Brain Sciences

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Open AccessReview

Coagulopathy in the Setting of Mild Traumatic Brain Injury: Truths and Consequences

by Joseph P. Herbert, Andrew R. Guillotte, Richard D. Hammer and N. Scott Litofsky

Brain Sci. 2017, 7(7), 92; https://doi.org/10.3390/brainsci7070092 - 22 Jul 2017

Cited by 25 | Viewed by 6735

Mild traumatic brain injury (mTBI) is a common, although poorly-defined clinical entity. Despite its initially mild presentation, patients with mTBI can rapidly deteriorate, often due to significant expansion of intracranial hemorrhage. TBI-associated coagulopathy is the topic of significant clinical and basic science research. [...] Read more.

Mild traumatic brain injury (mTBI) is a common, although poorly-defined clinical entity. Despite its initially mild presentation, patients with mTBI can rapidly deteriorate, often due to significant expansion of intracranial hemorrhage. TBI-associated coagulopathy is the topic of significant clinical and basic science research. Unlike trauma-induced coagulopathy (TIC), TBI-associated coagulopathy does not generally follow widespread injury or global hypoperfusion, suggesting a distinct pathogenesis. Although the fundamental mechanisms of TBI-associated coagulopathy are far from clearly elucidated, several candidate molecules (tissue plasminogen activator (tPA), urokinase plasminogen activator (uPA), tissue factor (TF), and brain-derived microparticles (BDMP)) have been proposed which might explain how even minor brain injury can induce local and systemic coagulopathy. Here, we review the incidence, proposed mechanisms, and common clinical tests relevant to mTBI-associated coagulopathy and briefly summarize our own institutional experience in addition to identifying areas for further research. Full article

(This article belongs to the Special Issue Mild Traumatic Brain Injury (mTBI): Medical Treatments and Complications)

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Open AccessArticle

Using Machine Learning to Discover Latent Social Phenotypes in Free-Ranging Macaques

by Seth Madlon-Kay, Lauren Brent, Michael Montague, Katherine Heller and Michael Platt

Brain Sci. 2017, 7(7), 91; https://doi.org/10.3390/brainsci7070091 - 21 Jul 2017

Cited by 11 | Viewed by 6461

Abstract

Investigating the biological bases of social phenotypes is challenging because social behavior is both high-dimensional and richly structured, and biological factors are more likely to influence complex patterns of behavior rather than any single behavior in isolation. The space of all possible patterns [...] Read more.

Investigating the biological bases of social phenotypes is challenging because social behavior is both high-dimensional and richly structured, and biological factors are more likely to influence complex patterns of behavior rather than any single behavior in isolation. The space of all possible patterns of interactions among behaviors is too large to investigate using conventional statistical methods. In order to quantitatively define social phenotypes from natural behavior, we developed a machine learning model to identify and measure patterns of behavior in naturalistic observational data, as well as their relationships to biological, environmental, and demographic sources of variation. We applied this model to extensive observations of natural behavior in free-ranging rhesus macaques, and identified behavioral states that appeared to capture periods of social isolation, competition over food, conflicts among groups, and affiliative coexistence. Phenotypes, represented as the rate of being in each state for a particular animal, were strongly and broadly influenced by dominance rank, sex, and social group membership. We also identified two states for which variation in rates had a substantial genetic component. We discuss how this model can be extended to identify the contributions to social phenotypes of particular genetic pathways. Full article

(This article belongs to the Special Issue Best Practices in Social Neuroscience)

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Open AccessArticle

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

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

Brain Sci. 2017, 7(7), 90; https://doi.org/10.3390/brainsci7070090 - 21 Jul 2017

Cited by 44 | Viewed by 5954

Abstract

Subjects’ interaction is the core of most human activities. This is the reason why a lack of coordination is often the cause of missing goals, more than individual failure. While there are different subjective and objective measures to assess the level of mental [...] Read more.

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

(This article belongs to the Special Issue Best Practices in Social Neuroscience)

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Open AccessArticle

Transgenerational Social Stress Alters Immune–Behavior Associations and the Response to Vaccination

by Alexandria Hicks-Nelson, Gillian Beamer, Kursat Gurel, Rachel Cooper and Benjamin C. Nephew

Brain Sci. 2017, 7(7), 89; https://doi.org/10.3390/brainsci7070089 - 21 Jul 2017

Cited by 7 | Viewed by 5333

Abstract

Similar to the multi-hit theory of schizophrenia, social behavior pathologies are mediated by multiple factors across generations, likely acting additively, synergistically, or antagonistically. Exposure to social adversity, especially during early life, has been proposed to induce depression symptoms through immune mediated mechanisms. Basal [...] Read more.

