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      Theta, Mental Flexibility, and Post-Traumatic Stress Disorder: Connecting in the Parietal Cortex

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          Abstract

          Post-traumatic stress disorder (PTSD) is a mental health injury characterised by re-experiencing, avoidance, numbing and hyperarousal. Whilst the aetiology of the disorder is relatively well understood, there is debate about the prevalence of cognitive sequelae that manifest in PTSD. In particular, there are conflicting reports about deficits in executive function and mental flexibility. Even less is known about the neural changes that underlie such deficits. Here, we used magnetoencephalography to study differences in functional connectivity during a mental flexibility task in combat-related PTSD (all males, mean age = 37.4, n = 18) versus a military control (all males, mean age = 33.05, n = 19) group. We observed large-scale increases in theta connectivity in the PTSD group compared to controls. The PTSD group performance was compromised in the more attentionally-demanding task and this was characterised by 'late-stage' theta hyperconnectivity, concentrated in network connections involving right parietal cortex. Furthermore, we observed significant correlations with the connectivity strength in this region with a number of cognitive-behavioural outcomes, including measures of attention, depression and anxiety. These findings suggest atypical coordination of neural synchronisation in large scale networks contributes to deficits in mental flexibility for PTSD populations in timed, attentionally-demanding tasks, and this propensity toward network hyperconnectivity may play a more general role in the cognitive sequelae evident in this disorder.

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          Most cited references39

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          Phase lag index: assessment of functional connectivity from multi channel EEG and MEG with diminished bias from common sources.

          To address the problem of volume conduction and active reference electrodes in the assessment of functional connectivity, we propose a novel measure to quantify phase synchronization, the phase lag index (PLI), and compare its performance to the well-known phase coherence (PC), and to the imaginary component of coherency (IC). The PLI is a measure of the asymmetry of the distribution of phase differences between two signals. The performance of PLI, PC, and IC was examined in (i) a model of 64 globally coupled oscillators, (ii) an EEG with an absence seizure, (iii) an EEG data set of 15 Alzheimer patients and 13 control subjects, and (iv) two MEG data sets. PLI and PC were more sensitive than IC to increasing levels of true synchronization in the model. PC and IC were influenced stronger than PLI by spurious correlations because of common sources. All measures detected changes in synchronization during the absence seizure. In contrast to PC, PLI and IC were barely changed by the choice of different montages. PLI and IC were superior to PC in detecting changes in beta band connectivity in AD patients. Finally, PLI and IC revealed a different spatial pattern of functional connectivity in MEG data than PC. The PLI performed at least as well as the PC in detecting true changes in synchronization in model and real data but, at the same token and like-wise the IC, it was much less affected by the influence of common sources and active reference electrodes. Copyright 2007 Wiley-Liss, Inc.
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            Dopaminergic foundations of schizotypy as measured by the German version of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE)—a suitable endophenotype of schizophrenia

            The concept of schizotypy or “psychosis proneness” captures individual differences in perceptual, cognitive, and affective experiences that may relate to a range of psychotic disorders. The concept is an important way to assess the contribution of pre-existing psychological and genetically based biological features to the development of illnesses such as schizophrenia (so called endophenotypes). The Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE) is a widely used multi-dimensional measure of the construct and consists of four scales which mirror several groups of psychotic symptoms: Unusual Experiences (UnEx; positive symptoms), Cognitive Disorganization (CogDis; cognitive symptoms), Introvertive Anhedonia (IntAn; negative symptoms), and Impulsive Nonconformity (ImpNon; impulsive and antisocial symptoms). For the purpose of evaluating the suitability of schizotypy as an endophenotype of schizophrenia the current version of the O-LIFE was translated into German: its psychometric properties (including re-test reliability and construct validity) were examined in a large sample (n > 1200) and compared to those of the English original. The German version was both highly reliable and consistent with the original. The study aimed to show that schizotypy as measured by the O-LIFE can indeed be regarded as an endophenotype of schizophrenia in terms of genetic associations regarding relevant dopamine-related candidate polymorphisms of schizotypy [i.e., Val158Met-polymorphism of the COMT gene, uVNTR of the MAOA gene, Taq1A-polymorphism of the DRD2 gene, VNTR of the SLC6A3 (DAT) gene]. We also wanted to compare the genetic associations of the O-LIFE to those published using other operationalizations of schizotypy. Our results show a large number of significant associations and borderline-significant trends between the O-LIFE sub-scales and a range of genes, thereby supporting using the O-LIFE in the search for endophenotypic markers.
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              High-frequency brain activity and muscle artifacts in MEG/EEG: a review and recommendations

              In recent years high-frequency brain activity in the gamma-frequency band (30–80 Hz) and above has become the focus of a growing body of work in MEG/EEG research. Unfortunately, high-frequency neural activity overlaps entirely with the spectral bandwidth of muscle activity (~20–300 Hz). It is becoming appreciated that artifacts of muscle activity may contaminate a number of non-invasive reports of high-frequency activity. In this review, the spectral, spatial, and temporal characteristics of muscle artifacts are compared with those described (so far) for high-frequency neural activity. In addition, several of the techniques that are being developed to help suppress muscle artifacts in MEG/EEG are reviewed. Suggestions are made for the collection, analysis, and presentation of experimental data with the aim of reducing the number of publications in the future that may contain muscle artifacts.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                24 April 2015
                2015
                : 10
                : 4
                : e0123541
                Affiliations
                [1 ]Department of Diagnostic Imaging, Hospital for Sick Children, Toronto, Canada
                [2 ]Neuroscience & Mental Health Program, Hospital for Sick Children Research Institute, Toronto, Canada
                [3 ]Directorate of Mental Health, Canadian Forces Health Services, Ottawa, Canada
                [4 ]Department of Medical Imaging, University of Toronto, Toronto, Canada
                [5 ]Department of Psychology, University of Toronto, Toronto, Canada
                [6 ]Canadian Forces Environmental Medicine Establishment, Toronto, Canada
                [7 ]Defence Research and Development Canada, Toronto, Canada
                [8 ]Division of Neurology, Hospital for Sick Children, Toronto, Canada
                Osaka University Graduate School of Medicine, JAPAN
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: PNS RJ MJT EWP EWP MJT PNS PAS RJG. Performed the experiments: EWP MJT. Analyzed the data: BTD SMD. Contributed reagents/materials/analysis tools: SMD. Wrote the paper: BTD SMD MJT EWP. Recruited participants: PAS RJG. Behavioural and clinical assessments: PAS RJG.

                Article
                PONE-D-14-33153
                10.1371/journal.pone.0123541
                4409115
                25909654
                a74a661d-e0a3-4060-8707-33b98f786631
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 1 August 2014
                : 4 March 2015
                Page count
                Figures: 5, Tables: 1, Pages: 17
                Funding
                This work was supported by funding from Defence Research and Development Canada (DRDC) (Contract #: W7719-135182/001/TOR; http://www.drdc-rddc.gc.ca/en/index.page) and the Canadian Forces Health Services ( http://www.forces.gc.ca/en/caf-community-health-services/index.page) to MJT and EWP. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                Cognitivebehavioural outcomes are restricted due to the clinical nature of this study and the Defence Research and Development Canada Research Ethic Board restrictions on data availability. Neuroimaging data can be requested from either Dr Margot J Taylor ( margot.taylor@ 123456sickkids.ca ) or Dr Elizabeth W Pang ( liz.pang@ 123456sickkids.ca ).

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