized therapies for kidney diseases are still at the preliminary stage mainly due to high costs of such analyses and the complex nature of human genome. This review will focus on several areas of interest: renal disease pathogenesis, diagnosis, treatment, rate of progression and the prediction of prognosis.

  20. Increased prevalence of psychopathology and maladaptive personality traits after long-term cure of Cushing's disease.

    Science.gov (United States)

    Tiemensma, Jitske; Biermasz, Nienke R; Middelkoop, Huub A M; van der Mast, Roos C; Romijn, Johannes A; Pereira, Alberto M

    2010-10-01

    Psychopathology and maladaptive personality traits are often observed during the active phase of Cushing's disease (CD). We hypothesized that patients with long-term cure of CD show persistent psychopathology and maladaptive personality traits. Four questionnaires on frequently occurring psychopathology in somatic illnesses were used, including the Apathy Scale, Irritability Scale, Hospital Anxiety and Depression Scale, and Mood and Anxiety Symptoms Questionnaire short-form. Personality was assessed using the Dimensional Assessment of Personality Pathology short-form (DAPPs). We included 51 patients cured of CD (16% men, 53 ± 13 yr) and 51 matched controls. In addition, we included 55 patients treated for nonfunctioning pituitary macroadenomas (55% men, 62 ± 10 yr), and 55 matched controls. Mean duration of remission was 11 yr (range 1-32 yr). Compared with matched controls, patients cured from CD scored significantly worse on virtually all questionnaires. Compared with nonfunctioning pituitary macroadenoma patients, patients treated for CD scored worse on apathy (P Personality Pathology short-form (P maladaptive personality traits. These observations suggest irreversible effects of previous glucocorticoid excess on the central nervous system rather than an effect of pituitary tumors and/or their treatment in general. This may also be of relevance for patients treated with high doses of exogenous glucocorticoids.

  1. Large-Scale Functional Brain Network Abnormalities in Alzheimer’s Disease: Insights from Functional Neuroimaging

    Directory of Open Access Journals (Sweden)

    Bradford C. Dickerson

    2009-01-01

    Full Text Available Functional MRI (fMRI studies of mild cognitive impairment (MCI and Alzheimer’s disease (AD have begun to reveal abnormalities in large-scale memory and cognitive brain networks. Since the medial temporal lobe (MTL memory system is a site of very early pathology in AD, a number of studies have focused on this region of the brain. Yet it is clear that other regions of the large-scale episodic memory network are affected early in the disease as well, and fMRI has begun to illuminate functional abnormalities in frontal, temporal, and parietal cortices as well in MCI and AD. Besides predictable hypoactivation of brain regions as they accrue pathology and undergo atrophy, there are also areas of hyperactivation in brain memory and cognitive circuits, possibly representing attempted compensatory activity. Recent fMRI data in MCI and AD are beginning to reveal relationships between abnormalities of functional activity in the MTL memory system and in functionally connected brain regions, such as the precuneus. Additional work with “resting state” fMRI data is illuminating functional-anatomic brain circuits and their disruption by disease. As this work continues to mature, it will likely contribute to our understanding of fundamental memory processes in the human brain and how these are perturbed in memory disorders. We hope these insights will translate into the incorporation of measures of task-related brain function into diagnostic assessment or therapeutic monitoring, which will hopefully one day be useful for demonstrating beneficial effects of treatments being tested in clinical trials.

  2. Forgiveness and Personality Type among Men and Women Suffering from Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Elham Foroozandeh

    2014-07-01

    Full Text Available Background: Role of personality and some components of behaviors, traits and emotions as effective factors on coronary heart diseases (CHD were presented nearly 50 years ago with the concept of “type A” behavior, a compound of hostility, impatience, competitiveness and dominance. Later studies showed crucial role of other traits and behaviors like anger, introversion, depression and forgiveness. Objective: The aim of this study was to compare personality type and forgiveness in the patients suffering from cardiovascular diseases based on gender. Materials and method: The cross sectional study was designed and sample was collected from men and women referred to cardiologists (within the age range of 23-75 years old from the patients of Shahid Rajaee Heart Hospital of Tehran, Iran from December 2010 to March 2011. Total 87 subjects were selected using random method. The study subjects were given two questionnaires: personality type A (with two factors: TA1, pathologic behaviors of type A personality and TA2, non pathologic behaviors of type A personality and Interpersonal Forgiveness Inventory (IFI, with three subscales namely reestablishment of relationship, control of revenge and realistic perception. Data were analyzed using SPSS software. Results: Mean(±SD age of men was 50.5±11.6 years (n=33 and 55.7±14.4 years in women (n=54. Mean duration of suffering from cardiovascular diseases in men was 7.8 years and in women was 9.10 years. The study found high mean scores of type A pathologic but not non pathologic type A among women compared to men (p<0.038 and no statistically significant differences in forgiveness subscales. Conclusion: The study revealed significant difference between women and men suffering from cardiovascular disease in pathologic type A (TA1 and negative relationship between pathologic type A and forgiveness.

  3. Clinically silent preoperative brain injuries do not worsen with surgery in neonates with congenital heart disease.

    Science.gov (United States)

    Block, A J; McQuillen, P S; Chau, V; Glass, H; Poskitt, K J; Barkovich, A J; Esch, M; Soulikias, W; Azakie, A; Campbell, A; Miller, S P

    2010-09-01

    Preoperative brain injury, particularly stroke and white matter injury, is common in neonates with congenital heart disease. The objective of this study was to determine the risk of hemorrhage or extension of preoperative brain injury with cardiac surgery. This dual-center prospective cohort study recruited 92 term neonates, 62 with transposition of the great arteries and 30 with single ventricle physiology, from 2 tertiary referral centers. Neonates underwent brain magnetic resonance imaging scans before and after cardiac surgery. Brain injury was identified in 40 (43%) neonates on the preoperative magnetic resonance imaging scan (median 5 days after birth): stroke in 23, white matter injury in 21, and intraventricular hemorrhage in 7. None of the brain lesions presented clinically with overt signs or seizures. Preoperative brain injury was associated with balloon atrial septostomy (P = .003) and lowest arterial oxygen saturation (P = .007); in a multivariable model, only the effect of balloon atrial septostomy remained significant when adjusting for lowest arterial oxygen saturation. On postoperative magnetic resonance imaging in 78 neonates (median 21 days after birth), none of the preoperative lesions showed evidence of extension or hemorrhagic transformation (0/40 [95% confidence interval: 0%-7%]). The presence of preoperative brain injury was not a significant risk factor for acquiring new injury on postoperative magnetic resonance imaging (P = .8). Clinically silent brain injuries identified preoperatively in neonates with congenital heart disease, including stroke, have a low risk of progression with surgery and cardiopulmonary bypass and should therefore not delay clinically indicated cardiac surgery. In this multicenter cohort, balloon atrial septostomy remains an important risk factor for preoperative brain injury, particularly stroke. 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  4. MRI of the brain and craniocervical junction in Morquio`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Hughes, D.G. [Department of Radiology, Hope Hospital, Stott Lane, Salford, Manchester M6 8HD (United Kingdom); Chadderton, R.D. [Department of Neurosurgery, Hope Hospital, Salford, Manchester M6 8HD (United Kingdom); Cowie, R.A. [Department of Neurosurgery, Hope Hospital, Salford, Manchester M6 8HD (United Kingdom); Wraith, J.E. [Willink Biochemical Genetics Unit, Royal Manchester Children`s Hospital, Manchester M27 4HA (United Kingdom); Jenkins, J.P.R. [Department of Clinical Radiology, Manchester Royal Infirmary, Oxford Road, Manchester (United Kingdom)

    1997-05-01

    We reviewed MRI of the brain and cervical spine in 11 patients with Morquio`s disease. No abnormality was seen in the brain. The odontoid peg was abnormal in all patients, with varying degrees of cord compression due to an anterior soft tissue mass and indentation by the posterior arch of the atlas. The degree of cord compression was more marked than suggested by the symptoms and signs. We recommend MRI of the cervical spine in children with Morquio`s disease before the development of neurological symptoms, to optimise the timing and type of surgical intervention. (orig.). With 5 figs., 2 tabs.

  5. Intraoperative fluorescence imaging for personalized brain tumor resection: Current state and future directions

    Directory of Open Access Journals (Sweden)

    Evgenii Belykh

    2016-10-01

    Full Text Available Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical theranostics. In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients, as well as future applications of recent laboratory and translational studies.Methods: Review of the literature.Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-ALA and ICG, less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine can be used for rapid tumor detection and pathological tissue examination. Other emerging agents such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.Conclusion: We are standing on the doorstep of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

  6. Behavioral Treatment for Pathological Gambling in Persons with Acquired Brain Injury

    Science.gov (United States)

    Guercio, John M.; Johnson, Taylor; Dixon, Mark R.

    2012-01-01

    The present investigation examined a behavior-analytic clinical treatment package designed to reduce the pathological gambling of 3 individuals with acquired brain injury. A prior history of pathological gambling of each patient was assessed via caregiver report, psychological testing, and direct observation of gambling behavior. Using an 8-week…

  7. Nationwide study of antipsychotic use among community-dwelling persons with Alzheimer's disease in Finland.

    Science.gov (United States)

    Laitinen, Marja-Liisa; Bell, J Simon; Lavikainen, Piia; Lönnroos, Eija; Sulkava, Raimo; Hartikainen, Sirpa

    2011-12-01

    Antipsychotics continue to be widely used in the treatment of behavioral and psychological symptoms of dementia despite their limited effectiveness and well-known risks, including increased mortality. Our aim was to investigate the national pattern of antipsychotic use among community-dwelling persons with and without Alzheimer's disease (AD) in Finland. The Social Insurance Institution of Finland (SII) identified all persons with a verified diagnosis of AD in Finland on 31 December 2005. A control for each person with AD, matched in terms of age, sex and region of residence, was also identified. Data on reimbursed drug purchases in 2005 were extracted from the Finnish National Prescription Register. Conditional logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the use of antipsychotics. The study population comprised 28,089 matched pairs of persons with and without AD (mean age 80.0 years, SD 6.8, 32.2% men). The annual prevalence of antipsychotic use was higher among persons with than without AD (22.1% vs. 4.4%, adjusted OR = 5.91; 95% CI 5.91-6.31). Among persons with AD, the prevalence of antipsychotic use was similar across all age groups. Of the antipsychotic users, 85.2% with AD and 51.3% without AD purchased second generation antipsychotics. Most antipsychotic prescriptions - 67.8% in the AD and 62.9% in the non-AD group - were generated in primary care situations. One-fifth of persons with AD used antipsychotic drugs. Antipsychotic use was six times more prevalent among persons with AD than without AD. Most antipsychotics were prescribed by primary care physicians.

  8. Clinical course of brain stroke in the persons exposed to ionizing radiation under the production conditions

    Energy Technology Data Exchange (ETDEWEB)

    Bouchmanov, A. [State Research Center of Russia, Moscow (Russian Federation). Inst. of Biophysics

    2000-05-01

    The purpose was to study the risk factors and clinical course of brain strokes in professionally exposed workers being employed in plutonium production in comparison with a control group. The method and materials of study -clinical supervision and clinical database creation on 162 cases of brain stroke (128 males and 34 females) developed among professionally exposed workers. Age of patient varied from 21 to 68 years (in average -51.6 y.). The control group consisted of patients with the same diagnosis, worked on the same enterprise, but non-exposed to radiation. Data on the totally accumulated dose of external gamma radiation were received on the base of the individual dosimeters (from 0.1 cSv to 52 cSv, in average about 13 cSv); the plutonium-239 body content was estimated accordingly to the level of urine radionuclide excretion (from 0.4 kBq to 1.6 kBq, in average about 0.33 kBq). Muscle's hypertinsion and pathological great-toe reflexes in paretic legs and hands, hemianopsia, impressive and ataxic aphasia prevailed in the patients with ischemic brain strokes in system of internal carotid artery, exposed to radiation. The changes of muscle's tension, ataxia and nystagmus were marked more often in the professionals with ischemic brain strokes in system of vertebrobasilar artery. The illness proceeded more easy and with smaller frequency of frustration of consciousness and algesthesia, irrespective of a type ischemic brain strokes in the people exposed to ionizing radiation, than in patients of non-irradiated group. It was found that the arterial hypertension appeared to be the main risk factor for the brain stroke in both groups of patients (in 81.48% and 91.15% of cases). There was no marked differences in significance of risk factors and in main clinical parameters of various types of ischemic brain strokes among the patients professionally exposed to radiation in comparison with a control group. (author)

  9. Quantifying structural alterations in Alzheimer's disease brains using quantitative phase imaging (Conference Presentation)

    Science.gov (United States)

    Lee, Moosung; Lee, Eeksung; Jung, JaeHwang; Yu, Hyeonseung; Kim, Kyoohyun; Yoon, Jonghee; Lee, Shinhwa; Jeong, Yong; Park, YongKeun

    2017-02-01

    Imaging brain tissues is an essential part of neuroscience because understanding brain structure provides relevant information about brain functions and alterations associated with diseases. Magnetic resonance imaging and positron emission tomography exemplify conventional brain imaging tools, but these techniques suffer from low spatial resolution around 100 μm. As a complementary method, histopathology has been utilized with the development of optical microscopy. The traditional method provides the structural information about biological tissues to cellular scales, but relies on labor-intensive staining procedures. With the advances of illumination sources, label-free imaging techniques based on nonlinear interactions, such as multiphoton excitations and Raman scattering, have been applied to molecule-specific histopathology. Nevertheless, these techniques provide limited qualitative information and require a pulsed laser, which is difficult to use for pathologists with no laser training. Here, we present a label-free optical imaging of mouse brain tissues for addressing structural alteration in Alzheimer's disease. To achieve the mesoscopic, unlabeled tissue images with high contrast and sub-micrometer lateral resolution, we employed holographic microscopy and an automated scanning platform. From the acquired hologram of the brain tissues, we could retrieve scattering coefficients and anisotropies according to the modified scattering-phase theorem. This label-free imaging technique enabled direct access to structural information throughout the tissues with a sub-micrometer lateral resolution and presented a unique means to investigate the structural changes in the optical properties of biological tissues.

  10. Agrin in Alzheimer's Disease: Altered Solubility and Abnormal Distribution within Microvasculature and Brain Parenchyma

    Science.gov (United States)

    Donahue, John E.; Berzin, Tyler M.; Rafii, Michael S.; Glass, David J.; Yancopoulos, George D.; Fallon, Justin R.; Stopa, Edward G.