Similar to the multi-hit theory of schizophrenia, social behavior pathologies are mediated by multiple factors across generations, likely acting additively, synergistically, or antagonistically. Exposure to social adversity, especially during early life, has been proposed to induce depression symptoms through immune mediated mechanisms. Basal immune factors are altered in a variety of neurobehavioral models. In the current study, we assessed two aspects of a transgenerational chronic social stress (CSS) rat model and its effects on the immune system. First, we asked whether exposure of F0 dams and their F1 litters to CSS changes basal levels of IL-6, TNF, IFN-γ, and social behavior in CSS F1 female juvenile rats. Second, we asked whether the F2 generation could generate normal immunological responses following vaccination with Mycobacterium bovis Bacillus Calmette–Guérin (BCG). We report several changes in the associations between social behaviors and cytokines in the F1 juvenile offspring of the CSS model. It is suggested that changes in the immune–behavior relationships in F1 juveniles indicate the early stages of immune mediated disruption of social behavior that becomes more apparent in F1 dams and the F2 generation. We also report preliminary evidence of elevated IL-6 and impaired interferon-gamma responses in BCG-vaccinated F2 females. In conclusion, transgenerational social stress alters both immune–behavior associations and responses to vaccination. It is hypothesized that the effects of social stress may accumulate over generations through changes in the immune system, establishing the immune system as an effective preventative or treatment target for social behavior pathologies. Full article

(This article belongs to the Special Issue Best Practices in Social Neuroscience)

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Open AccessReview

Mini Review of Controlled Cortical Impact: A Well-Suited Device for Concussion Research

by Nicole Osier and C. Edward Dixon

Brain Sci. 2017, 7(7), 88; https://doi.org/10.3390/brainsci7070088 - 20 Jul 2017

Cited by 13 | Viewed by 5823

Abstract

Mild traumatic brain injury (mTBI) is increasingly recognized as a significant public health problem which warrants additional research. Part of the effort to understand mTBI and concussion includes modeling in animals. Controlled cortical impact (CCI) is a commonly employed and well-characterized model of [...] Read more.

Mild traumatic brain injury (mTBI) is increasingly recognized as a significant public health problem which warrants additional research. Part of the effort to understand mTBI and concussion includes modeling in animals. Controlled cortical impact (CCI) is a commonly employed and well-characterized model of experimental TBI that has been utilized for three decades. Today, several commercially available pneumatic- and electromagnetic-CCI devices exist as do a variety of standard and custom injury induction tips. One of CCI’s strengths is that it can be scaled to a number of common laboratory animals. Similarly, the CCI model can be used to produce graded TBI ranging from mild to severe. At the mild end of the injury spectrum, CCI has been applied in many ways, including to study open and closed head mTBI, repeated injuries, and the long-term deficits associated with mTBI and concussion. The purpose of this mini-review is to introduce the CCI model, discuss ways the model can be applied to study mTBI and concussion, and compare CCI to alternative pre-clinical TBI models. Full article

(This article belongs to the Special Issue Mild Traumatic Brain Injury (mTBI): Medical Treatments and Complications)

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Open AccessReview

Morphological and Molecular Basis of Cytoplasmic Dilation and Swelling in Cortical Migrating Neurons

by Yoshiaki V. Nishimura, Yo-ichi Nabeshima and Takeshi Kawauchi

Brain Sci. 2017, 7(7), 87; https://doi.org/10.3390/brainsci7070087 - 19 Jul 2017

Cited by 9 | Viewed by 7433

Abstract

During corticogenesis, neuronal migration is an essential step for formation of a functional brain, and abnormal migration is known to cause various neurological disorders. Neuronal migration is not just a simple movement of the cell body, but a consequence of various morphological changes [...] Read more.

During corticogenesis, neuronal migration is an essential step for formation of a functional brain, and abnormal migration is known to cause various neurological disorders. Neuronal migration is not just a simple movement of the cell body, but a consequence of various morphological changes and coordinated subcellular events. Recent advances in in vivo and ex vivo cell biological approaches, such as in utero gene transfer, slice culture and ex vivo chemical inhibitor techniques, have revealed details of the morphological and molecular aspects of neuronal migration. Migrating neurons have been found to have a unique structure, dilation or swelling, at the proximal region of the leading process; this structure is not found in other migrating cell types. The formation of this structure is followed by nuclear deformation and forward movement, and coordination of this three-step sequential morphological change (the dilation/swelling formation, nuclear elongation and nuclear movement) is essential for proper neuronal migration and the construction of a functional brain structure. In this review, we will introduce the morphological features of this unique structure in migrating neurons and summarize what is known about the molecules regulating the dilation/swelling formation and nuclear deformation and movement. Full article

(This article belongs to the Special Issue Neuronal Migration and Cortical Development)

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Open AccessArticle

Bilinguals’ Working Memory (WM) Advantage and Their Dual Language Practices

by Eunju Yang

Brain Sci. 2017, 7(7), 86; https://doi.org/10.3390/brainsci7070086 - 18 Jul 2017

Cited by 15 | Viewed by 7546

Abstract

The present study investigates a possible working memory (WM) difference between monolingual and bilingual groups and explores the relationship between their WM advantage and language practices. A mixed methods design was employed for the study. To measure participants’ WM, auditory and visual digit [...] Read more.

