Magnetic resonance-guided focused ultrasound capsulotomy for refractory obsessive compulsive disorder and major depressive disorder: clinical and imaging results from two phase I trials.

Obsessive compulsive disorder (OCD) and major depressive disorder (MDD) are common, often refractory, neuropsychiatric conditions for which new treatment approaches are urgently needed. Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel surgical technique permitting incisionless ablative neurosurgery. We examined the safety profile, clinical response, and imaging correlates of MRgFUS bilateral anterior capsulotomy in patients with refractory obsessive compulsive disorder (OCD, N = 6) and major depressive disorder (MDD, n = 6). There were no serious adverse events. Nonserious adverse events included headaches and pin-site swelling in 7/12 patients. The response rate was 4/6 and 2/6 in the OCD and MDD cohorts respectively. To delineate the white-matter tracts impacted by capsulotomy, a normative diffusion MRI-based structural connectome was used, revealing tracts terminating primarily in the frontal pole, medial thalamus, striatum, and medial-temporal lobe. Positron emission tomography (PET) analysis (nine subjects) revealed widespread decreases in metabolism bilaterally in the cerebral hemispheres at 6 months post treatment, as well as in the right hippocampus, amygdala, and putamen. A pretreatment seed-to-voxel resting-state functional magnetic resonance imaging (rs-fMRI) analysis (12 subjects) revealed three voxel clusters significantly associated with eventual clinical response. MRgFUS capsulotomy appears to be safe, well tolerated, and according to these initial results, may be an important treatment option for patients with refractory OCD and MDD. MRgFUS capsulotomy results in both targeted and widespread changes in neural activity, and neuroimaging may hold potential for the prediction of outcome.

Examining cognitive change in magnetic resonance-guided focused ultrasound capsulotomy for psychiatric illness.

Magnetic resonance-guided focused ultrasound (MRgFUS) anterior capsulotomy is a novel treatment option for patients with refractory obsessive compulsive disorder (OCD) or major depressive disorder (MDD). However, there is concern that lesional psychiatric surgery procedures may have adverse effects on cognition. In this study, we examined whether MRgFUS capsulotomy causes cognitive decline in patients with psychiatric illness. Ten patients with refractory OCD (n = 5) or MDD (n = 5) underwent MRgFUS capsulotomy. Cognitive functioning was measured at baseline as well as 6 months and 12 months postoperatively, with a battery of neuropsychological tests assessing domains of executive function, memory, and processing speed. Scores were analyzed at the individual-level, and changes ≥2 standard deviations were considered clinically significant. We also examined whether changes in clinical symptoms were associated with changes in cognitive performance. At baseline intellectual functioning was in the average to high-average range for the group. Following MRgFUS capsulotomy, there were no deteriorations in cognition that reached ≥2 standard deviations at 6 or 12 months. Eight out of ten patients demonstrated a ≥2 standard deviation improvement in at least one cognitive score at 6 or 12 months postoperatively. Improvements in clinical symptoms correlated significantly with self-reported improvements in frontal lobe function (p < 0.05), but not with objective measures of cognitive functioning. To summarize, MRgFUS capsulotomy did not result in cognitive decline in this cohort of patients with refractory OCD or MDD, suggesting that this procedure can be offered to patients with a very low risk of cognitive side effects.