    1999-05-01

    Agrin is a heparan sulfate proteoglycan that is widely expressed in neurons and microvascular basal lamina in the rodent and avian central nervous system. Agrin induces the differentiation of nerve-muscle synapses, but its function in either normal or diseased brains is not known. Alzheimer's disease (AD) is characterized by loss of synapses, changes in microvascular architecture, and formation of neurofibrillary tangles and senile plaques. Here we have asked whether AD causes changes in the distribution and biochemical properties of agrin. Immunostaining of normal, aged human central nervous system revealed that agrin is expressed in neurons in multiple brain areas. Robust agrin immunoreactivity was observed uniformly in the microvascular basal lamina. In AD brains, agrin is highly concentrated in both diffuse and neuritic plaques as well as neurofibrillary tangles; neuronal expression of agrin also was observed. Furthermore, patients with AD had microvascular alterations characterized by thinning and fragmentation of the basal lamina. Detergent extraction and Western blotting showed that virtually all the agrin in normal brain is soluble in 1% SDS. In contrast, a large fraction of the agrin in AD brains is insoluble under these conditions, suggesting that it is tightly associated with β -amyloid. Together, these data indicate that the agrin abnormalities observed in AD are closely linked to β -amyloid deposition. These observations suggest that altered agrin expression in the microvasculature and the brain parenchyma contribute to the pathogenesis of AD.

  11. My encounters with Krabbe disease: A personal recollection of a 40-Year journey with young colleagues.

    Science.gov (United States)

    Suzuki, Kunihiko

    2016-11-01

    In this hybrid of a personal essay and a subjective review, I am attempting to convey the sense of an adventure I myself experienced in exploring various aspects of Krabbe disease, which occupied a significant portion of my life as a biomedical researcher. This is meant to be a personal summary, and I have no pretense of this being an objective scholarly review. Since the first description of the disease by Krabbe 100 years ago, knowledge about the disease has advanced significantly. The main contributions from my laboratory, always the fruits of dedicated efforts of talented young colleagues, include the identification of the genetic defect as deficiency of galactosylceramidase, proposal of the psychosine hypothesis as the pathogenetic mechanism to explain the unique phenotypic characteristics of the disease, detailed delineations of the substrate specificities of the two lysosomal β-galactosidases, discovery of the twitcher mutant as a convenient and useful mouse model, and identification of saposin A as a specific galactosylceramide activator protein and as the second causative gene for globoid cell leukodystrophy. Now, attempts are being made in many laboratories for meaningful therapy, unthinkable when I started working on this disease. Despite these advances, there are still many unknowns and uncertainties about Krabbe disease waiting to be clarified. © 2016 Wiley Periodicals, Inc.

  12. The relationship between brain behavioral systems and the characteristics of the five factor model of personality with aggression among Iranian students

    Directory of Open Access Journals (Sweden)

    Saeid Komasi

    2016-07-01

    Full Text Available Abstract: Background: Aggression is one of the negative components of emotion and it is usually considered to be the outcome of the activity of the Behavioral Inhibition and the Behavioral Activation System (BIS/BAS: components which can be considered as predisposing factors for personality differences. Therefore, the purpose of this study was to investigate the relationship between brain behavioral systems and the characteristics of the five factor model of personality with aggression among students. Methods: The present study has a correlation descriptive design. The research population included all of the Razi University students in the academic year of 2012 -2013. The sampling was carried out with a random stratified method and 360 people (308 female and 52 male were studied according to a table of Morgan. The study instruments were Buss and Perry Aggression Questionnaire, NEO Personality Inventory (Short Form, and Carver and White scale for BAS/BIS. Finally, SPSS20 was utilized to analyze the data using Pearson correlation,regression analysis, and canonical correlation. Results: The data showed a significant positive relationship between the neurosis and agreeableness personality factors with aggression; but there is a significant negative relationship between the extrov ersion, openness, and conscientiousness personality factors with aggression. Furthermore, there is a significant positive relationship between all the components of brain behavioral systems (impulsivity, novelty seeking, sensitivity, tender and aggressio n. The results of regression analysis indicated the personality characteristics and the brain behavioral systems which can predict 29 percent of the changes to aggression, simultaneously. Conclusions: According to a predictable level of aggressiveness by the personality characteristics and brain behavioral systems, it is possible to identify the personality characteristics and template patterns of brain behavioral systems

  13. The picture of happiness in Alzheimer's disease: living a life congruent with personal values.

    Science.gov (United States)

    Shell, Lynn

    2015-01-01

    It is generally understood that happiness is an important goal of dementia care, though evaluation has been challenging. Concerns about cognitive and communicative limitations have led to the use of proxy reports to assess positive affect. However, proxy reports have been shown to differ from appraisals obtained by the person with Alzheimer's disease (AD). This article reports on a qualitative study of happiness in a sample of 12 persons with mild to moderate AD using photo-elicitation and individual interviews for data collection. Results demonstrate people with mild to moderate AD can provide meaningful evaluations of happiness, and that lifelong values continue to be important in the presence of AD. This study suggests photographs may offer a novel approach to obtain a contextualized understanding of happiness and other values in this population which may lead to the development of person centered interventions aimed to improve the individual's quality of life. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Prominent diseases among internally displaced persons after Mt. Merapi eruption in Indonesia

    Directory of Open Access Journals (Sweden)

    Ahmad Fuady

    2014-02-01

    Full Text Available AbstrakLatar belakang: Letusan gunung berapi menyebabkan dampak kesehatan yang luas. Selain menyebabkan kematian dan luka bakar, paparan terhadap material vulkanik dapat mengiritasi saluran pernapasan, kulit dan mata. Studi ini bertujuan menilai penyakit yang menonjol pada pengungsi setelah letusan Merapi di Indonesia. Metode:Studi ini merupakan studi potong lintang, bersamaan dengan pemberian bantuan kesehatan oleh Fakultas Kedokteran Universitas Indonesia, pada pekan pertama dan kedua setelah letusan kedua Merapi, di 12 lokasi pengungsian dalam area kecamatan Muntilan dan Mertayudan. Analisis pola penyakit dilakukan setelah mengelompokkan diagnosis kerja sesuai Klasifikasi Penyakit Internasional versi 10 (ICD-10. Hasil:Dengan rentang 1-4 diagnosis per orang, sejumlah 804 penyakit atau kelainan dianalisis. Lima penyakit terbanyak pada pekan pertama setelah letusan Merapi kedua adalah (1 penyakit saluran pernapasan, (2 penyakit jaringan lunak lainnya yang tidak terklasifikasi, (3 hipertensi, dan (4 kelainan episodik dan paroksismal. Proporsi penyakit saluran pernapasan, hipertensi, dan penyakit jaringan kulit dan subkutan meningkat pada pekan kedua. Kesimpulan:Penyakit saluran pernapasan, hipertensi, dan penyakit jaringan kulit dan subkutan meningkat pada pekan kedua setelah letusan kedua Merapi dibandingkan dengan pekan pertama. (Health Science Indones 2013;2:59-63Kata kunci: Merapi, pengungsi, perubahan penyakit yang menonjolAbstractBackground:Volcano eruptions may result in a wide range of health impacts. Exposure to volcanic materials may irritate respiratory tract, eyes, and skin, in addition to death and heat injury. Mount Merapi had two consecutive eruptions on 2010 and resulted in high number of mortality and morbidity. This study aimed at assessing prominent diseases among internally displaced persons after Merapi eruption in Indonesia. Methods:It is a cross sectional study, attached on delivery of medical aids by Faculty of Medicine

  15. Prominent diseases among internally displaced persons after Mt. Merapi eruption in Indonesia

    Directory of Open Access Journals (Sweden)

    Ahmad Fuady

    2014-02-01

    Full Text Available AbstrakLatar belakang: Letusan gunung berapi menyebabkan dampak kesehatan yang luas. Selain menyebabkan kematian dan luka bakar, paparan terhadap material vulkanik dapat mengiritasi saluran pernapasan, kulit dan mata. Studi ini bertujuan menilai penyakit yang menonjol pada pengungsi setelah letusan Merapi di Indonesia. Metode:Studi ini merupakan studi potong lintang, bersamaan dengan pemberian bantuan kesehatan oleh Fakultas Kedokteran Universitas Indonesia, pada pekan pertama dan kedua setelah letusan kedua Merapi, di 12 lokasi pengungsian dalam area kecamatan Muntilan dan Mertayudan. Analisis pola penyakit dilakukan setelah mengelompokkan diagnosis kerja sesuai Klasifikasi Penyakit Internasional versi 10 (ICD-10. Hasil:Dengan rentang 1-4 diagnosis per orang, sejumlah 804 penyakit atau kelainan dianalisis. Lima penyakit terbanyak pada pekan pertama setelah letusan Merapi kedua adalah (1 penyakit saluran pernapasan, (2 penyakit jaringan lunak lainnya yang tidak terklasifikasi, (3 hipertensi, dan (4 kelainan episodik dan paroksismal. Proporsi penyakit saluran pernapasan, hipertensi, dan penyakit jaringan kulit dan subkutan meningkat pada pekan kedua. Kesimpulan:Penyakit saluran pernapasan, hipertensi, dan penyakit jaringan kulit dan subkutan meningkat pada pekan kedua setelah letusan kedua Merapi dibandingkan dengan pekan pertama. (Health Science Indones 2013;2:59-63Kata kunci: Merapi, pengungsi, perubahan penyakit yang menonjolAbstractBackground:Volcano eruptions may result in a wide range of health impacts. Exposure to volcanic materials may irritate respiratory tract, eyes, and skin, in addition to death and heat injury. Mount Merapi had two consecutive eruptions on 2010 and resulted in high number of mortality and morbidity. This study aimed at assessing prominent diseases among internally displaced persons after Merapi eruption in Indonesia. Methods:It is a cross sectional study, attached on delivery of medical aids by Faculty of Medicine

  16. Neuron-specific enolase in cerebrospinal fluid and plasma of patients with acute ischemic brain disease

    Directory of Open Access Journals (Sweden)

    Selaković Vesna M.

    2003-01-01

    Full Text Available The objective of this research was to determine the dynamics of change of neuron-specific enolase concentration in patients with acute ischemic brain disease in cerebrospinal fluid and plasma. The study included 103 patients, their mean age 58-66 years. The control group consisted of 16 patients, of matching age and sex, with radicular lesions of discal origin, subjected to diagnostic radiculography. Concentration of neuron-specific enolase was measured by a flouroimmunometric method. The results showed that the concentration of neuron-specific enolase in cerebrospinal fluid and plasma of patients with brain ischemic disease within first seven days significantly increased compared to the control. The highest increase of concentration was established in brain infarction, somewhat lower in reversible ischemic attack, and the lowest in transient ischemic attack. Maximal concentration was established on the 3rd-4th day upon the brain infarction. Neuron-specific enolase concentration in cerebrospinal fluid and plasma may be an indicator of pathophysiological processes in the acute phase of brain ischemia and is significant in early diagnostics and therapy of the disease.

  17. Gut-brain actions underlying comorbid anxiety and depression associated with inflammatory bowel disease.

    Science.gov (United States)

    Abautret-Daly, Áine; Dempsey, Elaine; Parra-Blanco, Adolfo; Medina, Carlos; Harkin, Andrew

    2017-03-08

    Introduction Inflammatory bowel disease (IBD) is a chronic relapsing and remitting disorder characterised by inflammation of the gastrointestinal tract. There is a growing consensus that IBD is associated with anxiety- and depression-related symptoms. Psychological symptoms appear to be more prevalent during active disease states with no difference in prevalence between Crohn's disease and ulcerative colitis. Behavioural disturbances including anxiety- and depression-like symptoms have also been observed in animal models of IBD. The likely mechanisms underlying the association are discussed with particular reference to communication between the gut and brain. The close bidirectional relationship known as the gut-brain axis includes neural, hormonal and immune communication links. Evidence is provided for a number of interacting factors including activation of the inflammatory response system in the brain, the hypothalamic-pituitary-adrenal axis, and brain areas implicated in altered behaviours, changes in blood brain barrier integrity, and an emerging role for gut microbiota and response to probiotics in IBD. Discussion The impact of psychological stress in models of IBD remains somewhat conflicted, however, it is weighted in favour of stress or early stressful life events as risk factors in the development of IBD, stress-induced exacerbation of inflammation and relapse. It is recommended that patients with IBD be screened for psychological disturbance and treated accordingly as intervention can improve quality of life and may reduce relapse rates.

  18. Brain changes in Alzheimer's disease patients with implanted encapsulated cells releasing nerve growth factor.

    Science.gov (United States)

    Ferreira, Daniel; Westman, Eric; Eyjolfsdottir, Helga; Almqvist, Per; Lind, Göran; Linderoth, Bengt; Seiger, Ake; Blennow, Kaj; Karami, Azadeh; Darreh-Shori, Taher; Wiberg, Maria; Simmons, Andrew; Wahlund, Lars-Olof; Wahlberg, Lars; Eriksdotter, Maria

    2015-01-01

    New therapies with disease-modifying effects are urgently needed for treating Alzheimer's disease (AD). Nerve growth factor (NGF) protein has demonstrated regenerative and neuroprotective effects on basal forebrain cholinergic neurons in animal studies. In addition, AD patients treated with NGF have previously shown improved cognition, EEG activity, nicotinic binding, and glucose metabolism. However, no study to date has analyzed brain atrophy in patients treated with NGF producing cells. In this study we present MRI results of the first clinical trial in patients with AD using encapsulated NGF biodelivery to the basal forebrain. Six AD patients received the treatment during twelve months. Patients were grouped as responders and non-responders according to their twelve-months change in MMSE. Normative values were created from 131 AD patients from ADNI, selecting 36 age- and MMSE-matched patients for interpreting the longitudinal changes in MMSE and brain atrophy. Results at baseline indicated that responders showed better clinical status and less pathological levels of cerebrospinal fluid (CSF) Aβ1-42. However, they showed more brain atrophy, and neuronal degeneration as evidenced by higher CSF levels of T-tau and neurofilaments. At follow-up, responders showed less brain shrinkage and better progression in the clinical variables and CSF biomarkers. Noteworthy, two responders showed less brain shrinkage than the normative ADNI group. These results together with previous evidence supports the idea that encapsulated biodelivery of NGF might have the potential to become a new treatment strategy for AD with both symptomatic and disease-modifying effects.

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

    DEFF Research Database (Denmark)

    Nilsson, Tatjana; Bogdanovic, Nenad; Volkman, Inga

    2006-01-01

    The amyloid precursor protein can through ligand-mimicking induce expression of ornithine decarboxylase (ODC), the initial and rate-limiting enzyme in polyamine biosynthesis. We report here the regional distribution and cellular localization of ODC immunoreactivity in Alzheimer's disease (AD...

  20. Targeting the Gut-Brain axis in Parkinson's disease

    NARCIS (Netherlands)

    Perez Pardo, P.

    2017-01-01

    Parkinson’s disease (PD) is the most common progressive movement disorder, with increasing age being the greatest risk factor for its development. PD is hallmarked by the progressive degeneration of dopaminergic nigrostriatal neurons, with reductions in striatal dopamine levels resulting in the

  1. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains.

    Science.gov (United States)

    Ledesma, Maria Dolores; Abad-Rodriguez, José; Galvan, Cristian; Biondi, Elisa; Navarro, Pilar; Delacourte, Andre; Dingwall, Colin; Dotti, Carlos G

    2003-12-01

    The serine protease plasmin can efficiently degrade amyloid peptide in vitro, and is found at low levels in the hippocampus of patients with Alzheimer's disease (AD). The cause of such paucity remains unknown. We show here that the levels of total brain plasminogen and plasminogen-binding molecules are normal in these brain samples, yet plasminogen membrane binding is greatly reduced. Biochemical analysis reveals that the membranes of these brains have a mild, still significant, cholesterol reduction compared to age-matched controls, and anomalous raft microdomains. This was reflected by the loss of raft-enriched proteins, including plasminogen-binding and -activating molecules. Using hippocampal neurons in culture, we demonstrate that removal of a similar amount of membrane cholesterol is sufficient to induce raft disorganization, leading to reduced plasminogen membrane binding and low plasmin activity. These results suggest that brain raft alterations may contribute to AD by rendering the plasminogen system inefficient.