The present study investigates a possible working memory (WM) difference between monolingual and bilingual groups and explores the relationship between their WM advantage and language practices. A mixed methods design was employed for the study. To measure participants’ WM, auditory and visual digit span tasks were conducted on the different language groups: 20 Korean near-monolinguals, and 40 Korean–English bilinguals with two different levels of second language (L2) proficiency. Bilinguals’ daily language practices were explored through semi-structured interviews with eight bilinguals. The convergence of the findings from both tests and interview data suggests that knowing two languages does not guarantee bilingual WM advantages over monolinguals, but the advantage might be linked to bilinguals’ unique L2 use environment where they need to hold incoming L2 information while decoding it. Full article

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Open AccessArticle

Sensory and Physico-Psychological Metaphor Comprehension in Children with ASD: A Preliminary Study on the Outcomes of a Treatment

by Sergio Melogno, Maria Antonietta Pinto and Gloria Di Filippo

Brain Sci. 2017, 7(7), 85; https://doi.org/10.3390/brainsci7070085 - 17 Jul 2017

Cited by 21 | Viewed by 5119

Abstract

Recent research into difficulties in figurative language in children with ASD highlighted that it is possible to devise training interventions to overcome these difficulties by teaching specific strategies. This study describes how children with ASD can improve their capability to explain metaphors with [...] Read more.

Recent research into difficulties in figurative language in children with ASD highlighted that it is possible to devise training interventions to overcome these difficulties by teaching specific strategies. This study describes how children with ASD can improve their capability to explain metaphors with a treatment. Two types of metaphors, in the “X is Y” form, were addressed: sensory and physico-psychological. To face the difficulties posed by these metaphors, the adult taught two strategies: inserting the connective “is like” between “X” and “Y”, which transforms the metaphor into a simile; comparing “X” and “Y” by means of thinking maps. Two tests of metaphor comprehension were used, one based on sensory and the other on physico-psychological metaphors. Sixteen 10 year-old children participated into the study, including an experimental group formed by 8 children with ASD (n = 4) which had received the treatment, and a control group (n = 4) which had not, and 8 typically-developing (TD) children. At the post-test, the experimental group significantly outperformed the controls in explaining both types of metaphors, but only in the sensory metaphors did their performances reach TD children’s levels. These results illuminate how clinical treatment can positively influence the developmental trajectories of metaphor comprehension. Full article

(This article belongs to the Special Issue Autism Spectrum Disorder: From Etio-Pathology to Treatment)

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Open AccessReview

Structural and Functional Neuroimaging of Visual Hallucinations in Lewy Body Disease: A Systematic Literature Review

by Stefania Pezzoli, Annachiara Cagnin, Oliver Bandmann and Annalena Venneri

Brain Sci. 2017, 7(7), 84; https://doi.org/10.3390/brainsci7070084 - 15 Jul 2017

Cited by 33 | Viewed by 9181

Abstract

Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural [...] Read more.

Patients with Lewy body disease (LBD) frequently experience visual hallucinations (VH), well-formed images perceived without the presence of real stimuli. The structural and functional brain mechanisms underlying VH in LBD are still unclear. The present review summarises the current literature on the neural correlates of VH in LBD, namely Parkinson’s disease (PD), and dementia with Lewy bodies (DLB). Following a systematic literature search, 56 neuroimaging studies of VH in PD and DLB were critically reviewed and evaluated for quality assessment. The main structural neuroimaging results on VH in LBD revealed grey matter loss in frontal areas in patients with dementia, and parietal and occipito-temporal regions in PD without dementia. Parietal and temporal hypometabolism was also reported in hallucinating PD patients. Disrupted functional connectivity was detected especially in the default mode network and fronto-parietal regions. However, evidence on structural and functional connectivity is still limited and requires further investigation. The current literature is in line with integrative models of VH suggesting a role of attention and perception deficits in the development of VH. However, despite the close relationship between VH and cognitive impairment, its associations with brain structure and function have been explored only by a limited number of studies. Full article

(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)

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Open AccessReview

Cognitive Changes in the Spinocerebellar Ataxias Due to Expanded Polyglutamine Tracts: A Survey of the Literature

by Evelyn Lindsay and Elsdon Storey

Brain Sci. 2017, 7(7), 83; https://doi.org/10.3390/brainsci7070083 - 14 Jul 2017

Cited by 29 | Viewed by 5209

Abstract

The dominantly-inherited ataxias characterised by expanded polyglutamine tracts—spinocere bellar ataxias (SCAs) 1, 2, 3, 6, 7, 17, dentatorubral pallidoluysian atrophy (DRPLA) and, in part, SCA 8—have all been shown to result in various degrees of cognitive impairment. We survey the literature on the [...] Read more.

The dominantly-inherited ataxias characterised by expanded polyglutamine tracts—spinocere bellar ataxias (SCAs) 1, 2, 3, 6, 7, 17, dentatorubral pallidoluysian atrophy (DRPLA) and, in part, SCA 8—have all been shown to result in various degrees of cognitive impairment. We survey the literature on the cognitive consequences of each disorder, attempting correlation with their published neuropathological, magnetic resonance imaging (MRI) and clinical features. We suggest several psychometric instruments for assessment of executive function, whose results are unlikely to be confounded by visual, articulatory or upper limb motor difficulties. Finally, and with acknowledgement of the inadequacies of the literature to date, we advance a tentative classification of these disorders into three groups, based on the reported severity of their cognitive impairments, and correlated with their neuropathological topography and MRI findings: group 1—SCAs 6 and 8—mild dysexecutive syndrome based on disruption of cerebello-cortical circuitry; group 2—SCAs 1, 2, 3, and 7—more extensive deficits based largely on disruption of striatocortical in addition to cerebello-cerebral circuitry; and group 3—SCA 17 and DRPLA—in which cognitive impairment severe enough to cause a dementia syndrome is a frequent feature. Full article

