The effects of varying pulse repetition frequencies and duty cycles for transcranial focused ultrasound (tFUS) of the ventral capsule/ventral striatum for obsessive-compulsive disorder

Abstract Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and/or compulsive behaviors. Deep brain stimulation (DBS) of ventral capsule/ventral striatum (VC/VS) has shown to be effective for treatment-resistant OCD. However, DBS is associated with neurosurgical risks and side effects. Transcranial focused ultrasound (tFUS) is a novel brain stimulation method that has the capability to modulate deeper subcortical brain regions, such as the VC/VS, noninvasively. In this active-control parameter exploration study, we investigated the effects of 3 different tFUS stimulation protocols on the VC/VS and the wider corticostriatal circuit (Protocol A: Pulse Repetition Frequency [PRF]=10 Hz, 5% Duty Cycle (DC), Protocol B: PRF=125 Hz, 5% DC, Protocol C: PRF=125 Hz, 50% DC). These tFUS parameters had differential effects on Blood Oxygen Level Dependent (BOLD) activation in the corticostriatal network: 1. Protocol A was associated with decreased BOLD activation in the putamen (p=0.004), 2. Protocol B had no effect on BOLD activation in the corticostriatal network, and 3. Protocol C was associated with a trending decrease (p = 0.06) in BOLD activation in the putamen. The tfUS parameters also had differential effects on Arterial Spin Labeling (ASL) perfusion: 1. Protocol A was associated with a trending decrease in VC/VS perfusion (p=0.17), 2. Protocol B was associated with a trending increase in VC/VS perfusion (p=0.15), and 3. Protocol C had no effect on VC/VS perfusion. Importantly, tFUS of the entorhinal cortex (ErC), included as a control region, was not associated with changes in corticostriatal BOLD activation during the reward task, nor was ErC tFUS associated with changes in VC/VS ASL perfusion. These findings demonstrate the varying effects of different pulse repetition frequencies and duty cycles on BOLD activation and ASL perfusion in the corticostriatal network and their potential for treatment of OCD. Research Category and Technology and Methods Translational Research: 6. Pulsed Ultrasound (pUS) Keywords: Transcranial Focused Ultrasound, Ventral capsule/ventral striatum, Corticostriatal network, Obsessive-compulsive disorder