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      Association between memory impairment and brain metabolite concentrations in North Korean refugees with posttraumatic stress disorder

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          Abstract

          Individuals with posttraumatic stress disorder (PTSD) had experiences of enormous psychological stress that can result in neurocognitive and neurochemical changes. To date, the causal relationship between them remains unclear. The present study is to investigate the association between neurocognitive characteristics and neural metabolite concentrations in North Korean refugees with PTSD. A total of 53 North Korean refugees with or without PTSD underwent neurocognitive function tests. For neural metabolite scanning, magnetic resonance spectroscopy of the hippocampus and anterior cingulate cortex (ACC) has been conducted. We assessed between-group differences in neurocognitive test scores and metabolite levels. Additionally, a multiple regression analysis was carried out to evaluate the association between neurocognitive function and metabolite levels in patients with PTSD. Memory function, but not other neurocognitive functions, was significantly lower in the PTSD group compared with the non-PTSD group. Hippocampal N-acetylaspartate (NAA) levels were not different between groups; however, NAA levels were significantly lower in the ACC of the PTSD group than the non-PTSD group (t = 2.424, p = 0.019). The multiple regression analysis showed a negative association between hippocampal NAA levels and delayed recall score on the auditory verbal learning test (β = -1.744, p = 0.011) in the non-PTSD group, but not in the PTSD group. We identified specific memory impairment and the role of NAA levels in PTSD. Our findings suggest that hippocampal NAA has a protective role in memory impairment and development of PTSD after exposure to traumatic events.

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          Neurocircuitry models of posttraumatic stress disorder and extinction: human neuroimaging research--past, present, and future.

          The prevailing neurocircuitry models of anxiety disorders have been amygdalocentric in form. The bases for such models have progressed from theoretical considerations, extrapolated from research in animals, to in vivo human imaging data. For example, one current model of posttraumatic stress disorder (PTSD) has been highly influenced by knowledge from rodent fear conditioning research. Given the phenomenological parallels between fear conditioning and the pathogenesis of PTSD, we have proposed that PTSD is characterized by exaggerated amygdala responses (subserving exaggerated acquisition of fear associations and expression of fear responses) and deficient frontal cortical function (mediating deficits in extinction and the capacity to suppress attention/response to trauma-related stimuli), as well as deficient hippocampal function (mediating deficits in appreciation of safe contexts and explicit learning/memory). Neuroimaging studies have yielded convergent findings in support of this model. However, to date, neuroimaging investigations of PTSD have not principally employed conditioning and extinction paradigms per se. The recent development of such imaging probes now sets the stage for directly testing hypotheses regarding the neural substrates of fear conditioning and extinction abnormalities in PTSD.
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            The stressed hippocampus, synaptic plasticity and lost memories.

            Stress is a biologically significant factor that, by altering brain cell properties, can disturb cognitive processes such as learning and memory, and consequently limit the quality of human life. Extensive rodent and human research has shown that the hippocampus is not only crucially involved in memory formation, but is also highly sensitive to stress. So, the study of stress-induced cognitive and neurobiological sequelae in animal models might provide valuable insight into the mnemonic mechanisms that are vulnerable to stress. Here, we provide an overview of the neurobiology of stress memory interactions, and present a neural endocrine model to explain how stress modifies hippocampal functioning.
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              Prefrontal mechanisms in extinction of conditioned fear.

              Interest in the medial prefrontal cortex (mPFC) as a source of behavioral inhibition has increased with the mounting evidence for a functional role of the mPFC in extinction of conditioned fear. In fear extinction, a tone-conditioned stimulus (CS) previously paired with a footshock is presented repeatedly in the absence of footshock, causing fear responses to diminish. Here, we review converging evidence from different laboratories implicating the mPFC in memory circuits for fear extinction: (1) lesions of mPFC impair recall of extinction under various conditions, (2) extinction potentiates mPFC physiological responses to the CS, (3) mPFC potentiation is correlated with extinction behavior, and (4) stimulation of mPFC strengthens extinction memory. These findings support Pavlov's original notion that extinction is new learning, rather than erasure of conditioning. In people suffering from posttraumatic stress disorder (PTSD), homologous areas of ventral mPFC show morphological and functional abnormalities, suggesting that extinction circuits are compromised in PTSD. Strategies for augmenting prefrontal function for clinical benefit are discussed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: MethodologyRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: Visualization
                Role: Formal analysisRole: MethodologyRole: SoftwareRole: Visualization
                Role: MethodologyRole: ResourcesRole: Supervision
                Role: InvestigationRole: Resources
                Role: InvestigationRole: Resources
                Role: Investigation
                Role: ConceptualizationRole: Data curationRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                7 December 2017
                2017
                : 12
                : 12
                : e0188953
                Affiliations
                [1 ] Department of Psychiatry, Seoul National University Hospital, Seoul, Republic of Korea
                [2 ] Department of Radiology, Chungbuk National University Hospital, Cheongju, Republic of Korea
                [3 ] Computational NeuroImage Analysis Laboratory, Department of Biomedical Engineering, Hanyang University, Seoul, Republic of Korea
                [4 ] Department of Psychiatry and Institute of Human Behavioral Medicine in SNU-MRC, Seoul National University College of Medicine, Seoul, Republic of Korea
                [5 ] Department of Psychiatry, National Medical Center, Seoul, Republic of Korea
                Max Planck Institute for Psychiatry, GERMANY
                Author notes

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

                Author information
                http://orcid.org/0000-0003-4507-6108
                Article
                PONE-D-17-11200
                10.1371/journal.pone.0188953
                5720673
                29216235
                34a03d48-6815-4075-915b-aaae206929dc
                © 2017 Shin et al

                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
                : 22 March 2017
                : 13 November 2017
                Page count
                Figures: 1, Tables: 4, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100003648, National Medical Center;
                Award ID: NMC2012-MS-03
                Award Recipient :
                This work was supported by Research Program funded by National Medical Center, Research Institute (grant number: NMC2012-MS-03). The funding sources had no further role in the study design, collection, analysis, interpretation of the data, writing of the report, and in the decision to submit this report for publication. The corresponding authors had full access to the data in the study and had final responsibility for the decision to submit for publication.
                Categories
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                Medicine and Health Sciences
                Mental Health and Psychiatry
                Neuropsychiatric Disorders
                Anxiety Disorders
                Post-Traumatic Stress Disorder
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                Mental Health and Psychiatry
                Neuroses
                Anxiety Disorders
                Post-Traumatic Stress Disorder
                Biology and Life Sciences
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                Memory
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                Biochemistry
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                Recall (Memory)
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                Diagnostic Medicine
                Diagnostic Radiology
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