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      In Search of the Trauma Memory: A Meta-Analysis of Functional Neuroimaging Studies of Symptom Provocation in Posttraumatic Stress Disorder (PTSD)

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          Abstract

          Notwithstanding some discrepancy between results from neuroimaging studies of symptom provocation in posttraumatic stress disorder (PTSD), there is broad agreement as to the neural circuit underlying this disorder. It is thought to be characterized by an exaggerated amygdalar and decreased medial prefrontal activation to which the elevated anxiety state and concomitant inadequate emotional regulation are attributed. However, the proposed circuit falls short of accounting for the main symptom, unique among anxiety disorders to PTSD, namely, reexperiencing the precipitating event in the form of recurrent, distressing images and recollections. Owing to the technical demands, neuroimaging studies are usually carried out with small sample sizes. A meta-analysis of their findings is more likely to cast light on the involved cortical areas. Coordinate-based meta-analyses employing ES-SDM (Effect Size Signed Differential Mapping) were carried out on 19 studies with 274 PTSD patients. Thirteen of the studies included 145 trauma-exposed control participants. Comparisons between reactions to trauma-related stimuli and a control condition and group comparison of reactions to the trauma-related stimuli were submitted to meta-analysis. Compared to controls and the neutral condition, PTSD patients showed significant activation of the mid-line retrosplenial cortex and precuneus in response to trauma-related stimuli. These midline areas have been implicated in self-referential processing and salient autobiographical memory. PTSD patients also evidenced hyperactivation of the pregenual/anterior cingulate gyrus and bilateral amygdala to trauma-relevant, compared to neutral, stimuli. Patients showed significantly less activation than controls in sensory association areas such as the bilateral temporal gyri and extrastriate area which may indicate that the patients’ attention was diverted from the presented stimuli by being focused on the elicited trauma memory. Being involved in associative learning and priming, the retrosplenial cortex may have an important function in relation to trauma memory, in particular, the intrusive reexperiencing of the traumatic event.

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          Searching for a baseline: functional imaging and the resting human brain.

          Functional brain imaging in humans has revealed task-specific increases in brain activity that are associated with various mental activities. In the same studies, mysterious, task-independent decreases have also frequently been encountered, especially when the tasks of interest have been compared with a passive state, such as simple fixation or eyes closed. These decreases have raised the possibility that there might be a baseline or resting state of brain function involving a specific set of mental operations. We explore this possibility, including the manner in which we might define a baseline and the implications of such a baseline for our understanding of brain function.
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            Central cancellation of self-produced tickle sensation.

            A self-produced tactile stimulus is perceived as less ticklish than the same stimulus generated externally. We used fMRI to examine neural responses when subjects experienced a tactile stimulus that was either self-produced or externally produced. More activity was found in somatosensory cortex when the stimulus was externally produced. In the cerebellum, less activity was associated with a movement that generated a tactile stimulus than with a movement that did not. This difference suggests that the cerebellum is involved in predicting the specific sensory consequences of movements, providing the signal that is used to cancel the sensory response to self-generated stimulation.
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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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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2013
                25 March 2013
                : 8
                : 3
                : e58150
                Affiliations
                [1 ]Clinical Psychology Unit, Department of Psychology, University of Wuppertal, Wuppertal, Germany
                [2 ]Neurology Clinic, University of Düsseldorf, Düsseldorf, Germany
                [3 ]Statistics Unit, Department of Psychology, University of Wuppertal, Wuppertal, Germany
                Bellvitge Biomedical Research Institute-IDIBELL, Spain
                Author notes

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

                Conceived and designed the experiments: GS ML. Analyzed the data: JC BS HK. Contributed reagents/materials/analysis tools: RS. Wrote the paper: GS RJS.

                Article
                PONE-D-12-32657
                10.1371/journal.pone.0058150
                3607590
                23536785
                35c13eb2-5484-44cf-9cae-0ffd057f6080
                Copyright @ 2013

                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
                : 23 October 2012
                : 31 January 2013
                Page count
                Pages: 11
                Funding
                The study was funded by the University of Wuppertal. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology
                Neuroscience
                Neuroimaging
                Fmri
                Medicine
                Clinical Research Design
                Meta-Analyses
                Mental Health
                Psychiatry
                Anxiety Disorders
                Psychology
                Cognitive Psychology
                Memory
                Psychological Stress
                Neurology
                Neuroimaging
                Social and Behavioral Sciences
                Psychology
                Clinical Psychology
                Psychological Stress

                Uncategorized
                Uncategorized

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