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Local and Global Changes in Brain Metabolism during Deep Brain Stimulation for Obsessive-Compulsive Disorder.

ABSTRACT: Recent approaches have suggested that deep brain stimulation (DBS) for obsessive-compulsive disorder relies on distributed networks rather than local brain modulation. However, there is insufficient data on how DBS affects brain metabolism both locally and globally. We enrolled three patients with treatment-refractory obsessive-compulsive disorder with ongoing DBS of the bilateral ventral capsule/ventral striatum. Patients underwent resting-state 18F-fluorodeoxyglucose and positron emission tomography in both stimulation ON and OFF conditions. All subjects showed relative hypometabolism in prefronto-basal ganglia-thalamic networks compared to a healthy control cohort when stimulation was switched OFF. Switching the stimulation ON resulted in differential changes in brain metabolism. Locally, volumes of activated tissue at stimulation sites (n = 6) showed a significant increase in metabolism during DBS ON compared to DBS OFF (Mean difference 4.5 % ± SD 2.8; p = 0.012). Globally, differential changes were observed across patients encompassing prefrontal increase in metabolism in ON vs. OFF condition. Bearing in mind limitations of the small sample size, we conclude that DBS of the ventral capsule/ventral striatum for obsessive-compulsive disorder increases brain metabolism locally. Across distributed global networks, DBS appears to exert differential effects, possibly depending on localization of stimulation sites and response to the intervention.

SUBMITTER: Baldermann JC

PROVIDER: S-EPMC6770477 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Local and Global Changes in Brain Metabolism during Deep Brain Stimulation for Obsessive-Compulsive Disorder.

Baldermann Juan Carlos JC Bohn Karl Peter KP Hammes Jochen J Schüller Canan Beate CB Visser-Vandewalle Veerle V Drzezga Alexander A Kuhn Jens J

Brain sciences 20190830 9

Recent approaches have suggested that deep brain stimulation (DBS) for obsessive-compulsive disorder relies on distributed networks rather than local brain modulation. However, there is insufficient data on how DBS affects brain metabolism both locally and globally. We enrolled three patients with treatment-refractory obsessive-compulsive disorder with ongoing DBS of the bilateral ventral capsule/ventral striatum. Patients underwent resting-state <sup>18</sup>F-fluorodeoxyglucose and positron em ...[more]

PMID: 31480355

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Project description:OBJECTIVE Deep brain stimulation (DBS) is a reversible, nonlesion-based treatment for patients with intractable obsessive-compulsive disorder (OCD). The first studies on DBS for OCD stimulating the ventral capsule/ventral striatum (VC/VS) yielded encouraging results for this neuroanatomical site's therapeutic efficacy. This investigation was conducted to better understand which regions of the cortico-striatal-thalamic-cortical network were acutely affected by VC/VS DBS for OCD. Furthermore, the objective was to identify which brain regions demonstrated changes in perfusion, as stimulation was applied across a dorsoventral lead axis that corresponded to different anatomical locations in the VC/VS. METHODS Six patients receiving VC/VS DBS for OCD underwent oxygen-15 positron emission tomography (15O-PET) scanning. Monopolar DBS was delivered at each of the 4 different electrodes on the stimulating lead in the VC/VS. The data were analyzed using SPM5. Paired t-tests were run in SPSS to identify significant changes in regional cerebral blood flow (rCBF) between stimulation conditions. Pearson's r correlations were run between these significant changes in rCBF and changes in OCD and depressive symptom severity. RESULTS Perfusion in the dorsal anterior cingulate cortex (dACC) significantly increased when monopolar DBS was turned on at the most ventral DBS contact, and this increase in dACC activity was correlated with reductions in depressive symptom severity (r(5) = -0.994, p = 0.001). Perfusion in the thalamus, striatum, and globus pallidus significantly increased when DBS was turned on at the most dorsal contact. CONCLUSIONS DBS of the VC/VS appears to modulate activity in the regions implicated in the pathophysiology of OCD. Different regions in the cortico-striatal-thalamic-cortical circuit showed increased perfusion based on whether the stimulation was more ventral or dorsal along the lead axis in the VC/VS. Evidence was found that DBS at the most ventral site was associated with clinical changes in depressive symptom severity, but not OCD symptom severity.

Project description:BACKGROUND: In spite of advances in psychotherapy and pharmacotherapy, there are still a significant number of patients with depression and obsessive-compulsive disorder that are not aided by either intervention. Although still in the experimental stage, deep brain stimulation (DBS) offers many advantages over other physically-invasive procedures as a treatment for these psychiatric disorders. The purpose of this study is to systematically review reports on clinical trials of DBS for obsessive-compulsive disorder (OCD) and treatment-resistant depression (TRD). Locations for stimulation, success rates and effects of the stimulation on brain metabolism are noted when available. The first observation of the effects of DBS on OCD and TRD came in the course of using DBS to treat movement disorders. Reports of changes in OCD and depression during such studies are reviewed with particular attention to electrode locations and associated adverse events; although these reports were adventitious observations rather than planned. Subsequent studies have been guided by more precise theories of structures involved in DBS and OICD. This study suggests stimulation sites and prognostic indicators for DBS. We also briefly review tractography, a relatively new procedure that holds great promise for the further development of DBS. METHODS: Articles were retrieved from MEDLINE via PubMed. Relevant references in retrieved articles were followed up. We included all articles reporting on studies of patients selected for having OCD or TRD. Adequacy of the selected studies was evaluated by the Jadad scale. Evaluation criteria included: number of patients, use of recognized psychiatric rating scales, and use of brain blood flow measurements. Success rates classified as "improved" or "recovered" were recorded. Studies of DBS for movement disorders were included if they reported coincidental relief of depression or reduction in OCD. Most of the studies involved small numbers of subjects so individual studies were reviewed. RESULTS: While the number of cases was small, these were extremely treatment-resistant patients. While not everyone responded, about half the patients did show dramatic improvement. Associated adverse events were generally trivial in younger psychiatric patients but often severe in older movement disorder patients. The procedures differed from study to study, and the numbers of patients was usually too small to do meaningful statistics or make valid inferences as to who will respond to treatment. CONCLUSIONS: DBS is considered a promising technique for OCD and TRD. Outstanding questions about patient selection and electrode placement can probably be resolved by (a) larger studies, (b) genetic studies and (c) imaging studies (MRI, fMRI, PET, and tractography).

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Local and Global Changes in Brain Metabolism during Deep Brain Stimulation for Obsessive-Compulsive Disorder.

Publications

Local and Global Changes in Brain Metabolism during Deep Brain Stimulation for Obsessive-Compulsive Disorder.

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