Neuromodulation for obsessive-compulsive disorder

Abstract

Neuromodulation shows increasing promise in the treatment of psychiatric disorders, particularly obsessive-compulsive disorder (OCD). Development of tools and techniques including deep brain stimulation, transcranial magnetic stimulation, and electroconvulsive therapy may yield additional options for patients who fail to respond to standard treatments. This article reviews the motivation for and use of these treatments in OCD. We begin with a brief description of the illness followed by discussion of the circuit models thought to underlie the disorder. These circuits provide targets for intervention. Basal ganglia and talamocortical pathophysiology, including cortico-striato-thalamo-cortical loops is a focus of this discussion. Neuroimaging findings and historical treatments that led to the use of neuromodulation for OCD are presented. We then present evidence from neuromodulation studies using deep brain stimulation, electroconvulsive therapy, and transcranial magnetic stimulation, with targets including nucleus accumbens, subthalamic nucleus inferior thalamic peduncle, dorsolateral prefrontal cortex, supplementary motor area, and orbitofrontal cortex. Finally, we explore potential future neuromodulation approaches that may further refine and improve treatment.

Fig. 1

Neurocircuitry: cortico-striato-thalamocortical loops. Pathways in motor, associative, and limbic circuitry. (a) Motor circuit. Neurons from the sensorimotor cortex project to the posterolateral putamen (Put), which, in turn, projects to the posterolateral region of the target nuclei: (i) the direct circuit to the globus pallidus pars interna (GPi) and (ii) the indirect circuit connecting the posterior putamen (Put) to the globus pallidus pars externa (GPe), the subthalamic nucleus (STN) and the GPi. The GPi is the primary output nucleus of the basal ganglia to the cortex via the ventrolateral thalamus. (b) Associative circuit. This circuit originates in the dorsolateral prefrontal and lateral orbitofrontal cortices; projections include the striatal caudate nucleus (Cn) and anteromedial portion of the Put, and subsequently projections to the dorsomedial region of the GPi, and anteromedial portions of the GPe and STN. These, in turn, project onto the GPi and back to the cortex via the ventral anterior nuclei of the thalamus. (c) Limbic circuit. Here, the hippocampus, amygdala, paralimbic and limbic cortices project to the ventral striatum (ventral portion of the caudate and putamen, including nucleus accumbens). The ventral striatum projects to the limbic portion of the GPe, medioventral STN, ventral GPi, and to the cortex via the mediodorsal nucleus of the thalamus. Reproduced with permission from Krack et al. [10]

Fig. 2

Three-dimensional illustration of deep brain stimulation (DBS) in ventral capsule/ventral striatum. This model demonstrates leads and brain structures on the axial plane 5 mm below the intercommisural plane as viewed posterior to anterior. The trajectory of the leads follows the anterior limb of the internal capsule. Each lead has 4 contacts, but only 3 are shown (contacts #0, #1, and #2); contact #3 is hidden by the caudate nucleus. The most ventral contact (#0) is active, as represented by red radiating stimulation fields. GPe = globus pallidus externus; GPi = globus pallidus internus. Image courtesy of Kirk Finnis, Ph.D. [Medtronic Inc., USA]