  2. GLP-1 analog raises glucose transport capacity of blood-brain barrier in Alzheimer's disease

    DEFF Research Database (Denmark)

    Gejl, M.; Brock, B.; Egefjord, L.

    2017-01-01

    Objectives: Glucose enters the brain tissue from plasma by facilitated diffusion across the two membranes of the endothelium of the blood-brain barrier (BBB), mediated by the glucose transporter 1 (GLUT1). There is evidence in Alzheimer's disease (AD) of reduction of glucose transport across...... claim that the GLP-1 analog liraglutide may prevent the decline of blood-brain glucose transfer in AD. Methods: In this 26-week test of the hypothesis, we randomized 38 patients with AD to treatment with the GLP-1 analog liraglutide (n = 18) or placebo (n = 20). We determined blood-brain glucose...... transport capacity (Tmax) with [18F]FDG (FDG) (ClinicalTrials.gov NCT01469351). Results: In both groups, the Tmax estimates declined in proportion to the duration of AD. The GLP-1 analog treatment very significantly (P 

  3. Brain Dynamics: Methodological Issues and Applications in Psychiatric and Neurologic Diseases

    Science.gov (United States)

    Pezard, Laurent

    The human brain is a complex dynamical system generating the EEG signal. Numerical methods developed to study complex physical dynamics have been used to characterize EEG since the mid-eighties. This endeavor raised several issues related to the specificity of EEG. Firstly, theoretical and methodological studies should address the major differences between the dynamics of the human brain and physical systems. Secondly, this approach of EEG signal should prove to be relevant for dealing with physiological or clinical problems. A set of studies performed in our group is presented here within the context of these two problematic aspects. After the discussion of methodological drawbacks, we review numerical simulations related to the high dimension and spatial extension of brain dynamics. Experimental studies in neurologic and psychiatric disease are then presented. We conclude that if it is now clear that brain dynamics changes in relation with clinical situations, methodological problems remain largely unsolved.

  4. Nanotechnology-mediated nose to brain drug delivery for Parkinson's disease: a mini review.

    Science.gov (United States)

    Kulkarni, Abhijeet D; Vanjari, Yogesh H; Sancheti, Karan H; Belgamwar, Veena S; Surana, Sanjay J; Pardeshi, Chandrakantsing V

    2015-01-01

    Nose to brain delivery of neurotherapeutics have been tried by several researchers to explore the virtues of this route viz. circumvention of BBB, avoidance of hepatic metabolism, practicality, safety, ease of administration and non-invasiveness. Nanoparticle (NP) therapeutics is an emerging modality for the treatment of Parkinson's disease (PD) as it offers targeted delivery and enhances the therapeutic efficacy and/or bioavailability of neurotherapeutics. This review presents a concise incursion into the nanomedicines suitable for PD therapy delivered via naso-brain transport. Clinical signs of PD, its pathophysiology, specific genetic determinants, diagnosis and therapy involved have been hashed out. Properties of brain-targeting NPs, transport efficacy and various nanocarriers developed so far also been furnished. In our opinion, nanotechnology-enabled naso-brain drug delivery is an excellent means of delivering neurotherapeutics and is a promising avenue for researchers to develop new formulations for the effective management of PD.

  5. Terahertz spectroscopy of brain tissue from a mouse model of Alzheimer's disease

    Science.gov (United States)

    Shi, Lingyan; Shumyatsky, Pavel; Rodríguez-Contreras, Adrián; Alfano, Robert

    2016-01-01

    The terahertz (THz) absorption and index of refraction of brain tissues from a mouse model of Alzheimer's disease (AD) and a control wild-type (normal) mouse were compared using THz time-domain spectroscopy (THz-TDS). Three dominating absorption peaks associated to torsional-vibrational modes were observed in AD tissue, at about 1.44, 1.8, and 2.114 THz, closer to the peaks of free tryptophan molecules than in normal tissue. A possible reason is that there is more free tryptophan in AD brain tissue, while in normal brain tissue more tryptophan is attached to other molecules. Our study suggests that THz-absorption modes may be used as an AD biomarker fingerprint in brain, and that THz-TDS is a promising technique for early diagnosis of AD.

  6. Midbrain morphology reflects extent of brain damage in Krabbe disease

    Energy Technology Data Exchange (ETDEWEB)

    Zuccoli, Giulio; Narayanan, Srikala; Panigrahy, Ashok [Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Section of Neuroradiology, Pittsburgh, PA (United States); Poe, Michele D.; Escolar, Maria L. [University of Pittsburgh, Program for the Study of Neurodevelopment in Rare Disorders, Children' s Hospital of Pittsburgh of University of Pittsburgh Medical Center, Pittsburgh, PA (United States)

    2015-07-15

    To study the relationships between midbrain morphology, Loes score, gross motor function, and cognitive function in infantile Krabbe disease. Magnetic resonance imaging (MRI) scans were evaluated by two neuroradiologists blinded to clinical status and neurodevelopmental function of children with early or late infantile Krabbe disease. A simplified qualitative 3-point scoring system based on midbrain morphology on midsagittal MRI was used. A score of 0 represented normal convex morphology of the midbrain, a score of 1 represented flattening of the midbrain, and a score of 3 represented concave morphology of the midbrain (hummingbird sign). Spearman correlations were estimated between this simplified MRI scoring system and the Loes score, gross motor score, and cognitive score. Forty-two MRIs of 27 subjects were reviewed. Analysis of the 42 scans showed normal midbrain morphology in 3 (7.1 %) scans, midbrain flattening in 11 (26.2 %) scans, and concave midbrain morphology (hummingbird sign) in 28 (66.7 %) scans. Midbrain morphology scores were positively correlated with the Loes score (r = 0.81, p < 0.001) and negatively correlated with both gross motor and cognitive scores (r = -.84, p < 0.001; r = -0.87, p < 0.001, respectively). The inter-rater reliability for the midbrain morphology scale was κ =.95 (95 % CI: 0.86-1.0), and the inter-rater reliability for the Loes scale was κ =.58 (95 % CI: 0.42-0.73). Midbrain morphology scores of midsagittal MRI images correlates with cognition and gross motor function in children with Krabbe disease. This MRI scoring system represents a simple but reliable method to assess disease progression in patients with infantile Krabbe disease. (orig.)

  7. A qualitative assessment of personal and social responsibility for kidney disease: the Increasing Kidney Disease Awareness Network Transplant Project.

    Science.gov (United States)

    Spigner, Clarence; Lyles, Courtney Rees; Galvin, Georgia; Sabin, Janice; Davis, Connie; Dick, Andre; Young, Bessie A

    2011-01-01

    Limited qualitative research has explored opinions of kidney disease health care providers regarding racial and ethnic disparities in access to and receipt of kidney transplantation. Key informant interviews were conducted among transplant nephrologists, nephrologists, transplant social workers, and transplant coordinators to determine barriers to transplantation among African Americans compared to whites with end-stage renal disease (ESRD). Thirty-eight interviews were audio recorded and transcribed to hardcopy for content analysis. Grounded theory was used to determine dominant themes within the interviews. Reliability and validity were ensured by several coinvestigators independently sorting verbatim responses used for generating themes and subsequent explanations. Several major categories arose from analysis of the transcripts. Under the category of personal and social responsibility for kidney transplantation, interviews revealed 4 major themes: negative personal behaviors, acquisition of and lack of self-treatment of comorbid conditions, lack of individual responsibility, and the need for more social responsibility. Many providers perceived patients as being largely responsible for the development of ESRD, while some providers expressed the idea that more social responsibility was needed to improve poor health status and disparities in kidney transplantation rates. Kidney disease health providers seemed torn between notions of patients' accountability and social responsibility for racial disparities in chronic kidney disease and ESRD. Further research is needed to clarify which aspects contribute most to disparities in access to transplantation.

  8. Gender differences in brain structure and resting-state functional connectivity related to narcissistic personality.

    Science.gov (United States)

    Yang, Wenjing; Cun, Lingli; Du, Xue; Yang, Junyi; Wang, Yanqiu; Wei, Dongtao; Zhang, Qinglin; Qiu, Jiang

    2015-06-25

    Although cognitive and personality studies have observed gender differences in narcissism, the neural bases of these differences remain unknown. The current study combined the voxel-based morphometry and resting state functional connectivity (rsFC) analyses to explore the sex-specific neural basis of narcissistic personality. The VBM results showed that the relationship between narcissistic personality and regional gray matter volume (rGMV) differed between sexes. Narcissistic scores had a significant positive correlation with the rGMV of the right SPL in females, but not in males. Further analyses were conducted to investigate the sex-specific relationship between rsFC and narcissism, using right SPL/frontal eye fields (FEF) as the seed regions (key nodes of the dorsal attention network, DAN). Interestingly, decreased anticorrelations between the right SPL/FEF and areas of the precuneus and middle frontal gyrus (key nodes of the the default mode network, DMN) were associated with higher narcissistic personality scores in males, whereas females showed the opposite tendency. The findings indicate that gender differences in narcissism may be associated with differences in the intrinsic and dynamic interplay between the internally-directed DMN and the externally-directed TPN. Morphometry and functional connectivity analyses can enhance our understanding of the neural basis of sex-specific narcissism.

  9. Brain structure in narcissistic personality disorder: a VBM and DTI pilot study.

    Science.gov (United States)

    Nenadic, Igor; Güllmar, Daniel; Dietzek, Maren; Langbein, Kerstin; Steinke, Johanna; Gaser, Christian

    2015-02-28

    We analysed T1-weighted MRI scans using voxel-based morphometry (VBM) and tract-based spatial statistics (TBBS) on diffusion tensor images (DTI) in narcissistic personality disorder (NaPD) patients and healthy controls. Grey matter deficits include right prefrontal and bilateral medial prefrontal/anterior cingulate cortices, and decreased fractional anisotropy in right frontal lobe white matter.

  10. Personality and complex brain networks: The role of openness to experience in default network efficiency

    OpenAIRE

    2015-01-01

    Abstract The brain's default network (DN) has been a topic of considerable empirical interest. In fMRI research, DN activity is associated with spontaneous and self‐generated cognition, such as mind‐wandering, episodic memory retrieval, future thinking, mental simulation, theory of mind reasoning, and creative cognition. Despite large literatures on developmental and disease‐related influences on the DN, surprisingly little is known about the factors that impact normal variation in DN functio...

  11. Video prompting versus other instruction strategies for persons with Alzheimer's disease.

    Science.gov (United States)

    Perilli, Viviana; Lancioni, Giulio E; Hoogeveen, Frans; Caffó, Alessandro; Singh, Nirbhay; O'Reilly, Mark; Sigafoos, Jeff; Cassano, Germana; Oliva, Doretta

    2013-06-01

    Two studies assessed the effectiveness of video prompting as a strategy to support persons with mild and moderate Alzheimer's disease in performing daily activities. In study I, video prompting was compared to an existing strategy relying on verbal instructions. In study II, video prompting was compared to another existing strategy relying on static pictorial cues. Video prompting and the other strategies were counterbalanced across tasks and participants and compared within alternating treatments designs. Video prompting was effective in all participants. Similarly effective were the other 2 strategies, and only occasional differences between the strategies were reported. Two social validation assessments showed that university psychology students and graduates rated the patients' performance with video prompting more favorably than their performance with the other strategies. Video prompting may be considered a valuable alternative to the other strategies to support daily activities in persons with Alzheimer's disease.

  12. Whole-brain atrophy differences between progressive supranuclear palsy and idiopathic Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Carlos Guevara

    2016-09-01

    Full Text Available Background: The absence of markers for ante-mortem diagnosis of progressive supranuclear palsy (PSP results in this disorder’s being commonly mistaken for other conditions, such as idiopathic Parkinson's disease (IPD. Such mistakes occur particularly in the initial stages, when ‘plus syndrome’ has not yet clinically emerged.Objective. To investigate global brain volume and tissue loss in patients with PSP relative to patients with IPD and healthy controls and correlations between clinical parameters and magnetic resonance imaging (MRI-derived brain volume estimates.Methods: T1-weighted images were obtained from three groups of Chilean Latin American adults: 21 patients with IPD, 18 patients with PSP and 14 healthy controls. We used Structural Imaging Evaluation with Normalization of Atrophy (SIENAX to assess white matter, gray matter and whole-brain volumes (normalized to cranial volume. Imaging data were used to analyze putative correlations with the clinical status of PSP and IPD patients using the Unified Parkinson’s Disease Rating Scale Part III, Hoehn and Yahr, the Clinical Global Impression for Disease Severity Scale and the Frontal Assessment Battery.Results: PSP patients had significantly lower whole brain volume than both IPD patients and controls. Whole brain volume reduction in PSP patients was primarily attributable to gray matter volume reduction. We found a significant correlation between brain volume reduction and clinical status in the PSP group.Conclusions: At the group level, whole brain and gray matter volumes differentiated patients with PSP from patients with IPD. There was also significant clinical-imaging correlations with motor disturbances in PSP.

  13. Whole-Brain Atrophy Differences between Progressive Supranuclear Palsy and Idiopathic Parkinson’s Disease

    Science.gov (United States)

    Guevara, Carlos; Bulatova, Katherina; Barker, Gareth J.; Gonzalez, Guido; Crossley, Nicolas A.; Kempton, Matthew J.

    2016-01-01

    Background: The absence of markers for ante-mortem diagnosis of progressive supranuclear palsy (PSP), results in this disorder being commonly mistaken for other conditions, such as idiopathic Parkinson’s disease (IPD). Such mistakes occur particularly in the initial stages, when “plus syndrome” has not yet clinically emerged. Objective: To investigate the global brain volume and tissue loss in patients with PSP relative to patients with IPD and healthy controls and correlations between clinical parameters and magnetic resonance imaging (MRI)-derived brain volume estimates. Methods: T1-weighted images were obtained from three groups of Chilean Latin American adults: 21 patients with IPD, 18 patients with PSP and 14 healthy controls. We used Structural Imaging Evaluation with Normalization of Atrophy (SIENAX) to assess white matter, gray matter and whole-brain volumes (normalized to cranial volume). Imaging data were used to analyze putative correlations with the clinical status of PSP and IPD patients using the Unified Parkinson’s Disease Rating Scale Part III (UPDRS III), Hoehn and Yahr (H&Y), the Clinical Global Impression for Disease Severity Scale (CGI-S) and the Frontal Assessment Battery (FAB). Results: PSP patients had significantly lower whole brain volume than both IPD patients and controls. Whole brain volume reduction in PSP patients was primarily attributable to gray matter volume reduction. We found a significant correlation between brain volume reduction and clinical status in the PSP group. Conclusions: At the group level, the whole brain and gray matter volumes differentiated patients with PSP from patients with IPD. There was also significant clinical-imaging correlations with motor disturbances in PSP. PMID:27679572

  14. Perceived threat of Alzheimer disease (AD): the role of personal experience with AD.

    Science.gov (United States)

    Suhr, Julie A; Kinkela, Jessica H

    2007-01-01

    The fear of developing Alzheimer disease (AD) is highly salient, particularly for biologic family members. The current study evaluated social/cognitive explanations for perceived AD threat beyond genetic relatedness, including personal experience with AD, belief in negative aging stereotypes, and performance on delayed memory tasks. Participants were 97 healthy older adults aged 50 to 85, self-referred for a free community memory screen. Results showed that, as expected, personal AD experience was related to perceived AD threat. Furthermore, consistent with expectations, AD experience moderated the relationship between perceived AD threat and other explanatory variables, including age, belief in negative aging stereotypes, and cognitive performance. In those with AD experience, whether genetic or not, younger age was associated with more perceived AD threat, but an inverse relationship was seen in those without AD experience. Those with genetic AD experience seem particularly vulnerable to the effects of negative age stereotype beliefs on perceived AD threat, and show an inverse relationship between their actual cognitive performance and their perception of personal AD threat. Results highlight the importance of considering personal experience with AD when assessing a person's self-reported concerns about AD or his/her own memory changes.

