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      The Innate Alarm System and Subliminal Threat Presentation in Posttraumatic Stress Disorder: Neuroimaging of the Midbrain and Cerebellum

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          Abstract

          Background

          The innate alarm system, a network of interconnected midbrain, other brainstem, and thalamic structures, serves to rapidly detect stimuli in the environment prior to the onset of conscious awareness. This system is sensitive to threatening stimuli and has evolved to process these stimuli subliminally for hastened responding. Despite the conscious unawareness, the presentation of subliminal threat stimuli generates increased activation of limbic structures, including the amygdala and insula, as well as emotionally evaluative structures, including the cerebellum and orbitofrontal cortex. Posttraumatic stress disorder (PTSD) is associated with an increased startle response and decreased extinction learning to conditioned threat. The role of the innate alarm system in the clinical presentation of PTSD, however, remains poorly understood.

          Methods

          Here, we compare midbrain, brainstem, and cerebellar activation in persons with PTSD (n = 26) and matched controls (n = 20) during subliminal threat presentation. Subjects were presented with masked trauma-related and neutral stimuli below conscious threshold. Contrasts of subliminal brain activation for the presentation of neutral stimuli were subtracted from trauma-related brain activation. Group differences in activation, as well as correlations between clinical scores and PTSD activation, were examined. Imaging data were preprocessed utilizing the spatially unbiased infratentorial template toolbox within SPM12.

          Results

          Analyses revealed increased midbrain activation in PTSD as compared to controls in the superior colliculus, periaqueductal gray, and midbrain reticular formation during subliminal threat as compared to neutral stimulus presentation. Controls showed increased activation in the right cerebellar lobule V during subliminal threat presentation as compared to PTSD. Finally, a negative correlation emerged between PTSD patient scores on the Multiscale Dissociation Inventory for the Depersonalization/Derealization subscale and activation in the right lobule V of the cerebellum during the presentation of subliminal threat as compared to neutral stimuli.

          Conclusion

          We interpret these findings as evidence of innate alarm system overactivation in PTSD and of the prominent role of the cerebellum in the undermodulation of emotion observed in PTSD.

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          Most cited references81

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          Evidence for topographic organization in the cerebellum of motor control versus cognitive and affective processing.

          Patients with cerebellar damage often present with the cerebellar motor syndrome of dysmetria, dysarthria and ataxia, yet cerebellar lesions can also result in the cerebellar cognitive affective syndrome (CCAS), including executive, visual spatial, and linguistic impairments, and affective dysregulation. We have hypothesized that there is topographic organization in the human cerebellum such that the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis is the anatomical substrate of the limbic cerebellum. Here we analyze anatomical, functional neuroimaging, and clinical data to test this hypothesis. We find converging lines of evidence supporting regional organization of motor, cognitive, and limbic behaviors in the cerebellum. The cerebellar motor syndrome results when lesions involve the anterior lobe and parts of lobule VI, interrupting cerebellar communication with cerebral and spinal motor systems. Cognitive impairments occur when posterior lobe lesions affect lobules VI and VII (including Crus I, Crus II, and lobule VIIB), disrupting cerebellar modulation of cognitive loops with cerebral association cortices. Neuropsychiatric disorders manifest when vermis lesions deprive cerebro-cerebellar-limbic loops of cerebellar input. We consider this functional topography to be a consequence of the differential arrangement of connections of the cerebellum with the spinal cord, brainstem, and cerebral hemispheres, reflecting cerebellar incorporation into the distributed neural circuits subserving movement, cognition, and emotion. These observations provide testable hypotheses for future investigations. Copyright (c) 2009 Elsevier Srl. All rights reserved.
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            Development and validation of a brief screening version of the Childhood Trauma Questionnaire.