(This article belongs to the Special Issue Polyglutamine (PolyQ) Disorders)

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Open AccessReview

Dynamic Hippocampal and Prefrontal Contributions to Memory Processes and Representations Blur the Boundaries of Traditional Cognitive Domains

by Rachael D. Rubin, Hillary Schwarb, Heather D. Lucas, Michael R. Dulas and Neal J. Cohen

Brain Sci. 2017, 7(7), 82; https://doi.org/10.3390/brainsci7070082 - 12 Jul 2017

Cited by 38 | Viewed by 11794

Abstract

The hippocampus has long been known to be a critical component of the memory system involved in the formation and use of long-term declarative memory. However, recent findings have revealed that the reach of hippocampal contributions extends to a variety of domains and [...] Read more.

The hippocampus has long been known to be a critical component of the memory system involved in the formation and use of long-term declarative memory. However, recent findings have revealed that the reach of hippocampal contributions extends to a variety of domains and tasks that require the flexible use of cognitive and social behavior, including domains traditionally linked to prefrontal cortex (PFC), such as decision-making. In addition, the prefrontal cortex (PFC) has gained traction as a necessary part of the memory system. These findings challenge the conventional characterizations of hippocampus and PFC as being circumscribed to traditional cognitive domains. Here, we emphasize that the ability to parsimoniously account for the breadth of hippocampal and PFC contributions to behavior, in terms of memory function and beyond, requires theoretical advances in our understanding of their characteristic processing features and mental representations. Notably, several literatures exist that touch upon this issue, but have remained disjointed because of methodological differences that necessarily limit the scope of inquiry, as well as the somewhat artificial boundaries that have been historically imposed between domains of cognition. In particular, this article focuses on the contribution of relational memory theory as an example of a framework that describes both the representations and processes supported by the hippocampus, and further elucidates the role of the hippocampal–PFC network to a variety of behaviors. Full article

(This article belongs to the Special Issue Interaction Between the Prefrontal Cortex and Hippocampus in Memory Storage and Retrieval)

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Open AccessArticle

Evidences from Rewarding System, FRN and P300 Effect in Internet-Addiction in Young People

by Michela Balconi, Irene Venturella and Roberta Finocchiaro

Brain Sci. 2017, 7(7), 81; https://doi.org/10.3390/brainsci7070081 - 12 Jul 2017

Cited by 33 | Viewed by 7023

Abstract

The present research explored rewarding bias and attentional deficits in Internet addiction (IA) based on the IAT (Internet Addiction Test) construct, during an attentional inhibitory task (Go/NoGo task). Event-related Potentials (ERPs) effects (Feedback Related Negativity (FRN) and P300) were monitored in concomitance with [...] Read more.

The present research explored rewarding bias and attentional deficits in Internet addiction (IA) based on the IAT (Internet Addiction Test) construct, during an attentional inhibitory task (Go/NoGo task). Event-related Potentials (ERPs) effects (Feedback Related Negativity (FRN) and P300) were monitored in concomitance with Behavioral Activation System (BAS) modulation. High-IAT young participants showed specific responses to IA-related cues (videos representing online gambling and videogames) in terms of cognitive performance (decreased Response Times, RTs; and Error Rates, ERs) and ERPs modulation (decreased FRN and increased P300). Consistent reward and attentional biases was adduced to explain the cognitive “gain” effect and the anomalous response in terms of both feedback behavior (FRN) and attentional (P300) mechanisms in high-IAT. In addition, BAS and BAS-Reward subscales measures were correlated with both IAT and ERPs variations. Therefore, high sensitivity to IAT may be considered as a marker of dysfunctional reward processing (reduction of monitoring) and cognitive control (higher attentional values) for specific IA-related cues. More generally, a direct relationship among reward-related behavior, Internet addiction and BAS attitude was suggested. Full article

(This article belongs to the Special Issue Neurological Research on Learning, Reward and Decision Making)

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Open AccessArticle

Creativity Assessment in Subjects with Tourette Syndrome vs. Patients with Parkinson’s Disease: A Preliminary Study

by Carlotta Zanaboni Dina, Mauro Porta, Christian Saleh and Domenico Servello

Brain Sci. 2017, 7(7), 80; https://doi.org/10.3390/brainsci7070080 - 09 Jul 2017

Cited by 7 | Viewed by 4752

Abstract

(1) Background: Literature suggests that high levels of dopamine are associated with creative thoughts. Tourette Syndrome (TS) patients have high dopamine levels, while Parkinson’s Disease (PD) subjects have low dopamine levels. Consequently, TS individuals are supposed to have a major and PD patients [...] Read more.

