Noninvasive Stimulation of the Nucleus Accumbens using Transcranial Focused Ultrasound

13 

Abstract Submission 

Xiaolong Peng¹, Dillon Connolly¹, Falon Sutton¹, John Robinson¹, Brenna Baker-Vogel¹, Edward Short¹, Bashar Badran¹

¹Medical University of South Carolina, Charleston, SC

Xiaolong Peng  
Medical University of South Carolina
Charleston, SC

Dillon Connolly  
Medical University of South Carolina
Charleston, SC

Falon Sutton  
Medical University of South Carolina
Charleston, SC

John Robinson  
Medical University of South Carolina
Charleston, SC

Brenna Baker-Vogel  
Medical University of South Carolina
Charleston, SC

Edward Short  
Medical University of South Carolina
Charleston, SC

Bashar Badran, PhD  
Medical University of South Carolina
Charleston, SC

Transcranial focused ultrasound (tFUS) is an emerging noninvasive neuromodulation technique that can stimulate deep brain regions with a high spatial resolution [1, 2]. Previous clinical trials have demonstrated that tFUS can attenuate sensory processing [3], pain [4], and modulate self-reported mood and mental vigor [5] by stimulating specific brain targets, including the thalamus and lateral frontal gyrus. The penetrative depth and spatial resolution of tFUS expand the scope of traditional noninvasive neuromodulation approaches to previously inaccessible regions, such as the nucleus accumbens (NAc). NAc is a key node of the brain reward circuit [6], and dysregulation of this region has been demonstrated to contribute to pathological markers of addiction such as cue reactivity and drug-seeking behavior in substance use disorder (SUD) making it a potential therapeutic target for tFUS [7]. In this pilot study, we investigated whether tFUS on NAc can modulate the reward network.

Ten healthy individuals (7 females, mean age ± SD: 31 ± 8.39 years) were recruited for this single-blind, sham-controlled, pilot study. All participants were randomly assigned to either the active tFUS group (N=5) or the sham group (N=5). Participants attended a single experimental visit, and all research methods were conducted within a Siemens 3T Prisma MRI scanner. First, a structural T1 MRI scan was acquired, followed by pre-tFUS resting-state functional MRI (fMRI; four, 6-minute scans). Then, 20 minutes of either active or sham tFUS was administered targeting the left NAc during concurrent fMRI acquisition (two, 10-minute scans). Lastly, a post-tFUS resting-state fMRI was acquired (four, 6-minute scans). This study was approved by the MUSC IRB, registered on ClinicalTrials.gov (NCT05986019), and all participants signed the informed consent before enrollment. The real-time tFUS targeting was conducted within the bore of the MRI prior to ensuring the tFUS transducer was in the correct position to deliver ultrasound to the NAc target as described in our previous study (Figure 1a & b) [4]. After tFUS targeting, the concurrent tFUS-fMRI scan was performed. Each tFUS-fMRI run consisted of a 30s tFUS "ON" block, followed by a 30s "OFF" block, and repeated ten times. During the tFUS "ON" block, ultrasound stimulations were generated using the BrainSonix BXPulsar 1002 tFUS System with sonication parameters as follows: Fundamental frequency = 650 kHz, Pulse repetition frequency = 10 Hz, Pulse width = 5 ms, Duty cycle = 5%, Sonication duration = 30 s, ISPTA.0 = 995 mW/cm2, ISPTA.3 = 719 mW/cm2, Peak rarefactional pressure = 0.72 MPa. For the sham group, the tFUS system was set up identically to the active tFUS group, including targeting, however, tFUS was not turned on during the tFUS-fMRI scan. Both tFUS/fMRI and resting fMRI data were preprocessed using the same procedures as described in our previous study [8, 9].

The brain activation maps demonstrated that tFUS on the left NAc reduced the brain activities in the anterior part of the bilateral NAc and most regions of the left posterior NAc (Figure 1c; two-sample t-test, p < 0.05), indicating that tFUS can directly inhibit NAc activities. Additionally, we also demonstrated a significantly increased functional connectivity between the NAc and mPFC after tFUS on the left NAc in the active group (Figure 1d; paired t-test, t = 2.850, p = 0.046), however, no significant changes were observed in the sham group (t = 0.041, p = 0.969).

This study demonstrates the feasibility and safety of this novel technique for deep brain stimulation. Furthermore, these preliminary findings suggest that tFUS could be potentially a promising neuromodulation tool for the direct and noninvasive management of the NAc and shed new light on the treatment for SUD and other brain diseases that involve reward processing.

Deep Brain Stimulation ¹

Sonic/Ultrasound ²

Addictions

FUNCTIONAL MRI

ULTRASOUND