Testing a Neurobiological Model of Depersonalization Disorder Using Repetitive Transcranial Magnetic Stimulation☆

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Abstract

Background

Depersonalization disorder (DPD) includes changes in subjective experiencing of self, encompassing emotional numbing. Functional magnetic resonance imaging (fMRI) has pointed to ventrolateral prefrontal cortex (VLPFC) inhibition of insula as a neurocognitive correlate of the disorder.

Objective

We hypothesized that inhibition to right VLPFC using repetitive transcranial magnetic stimulation (rTMS) would lead to increased arousal and reduced symptoms.

Methods

Patients with medication-resistant DSM-IV DPD ( N = 17) and controls ( N = 20) were randomized to receive one session of right-sided rTMS to VLPFC or temporo-parietal junction (TPJ). 1Hz rTMS was guided using neuronavigation and delivered for 15 min. Co-primary outcomes were: (a) maximum skin conductance capacity, and (b) reduction in depersonalization symptoms (Cambridge Depersonalisation Scale (CDS) [state version]). Secondary outcomes included spontaneous fluctuations (SFs) and event-related skin conductance responses.

Results

In patients with DPD, rTMS to VLPFC led to increased electrodermal capacity, namely maximum skin conductance deflections. Patients but not controls also showed increased SFs post rTMS. Patients who had either VLPFC or TPJ rTMS showed a similar significant reduction in symptoms. Event-related electrodermal activity did not change.

Conclusions

A single session of right-sided rTMS to VLPFC (but not TPJ) significantly increased physiological arousal capacity supporting our model regarding the relevance of increased VLPFC activity to emotional numbing in DPD. rTMS to both sites led to reduced depersonalization scores but since this was independent of physiological arousal, this may be a non-specific effect. TMS is a potential therapeutic option for DPD; modulation of VLPFC, if replicated, is a plausible mechanism.

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Most cited references 48

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This article is based on a consensus conference, which took place in Certosa di Pontignano, Siena (Italy) on March 7-9, 2008, intended to update the previous safety guidelines for the application of transcranial magnetic stimulation (TMS) in research and clinical settings. Over the past decade the scientific and medical community has had the opportunity to evaluate the safety record of research studies and clinical applications of TMS and repetitive TMS (rTMS). In these years the number of applications of conventional TMS has grown impressively, new paradigms of stimulation have been developed (e.g., patterned repetitive TMS) and technical advances have led to new device designs and to the real-time integration of TMS with electroencephalography (EEG), positron emission tomography (PET) and functional magnetic resonance imaging (fMRI). Thousands of healthy subjects and patients with various neurological and psychiatric diseases have undergone TMS allowing a better assessment of relative risks. The occurrence of seizures (i.e., the most serious TMS-related acute adverse effect) has been extremely rare, with most of the few new cases receiving rTMS exceeding previous guidelines, often in patients under treatment with drugs which potentially lower the seizure threshold. The present updated guidelines review issues of risk and safety of conventional TMS protocols, address the undesired effects and risks of emerging TMS interventions, the applications of TMS in patients with implanted electrodes in the central nervous system, and safety aspects of TMS in neuroimaging environments. We cover recommended limits of stimulation parameters and other important precautions, monitoring of subjects, expertise of the rTMS team, and ethical issues. While all the recommendations here are expert based, they utilize published data to the extent possible.

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Author and article information

Contributors

Anthony S. David

Journal

Journal ID (nlm-ta): Brain Stimul

Journal ID (iso-abbrev): Brain Stimul

Title: Brain Stimulation

Publisher: Elsevier

ISSN (Print): 1935-861X

Publication date PMC-release: 1 March 2014

Publication date (Print): March 2014

Volume: 7

Issue: 2

Pages: 252-259

Affiliations

[a ]Section of Cognitive Neuropsychiatry, Department of Psychosis Studies, Institute of Psychiatry, King's College London, Denmark Hill, London SE5 8AF, UK

[b ]MRC Human Movement and Balance Unit, Institute of Cognitive Neuroscience, University College London, UK

[c ]Institut Universitaire en Santé Mentale, Douglas McGill University, Montreal, Canada

Author notes

[∗ ]Corresponding author. anthony.david@ 123456kcl.ac.uk

Article

Publisher ID: S1935-861X(13)00386-0

DOI: 10.1016/j.brs.2013.12.002

PMC ID: 3968882

PubMed ID: 24439959

SO-VID: 163811a0-3004-46fa-9007-7fa53a8b874b

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 7 August 2013

Date revision received : 15 October 2013

Date accepted : 4 December 2013

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