(1) Background: Literature suggests that high levels of dopamine are associated with creative thoughts. Tourette Syndrome (TS) patients have high dopamine levels, while Parkinson’s Disease (PD) subjects have low dopamine levels. Consequently, TS individuals are supposed to have a major and PD patients less creative output. Moreover, dopamine medications may alter the level of creativity, and therefore Quality of Life, in both pathologies. (2) Methods: The aim of the study was to verify the hypothesis of TS patients having higher creative scores than PD patients. The assessment consisted of the administration of the Creative Thinking ASK Test. There were 54 participants—36 males and 18 females—i.e., 27 TS patients and 27 PD subjects. Age of the sample was 35 to 57 years old, high school certificate was required. (3) Results: TS sample (103.11 ASK average score) was more creative than PD sample (94.11 ASK average score). (4) Conclusions: The results supported the aforementioned hypothesis: TS sample resulted in having higher creative scores than PD sample. Dopamine and other neurotransmitters of TS and PS appear to affect subject’s creativity. Further studies with creative assessments in TS and PD patients are needed to support the preliminary results of our study. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

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Open AccessArticle

Multiple Mild Traumatic Brain Injuries Are Associated with Increased Rates of Health Symptoms and Gulf War Illness in a Cohort of 1990–1991 Gulf War Veterans

by Megan K. Yee, Patricia A. Janulewicz, Daniel R. Seichepine, Kimberly A. Sullivan, Susan P. Proctor and Maxine H. Krengel

Brain Sci. 2017, 7(7), 79; https://doi.org/10.3390/brainsci7070079 - 09 Jul 2017

Cited by 30 | Viewed by 5820

Abstract

Recent research demonstrated a relation between traumatic brain injury (TBI), health symptoms and diagnosis of Gulf War Illness (GWI) in Gulf War Veterans, but no study has examined the impact of multiple mild TBIs (mTBIs). A total of 229 male Gulf War Veterans [...] Read more.

Recent research demonstrated a relation between traumatic brain injury (TBI), health symptoms and diagnosis of Gulf War Illness (GWI) in Gulf War Veterans, but no study has examined the impact of multiple mild TBIs (mTBIs). A total of 229 male Gulf War Veterans from the Ft Devens Cohort were categorized by a number of mTBIs reported. One-way ANOVA and chi-square test of independence were used to test for differences in total reported health symptoms and diagnosis of chronic multisymptom illness (CMI) or Kansas GWI criteria, two of the most common case definitions of GWI. A total of 72 veterans reported no mTBIs (31.4%), 26 reported one mTBI (11.4%), 25 reported two mTBIs (10.9%), and 106 veterans reported sustaining three or more mTBIs (46.3%). Veterans reporting two or more mTBIs (p < 0.01) or three or more mTBIs (p < 0.001) endorsed significantly higher rates of health symptoms than Veterans reporting no mTBIs. Significantly higher rates of CMI (p = 0.035) and Kansas GWI criteria (p < 0.001) were seen in the three or more mTBI group. Results suggest two mTBIs increase risk of health symptoms, but three mTBIs may be the threshold needed to sustain chronic symptom reporting needed for a formal diagnosis. These findings highlight the importance of implementing policies and procedures monitoring head injuries in military personnel. Full article

(This article belongs to the Special Issue Mild Traumatic Brain Injury (mTBI): Medical Treatments and Complications)

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Open AccessReview

Multiple Sclerosis: Immunopathology and Treatment Update

by Narges Dargahi, Maria Katsara, Theodore Tselios, Maria-Eleni Androutsou, Maximilian De Courten, John Matsoukas and Vasso Apostolopoulos

Brain Sci. 2017, 7(7), 78; https://doi.org/10.3390/brainsci7070078 - 07 Jul 2017

Cited by 185 | Viewed by 23695

Abstract

The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies [...] Read more.

The treatment of multiple sclerosis (MS) has changed over the last 20 years. All immunotherapeutic drugs target relapsing remitting MS (RRMS) and it still remains a medical challenge in MS to develop a treatment for progressive forms. The most common injectable disease-modifying therapies in RRMS include β-interferons 1a or 1b and glatiramer acetate. However, one of the major challenges of injectable disease-modifying therapies has been poor treatment adherence with approximately 50% of patients discontinuing the therapy within the first year. Herein, we go back to the basics to understand the immunopathophysiology of MS to gain insights in the development of new improved drug treatments. We present current disease-modifying therapies (interferons, glatiramer acetate, dimethyl fumarate, teriflunomide, fingolimod, mitoxantrone), humanized monoclonal antibodies (natalizumab, ofatumumab, ocrelizumab, alemtuzumab, daclizumab) and emerging immune modulating approaches (stem cells, DNA vaccines, nanoparticles, altered peptide ligands) for the treatment of MS. Full article

(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)

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Open AccessBrief Report

Localization of Fibrinogen in the Vasculo-Astrocyte Interface after Cortical Contusion Injury in Mice

by Nino Muradashvili, Suresh C. Tyagi and David Lominadze

Brain Sci. 2017, 7(7), 77; https://doi.org/10.3390/brainsci7070077 - 06 Jul 2017

Cited by 20 | Viewed by 4709

Abstract

Besides causing neuronal damage, traumatic brain injury (TBI) is involved in memory reduction, which can be a result of alterations in vasculo-neuronal interactions. Inflammation following TBI is involved in elevation of blood content of fibrinogen (Fg), which is known to enhance cerebrovascular permeability, [...] Read more.

