Treating Obsessive-Compulsive Disorder by Invasively Modulating Thoughts, Feelings, or Both

Abstract

The defining characteristic of pathological compulsions is that they are carried out to reduce momentary distress, even though performing the compulsive act or thought is rationally not in the individual’s true best interest. This inability to flexibly adapt is a prominent component of obsessive-compulsive disorder (OCD) and closely related illnesses such as Tourette syndrome and is also observed in substance use disorders ( 1 Figee M. Pattij T. Willuhn I. Luigjes J. van den Brink W. Goudriaan A. et al. Compulsivity in obsessive-compulsive disorder and addictions. Eur Neuropsychopharmacol. 2016; 26: 856-868 Crossref PubMed Scopus (111) Google Scholar ). Following the 20th century experience with ablative procedures such as capsulotomy, deep brain stimulation (DBS) was applied to the treatment of OCD. Electrodes are most commonly placed within the anterior limb of the internal capsule (ALIC), modulating cortico-basal ganglia-thalamo-cortical parallel white matter loops relevant to limbic, associative, and motor functions, respectively. ALIC stimulation has proven to be a highly effective treatment for severe OCD ( 2 Smith AH, Mayberg HS, Figee M (in press): Neuromodulation and psychiatric disorders. In: Nestler EJ, Charney DS, editors. Neurobiology of Mental Illness, 6th ed. New York: Oxford University Press. Google Scholar ). DBS to a different anatomical location, the subthalamic nucleus (STN), was initially developed for Parkinson’s disease, but positive early experience in patients with comorbid Parkinson’s disease and OCD led to research establishing high-frequency stimulation straight to the STN as clinically efficacious for OCD ( 3 Mallet L. Polosan M. Jaafari N. Baup N. Welter M.L. Fontaine D. et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008; 359: 2121-2134 Crossref PubMed Scopus (687) Google Scholar ). In a similar manner, promising early pilot studies led to further exploration of other targets. These include the bed nucleus of the stria terminalis, the “extended amygdala” located between the ALIC and STN targets ( 4 Mosley P.E. Windels F. Morris J. Coyne T. Marsh R. Giorni A. et al. A randomised, double-blind, sham-controlled trial of deep brain stimulation of the bed nucleus of the stria terminalis for treatment-resistant obsessive-compulsive disorder. Transl Psychiatry. 2021; 11: 190 Crossref PubMed Scopus (38) Google Scholar ). More recently, evidence has emerged for the effectiveness of stimulation delivered deeper in the midbrain than the STN, adjacent to the ventral tegmental area (VTA)—a source of dopaminergic projections to the cortex (via the medial forebrain bundle [MFB]) and a recipient of proposed regulatory projections back from the cortex (via the “supralateral MFB”) ( 5 Meyer D.M. Spanier S. Kilian H.M. Reisert M. Urbach H. Sajonz B.E. et al. Efficacy of superolateral medial forebrain bundle deep brain stimulation in obsessive-compulsive disorder. Brain Stimul. 2022; 15: 582-585 Abstract Full Text Full Text PDF Scopus (3) Google Scholar ). SEE CORRESPONDING ARTICLE ON PAGE 1010 SEE CORRESPONDING ARTICLE ON PAGE 1010 The Rostral Zona Incerta: A Subcortical Integrative Hub and Potential Deep Brain Stimulation Target for Obsessive-Compulsive DisorderBiological PsychiatryVol. 93Issue 11PreviewThe zona incerta (ZI) is involved in mediating survival behaviors and is connected to a wide range of cortical and subcortical structures, including key basal ganglia nuclei. Based on these connections and their links to behavioral modulation, we propose that the ZI is a connectional hub for mediating between top-down and bottom-up control and a possible target for deep brain stimulation for obsessive-compulsive disorder. Full-Text PDF