Non-invasive suppression of the human nucleus accumbens (NAc) with transcranial focused ultrasound (tFUS) modulates the reward network: a pilot study

Abstract

Background: The nucleus accumbens (NAc) is a key node of the brain reward circuit driving reward-related behavior. Dysregulation of NAc has been demonstrated to contribute to pathological markers of addiction in substance use disorder (SUD) making it a potential therapeutic target for brain stimulation. Transcranial focused ultrasound (tFUS) is an emerging non-invasive brain stimulation approach that can modulate deep brain regions with a high spatial resolution. However, there is currently no evidence showing how the brain activity of NAc and brain functional connectivity within the reward network neuromodulated by tFUS on the NAc.

Methods: In this pilot study, we carried out a single-blind, sham-controlled clinical trial using functional magnetic resonance imaging (fMRI) to investigate the underlying mechanism of tFUS neuromodulating the reward network through NAc in ten healthy adults. Specifically, the experiment consists of a 20-min concurrent tFUS/fMRI scan and two 24-min resting-state fMRI before and after the tFUS session.

Results: Firstly, our results demonstrated the feasibility and safety of 20-min tFUS on NAc. Additionally, our findings demonstrated that bilateral NAc was inhibited during tFUS on the left NAc compared to sham. Lastly, increased functional connectivity between the NAc and medial prefrontal cortex (mPFC) was observed after tFUS on the left NAc, but no changes for the sham group.

Conclusion: Delivering tFUS to the NAc can modulate brain activations and functional connectivity within the reward network. These preliminary findings suggest that tFUS could be potentially a promising neuromodulation tool for the direct and non-invasive management of the NAc and shed new light on the treatment for SUD and other brain diseases that involve reward processing.

Keywords: fMRI; focused ultrasound; nucleus accumbens; reward network; tFUS.

FIGURE 1

The procedure of tFUS target in left NAc. (A) Schematic of delivering ultrasound to the left NAc using tFUS. The red circled cross shows the location of the planned tFUS target—left NAc. (B) An example of the real-time tFUS target navigation procedure in the MRI scanner. These images were acquired from a rapid structure MRI sequence that captured the brain anatomy and the tFUS transducer. The bright circles and dots pointed by the red arrows show the location of the tFUS transducer. Digitized lines were created that intersect the fixed fiducials that are incorporated into the tFUS transducer. Specifically, the red line aligned with the back of the transducer. The blue line and the green line are orthogonal to the center of the transducer and extend into the left NAc target.

FIGURE 2

Transcranial focused ultrasound (tFUS) induces inhibited brain activation in NAc. Decreased brain activities were observed in the anterior part of the bilateral NAc and most regions of the left posterior NAc (two-sample t-test, p < 0.05, uncorrected) in the tFUS active group compared to the sham group, indicating that tFUS inhibited NAc activities. Note that, these deactivation maps were estimated based on group data comparison between active group and sham group within the NAc. Each figure on the right panel depicts different slices through the striatum. The numbers in the bottom right corners represent the slice number; ascending numbers go from anterior to posterior.

FIGURE 3

Functional connectivity between NAc and mPFC increases after tFUS on left NAc. A significantly increased functional connectivity between the NAc and mPFC was obtained after stimulating the left NAc in the active group (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), indicate that tFUS can modulate NAc functional connections to the mPFC within the reward network. The asterisks (*) indicate significance at p < 0.05.