Besides causing neuronal damage, traumatic brain injury (TBI) is involved in memory reduction, which can be a result of alterations in vasculo-neuronal interactions. Inflammation following TBI is involved in elevation of blood content of fibrinogen (Fg), which is known to enhance cerebrovascular permeability, and thus, enhance its deposition in extravascular space. However, the localization of Fg in the extravascular space and its possible interaction with nonvascular cells are not clear. The localization of Fg deposition in the extravascular space was defined in brain samples of mice after cortical contusion injury (CCI) and sham-operation (control) using immunohistochemistry and laser-scanning confocal microscopy. Memory changes were assessed with new object recognition and Y-maze tests. Data showed a greater deposition of Fg in the vascular and astrocyte endfeet interface in mice with CCI than in control animals. This effect was accompanied by enhanced neuronal degeneration and reduction in short-term memory in mice with CCI. Thus, our results suggest that CCI induces increased deposition of Fg in the vasculo-astrocyte interface, and is accompanied by neuronal degeneration, which may result in reduction of short-term memory. Full article

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Open AccessArticle

P300 Source Localization Contrasts in Body-Focused Repetitive Behaviors and Tic Disorders

by Geneviève Sauvé, Simon Morand-Beaulieu, Kieron P. O’Connor, Pierre J. Blanchet and Marc E. Lavoie

Brain Sci. 2017, 7(7), 76; https://doi.org/10.3390/brainsci7070076 - 01 Jul 2017

Cited by 3 | Viewed by 6780

Abstract

Tic disorders (TD) and body-focused repetitive behaviors (BFRB) have similar phenotypes that can be challenging to distinguish in clinical settings. Both disorders show high rates of comorbid psychiatric conditions, dysfunctional basal ganglia activity, atypical cortical functioning in the prefrontal and motor cortical regions, [...] Read more.

Tic disorders (TD) and body-focused repetitive behaviors (BFRB) have similar phenotypes that can be challenging to distinguish in clinical settings. Both disorders show high rates of comorbid psychiatric conditions, dysfunctional basal ganglia activity, atypical cortical functioning in the prefrontal and motor cortical regions, and cognitive deficits. Clinicians frequently confound the two disorders and it is important to find reliable objective methods to discriminate TD and BFRB. Neuropsychological tests and event-related potential (ERP) studies have yielded inconsistent results regarding a possible context updating deficit in TD and BFRB patients. However, most previous studies did not control for the presence of comorbid psychiatric condition and medication status, which might have confounded the findings reported to date. Hence, we aimed to investigate the psychophysiology of working memory using ERP in carefully screened TD and BFRB patients excluding those with psychiatric comorbidity and those taking psychoactive medication. The current study compared 12 TD patients, 12 BRFB patients, and 15 healthy control participants using a motor oddball task (button press). The P300 component was analyzed as an index of working memory functioning. Results showed that BFRB patients had decreased P300 oddball effect amplitudes over the right hemisphere compared to the TD and control groups. Clinical groups presented different scalp distributions compared to controls, which could represent a potential endophenotype candidate of BFRB and TD. Full article

(This article belongs to the Special Issue Cerebral Etiology and Treatment of the Gilles de la Tourette Syndrome)

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Open AccessArticle

Subtitling for d/Deaf and Hard-of-Hearing Children: Current Practices and New Possibilities to Enhance Language Development

by Ana Tamayo and Frederic Chaume

Brain Sci. 2017, 7(7), 75; https://doi.org/10.3390/brainsci7070075 - 30 Jun 2017

Cited by 15 | Viewed by 8229

Abstract

In order to understand and fully comprehend a subtitle, two parameters within the linguistic code of audiovisual texts are key in the processing of the subtitle itself, namely, vocabulary and syntax. Through a descriptive and experimental study, the present article explores the transfer [...] Read more.

In order to understand and fully comprehend a subtitle, two parameters within the linguistic code of audiovisual texts are key in the processing of the subtitle itself, namely, vocabulary and syntax. Through a descriptive and experimental study, the present article explores the transfer of the linguistic code of audiovisual texts in subtitling for deaf and hard-of-hearing children in three Spanish TV stations. In the first part of the study, we examine current practices in Spanish TV captioning to analyse whether syntax and vocabulary are adapted to satisfy deaf children’s needs and expectations regarding subtitle processing. In the second part, we propose some alternative captioning criteria for these two variables based on the needs of d/Deaf and hard-of-hearing (DHH) children, suggesting a more appropriate way of displaying the written linguistic code for deaf children. Although no specific distinction will be made throughout this paper, it is important to refer to these terms as they have been widely used in the literature. Neves (2008) distinguishes between the “Deaf”, who belong to a linguistic minority, use sign language as their mother tongue, and usually identify with a Deaf community and culture; the “deaf”, who normally have an oral language as their mother tongue and feel part of the hearing community; and the “hard of hearing”, who have residual hearing and, therefore, share the world and the sound experience of hearers. In the experimental study, 75 Spanish DHH children aged between 8 and 13 were exposed to two options: the actual broadcast captions on TV, and the alternative captions created by the authors. The data gathered from this exposure were used to analyse the children’s comprehension of these two variables in order to draw conclusions about the suitability of the changes proposed in the alternative subtitles. Full article