  15. Feasibility of Using Cranial Electrotherapy Stimulation for Pain in Persons with Parkinson's Disease

    Directory of Open Access Journals (Sweden)

    Diana H. Rintala

    2010-01-01

    Full Text Available Objectives. To assess the feasibility of treating musculoskeletal pain in the lower back and/or lower extremities in persons with Parkinson's disease (PD with cranial electrotherapy stimulation (CES. Design. Randomized, controlled, double-blind trial. Setting. Veterans Affairs Medical Center, Community. Participants. Nineteen persons with PD and pain in the lower back and/or lower extremities. Thirteen provided daily pain rating data. Intervention. Of the thirteen participants who provided daily pain data, 6 were randomly provided with active CES devices and 7 with sham devices to use at home 40 minutes per day for six weeks. They recorded their pain ratings on a 0-to-10 scale immediately before and after each session. Main Outcome Measure. Average daily change in pain intensity. Results. Persons receiving active CES had, on average, a 1.14-point decrease in pain compared with a 0.23-point decrease for those receiving sham CES (Wilcoxon Z=−2.20, P=.028. Conclusion. Use of CES at home by persons with PD is feasible and may be somewhat helpful in decreasing pain. A larger study is needed to determine the characteristics of persons who may experience meaningful pain reduction with CES. Guidelines for future studies are provided.

  16. Diagnostic Usefulness of 3 Tesla MRI of the Brain for Cushing Disease in a Child

    OpenAIRE

    Ono, Erina; Ozawa, Ayako; Matoba, Kaori; Motoki, Takanori; Tajima, Asako; Miyata, Ichiro; Ito, Junko; Inoshita, Naoko; Yamada, Syozo; Ida, Hiroyuki

    2011-01-01

    It is sometimes difficult to confirm the location of a microadenoma in Cushing disease. Recently, we experienced an 11-yr-old female case of Cushing disease with hyperprolactinemia. She was referred to our hospital because of decrease of height velocity with body weight gain. On admission, she had typical symptoms of Cushing syndrome. Although no pituitary microadenomas were detected on 1.5 Tesla MRI of the brain, endocrinological examinations including IPS and CS sampling were consistent wit...

  17. Evidence for enhanced aluminum concentration in brain tissue from Alzheimer's disease patients using PIXE

    Science.gov (United States)

    Debray, M. E.; Kreiner, A. J.; Buhler, M.; Cardona, M. A.; Hojman, D.; Kesque, J. M.; Levinton, G.; Menéndez, J. J.; Naab, F.; Ozafrán, M. J.; Somacal, H.; Vázquez, M. E.; Grahmann, H.; Davidson, M.; Davidson, J.; Levin, M. E.; Mangone, C. A.; Caccuri, R. L.; Tokuda, A.; Eurnekian, A. A.; González, D.; López, C.; Roses, O. E.

    1997-02-01

    The Particle Induced X-Ray Emission (PIXE) analytical technique with 16O ion beams (18 MeV) was applied to the study of elemental composition at different brain regions of patients with a confirmed post-mortem diagnosis of Alzheimer's disease and in samples from control subjects. The results obtained in the actual study show a clear correlation between occurrence of Alzheimer's disease and the presence and increased concentration of aluminum (Al).

  18. Quantitative analysis of gait and balance response to deep brain stimulation in Parkinson's disease

    OpenAIRE

    Mera, Thomas O.; Filipkowski, Danielle E.; Riley, David E.; Whitney, Christina M.; Walter, Benjamin L.; Gunzler, Steven A; Giuffrida, Joseph P

    2012-01-01

    Gait and balance disturbances in Parkinson’s disease (PD) can be debilitating and may lead to increased fall risk. Deep brain stimulation (DBS) is a treatment option once therapeutic benefits from medication are limited due to motor fluctuations and dyskinesia. Optimizing DBS parameters for gait and balance can be significantly more challenging than for other PD motor symptoms. Furthermore, inter-rater reliability of the standard clinical PD assessment scale, Unified Parkinson’s Disease Ratin...

  19. Parkinson’s Brain Disease Prediction Using Big Data Analytics

    Directory of Open Access Journals (Sweden)

    N. Shamli

    2016-06-01

    Full Text Available In healthcare industries, the demand for maintaining large amount of patients’ data is steadily growing due to rising population which has resulted in the increase of details about clinical and laboratory tests, imaging, prescription and medication. These data can be called “Big Data”, because of their size, complexity and diversity. Big data analytics aims at improving patient care and identifying preventive measures proactively. To save lives and recommend life style changes for a peaceful and healthier life at low costs. The proposed predictive analytics framework is a combination of Decision Tree, Support Vector Machine and Artificial Neural Network which is used to gain insights from patients. Parkinson’s disease voice dataset from UCI Machine learning repository is used as input. The experimental results show that early detection of disease will facilitate clinical monitoring of elderly people and increase the chances of their life span and improved lifestyle to lead peaceful life.

  20. Predictors of Loneliness in Caregivers of Persons with Parkinson’s Disease

    OpenAIRE

    McRae, Cynthia; Fazio, Emily; Hartsock, Gina; Kelley, Livia; Urbanski, Shawna; Russell, Dan

    2009-01-01

    This study examined loneliness among caregivers of individuals with Parkinson’s disease (PD). The sample included 70 caregivers (74% female; 96% spouses) who were currently living with the patient. A postal survey was sent to caregivers of persons with PD on the mailing list of a regional Parkinson association; response rate was 39%. Assessment instruments included the UCLA Loneliness Scale, Social Provisions Scale, Hoehn and Yahr (caregiver version), a perceived Self-Efficacy Scale developed...

  1. Role of Lipids in Brain Injury and Diseases.

    Science.gov (United States)

    Adibhatla, Rao Muralikrishna; Hatcher, J F

    2007-08-01

    Lipid metabolism is of particular interest due to its high concentration in CNS. The importance of lipids in cell signaling and tissue physiology is demonstrated by many CNS disorders and injuries that involve deregulated metabolism. The long suffering lipid field is gaining reputation and respect as evidenced through the Center of Biomedical Research Excellence in Lipidomics and Pathobiology (COBRE), Lipid MAPS (Metabolites And Pathways Strategy) Consortium sponsored by NIH, European initiatives for decoding the lipids through genomic approaches, and Genomics of Lipid-associated Disorder (GOLD) project initiated by Austrian government. This review attempts to provide an overview of the lipid imbalances associated with neurological disorders (Alzheimer's, Parkinson's; Niemann-Pick; Multiple sclerosis, Huntington, amyotrophic lateral sclerosis, schizophrenia, bipolar disorders and epilepsy) and CNS injury (Stroke, traumatic brain injury; and spinal cord injury) and a few provocative thoughts. Lipidomic analyses along with RNA silencing will provide new insights into the role of lipid intermediates in cell signaling and hopefully open new avenues for prevention or treatment options.

  2. Mechanisms linking brain insulin resistance to Alzheimer's disease

    OpenAIRE

    Maria Niures P.S. Matioli; Ricardo Nitrini

    2015-01-01

    Several studies have indicated that Diabetes Mellitus (DM) can increase the risk of developing Alzheimer's disease (AD). This review briefly describes current concepts in mechanisms linking DM and insulin resistance/deficiency to AD. Insulin/insulin-like growth factor (IGF) resistance can contribute to neurodegeneration by several mechanisms which involve: energy and metabolism deficits, impairment of Glucose transporter-4 function, oxidative and endoplasmic reticulum stress, mitochondrial dy...

  3. Repurposing diabetes drugs for brain insulin resistance in Alzheimer disease.

    Science.gov (United States)

    Yarchoan, Mark; Arnold, Steven E

    2014-07-01

    A growing body of clinical and epidemiological research suggests that two of the most common diseases of aging, type 2 diabetes (T2DM) and Alzheimer disease (AD), are linked. The nature of the association is not known, but this observation has led to the notion that drugs developed for the treatment of T2DM may be beneficial in modifying the pathophysiology of AD and maintaining cognitive function. Recent advances in the understanding of the biology of T2DM have resulted in a growing number of therapies that are approved or in clinical development for this disease. This review summarizes the evidence that T2DM and AD are linked, with a focus on the cellular and molecular mechanisms in common, and then assesses the various clinical-stage diabetes drugs for their potential activity in AD. At a time when existing therapies for AD offer only limited symptomatic benefit for some patients, additional clinical trials of diabetes drugs are needed to at least advance the care of T2DM patients at risk for or with comorbid AD and also to determine their value for AD in general. © 2014 by the American Diabetes Association.

  4. Reaching the Socially Isolated Person with Alzheimer's Disease Through Group Music Therapy - A Case Report

    Directory of Open Access Journals (Sweden)

    Vicky Abad

    2002-11-01

    Full Text Available The purpose of this report is to present a case on John, an 82 year old man with Alzheimer's disease, who resides in a dementia specific unit of a nursing home. People with dementia who require institutional care are often at risk of social isolation, due to the regressive nature of the disease, and the potential of developing behavioural disturbances. This case story demonstrates how group music therapy can be individually tailored to meet the needs of people with dementia who are socially isolated as a result of behavioural challenges, including aggressive and agitating behaviours, and therefore improve the quality of the person's life.

  5. Propranolol in the treatment of assaultive patients with organic brain disease.

    Science.gov (United States)

    Greendyke, R M; Schuster, D B; Wooton, J A

    1984-10-01

    Propranolol in doses up to 520 mg/day was administered to eight patients with organic brain disease characterized by violent and assaultive behavior refractory to conventional treatment. Improvement was demonstrated in the seven patients able to tolerate adequate drug dosages. Hypotension, bradycardia, and interactions with other medications constituted complications.

  6. Rest and action tremor in Parkinson's disease: effects of Deep Brain Stimulation

    NARCIS (Netherlands)

    Heida, Tjitske; Wentink, E.C.

    2010-01-01

    One of the cardinal symptoms of Parkinson’s disease is rest tremor. While rest tremor generally disappears during sleep and voluntary movement, action tremor may be triggered by voluntary movement, and may even be more disabling than rest tremor. Deep brain stimulation (DBS) in the subthalamic

  7. Blood-brain barrier P-glycoprotein function is not impaired in early Parkinson's disease

    NARCIS (Netherlands)

    Bartels, A. L.; van Berckel, B. N. M.; Lubberink, M.; Luurtsema, G.; Lammertsma, A. A.; Leenders, K. L.

    2008-01-01

    The cause of Parkinson's disease (PD) is unknown. Genetic susceptibility and exposure to environmental toxins contribute to specific neuronal loss in PD. Decreased blood-brain barrier (BBB) P-glycoprotein (P-gp) efflux function has been proposed as a possible causative link between toxin exposure an

  8. Effect of Transcranial Brain Stimulation for the Treatment of Alzheimer Disease: A Review

    OpenAIRE

    Raffaele Nardone; Jürgen Bergmann; Monica Christova; Francesca Caleri; Frediano Tezzon; Gunther Ladurner; Eugen Trinka; Stefan Golaszewski

    2011-01-01

    Available pharmacological treatments for Alzheimer disease (AD) have limited effectiveness, are expensive, and sometimes induce side effects. Therefore, alternative or complementary adjuvant therapeutic strategies have gained increasing attention. The development of novel noninvasive methods of brain stimulation has increased the interest in neuromodulatory techniques as potential therapeutic tool for cognitive rehabilitation in AD. In particular, repetitive transcranial magnetic stimulat...

  9. Subthalamic Nucleus Deep Brain Stimulation Changes Velopharyngeal Control in Parkinson's Disease

    Science.gov (United States)

    Hammer, Michael J.; Barlow, Steven M.; Lyons, Kelly E.; Pahwa, Rajesh

    2011-01-01

    Purpose: Adequate velopharyngeal control is essential for speech, but may be impaired in Parkinson's disease (PD). Bilateral subthalamic nucleus deep brain stimulation (STN DBS) improves limb function in PD, but the effects on velopharyngeal control remain unknown. We tested whether STN DBS would change aerodynamic measures of velopharyngeal…

  10. Tremor Reduction by Deep Brain Stimulation Is Associated With Gamma Power Suppression in Parkinson's Disease

    NARCIS (Netherlands)

    Beudel, Martijn; Little, Simon; Pogosyan, Alek; Ashkan, Keyoumars; Foltynie, Thomas; Limousin, Patricia; Zrinzo, Ludvic; Hariz, Marwan; Bogdanovic, Marko; Cheeran, Binith; Green, Alexander L.; Aziz, Tipu; Thevathasan, Wesley; Brown, Peter

    2015-01-01

    Objectives: Rest tremor is a cardinal symptom of Parkinson's disease (PD), and is readily suppressed by deep brain stimulation (DBS) of the subthalamic nucleus (STN). The therapeutic effect of the latter on bradykinesia and rigidity has been associated with the suppression of exaggerated beta (13-30

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

    NARCIS (Netherlands)

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

    2016-01-01

    Chronic dopamine depletion in Parkinson's disease leads to progressive motor and cognitive impairment, which is associated with the emergence of characteristic patterns of synchronous oscillatory activity within cortico-basal-ganglia circuits. Deep brain stimulation of the subthalamic nucleus is an

  12. Microprobe PIXE analysis of aluminium in the brains of patients with Alzheimer's disease

    Science.gov (United States)

    Yumoto, S.; Horino, Y.; Mokuno, Y.; Kakimi, S.; Fujii, K.

