Noninvasive modulation of deep brain circuits for treatment-resistant depression

Utah State Higher Education System--University Of Utah, Salt Lake City UT

Investigators

Abstract

Current interventions for depression lack the capability to directly, precisely, and noninvasively engage the deep brain circuits at the core of the illness. We have developed a non-significant-risk, MRI-compatible, individually-targeted, ultrasonic neuromodulation device that can stimulate deep circuits in humans noninvasively with a precision previously achievable only with surgically implanted electrodes. This R61/R33 project will evaluate the potential for this novel device to engage deep brain targets and modulate mood symptoms in individuals with treatment-resistant depression. The R61 phase will demonstrate target engagement by delivering low-intensity ultrasound to the subcallosal cingulate during functional magnetic resonance imaging. This phase aims to evaluate the intensity dependence, target specificity, and tolerability of this neuromodulation intervention. If predefined go/no-go criteria are met, the R33 phase will then evaluate the short-term effects of subcallosal cingulate neuromodulation using a randomized sham-controlled study design. The aims of this phase are to examine the associations between target engagement, short-term mood changes, and immediate changes in brain functional connectivity. The R33 also aims to evaluate tolerability and feasibility of a subsequent efficacy trial. This project will address an unmet need by providing new, noninvasive, circuit-directed treatment options for patients with treatment-resistant depression. Because this ultrasonic neuromodulation device offers access to deep brain structures with a unique combination of flexibility, precision, and noninvasiveness, the proposed work is expected to have broader positive impacts for understanding and treating other disorders of deep brain circuits.