(This article belongs to the Special Issue Audiovisual Integration in Early Language Development)

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Open AccessArticle

Hypermethylation of Synphilin-1, Alpha-Synuclein-Interacting Protein (SNCAIP) Gene in the Cerebral Cortex of Patients with Sporadic Parkinson’s Disease

by Khashayar Dashtipour, Ali Tafreshi, Charles Adler, Thomas Beach, Xin Chen, Geidy Serrano, Stephanie Tashiro and Charles Wang

Brain Sci. 2017, 7(7), 74; https://doi.org/10.3390/brainsci7070074 - 27 Jun 2017

Cited by 10 | Viewed by 4804

Abstract

Objective: To determine and compare DNA methylation patterns between patients with Parkinson’s disease (PD) and age- and sex-similar matched non-PD controls. Background: Epigenetic regulation is one of the major mechanisms for an organism to respond to the environment through changes in gene expression [...] Read more.

Objective: To determine and compare DNA methylation patterns between patients with Parkinson’s disease (PD) and age- and sex-similar matched non-PD controls. Background: Epigenetic regulation is one of the major mechanisms for an organism to respond to the environment through changes in gene expression and has been implicated in numerous disease processes. We would like to examine epigenetic modification patterns that may predispose or protect against PD. Methods: Frozen tissue samples of the human cerebral cortex from 12 PD patients and 12 subjects without PD pathology were obtained. Genome-wide DNA methylation profiling was performed using the Illumina HumanMethylation450 BeadChip array. Differential methylation was defined as a mean methylation level difference (delta β) of at least 0.20 (Δβ ≥ 0.20). Methylation regions with an absolute delta β value ≥ 0.20 were selected for further gene function studies. Results: We identified 2795 differentially methylated CpG sites in the frontal cortex of PD cases with a detection p-value of ≤ 0.01 and 328 differentially methylated CpG sites with a detection p-value of ≤ 0.001. A pattern of robust hypermethylation of synphilin-1, α-synuclein-interacting protein (SNCAIP) gene was found in the brain of PD cases (p = 4.93 × 10⁻⁷ and delta β = 0.60). Conclusion: Our findings support a link between SNCAIP methylation and PD risk. Hypomethylation of SNCAIP may function to protect against PD. The current results may suggest that the methylation status of SNCAIP could be useful as a marker in PD diagnosis and treatment and warrants further investigation. Full article

(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)

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Open AccessArticle

Astrocytic Expression of GSTA4 Is Associated to Dopaminergic Neuroprotection in a Rat 6-OHDA Model of Parkinson’s Disease

by Michael Jewett, Itzia Jimenez-Ferrer and Maria Swanberg

Brain Sci. 2017, 7(7), 73; https://doi.org/10.3390/brainsci7070073 - 26 Jun 2017

Cited by 12 | Viewed by 6511

Abstract

Idiopathic Parkinson’s disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been [...] Read more.

Idiopathic Parkinson’s disease (PD) is a complex disease caused by multiple, mainly unknown, genetic and environmental factors. The Ventral root avulsion 1 (Vra1) locus on rat chromosome 8 includes the Glutathione S-transferase alpha 4 (Gsta4) gene and has been identified in crosses between Dark Agouti (DA) and Piebald Virol Glaxo (PVG) rat strains as being associated to neurodegeneration after nerve and brain injury. The Gsta4 protein clears lipid peroxidation by-products, a process suggested to being implicated in PD. We therefore investigated whether PVG alleles in Vra1 are neuroprotective in a toxin-induced model of PD and if this effect is coupled to Gsta4. We performed unilateral 6-hydroxydopamine (6-OHDA) partial lesions in the striatum and compared the extent of neurodegeration in parental (DA) and congenic (DA.VRA1) rats. At 8 weeks after 6-OHDA lesion, DA.VRA1 rats displayed a higher density of remaining dopaminergic fibers in the dorsolateral striatum compared to DA rats (44% vs. 23%, p < 0.01), indicating that Vra1 alleles derived from the PVG strain protect dopaminergic neurons from 6-OHDA toxicity. Gsta4 gene expression levels in the striatum and midbrain were higher in DA.VRA1 congenic rats compared to DA at 2 days post-lesion (p < 0.05). The GSTA4 protein co-localized with astrocytic marker GFAP, but not with neuronal marker NeuN or microglial marker IBA1, suggesting astrocyte-specific expression. This is the first report on Vra1 protective effects on dopaminergic neurodegeneration and encourages further studies on Gsta4 in relation to PD susceptibility. Full article

(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)

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Open AccessReview

Clinicopathological Phenotype and Genetics of X-Linked Dystonia–Parkinsonism (XDP; DYT3; Lubag)

by Toshitaka Kawarai, Ryoma Morigaki, Ryuji Kaji and Satoshi Goto

Brain Sci. 2017, 7(7), 72; https://doi.org/10.3390/brainsci7070072 - 26 Jun 2017

Cited by 17 | Viewed by 9358

Abstract

X-linked dystonia–parkinsonism (XDP; OMIM314250), also referred to as DYT3 dystonia or “Lubag” disease, was first described as an endemic disease in the Philippine island of Panay. XDP is an adult-onset movement disorder characterized by progressive and severe dystonia followed by overt parkinsonism in [...] Read more.