    1996-04-01

    To investigate the cause of Alzheimer's disease (senile dementia), we examined aluminium (Al) in the rat liver, and in the brains (hippocampus) of Alzheimer's disease patients using heavy ion (5 MeV Si 3+) microprobe and proton (2 MeV) microprobe PIXE analysis. Heavy ion microprobes (3 MeV Si 2+) have several time's higher sensitivity for Al detection than 2 MeV proton microprobes. (1) In the rat liver, Al was detected in the cell nuclei, where phosphorus (P) was most densely distributed. (2) We also demonstrated Al in the cell nuclei isolated from Alzheimer's disease brains using heavy ion (5 MeV Si 3+) microprobes. Al spectra were detected using 2 MeV proton microprobes in the isolated brain cell nuclei. Al could not be observed in areas where P was present in relatively small amounts, or was absent. Our results indicate that Alzheimer's disease is caused by irreversible accumulation of Al in the nuclei of brain cells.

  13. Rest and action tremor in Parkinson's disease: effects of Deep Brain Stimulation

    NARCIS (Netherlands)

    Heida, T.; Wentink, E.C.

    2010-01-01

    One of the cardinal symptoms of Parkinson’s disease is rest tremor. While rest tremor generally disappears during sleep and voluntary movement, action tremor may be triggered by voluntary movement, and may even be more disabling than rest tremor. Deep brain stimulation (DBS) in the subthalamic nucle

  14. Microstructural brain abnormalities in Huntington's disease : A two-year follow-up

    NARCIS (Netherlands)

    Odish, Omar F F; Leemans, A; Reijntjes, Robert H A M; van den Bogaard, Simon J A; Dumas, Eve M.; Wolterbeek, Ron; Tax, Chantal M W; Kuijf, Hugo J.; Vincken, Koen L.; van der Grond, Jeroen; Roos, Raymund A C

    2015-01-01

    Objectives: To investigate both cross-sectional and time-related changes of striatal and whole-brain microstructural properties in different stages of Huntington's disease (HD) using diffusion tensor imaging. Experimental design: From the TRACK-HD study, premanifest gene carriers (preHD), early mani

  15. Personalized Comments on Challenges and Opportunities in Kidney Disease Therapeutics: The Glom-NExT Symposium.

    Science.gov (United States)

    Greka, Anna; Gibson, Deb; Mundel, Peter; Demetri, George; Hildebrandt, Friedhelm; Pollak, Martin; Florez, Jose

    2016-11-01

    In the face of ever-increasing incidence and prevalence of kidney disease worldwide, the unmet need for new treatments is unprecedented. Precision medicine is defined as the use of modern technologies to identify mechanisms of diseases in individual patients, and thus deploy treatment using tailored, targeted approaches, in the hopes of avoiding unnecessary toxicities and complications. Is there a place for kidney disease therapeutics in this space? If so, what is required to make significant progress toward precision nephrology? To answer these critical questions, we present a series of personalized comments corresponding to the responses offered to these very questions during the Inaugural Glom-NExT Symposium held at Harvard Medical School on October 23, 2014, a national meeting focused exclusively on kidney disease therapeutics. Copyright © 2016.

  16. Comorbidities as risk factors of chronic kidney disease in HIV-infected persons

    Directory of Open Access Journals (Sweden)

    Zofia Marchewka

    2015-12-01

    Full Text Available Significant survival prolongation in HIV-infected patients due to effective antiretroviral therapy is connected with increasing prevalence of chronic non-infective diseases in this population, among them chronic kidney disease. The pathogenesis of kidney disease in the setting of HIV includes conditions specific for HIV infection: direct effect of the virus, stage of immunodeficiency and drug toxicity. Chronic comorbidities, such as diabetes mellitus, hypertension, and hyperlipidemia, are additional significant risk factors of kidney disease. In HIV-infected individuals some distinct features of these conditions are observed, which are partly related to the virus and antiretroviral therapy. The article summarizes the effect of comorbidities on kidney function in HIV-infected persons.

  17. Brain stem and cerebellum volumetric analysis of Machado Joseph disease patients

    Directory of Open Access Journals (Sweden)

    S T Camargos

    2011-01-01

    Full Text Available Machado-Joseph disease, or spinocerebellar ataxia type 3(MJD/SCA3, is the most frequent late onset spinocerebellar ataxia and results from a CAG repeat expansion in the ataxin-3 gene. Previous studies have found correlation between atrophy of cerebellum and brainstem with age and CAG repeats, although no such correlation has been found with disease duration and clinical manifestations. In this study we test the hypothesis that atrophy of cerebellum and brainstem in MJD/SCA3 is related to clinical severity, disease duration and CAG repeat length as well as to other variables such as age and ICARS (International Cooperative Ataxia Rating Scale. Whole brain high resolution MRI and volumetric measurement with cranial volume normalization were obtained from 15 MJD/SCA3 patients and 15 normal, age and sex-matchedcontrols. We applied ICARS and compared the score with volumes and CAG number, disease duration and age. We found significant correlation of both brain stem and cerebellar atrophy with CAG repeat length, age, disease duration and degree of disability. The Spearman rank correlation was stronger with volumetric reduction of the cerebellum than with brain stem. Our data allow us to conclude that volumetric analysis might reveal progressive degeneration after disease onset, which in turn is linked to both age and number of CAG repeat expansions in SCA 3.

  18. The levels of soluble versus insoluble brain Abeta distinguish Alzheimer's disease from normal and pathologic aging.

    Science.gov (United States)

    Wang, J; Dickson, D W; Trojanowski, J Q; Lee, V M

    1999-08-01

    The abundance and solubility of Abeta peptides are critical determinants of amyloidosis in Alzheimer's disease (AD). Hence, we compared levels of total soluble, insoluble, and total Abeta1-40 and Abeta1-42 in AD brains with those in age-matched normal and pathologic aging brains using a sandwich enzyme-linked immunosorbent assay (ELISA). Since the measurement of Abeta1-40 and Abeta1-42 depends critically on the specificity of the monoclonal antibodies used in the sandwich ELISA, we first demonstrated that each assay is specific for Abeta1-40 or Abeta1-42 and the levels of these peptides are not affected by the amyloid precursor protein in the brain extracts. Thus, this sandwich ELISA enabled us to show that the average levels of total cortical soluble and insoluble Abeta1-40 and Abeta1-42 were highest in AD, lowest in normal aging, and intermediate in pathologic aging. Remarkably, the average levels of insoluble Abeta1-40 were increased 20-fold while the average levels of insoluble Abeta1-42 were increased only 2-fold in the AD brains compared to pathologic aging brains. Further, the soluble pools of Abeta1-40 and Abeta1-42 were the largest fractions of total Abeta in the normal brain (i.e., 50 and 23%, respectively), but they were the smallest in the AD brain (i.e., 2.7 and 0.7%, respectively) and intermediate (i.e., 8 and 0.8%, respectively) in pathologic aging brains. Thus, our data suggest that pathologic aging is a transition state between normal aging and AD. More importantly, our findings imply that a progressive shift of brain Abeta1-40 and Abeta1-42 from soluble to insoluble pools and a profound increase in the levels of insoluble Abeta1-40 plays mechanistic roles in the onset and/or progression of AD.

  19. Blood-brain barrier P-glycoprotein function in Alzheimer's disease.

    Science.gov (United States)

    van Assema, Daniëlle M E; Lubberink, Mark; Bauer, Martin; van der Flier, Wiesje M; Schuit, Robert C; Windhorst, Albert D; Comans, Emile F I; Hoetjes, Nikie J; Tolboom, Nelleke; Langer, Oliver; Müller, Markus; Scheltens, Philip; Lammertsma, Adriaan A; van Berckel, Bart N M

    2012-01-01

    A major pathological hallmark of Alzheimer's disease is accumulation of amyloid-β in senile plaques in the brain. Evidence is accumulating that decreased clearance of amyloid-β from the brain may lead to these elevated amyloid-β levels. One of the clearance pathways of amyloid-β is transport across the blood-brain barrier via efflux transporters. P-glycoprotein, an efflux pump highly expressed at the endothelial cells of the blood-brain barrier, has been shown to transport amyloid-β. P-glycoprotein function can be assessed in vivo using (R)-[(11)C]verapamil and positron emission tomography. The aim of this study was to assess blood-brain barrier P-glycoprotein function in patients with Alzheimer's disease compared with age-matched healthy controls using (R)-[(11)C]verapamil and positron emission tomography. In 13 patients with Alzheimer's disease (age 65 ± 7 years, Mini-Mental State Examination 23 ± 3), global (R)-[(11)C]verapamil binding potential values were increased significantly (P = 0.001) compared with 14 healthy controls (aged 62 ± 4 years, Mini-Mental State Examination 30 ± 1). Global (R)-[(11)C]verapamil binding potential values were 2.18 ± 0.25 for patients with Alzheimer's disease and 1.77 ± 0.41 for healthy controls. In patients with Alzheimer's disease, higher (R)-[(11)C]verapamil binding potential values were found for frontal, parietal, temporal and occipital cortices, and posterior and anterior cingulate. No significant differences between groups were found for medial temporal lobe and cerebellum. These data show altered kinetics of (R)-[(11)C]verapamil in Alzheimer's disease, similar to alterations seen in studies where P-glycoprotein is blocked by a pharmacological agent. As such, these data indicate that P-glycoprotein function is decreased in patients with Alzheimer's disease. This is the first direct evidence that the P-glycoprotein transporter at the blood-brain barrier is compromised in sporadic

  20. Understanding the Connection Between Traumatic Brain Injury and Alzheimer’s Disease: A Population Based Medical Record Review Analysis

    Science.gov (United States)

    2016-10-01

    AWARD NUMBER: W81XWH-15-1-0573 TITLE: Understanding the Connection Between Traumatic Brain Injury and Alzheimer’s Disease: A Population-Based...Sep 2015 - 14 Sep 2016 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Understanding the Connection Between Traumatic Brain Injury and Alzheimer’s Disease...TERMS Population; epidemiology; dementia; neurocognitive disorders; brain injuries; Parkinsonian disorders 16. SECURITY CLASSIFICATION OF: U 17

  1. The Effect of Disease-Modifying Drugs on Brain Atrophy in Relapsing-Remitting Multiple Sclerosis: A Meta-Analysis

    OpenAIRE

    Pierre Branger; Jean-Jacques Parienti; Maria Pia Sormani; Gilles Defer

    2016-01-01

    Background The quantification of brain atrophy in relapsing-remitting multiple sclerosis (RRMS) may serve as a marker of disease progression and treatment response. We compared the association between first-line (FL) or second-line (SL) disease-modifying drugs (DMDs) and brain volume changes over time in RRMS. Materials and Methods We reviewed clinical trials in RRMS between January 1, 1995 and June 1, 2014 that assessed the effect of DMDs and reported data on brain atrophy in Medline, Embase...

  2. A Derangement of the Brain Wound Healing Process May Cause Some Cases of Alzheimer’s Disease

    OpenAIRE

    Lehrer, Steven; Rheinstein, Peter H.

    2016-01-01

    A derangement of brain wound healing may cause some cases of Alzheimer’s disease. Wound healing, a highly complex process, has four stages: hemostasis, inflammation, repair, and remodeling. Hemostasis and the initial phases of inflammation in brain tissue are typical of all vascularized tissue, such as skin. However, distinct differences arise in brain tissue during the later stages of inflammation, repair, and remodeling, and closely parallel the changes of Alzheimer’s disease. Our hypothesi...

  3. Integrating Mental Health In Care For Noncommunicable Diseases: An Imperative For Person-Centered Care.

    Science.gov (United States)

    Patel, Vikram; Chatterji, Somnath

    2015-09-01

    Mental disorders such as depression and alcohol use disorders often co-occur with other common noncommunicable diseases such as diabetes and heart disease. Furthermore, noncommunicable diseases are frequently encountered in patients with severe mental disorders such as schizophrenia. The pathways underlying the comorbidity of mental disorders and noncommunicable diseases are complex. For example, mental and physical noncommunicable diseases may have common environmental risk factors such as unhealthy lifestyles, and treatments for one condition may have side effects that increase the risk of another condition. Building on the robust evidence base for effective treatments for a range of mental disorders, there is now a growing evidence base for how such treatments can be integrated into the care of people with noncommunicable diseases. The best-established delivery model is a team approach that features a nonspecialist case manager who coordinates care with primary care physicians and specialists. This approach maximizes efficiencies in person-centered care, which are essential for achieving universal health coverage for both noncommunicable diseases and mental disorders. A number of research gaps remain, but there is sufficient evidence for policy makers to immediately implement measures to integrate mental health and noncommunicable disease care in primary care platforms.

  4. Personality modulates the effects of emotional arousal and valence on brain activation

    OpenAIRE

    Kehoe, Elizabeth G.; Toomey, John M.; Balsters, Joshua H.; Bokde, Arun L.W.

    2011-01-01

    The influence of personality on the neural correlates of emotional processing is still not well characterized. We investigated the relationship between extraversion and neuroticism and emotional perception using functional magnetic resonance imaging (fMRI) in a group of 23 young, healthy women. Using a parametric modulation approach, we examined how the blood oxygenation level dependent (BOLD) signal varied with the participants’ ratings of arousal and valence, and whether levels of extravers...

  5. PHIT for Duty, a Personal Health Intervention Tool for Psychological Health and Traumatic Brain Injury

    Science.gov (United States)

    2016-06-01

    muscle relaxation ), tools (e.g., sleep hygiene checklist), and self-monitoring activities (e.g., alcohol use diary). All of these screening instruments...Persons with mild or moderate risk (i.e., subclinical scores), are presented with a suite of interventional, therapeutic, and monitoring activities to...cognitive behavior change (e.g., alcohol use), and self-monitoring activities . The mindfulness content comprises learning materials and meditation

  6. Upregulation of calpain activity precedes tau phosphorylation and loss of synaptic proteins in Alzheimer's disease brain.

    Science.gov (United States)

    Kurbatskaya, Ksenia; Phillips, Emma C; Croft, Cara L; Dentoni, Giacomo; Hughes, Martina M; Wade, Matthew A; Al-Sarraj, Safa; Troakes, Claire; O'Neill, Michael J; Perez-Nievas, Beatriz G; Hanger, Diane P; Noble, Wendy

    2016-03-31

    Alterations in calcium homeostasis are widely reported to contribute to synaptic degeneration and neuronal loss in Alzheimer's disease. Elevated cytosolic calcium concentrations lead to activation of the calcium-sensitive cysteine protease, calpain, which has a number of substrates known to be abnormally regulated in disease. Analysis of human brain has shown that calpain activity is elevated in AD compared to controls, and that calpain-mediated proteolysis regulates the activity of important disease-associated proteins including the tau kinases cyclin-dependent kinase 5 and glycogen kinase synthase-3. Here, we sought to investigate the likely temporal association between these changes during the development of sporadic AD using Braak staged post-mortem brain. Quantification of protein amounts in these tissues showed increased activity of calpain-1 from Braak stage III onwards in comparison to controls, extending previous findings that calpain-1 is upregulated at end-stage disease, and suggesting that activation of calcium-sensitive signalling pathways are sustained from early stages of disease development. Increases in calpain-1 activity were associated with elevated activity of the endogenous calpain inhibitor, calpastatin, itself a known calpain substrate. Activation of the tau kinases, glycogen-kinase synthase-3 and cyclin-dependent kinase 5 were also found to occur in Braak stage II-III brain, and these preceded global elevations in tau phosphorylation and the loss of post-synaptic markers. In addition, we identified transient increases in total amyloid precursor protein and pre-synaptic markers in Braak stage II-III brain, that were lost by end stage Alzheimer's disease, that may be indicative of endogenous compensatory responses to the initial stages of neurodegeneration. These findings provide insight into the molecular events that underpin the progression of Alzheimer's disease, and further highlight the rationale for investigating novel treatment

  7. Network science and the human brain: Using graph theory to understand the brain and one of its hubs, the amygdala, in health and disease.