            The goal of this study was to develop and validate a short form of the Childhood Trauma Questionnaire (the CTQ-SF) as a screening measure for maltreatment histories in both clinical and nonreferred groups. Exploratory and confirmatory factor analyses of the 70 original CTQ items were used to create a 28-item version of the scale (25 clinical items and three validity items) and test the measurement invariance of the 25 clinical items across four samples: 378 adult substance abusing patients from New York City, 396 adolescent psychiatric inpatients, 625 substance abusing individuals from southwest Texas, and 579 individuals from a normative community sample (combined N=1978). Results showed that the CTQ-SF's items held essentially the same meaning across all four samples (i.e., measurement invariance). Moreover, the scale demonstrated good criterion-related validity in a subsample of adolescents on whom corroborative data were available. These findings support the viability of the CTQ-SF across diverse clinical and nonreferred populations.
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              Neurobiological basis of failure to recall extinction memory in posttraumatic stress disorder.

              A clinical characteristic of posttraumatic stress disorder (PTSD) is persistently elevated fear responses to stimuli associated with the traumatic event. The objective herein is to determine whether extinction of fear responses is impaired in PTSD and whether such impairment is related to dysfunctional activation of brain regions known to be involved in fear extinction, viz., amygdala, hippocampus, ventromedial prefrontal cortex (vmPFC), and dorsal anterior cingulate cortex (dACC). Sixteen individuals diagnosed with PTSD and 15 trauma-exposed non-PTSD control subjects underwent a 2-day fear conditioning and extinction protocol in a 3-T functional magnetic resonance imaging scanner. Conditioning and extinction training were conducted on day 1. Extinction recall (or extinction memory) test was conducted on day 2 (extinguished conditioned stimuli presented in the absence of shock). Skin conductance response (SCR) was scored throughout the experiment as an index of the conditioned response. The SCR data revealed no significant differences between groups during acquisition and extinction of conditioned fear on day 1. On day 2, however, PTSD subjects showed impaired recall of extinction memory. Analysis of functional magnetic resonance imaging data showed greater amygdala activation in the PTSD group during day 1 extinction learning. During extinction recall, lesser activation in hippocampus and vmPFC and greater activation in dACC were observed in the PTSD group. The magnitude of extinction memory across all subjects was correlated with activation of hippocampus and vmPFC during extinction recall testing. These findings support the hypothesis that fear extinction is impaired in PTSD. They further suggest that dysfunctional activation in brain structures that mediate fear extinction learning, and especially its recall, underlie this impairment.
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                Author and article information

                Journal
                Chronic Stress (Thousand Oaks)
                Chronic Stress (Thousand Oaks)
                CSS
                spcss
                Chronic Stress
                SAGE Publications (Sage CA: Los Angeles, CA )
                2470-5470
                5 February 2019
                Jan-Dec 2019
                : 3
                : 2470547018821496
                Affiliations
                [1 ]Department of Neuroscience, Western University, London, Ontario, Canada
                [2 ]Department of Psychiatry, Western University, London, Ontario, Canada
                [3 ]Imaging Division, Lawson Health Research Institute, London, Ontario, Canada
                [4 ]Department of Theoretical Neuroscience, Central Institute of Mental Health Mannheim, Medical Faculty Mannheim, Heidelberg University, Heidelberg, Germany
                [5 ]Department of Psychology, Western University, London, Ontario, Canada
                [6 ]Mood Disorders Program, St. Joseph’s Healthcare, Hamilton, Ontario, Canada
                [7 ]Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
                [8 ]Homewood Research Institute, Guelph, Ontario, Canada
                Author notes
                [*]Ruth A. Lanius, Department of Psychiatry, Western University, University Hospital (Room C3-103), 339 Windermere Road, London, Ontario N6A 5A5, Canada. Email: ruth.lanius@ 123456lhsc.on.ca
                Author information
                https://orcid.org/0000-0002-6770-2715
                Article
                10.1177_2470547018821496
                10.1177/2470547018821496
                7219880
                32440590
                0fc721bc-e09f-4999-aec4-7f6f171682a3
                © The Author(s) 2019

                Creative Commons CC-BY: This article is distributed under the terms of the Creative Commons Attribution 4.0 License ( http://www.creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 9 October 2018
                : 28 November 2018
                Funding
                Funded by: Institute of Neurosciences, Mental Health and Addiction, FundRef https://doi.org/10.13039/501100000034;
                Award ID: 137150
                Award ID: 97914
                Categories
                Original Article
                Custom metadata
                January-December 2019

                posttraumatic stress disorder,neuroimaging,midbrain,subliminal threat,trauma,periaqueductal gray,cerebellum

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