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      Emotion-Motion Interactions in Conversion Disorder: An fMRI Study

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          Abstract

          Objectives

          To evaluate the neural correlates of implicit processing of negative emotions in motor conversion disorder (CD) patients.

          Methods

          An event related fMRI task was completed by 12 motor CD patients and 14 matched healthy controls using standardised stimuli of faces with fearful and sad emotional expressions in comparison to faces with neutral expressions. Temporal changes in the sensitivity to stimuli were also modelled and tested in the two groups.

          Results

          We found increased amygdala activation to negative emotions in CD compared to healthy controls in region of interest analyses, which persisted over time consistent with previous findings using emotional paradigms. Furthermore during whole brain analyses we found significantly increased activation in CD patients in areas involved in the ‘freeze response’ to fear (periaqueductal grey matter), and areas involved in self-awareness and motor control (cingulate gyrus and supplementary motor area).

          Conclusions

          In contrast to healthy controls, CD patients exhibited increased response amplitude to fearful stimuli over time, suggesting abnormal emotional regulation (failure of habituation / sensitization). Patients with CD also activated midbrain and frontal structures that could reflect an abnormal behavioral-motor response to negative including threatening stimuli. This suggests a mechanism linking emotions to motor dysfunction in CD.

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          Most cited references22

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          An investigation of the structural, connectional, and functional subspecialization in the human amygdala

          Although the amygdala complex is a brain area critical for human behavior, knowledge of its subspecialization is primarily derived from experiments in animals. We here employed methods for large‐scale data mining to perform a connectivity‐derived parcellation of the human amygdala based on whole‐brain coactivation patterns computed for each seed voxel. Voxels within the histologically defined human amygdala were clustered into distinct groups based on their brain‐wide coactivation maps. Using this approach, connectivity‐based parcellation divided the amygdala into three distinct clusters that are highly consistent with earlier microstructural distinctions. Meta‐analytic connectivity modelling then revealed the derived clusters' brain‐wide connectivity patterns, while meta‐data profiling allowed their functional characterization. These analyses revealed that the amygdala's laterobasal nuclei group was associated with coordinating high‐level sensory input, whereas its centromedial nuclei group was linked to mediating attentional, vegetative, and motor responses. The often‐neglected superficial nuclei group emerged as particularly sensitive to olfactory and probably social information processing. The results of this model‐free approach support the concordance of structural, connectional, and functional organization in the human amygdala and point to the importance of acknowledging the heterogeneity of this region in neuroimaging research. Hum Brain Mapp 34:3247–3266, 2013. © 2012 Wiley Periodicals, Inc.
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            Emotional stimuli and motor conversion disorder.

            Conversion disorder is characterized by neurological signs and symptoms related to an underlying psychological issue. Amygdala activity to affective stimuli is well characterized in healthy volunteers with greater amygdala activity to both negative and positive stimuli relative to neutral stimuli, and greater activity to negative relative to positive stimuli. We investigated the relationship between conversion disorder and affect by assessing amygdala activity to affective stimuli. We conducted a functional magnetic resonance imaging study using a block design incidental affective task with fearful, happy and neutral face stimuli and compared valence contrasts between 16 patients with conversion disorder and 16 age- and gender-matched healthy volunteers. The patients with conversion disorder had positive movements such as tremor, dystonia or gait abnormalities. We also assessed functional connectivity between the amygdala and regions associated with motor preparation. A group by affect valence interaction was observed. Post hoc analyses revealed that whereas healthy volunteers had greater right amygdala activity to fearful versus neutral compared with happy versus neutral as expected, there were no valence differences in patients with conversion disorder. There were no group differences observed. The time course analysis also revealed greater right amygdala activity in patients with conversion disorder for happy stimuli (t = 2.96, P = 0.006) (with a trend for fearful stimuli, t = 1.81, P = 0.08) compared with healthy volunteers, with a pattern suggestive of impaired amygdala habituation even when controlling for depressive and anxiety symptoms. Using psychophysiological interaction analysis, patients with conversion disorder had greater functional connectivity between the right amygdala and the right supplementary motor area during both fearful versus neutral, and happy versus neutral 'stimuli' compared with healthy volunteers. These results were confirmed with Granger Causality Modelling analysis indicating a directional influence from the right amygdala to the right supplementary motor area to happy stimuli (P < 0.05) with a similar trend observed to fearful stimuli (P = 0.07). Our data provide a potential neural mechanism that may explain why psychological or physiological stressors can trigger or exacerbate conversion disorder symptoms in some patients. Greater functional connectivity of limbic regions influencing motor preparatory regions during states of arousal may underlie the pathophysiology of motor conversion symptoms.
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              The involuntary nature of conversion disorder.

              What makes a movement feel voluntary, and what might make it feel involuntary? Motor conversion disorders are characterized by movement symptoms without a neurologic cause. Conversion movements use normal voluntary motor pathways, but the symptoms are paradoxically experienced as involuntary, or lacking in self-agency. Self-agency is the experience that one is the cause of one's own actions. The matched comparison between the prediction of the action consequences (feed-forward signal) and actual sensory feedback is believed to give rise to self-agency and has been in part associated with the right inferior parietal cortex. Using fMRI, we assessed the correlates of self-agency during conversion tremor. We used a within-subject fMRI block design to compare brain activity during conversion tremor and during voluntary mimicked tremor in 8 patients. The random effects group analysis showed that conversion tremor compared with voluntary tremor had right temporoparietal junction (TPJ) hypoactivity (p < 0.05 family-wise error whole brain corrected) and lower functional connectivity between the right TPJ, sensorimotor regions (sensorimotor cortices and cerebellar vermis), and limbic regions (ventral anterior cingulate and right ventral striatum). The right TPJ has been implicated as a general comparator of internal predictions with actual events. We propose that the right TPJ hypoactivity and lower TPJ and sensorimotor cortex interactions may reflect the lack of an appropriate sensory prediction signal. The lack of a match for the proprioceptive feedback would lead to the perception that the conversion movement is not self-generated.
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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
                10 April 2015
                2015
                : 10
                : 4
                : e0123273
                Affiliations
                [1 ]Section of Cognitive Neuropsychiatry, King’s College London, Institute of Psychiatry, London, SE5 8AF, United Kingdom
                [2 ]Laboratory for Behavioral Neurology and Imaging of Cognition, Fundamental Neurosciences, Geneva University, Rue Michel-Servet 1, 1211, Genève, Switzerland
                [3 ]Department of Neuroimaging, King’s College London, Institute of Psychiatry, London, SE5 8AF, United Kingdom
                [4 ]Department of Psychiatry, University of Melbourne, Austin Health, Heidelberg, VIC, 3084, Australia
                Vanderbilt University, UNITED STATES
                Author notes

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

                Conceived and designed the experiments: RK FZ AD. Performed the experiments: SA TN OOD FZ. Analyzed the data: SA OOD TN. Contributed reagents/materials/analysis tools: FZ OOD. Wrote the paper: SA TN OOD FZ RK AD.

                Article
                PONE-D-14-35767
                10.1371/journal.pone.0123273
                4393246
                25859660
                b8251460-c113-46cd-98dc-02a86fda9047
                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
                : 11 August 2014
                : 20 February 2015
                Page count
                Figures: 3, Tables: 2, Pages: 11
                Funding
                The study was funded by a UK Medical Research Council Milstein Grant. S.A. was supported by the Boursière d'Excellence grant (University of Geneva). T.R.N. and A.S.D. were supported by the National Institute for Health Research (NIHR) Mental Health Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and the Institute of Psychiatry, King's College London. F.Z. received funding support from NIHR and the MRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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