    Science.gov (United States)

    Mears, David; Pollard, Harvey B

    2016-06-01

    Over the past 15 years, the emerging field of network science has revealed the key features of brain networks, which include small-world topology, the presence of highly connected hubs, and hierarchical modularity. The value of network studies of the brain is underscored by the range of network alterations that have been identified in neurological and psychiatric disorders, including epilepsy, depression, Alzheimer's disease, schizophrenia, and many others. Here we briefly summarize the concepts of graph theory that are used to quantify network properties and describe common experimental approaches for analysis of brain networks of structural and functional connectivity. These range from tract tracing to functional magnetic resonance imaging, diffusion tensor imaging, electroencephalography, and magnetoencephalography. We then summarize the major findings from the application of graph theory to nervous systems ranging from Caenorhabditis elegans to more complex primate brains, including man. Focusing, then, on studies involving the amygdala, a brain region that has attracted intense interest as a center for emotional processing, fear, and motivation, we discuss the features of the amygdala in brain networks for fear conditioning and emotional perception. Finally, to highlight the utility of graph theory for studying dysfunction of the amygdala in mental illness, we review data with regard to changes in the hub properties of the amygdala in brain networks of patients with depression. We suggest that network studies of the human brain may serve to focus attention on regions and connections that act as principal drivers and controllers of brain function in health and disease.

  8. Noninvasive brain stimulation for Parkinson's disease and dystonia.

    Science.gov (United States)

    Wu, Allan D; Fregni, Felipe; Simon, David K; Deblieck, Choi; Pascual-Leone, Alvaro

    2008-04-01

    Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are promising noninvasive cortical stimulation methods for adjunctive treatment of movement disorders. They avoid surgical risks and provide theoretical advantages of specific neural circuit neuromodulation. Neuromodulatory effects depend on extrinsic stimulation factors (cortical target, frequency, intensity, duration, number of sessions), intrinsic patient factors (disease process, individual variability and symptoms, state of medication treatment), and outcome measures. Most studies to date have shown beneficial effects of rTMS or tDCS on clinical symptoms in Parkinson's disease (PD) and support the notion of spatial specificity to the effects on motor and nonmotor symptoms. Stimulation parameters have varied widely, however, and some studies are poorly controlled. Studies of rTMS or tDCS in dystonia have provided abundant data on physiology, but few on clinical effects. Multiple mechanisms likely contribute to the clinical effects of rTMS and tDCS in movement disorders, including normalization of cortical excitability, rebalancing of distributed neural network activity, and induction of dopamine release. It remains unclear how to individually adjust rTMS or tDCS factors for the most beneficial effects on symptoms of PD or dystonia. Nonetheless, the noninvasive nature, minimal side effects, positive effects in preliminary clinical studies, and increasing evidence for rational mechanisms make rTMS and tDCS attractive for ongoing investigation.

  9. Commentaryon using the SF-36 or MOS-HIV in studies of persons with HIV disease

    Directory of Open Access Journals (Sweden)

    Hays Ron D

    2003-07-01

    Full Text Available Abstract The purposewas to compare and comment on use of the SF-36 and MOS-HIV instrumentsin studies of persons with HIV disease. Three medical informationdatabases were searched to identify examples of HIV studies thatincluded the MOS-HIV or SF-36. Thirty-nine and 14 published articleswere identified for illustration in comparing the use of the MOS-HIVand SF-36 in HIV disease, respectively. Support for the reliabilityand construct validity of the MOS-HIV and SF-36 was found. Ceilingand floor effects were reported for both the MOS-HIV and SF-36;however, ceiling effects were more common for the MOS-HIV, in partdue to fewer items in the physical, social, and role functioningdomains. The MOS-HIV measures three domains hypothesized to be associatedwith the health deterioration of HIV disease not measured by theSF-36; however, these domains may not assess aspects of HIV diseasethat typify the majority of the persons with HIV disease today.National norms for the U.S. adult population (and other nationsare available for the SF-36. In addition, the SF-36 has been usedin a wide variety of patient populations, enabling comparisons ofHIV-infected persons with persons with other health conditions.No national norms for the MOS-HIV are available. We conclude thatthere is currently insufficient evidence in the literature to recommendthe use of the MOS-HIV over the SF-36 in HIV-infected persons. Althoughthe SF-36 is not targeted at HIV, it may be preferable to use theSF-36 over the MOS-HIV due to fewer ceiling effects, availabilityof national norms, and the vast amount of data for other populationsin the U.S. and around the world. Head-to-head comparisons demonstratingthe unique value of the MOS-HIV over the SF-36 are clearly needed.More importantly, additional work needs to be directed at comparingthe MOS-HIV and other putatively HIV-targeted instruments to oneanother to help demarcate aspects of HRQOL that are truly genericversus specific to HIV disease

  10. High-intensity resistance training amplifies muscle hypertrophy and functional gains in persons with Parkinson's disease.

    Science.gov (United States)

    Dibble, Leland E; Hale, Tessa F; Marcus, Robin L; Droge, John; Gerber, J Parry; LaStayo, Paul C

    2006-09-01

    Strength deficits in persons with Parkinson's disease (PD) have been identified as a contributor to bradykinesia. However, there is little research that examines the effect of resistance training on muscle size, muscle force production, and mobility in persons with PD. The purpose of this exploratory study was to examine, in persons with PD, the changes in quadriceps muscle volume, muscle force production, and mobility as a result of a 12-week high-force eccentric resistance training program and to compare the effects to a standard-care control. Nineteen individuals with idiopathic PD were recruited and consented to participate. Matched assignment for age and disease severity resulted in 10 participants in the eccentric group and 9 participants in the control group. All participants were tested prior to and following a 12-week intervention period with testing and training conducted at standardized times in their medication cycle. The eccentric group performed high-force quadriceps contractions on an eccentric ergometer 3 days a week for 12 weeks. The standard-care group exercise program encompassed standard exercise management of PD. The outcome variables were quadriceps muscle volume, muscle force, and mobility measures (6-minute walk, stair ascent/descent time). Each outcome variable was tested using separate one-way analyses of covariance on the difference scores. Muscle volume, muscle force, and functional status improvements occurred in persons with PD as a result of high-force eccentric resistance training. The eccentric group demonstrated significantly greater difference scores for muscle structure, stair descent, and 6-minute walk (P eccentric group consistently exceeded those in the standard-care group for all variables. To our knowledge, this is the first clinical trial to investigate and demonstrate the effects of eccentric resistance training on muscle hypertrophy, strength, and mobility in persons with PD. Additional research is needed to determine the

  11. Brain changes detected by functional magnetic resonance imaging and spectroscopy in patients with Crohn's disease.

    Science.gov (United States)

    Lv, Kun; Fan, Yi-Hong; Xu, Li; Xu, Mao-Sheng

    2017-05-28

    Crohn's disease (CD) is a chronic, non-specific granulomatous inflammatory disorder that commonly affects the small intestine and is a phenotype of inflammatory bowel disease (IBD). CD is prone to relapse, and its incidence displays a persistent increase in developing countries. However, the pathogenesis of CD is poorly understood, with some studies emphasizing the link between CD and the intestinal microbiota. Specifically, studies point to the brain-gut-enteric microbiota axis as a key player in the occurrence and development of CD. Furthermore, investigations have shown white-matter lesions and neurologic deficits in patients with IBD. Based on these findings, brain activity changes in CD patients have been detected by blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI). BOLD-fMRI functions by detecting a local increase in relative blood oxygenation that results from neurotransmitter activity and thus reflects local neuronal firing rates. Therefore, biochemical concentrations of neurotransmitters or metabolites may change in corresponding brain regions of CD patients. To further study this phenomenon, brain changes of CD patients can be detected non-invasively, effectively and accurately by BOLD-fMRI combined with magnetic resonance spectroscopy (MRS). This approach can further shed light on the mechanisms of the occurrence and development of neurological CD. Overall, this paper reviews the current status and prospects on fMRI and MRS for evaluation of patients with CD based on the brain-gut-enteric microbiota axis.

  12. An Anatomically Resolved Mouse Brain Proteome Reveals Parkinson Disease-relevant Pathways.

    Science.gov (United States)

    Jung, Sung Yun; Choi, Jong Min; Rousseaux, Maxime W C; Malovannaya, Anna; Kim, Jean J; Kutzera, Joachim; Wang, Yi; Huang, Yin; Zhu, Weimin; Maity, Suman; Zoghbi, Huda Yahya; Qin, Jun

    2017-04-01

    Here, we present a mouse brain protein atlas that covers 17 surgically distinct neuroanatomical regions of the adult mouse brain, each less than 1 mm(3) in size. The protein expression levels are determined for 6,500 to 7,500 gene protein products from each region and over 12,000 gene protein products for the entire brain, documenting the physiological repertoire of mouse brain proteins in an anatomically resolved and comprehensive manner. We explored the utility of our spatially defined protein profiling methods in a mouse model of Parkinson's disease. We compared the proteome from a vulnerable region (substantia nigra pars compacta) of wild type and parkinsonian mice with that of an adjacent, less vulnerable, region (ventral tegmental area) and identified several proteins that exhibited both spatiotemporal- and genotype-restricted changes. We validated the most robustly altered proteins using an alternative profiling method and found that these modifications may highlight potential new pathways for future studies. This proteomic atlas is a valuable resource that offers a practical framework for investigating the molecular intricacies of normal brain function as well as regional vulnerability in neurological diseases. All of the mouse regional proteome profiling data are published on line at http://mbpa.bprc.ac.cn/. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Transcranial magnetic stimulation of degenerating brain: a comparison of normal aging, Alzheimer's, Parkinson's and Huntington's disease.

    Science.gov (United States)

    Ljubisavljevic, M R; Ismail, F Y; Filipovic, S

    2013-07-01

    Although the brain's ability to change constantly in response to external and internal inputs is now well recognized the mechanisms behind it in normal aging and neurodegeneration are less well understood. To gain a better understanding, transcranial magnetic stimulation (TMS) has been used extensively to characterize non-invasively the cortical neurophysiology of the aging and degenerating brain. Furthermore, there has been a surge of studies examining whether repetitive TMS (rTMS) can be used to improve functional deficits in various conditions including normal aging, Alzheimer's and Parkinson's disease. The results of these studies in normal aging and neurodegeneration have emerged reasonably coherent in delineating the main pathology in spite of considerable technical limitations, omnipresent methodological variability, and extraordinary patient heterogeneity. Nevertheless, comparing and integrating what is known about TMS measurements of cortical excitability and plasticity in disorders that predominantly affect cortical brain structures with disorders that predominantly affect subcortical brain structures may provide better understanding of normal and abnormal brain aging fostering new. The present review provides a TMS perspective of changes in cortical neurophysiology and neurochemistry in normal aging and neurodegeneration by integrating what is revealed in individual TMS measurements of cortical excitability and plasticity in physiological aging, Alzheimer's, Parkinson's, and Huntington's, disease. The paper also reflects on current developments in utilizing TMS as a physiologic biomarker to discriminate physiologic aging from neurodegeneration and its potential as a method of therapeutic intervention.

  14. Brain region-specificity of palmitic acid-induced abnormalities associated with Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Melrose Joseph

    2008-06-01

    Full Text Available Abstract Background Alzheimer's disease (AD is a progressive, neurodegenerative disease mostly affecting the basal forebrain, cortex and hippocampus whereas the cerebellum is relatively spared. The reason behind this region-specific brain damage in AD is not well understood. Here, we report our data suggesting "differential free fatty acid metabolism in the different brain areas" as a potentially important factor in causing the region-specific damage observed in AD brain. Findings The astroglia from two different rat brain regions, cortex (region affected in AD and cerebellum (unaffected region, were treated with 0.2 mM of palmitic acid. The conditioned media were then transferred to the cortical neurons to study the possible effects on the two main, AD-associated protein abnormalities, viz. BACE1 upregulation and hyperphosphorylation of tau. The conditioned media from palmitic-acid treated cortical astroglia, but not the cerebellar astroglia, significantly elevated levels of phosphorylated tau and BACE1 in cortical neurons as compared to controls (47 ± 7% and 45 ± 4%, respectively. Conclusion The present data provide an experimental explanation for the region-specific damage observed in AD brain; higher fatty acid-metabolizing capacity of cortical astroglia as compared to cerebellar astroglia, may play a causal role in increasing vulnerability of cortex in AD, while sparing cerebellum.

  15. The role of ceramides in selected brain pathologies: ischemia/hypoxia, Alzheimer disease

    Directory of Open Access Journals (Sweden)

    Halina Car

    2012-05-01

    Full Text Available  Ceramides, members of the sphingolipids, are produced in the central nervous system by de novo synthesis, sphingomyelin hydrolysis or the so-called salvage pathway. They are engaged in formation of lipid rafts that are essential in regulation and transduction of signals coming to the cell from the environment. Ceramides represent the major transmitters of the sphingomyelin pathway of signal transduction. They regulate proliferation, differentiation, programmed cell death and senescence. Ceramide overexpression, mainly as a result of sphingomyelin hydrolysis, is a component of brain damage caused by ischemia and early reperfusion. Their high concentrations induce mitochondria-dependent neuronal apoptosis, exacerbate the synthesis of reactive oxygen species, decrease ATP level, inhibit electron transport and release cytochrome c, and activate caspase-3. Reduced ceramide accumulation in the brain, dependent mainly on ceramide synthesized de novo, may exert an anti-apoptotic effect after pre-conditioning. The increase of ceramide content in the brain was observed in Alzheimer disease and its animal models. Enhanced ceramide concentration in this pathology is an effect of their synthesis de novo or sphingomyelin metabolism augmentation. The ceramide pathway can directly stimulate biochemical changes in the brain noted at the onset of disease: tau overphosphorylation and β-amyloid peptide accumulation. The higher concentration of ceramides in blood in the pre-clinical phase of the illness may mark early brain changes.

  16. [The role of ceramides in selected brain pathologies: ischemia/hypoxia, Alzheimer disease].

    Science.gov (United States)

    Car, Halina; Zendzian-Piotrowska, Małgorzata; Fiedorowicz, Anna; Prokopiuk, Sławomir; Sadowska, Anna; Kurek, Krzysztof

    2012-05-30

     Ceramides, members of the sphingolipids, are produced in the central nervous system by de novo synthesis, sphingomyelin hydrolysis or the so-called salvage pathway. They are engaged in formation of lipid rafts that are essential in regulation and transduction of signals coming to the cell from the environment. Ceramides represent the major transmitters of the sphingomyelin pathway of signal transduction. They regulate proliferation, differentiation, programmed cell death and senescence. Ceramide overexpression, mainly as a result of sphingomyelin hydrolysis, is a component of brain damage caused by ischemia and early reperfusion. Their high concentrations induce mitochondria-dependent neuronal apoptosis, exacerbate the synthesis of reactive oxygen species, decrease ATP level, inhibit electron transport and release cytochrome c, and activate caspase-3. Reduced ceramide accumulation in the brain, dependent mainly on ceramide synthesized de novo, may exert an anti-apoptotic effect after pre-conditioning. The increase of ceramide content in the brain was observed in Alzheimer disease and its animal models. Enhanced ceramide concentration in this pathology is an effect of their synthesis de novo or sphingomyelin metabolism augmentation. The ceramide pathway can directly stimulate biochemical changes in the brain noted at the onset of disease: tau overphosphorylation and β-amyloid peptide accumulation. The higher concentration of ceramides in blood in the pre-clinical phase of the illness may mark early brain changes.