X-linked dystonia–parkinsonism (XDP; OMIM314250), also referred to as DYT3 dystonia or “Lubag” disease, was first described as an endemic disease in the Philippine island of Panay. XDP is an adult-onset movement disorder characterized by progressive and severe dystonia followed by overt parkinsonism in the later years of life. Among the primary monogenic dystonias, XDP has been identified as a transcriptional dysregulation syndrome with impaired expression of the TAF1 (TATA box-binding protein associated factor 1) gene, which is a critical component of the cellular transcription machinery. The major neuropathology of XDP is progressive neuronal loss in the neostriatum (i.e., the caudate nucleus and putamen). XDP may be used as a human disease model to elucidate the pathomechanisms by which striatal neurodegeneration leads to dystonia symptoms. In this article, we introduce recent advances in the understanding of the interplay between pathophysiology and genetics in XDP. Full article

(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)

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Open AccessCase Report

Phenotypic Discordance in Siblings with Identical Compound Heterozygous PARK2 Mutations

by David Isaacs, Daniel Claassen, Aaron B. Bowman and Peter Hedera

Brain Sci. 2017, 7(7), 71; https://doi.org/10.3390/brainsci7070071 - 24 Jun 2017

Cited by 7 | Viewed by 4756

Abstract

PARK2 mutations are the most common cause of early-onset Parkinson’s disease. No genotype-phenotype correlation exists, and phenotypic variability is quite common. We report two siblings with confirmed identical compound heterozygous mutations in the PARK2 gene manifesting strikingly different phenotypes. The older brother demonstrated [...] Read more.

PARK2 mutations are the most common cause of early-onset Parkinson’s disease. No genotype-phenotype correlation exists, and phenotypic variability is quite common. We report two siblings with confirmed identical compound heterozygous mutations in the PARK2 gene manifesting strikingly different phenotypes. The older brother demonstrated marked parkinsonism by his mid-20’s, whereas the younger brother developed exercise-induced dystonia in his mid-30’s with no subsequent clinical progression, highlighting the clinical heterogeneity of the disease and implying the role of other genetic and/or environmental factors in disease progression. The younger sibling, despite his mild symptoms, had a clearly abnormal dopamine transporter (DaT)-SPECT scan. To our knowledge, this is the first such reported case of an abnormal DaT-SPECT scan in a patient with biallelic PARK2 mutations who does not meet the clinical criteria for Parkinson’s disease. Full article

(This article belongs to the Special Issue Pathophysiology and Genetics of Movement Disorders)

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Open AccessReview

The Role of Peripheral CNS‐Directed Antibodies in Promoting Inflammatory CNS Demyelination

by Silke Kinzel and Martin S. Weber

Brain Sci. 2017, 7(7), 70; https://doi.org/10.3390/brainsci7070070 - 22 Jun 2017

Cited by 14 | Viewed by 6609

Abstract

In central nervous system (CNS) demyelinating disorders, such as multiple sclerosis (MS), neuromyelitis optica (NMO) and related NMO-spectrum disorders (NMO-SD), a pathogenic role for antibodies is primarily projected into enhancing ongoing CNS inflammation by directly binding to target antigens within the CNS. This [...] Read more.

In central nervous system (CNS) demyelinating disorders, such as multiple sclerosis (MS), neuromyelitis optica (NMO) and related NMO-spectrum disorders (NMO-SD), a pathogenic role for antibodies is primarily projected into enhancing ongoing CNS inflammation by directly binding to target antigens within the CNS. This scenario is supported at least in part, by antibodies in conjunction with complement activation in the majority of MS lesions and by deposition of anti-aquaporin-4 (AQP-4) antibodies in areas of astrocyte loss in patients with classical NMO. A currently emerging subgroup of AQP-4 negative NMO-SD patients expresses antibodies against myelin oligodendrocyte glycoprotein (MOG), again suggestive of their direct binding to CNS myelin. However, both known entities of anti-CNS antibodies, anti-AQP-4- as well as anti-MOG antibodies, are predominantly found in the serum, which raises the questions why and how a humoral response against CNS antigens is raised in the periphery, and in a related manner, what pathogenic role these antibodies may exert outside the CNS. In this regard, recent experimental and clinical evidence suggests that peripheral CNS-specific antibodies may indirectly activate peripheral CNS-autoreactive T cells by opsonization of otherwise unrecognized traces of CNS antigen in peripheral compartments, presumably drained from the CNS by its newly recognized lymphatic system. In this review, we will summarize all currently available data on both possible roles of antibodies in CNS demyelinating disorders, first, directly enhancing damage within the CNS, and second, promoting a peripheral immune response against the CNS. By elaborating on the latter scenario, we will develop the hypothesis that peripheral CNS-recognizing antibodies may have a powerful role in initiating acute flares of CNS demyelinating disease and that these humoral responses may represent a therapeutic target in its own right. Full article

(This article belongs to the Special Issue Pathophysiology and Imaging Diagnosis of Demyelinating Disorders)

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Brain Sci., Volume 7, Issue 7 (July 2017) – 23 articles

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