  17. Image-matching as a medical diagnostic support tool (DST) for brain diseases in children.

    Science.gov (United States)

    Huang, H K; Nielsen, J F; Nelson, Marvin D; Liu, Lifeng

    2005-01-01

    Imaging-matching is an important research area in imaging informatics. We have developed and evaluated a novel diagnostic support tool (DST) based on medical image matching using MR brain images. The approach consists of two steps, database generation and image matching. The database contains pre-diagnosed MR brain images. As the images are added to the database, they are registered to the 3D Talairach coordinate system. In addition, regions of interests (ROI) are generated, and image-processing techniques are used to extract relevant image parameters related to the brain and diseases from the ROIs and from the entire MR image. The second step is to retrieve relevant information from the database by performing image matching. In this step, the physician first submits a query image. The DST computes the similarity between the query image and each of the images in the database, and then presents the most similar images to the user. Since the database contains pre-diagnosed images, the retrieved cases tend to contain relevant diagnostic information. To evaluate the usefulness of the DST in a clinical setting, pediatric brain diseases were used. The database contains 2500 pediatric patients between ages 0 and 18 with brain Magnetic Resonance (MR) images of known brain lesions. A testbed was established at the Children's Hospital Los Angeles (CHLA) for acquiring MR images from the PACS server of patients with known lesions. These images were matched against those in the DST pediatric brain MR database. An expert pediatric neuroradiologist evaluated the matched results. We found that in most cases, the image-matching method was able to quickly retrieve images with relevant diagnostic content. The evaluation method and results are given.

  18. Oxidative modification of lipoic acid by HNE in Alzheimer disease brain

    Directory of Open Access Journals (Sweden)

    Sarita S. Hardas

    2013-01-01

    Full Text Available Alzheimer disease (AD is an age-related neurodegenerative disease characterized by the presence of three pathological hallmarks: synapse loss, extracellular senile plaques (SP and intracellular neurofibrillary tangles (NFTs. The major component of SP is amyloid β-peptide (Aβ, which has been shown to induce oxidative stress. The AD brain shows increased levels of lipid peroxidation products, including 4-hydroxy-2-nonenal (HNE. HNE can react covalently with Cys, His, or Lys residues on proteins, altering structure and function of the latter. In the present study we measured the levels of the HNE-modified lipoic acid in brain of subjects with AD and age-matched controls. Lipoic acid is a key co-factor for a number of proteins including pyruvate dehydrogenase and α-ketoglutarate dehydrogenase, key complexes for cellular energetics. We observed a significant decrease in the levels of HNE-lipoic acid in the AD brain compared to that of age-matched controls. To investigate this phenomenon further, the levels and activity of lipoamide dehydrogenase (LADH were measured in AD and control brains. Additionally, LADH activities were measured after in-vitro HNE-treatment to mice brains. Both LADH levels and activities were found to be significantly reduced in AD brain compared to age-matched control. HNE-treatment also reduced the LADH activity in mice brain. These data are consistent with a two-hit hypothesis of AD: oxidative stress leads to lipid peroxidation that, in turn, causes oxidative dysfunction of key energy-related complexes in mitochondria, triggering neurodegeneration. This study is consonant with the notion that lipoic acid supplementation could be a potential treatment for the observed loss of cellular energetics in AD and potentiate the antioxidant defense system to prevent or delay the oxidative stress in and progression of this devastating dementing disorder.

  19. Disrupted small-world brain networks in moderate Alzheimer's disease: a resting-state FMRI study.

    Directory of Open Access Journals (Sweden)

    Xiaohu Zhao

    Full Text Available The small-world organization has been hypothesized to reflect a balance between local processing and global integration in the human brain. Previous multimodal imaging studies have consistently demonstrated that the topological architecture of the brain network is disrupted in Alzheimer's disease (AD. However, these studies have reported inconsistent results regarding the topological properties of brain alterations in AD. One potential explanation for these inconsistent results lies with the diverse homogeneity and distinct progressive stages of the AD involved in these studies, which are thought to be critical factors that might affect the results. We investigated the topological properties of brain functional networks derived from resting functional magnetic resonance imaging (fMRI of carefully selected moderate AD patients and normal controls (NCs. Our results showed that the topological properties were found to be disrupted in AD patients, which showing increased local efficiency but decreased global efficiency. We found that the altered brain regions are mainly located in the default mode network, the temporal lobe and certain subcortical regions that are closely associated with the neuropathological changes in AD. Of note, our exploratory study revealed that the ApoE genotype modulates brain network properties, especially in AD patients.

  20. Plasma and brain fatty acid profiles in mild cognitive impairment and Alzheimer's disease.

    Science.gov (United States)

    Cunnane, Stephen C; Schneider, Julie A; Tangney, Christine; Tremblay-Mercier, Jennifer; Fortier, Mélanie; Bennett, David A; Morris, Martha Clare

    2012-01-01

    Alzheimer's disease (AD) is generally associated with lower omega-3 fatty acid intake from fish but despite numerous studies, it is still unclear whether there are differences in omega-3 fatty acids in plasma or brain. In matched plasma and brain samples provided by the Memory and Aging Project, fatty acid profiles were quantified in several plasma lipid classes and in three brain cortical regions. Fatty acid data were expressed as % composition and as concentrations (mg/dL for plasma or mg/g for brain). Differences in plasma fatty acid profiles between AD, mild cognitive impairment (MCI), and those with no cognitive impairment (NCI) were most apparent in the plasma free fatty acids (lower oleic acid isomers and omega-6 fatty acids in AD) and phospholipids (lower omega-3 fatty acids in AD). In brain, % DHA was lower only in phosphatidylserine of mid-frontal cortex and superior temporal cortex in AD compared to NCI (-14% and -12%, respectively; both p < 0.05). The only significant correlation between plasma and brain fatty acids was between % DHA in plasma total lipids and % DHA in phosphatidylethanolamine of the angular gyrus, but only in the NCI group (+0.77, p < 0.05). We conclude that AD is associated with altered plasma status of both DHA and other fatty acids unrelated to DHA, and that the lipid class-dependent nature of these differences reflects a combination of differences in intake and metabolism.

  1. Cognitive recovery and development after traumatic brain injury in childhood: a person-oriented, longitudinal study.

    Science.gov (United States)

    Jonsson, Catherine Aaro; Catroppa, Cathy; Godfrey, Celia; Smedler, Ann-Charlotte; Anderson, Vicki

    2013-01-15

    Influence of childhood traumatic brain injury (TBI) on cognitive recovery and subsequent development is poorly understood. In this longitudinal study we used cluster analysis to explore acute stage individual profiles of injury age and cognition in 118 children with traumatic brain injury. Repeated measures of cognitive function were conducted at 30 months, indicating recovery, and 10 years post-injury, indicating development. Nine clusters were identified. Recovery was evident in three clusters, two of them with low functioning profiles. Developmental gains occurred for three clusters and an acute profile of higher freedom from distractibility (FFD) and lower processing speed (PS) was related to positive differences. One cluster, average low functioning and especially low verbal comprehension, demonstrated a slower development than peers. This suggests that developmental change after TBI in childhood takes place on a continuum, with both chance of long-term catching up, and risk of poor development. An acute profile of higher FFD and lower PS seemed to reflect injury consequences and were followed by developmental gains. These results challenge previous findings, and warrant further investigation.

  2. Oxidative stress-mediated brain dehydroepiandrosterone (DHEA formation in Alzheimer’s disease diagnosis

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    Geogres eRammouz

    2011-11-01

    Full Text Available Neurosteroids are steroids made by brain cells independently of peripheral steroidogenic sources. The biosynthesis of most neurosteroids is mediated by proteins and enzymes similar to those identified in the steroidogenic pathway of adrenal and gonadal cells. Dehydroepiandrosterone (DHEA is a major neurosteroid identified in the brain. Over the years we have reported that, unlike other neurosteroids, DHEA biosynthesis in rat, bovine, and human brain is mediated by an oxidative stress-mediated mechanism, independent of the cytochrome P450 17a-hydroxylase/17,20-lyase (CYP17A1 enzyme activity found in the periphery. This alternative pathway is induced by pro-oxidant agents, such as Fe2+ and b-amyloid peptide. Neurosteroids are involved in many aspects of brain function, and as such, are involved in various neuropathologies, including Alzheimer’s disease (AD. AD is a progressive, yet irreversible neurodegenerative disease for which there are limited means for ante-mortem diagnosis. Using brain tissue specimens from control and AD patients, we provided evidence that DHEA is formed in the AD brain by the oxidative stress-mediated metabolism of an unidentified precursor, thus depleting levels of the precursor in the blood stream. We tested for the presence of this DHEA precursor in human serum using a Fe2+-based reaction and determined the amounts of DHEA formed. Fe2+ treatment of the serum resulted in a dramatic increase in DHEA levels in control patients, whereas only a moderate or no increase was observed in AD patients. The DHEA variation after oxidation correlated with the patients’ cognitive and mental status. In this review, we present the cumulative evidence for oxidative stress as a natural regulator of DHEA formation and the use of this concept to develop a blood-based diagnostic tool for neurodegenerative diseases linked to oxidative stress, such as AD.

  3. Brain and personality bases of insensitivity to infant cues in neglectful mothers: an event-related potential study.

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    Rodrigo, María José; León, Inmaculada; Quiñones, Ileana; Lage, Agustín; Byrne, Sonia; Bobes, María Antonieta

    2011-02-01

    This investigation examined the neural and personality correlates of processing infant facial expressions in mothers with substantiated neglect of a child under 5 years old. Event-related potentials (ERPs) were recorded from 14 neglectful and 14 control mothers as they viewed and categorized pictures of infant cries, laughs, and neutral faces. Maternal self-reports of anhedonia and empathy were also completed. Early (negative occipitotemporal component peaking at around 170 ms on the scalp [N170] and positive electrical potential peaking at about 200 ms [P200]) and late positive potential (LPP) components were selected. Both groups of mothers showed behavioral discrimination between the different facial expressions via reaction time and accuracy measures. Neglectful mothers did not exhibit increased N170 amplitude at temporal leads in response to viewing crying versus laughing and neutral expressions compared to control mothers. Both groups had greater P200 and LPP amplitudes at centroparietal leads in response to viewing crying versus neutral facial expressions. However, neglectful mothers displayed an overall attenuated brain response in LPP that was related to their higher scores in social anhedonia but not to their empathy scores. The ERP data suggest that the brain's failures in the early differentiation of cry stimuli and in the sustained processing of infant expressions related to social anhedonia may underlie the insensitive responding in neglectful mothers. The implications of these results for the design and evaluation of preventive interventions are discussed.

  4. Competition in the Brain. The Contribution of EEG and fNIRS Modulation and Personality Effects in Social Ranking.

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    Balconi, Michela; Vanutelli, Maria E

    2016-01-01

    In the present study, the social ranking perception in competition was explored. Brain response (alpha band oscillations, EEG; hemodynamic activity, O2Hb), as well as self-perception of social ranking, cognitive performance, and personality trait (Behavioral Activation System, BAS) were considered during a competitive joint-action. Subjects were required to develop a strategy to obtain a better outcome than a competitor (C) (in term of error rate, and response time, RT). A pre-feedback (without a specific feedback on the performance) and a post-feedback condition (which reinforced the improved performance) were provided. It was found that higher-BAS participants responded in greater measure to perceived higher cognitive performance (post-feedback condition), with increased left prefrontal activity, higher ranking perception, and a better real performance (reduced RTs). These results were explained in term of increased sense of self-efficacy and social position, probably based on higher-BAS sensitivity to reinforcing conditions. In addition, the hemispheric effect in favor of the left side characterized the competitive behavior, showing an imbalance for high-BAS in comparison to low-BAS in the case of a rewarding (post-feedback) context. Therefore, the present results confirmed the significance of BAS in modulating brain responsiveness, self-perceived social position, and real performance during an interpersonal competitive action which is considered highly relevant for social status.

  5. Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease: Is Inflammatory Signaling a Key Player?

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    Djordjevic, Jelena; Sabbir, Mohammad Golam; Albensi, Benedict C

    2016-01-01

    Traumatic brain injury (TBI) has become a significant medical and social concern within the last 30 years. TBI has acute devastating effects, and in many cases, seems to initiate long-term neurodegeneration. With advances in medical technology, many people are now surviving severe brain injuries and their long term consequences. Post trauma effects include communication problems, sensory deficits, emotional and behavioral problems, physical complications and pain, increased suicide risk, dementia, and an increased risk for chronic CNS diseases, such as Alzheimer's disease (AD). In this review, we provide an introduction to TBI and hypothesize how it may lead to neurodegenerative disease in general and AD in particular. In addition, we discuss the evidence that supports the hypothesis that TBI may lead to AD. In particular, we focus on inflammatory responses as key processes in TBI-induced secondary injury, with emphasis on nuclear factor kappa B (NF-κB) signaling.

  6. Nanoparticle technology for treatment of Parkinson's disease: the role of surface phenomena in reaching the brain.

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    Leyva-Gómez, Gerardo; Cortés, Hernán; Magaña, Jonathan J; Leyva-García, Norberto; Quintanar-Guerrero, David; Florán, Benjamín

    2015-07-01

    The absence of a definitive treatment for Parkinson's disease has driven the emerging investigation in the search for novel therapeutic alternatives. At present, the formulation of different drugs on nanoparticles has represented several advantages over conventional treatments. This type of multifunctional carrier, owing to its size and composition, has different interactions in biological systems that can lead to a decrease in ability to cross the blood-brain barrier. Therefore, this review focuses on the latest advances in obtaining nanoparticles for Parkinson's disease and provides an overview of technical aspects in the design of brain drug delivery of nanoparticles and an analysis of surface phenomena, a key aspect in the development of functional nanoparticles for Parkinson's disease.

  7. Characteristics of brain stem auditory evoked potentials in children with hearing impairment due to infectious diseases.

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    Ječmenica, Jovana Radovan; Opančina, Aleksandra Aleksandar Bajec

    2015-05-01

    Among objective audiologic tests, the most important were tests of brain stem auditory evoked potentials. The objective of the study was to test the configuration, degree of hearing loss, and response characteristics of auditory brain stem evoked potentials in children with hearing loss occurred due to infectious disease. A case control study design was used. The study group consisted of 54 patients referred for a hearing test because of infectious diseases caused by other agents or that occurred as congenital infection. Infectious agents have led to the emergence of various forms of sensorineural hearing loss. We have found deviations from the normal values of absolute and interwave latencies in some children in our group. We found that in the group of children who had the diseases such as purulent meningitis, or were born with rubella virus and cytomegalovirus infection, a retrocochlear damage was present in children with and without cochlear damage.

  8. Genes that affect brain structure and function identified by rare variant analyses of Mendelian neurologic disease

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    Karaca, Ender; Harel, Tamar; Pehlivan, Davut; Jhangiani, Shalini N.; Gambin, Tomasz; Akdemir, Zeynep Coban; Gonzaga-Jauregui, Claudia; Erdin, Serkan; Bayram, Yavuz; Campbell, Ian M.; Hunter, Jill V.; Atik, Mehmed M.; Van Esch, Hilde; Yuan, Bo; Wiszniewski, Wojciech; Isikay, Sedat; Yesil, Gozde; Yuregir, Ozge O.; Bozdogan, Sevcan Tug; Aslan, Huseyin; Aydin, Hatip; Tos, Tulay; Aksoy, Ayse; De Vivo, Darryl C.; Jain, Preti; Geckinli, B. Bilge; Sezer, Ozlem; Gul, Davut; Durmaz, Burak; Cogulu, Ozgur; Ozkinay, Ferda; Topcu, Vehap; Candan, Sukru; Cebi, Alper Han; Ikbal, Mevlit; Gulec, Elif Yilmaz; Gezdirici, Alper; Koparir, Erkan; Ekici, Fatma; Coskun, Salih; Cicek, Salih; Karaer, Kadri; Koparir, Asuman; Duz, Mehmet Bugrahan; Kirat, Emre; Fenercioglu, Elif; Ulucan, Hakan; Seven, Mehmet; Guran, Tulay; Elcioglu, Nursel; Yildirim, Mahmut Selman; Aktas, Dilek; Alikaşifoğlu, Mehmet; Ture, Mehmet; Yakut, Tahsin; Overton, John D.; Yuksel, Adnan; Ozen, Mustafa; Muzny, Donna M.; Adams, David R.; Boerwinkle, Eric; Chung, Wendy K.; Gibbs, Richard A.; Lupski, James R

    2015-01-01

    Development of the human nervous system involves complex interactions between fundamental cellular processes and requires a multitude of genes, many of which remain to be associated with human disease. We applied whole exome sequencing to 128 mostly consanguineous families with neurogenetic disorders that often included brain malformations. Rare variant analyses for both single nucleotide variant (SNV) and copy number variant (CNV) alleles allowed for identification of 45 novel variants in 43 known disease genes, 41 candidate genes, and CNVs in 10 families, with an overall potential molecular cause identified in >85% of families studied. Among the candidate genes identified, we found PRUNE, VARS, and DHX37 in multiple families, and homozygous loss of function variants in AGBL2, SLC18A2, SMARCA1, UBQLN1, and CPLX1. Neuroimaging and in silico analysis of functional and expression proximity between candidate and known disease genes allowed for further understanding of genetic networks underlying specific types of brain malformations. PMID:26539891

  9. Infectious Disease Management through Point-of-Care Personalized Medicine Molecular Diagnostic Technologies.

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    Bissonnette, Luc; Bergeron, Michel G

    2012-05-02

    Infectious disease management essentially consists in identifying the microbial cause(s) of an infection, initiating if necessary antimicrobial therapy against microbes, and controlling host reactions to infection. In clinical microbiology, the turnaround time of the diagnostic cycle (>24 hours) often leads to unnecessary suffering and deaths; approaches to relieve this burden include rapid diagnostic procedures and more efficient transmission or interpretation of molecular microbiology results. Although rapid nucleic acid-based diagnostic testing has demonstrated that it can impact on the transmission of hospital-acquired infections, we believe that such life-saving procedures should be performed closer to the patient, in dedicated 24/7 laboratories of healthcare institutions, or ideally at point of care. While personalized medicine generally aims at interrogating the genomic information of a patient, drug metabolism polymorphisms, for example, to guide drug choice and dosage, personalized medicine concepts are applicable in infectious diseases for the (rapid) identification of a disease-causing microbe and determination of its antimicrobial resistance profile, to guide an appropriate antimicrobial treatment for the proper management of the patient. The implementation of point-of-care testing for infectious diseases will require acceptance by medical authorities, new technological and communication platforms, as well as reimbursement practices such that time- and life-saving procedures become available to the largest number of patients.

  10. Infectious Disease Management through Point-of-Care Personalized Medicine Molecular Diagnostic Technologies

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    Luc Bissonnette

    2012-05-01

    Full Text Available Infectious disease management essentially consists in identifying the microbial cause(s of an infection, initiating if necessary antimicrobial therapy against microbes, and controlling host reactions to infection. In clinical microbiology, the turnaround time of the diagnostic cycle (>24 hours often leads to unnecessary suffering and deaths; approaches to relieve this burden include rapid diagnostic procedures and more efficient transmission or interpretation of molecular microbiology results. Although rapid nucleic acid-based diagnostic testing has demonstrated that it can impact on the transmission of hospital-acquired infections, we believe that such life-saving procedures should be performed closer to the patient, in dedicated 24/7 laboratories of healthcare institutions, or ideally at point of care. While personalized medicine generally aims at interrogating the genomic information of a patient, drug metabolism polymorphisms, for example, to guide drug choice and dosage, personalized medicine concepts are applicable in infectious diseases for the (rapid identification of a disease-causing microbe and determination of its antimicrobial resistance profile, to guide an appropriate antimicrobial treatment for the proper management of the patient. The implementation of point-of-care testing for infectious diseases will require acceptance by medical authorities, new technological and communication platforms, as well as reimbursement practices such that time- and life-saving procedures become available to the largest number of patients.

  11. Affective context interferes with brain responses during cognitive processing in borderline personality disorder: fMRI evidence

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    Soloff, Paul H.; White, Richard; Omari, Amro; Ramaseshan, Karthik; Diwadka, Vaibhav A.

    2015-01-01

    Emotion dysregulation in borderline personality disorder (BPD) is associated with loss of cognitive control in the face of intense negative emotion. Negative emotional context may interfere with cognitive processing through the dysmodulation of brain regions involved in regulation of emotion, impulse control, executive function and memory. Structural and metabolic brain abnormalities have been reported in these regions in BPD. Using novel fMRI protocols, we investigated the neural basis of negative affective interference with cognitive processing targeting these regions. Attention-driven Go No-Go and X-CPT (continuous performance test) protocols, using positive, negative and neutral Ekman faces, targeted the orbital frontal cortex (OFC) and the anterior cingulate cortex (ACC), respectively. A stimulus-driven Episodic Memory task, using images from the International Affective Pictures System, targeted the hippocampus (HIP). Participants comprised 23 women with BPD, who were compared with 15 healthy controls. When Negative>Positive faces were compared in the Go No-Go task, BPD subjects had hyper-activation relative to controls in areas reflecting task-relevant processing: the superior parietal/precuneus and thebasal ganglia. Decreased activation was also noted in the OFC, and increased activation in the amygdala (AMY). In the X-CPT, BPD subjects again showed hyper-activation in task-relevant areas: the superior parietal/precuneus and the ACC. In the stimulus-driven Episodic Memory task, BPD subjects had decreased activation relative to controls in the HIP, ACC, superior parietal/precuneus, and dorsal prefrontal cortex (dPFC) (for encoding), and the ACC, dPFC, and HIP for retrieval of Negative>Positive pictures, reflecting impairment of task-relevant functions. Negative affective interference with cognitive processing in BPD differs from that in healthy controls and is associated with functional abnormalities in brain networks reported to have structural or metabolic

  12. The Potential of the Human Connectome as a Biomarker of Brain Disease

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    Marcus eKaiser

    2013-08-01

    Full Text Available The human connectome at the level of fiber tracts between brain regions has been shown to differ in patients with brain disorders compared to healthy control groups. Nonetheless, there is a potentially large number of different network organizations for individual patients that could lead to cognitive deficits prohibiting correct diagnosis. Therefore changes that can distinguish groups might not be sufficient to diagnose the disease that an individual patient suffers from and to indicate the best treatment option for that patient. We describe the challenges introduced by the large variability of connectomes within healthy subjects and patients and outline three common strategies to use connectomes as biomarkers of brain diseases. Finally, we propose a fourth option in using models of simulated brain activity (the dynamic connectome based on structural connectivity rather than the structure (connectome itself as a biomarker of disease. Dynamic connectomes, in addition to currently used structural, functional, or effective connectivity, could be an important future biomarker for clinical applications.

  13. Improving memory in Parkinson's disease: a healthy brain ageing cognitive training program.

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    Naismith, Sharon L; Mowszowski, Loren; Diamond, Keri; Lewis, Simon J G

    2013-07-01

    This study aimed to evaluate the efficacy of a multifactorial 'healthy brain ageing cognitive training program' for Parkinson's disease. Using a single-blinded waitlist control design, 50 participants with Parkinson's disease were recruited from the Brain & Mind Research Institute, Sydney, Australia. The intervention encompassed both psychoeducation and cognitive training; each component lasted 1-hour. The 2-hour sessions were delivered in a group format, twice-weekly over a 7-week period. Multifactorial psychoeducation was delivered by a range of health professionals. In addition to delivering cognitive strategies, it targeted depression, anxiety, sleep, vascular risk factors, diet, and exercise. Cognitive training was computer-based and was conducted by clinical neuropsychologists. The primary outcome was memory. Secondary outcomes included other aspects of cognition and knowledge pertaining to the psychoeducation material. Results demonstrated that cognitive training was associated with significant improvements in learning and memory corresponding to medium to large effect sizes. Treatment was also associated with medium effect size improvements in knowledge. Although the study was limited by the lack of randomized allocation to treatment and control groups, these findings suggest that a healthy brain ageing cognitive training program may be a viable tool to improve memory and/or slow cognitive decline in people with Parkinson's disease. It also appeared successful for increasing awareness of adaptive and/or compensatory cognitive strategies, as well as modifiable risk factors to optimize brain functioning.

  14. Brain Microstructural Abnormalities Are Related to Physiological Alterations in End-Stage Renal Disease.

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    Zhigang Bai

    Full Text Available To study whole-brain microstructural alterations in patients with end-stage renal disease (ESRD and examine the relationship between brain microstructure and physiological indictors in the disease.Diffusion tensor imaging data were collected from 35 patients with ESRD (28 men, 18-61 years and 40 age- and gender-matched healthy controls (HCs, 32 men, 22-58 years. A voxel-wise analysis was then used to identify microstructural alterations over the whole brain in the ESRD patients compared with the HCs. Multiple biochemical measures of renal metabolin, vascular risk factors, general cognitive ability and dialysis duration were correlated with microstructural integrity for the patients.Compared to the HCs, the ESRD patients exhibited disrupted microstructural integrity in not only white matter (WM but also gray matter (GM regions, as characterized by decreased fractional anisotropy (FA and increased mean diffusivity (MD, axial diffusivity (AD and radial diffusivity (RD. Further correlation analyses revealed that the in MD, AD and RD values showed significantly positive correlations with the blood urea nitrogen in the left superior temporal gyrus and significantly negative correlations with the calcium levels in the left superior frontal gyrus (orbital part in the patients.Our findings suggest that ESRD is associated with widespread diffusion abnormalities in both WM and GM regions in the brain, and microstructural integrity of several GM regions are related to biochemical alterations in the disease.

  15. White Matter Lipids as a Ketogenic Fuel Supply in Aging Female Brain: Implications for Alzheimer's Disease.

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    Klosinski, Lauren P; Yao, Jia; Yin, Fei; Fonteh, Alfred N; Harrington, Michael G; Christensen, Trace A; Trushina, Eugenia; Brinton, Roberta Diaz

    2015-12-01

    White matter degeneration is a pathological hallmark of neurodegenerative diseases including Alzheimer's. Age remains the greatest risk factor for Alzheimer's and the prevalence of age-related late onset Alzheimer's is greatest in females. We investigated mechanisms underlying white matter degeneration in an animal model consistent with the sex at greatest Alzheimer's risk. Results of these analyses demonstrated decline in mitochondrial respiration, increased mitochondrial hydrogen peroxide production and cytosolic-phospholipase-A2 sphingomyelinase pathway activation during female brain aging. Electron microscopic and lipidomic analyses confirmed myelin degeneration. An increase in fatty acids and mitochondrial fatty acid metabolism machinery was coincident with a rise in brain ketone bodies and decline in plasma ketone bodies. This mechanistic pathway and its chronologically phased activation, links mitochondrial dysfunction early in aging with later age development of white matter degeneration. The catabolism of myelin lipids to generate ketone bodies can be viewed as a systems level adaptive response to address brain fuel and energy demand. Elucidation of the initiating factors and the mechanistic pathway leading to white matter catabolism in the aging female brain provides potential therapeutic targets to prevent and treat demyelinating diseases such as Alzheimer's and multiple sclerosis. Targeting stages of disease and associated mechanisms will be critical.

  16. Bilingualism as a contributor to cognitive reserve: evidence from brain atrophy in Alzheimer's disease.

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    Schweizer, Tom A; Ware, Jenna; Fischer, Corinne E; Craik, Fergus I M; Bialystok, Ellen

    2012-09-01

    Much of the research on delaying the onset of symptoms of Alzheimer's disease (AD) has focused on pharmacotherapy, but environmental factors have also been acknowledged to play a significant role. Bilingualism may be one factor contributing to 'cognitive reserve' (CR) and therefore to a delay in symptom onset. If bilingualism is protective, then the brains of bilinguals should show greater atrophy in relevant areas, since their enhanced CR enables them to function at a higher level than would be predicted from their level of disease. We analyzed a number of linear measurements of brain atrophy from the computed tomography (CT) scans of monolingual and bilingual patients diagnosed with probable AD who were matched on level of cognitive performance and years of education. Bilingual patients with AD exhibited substantially greater amounts of brain atrophy than monolingual patients in areas traditionally used to distinguish AD patients from healthy controls, specifically, the radial width of the temporal horn and the temporal horn ratio. Other measures of brain atrophy were comparable for the two groups. Bilingualism appears to contribute to increased CR, thereby delaying the onset of AD and requiring the presence of greater amounts of neuropathology before the disease is manifest.

  17. Effect of Acupuncture on the Auditory Evoked Brain Stem Potential in Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    王玲玲; 何崇; 刘跃光; 朱莉莉

    2002-01-01

    @@ Under the auditory evoked brain stem potential (ABP) examination, the latent period of V wave and the intermittent periods of III-V peak and I-V peak were significantly shortened in Parkinson's disease patients of the treatment group (N=29) after acupuncture treatment. The difference of cumulative scores in Webster's scale was also decreased in correlation analysis. The increase of dopamine in the brain and the excitability of the dopamine neurons may contribute to the therapeutic effects, in TCM terms, of subduing the pathogenic wind and tranquilizing the mind.

  18. Effect of acupuncture on the auditory evoked brain stem potential in Parkinson's disease.

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    Wang, Lingling; He, Chong; Liu, Yueguang; Zhu, Lili

    2002-03-01

    Under the auditory evoked brain stem potential (ABP) examination, the latent period of