Non-invasive suppression of the human nucleus accumbens (NAc) with transcranial focused ultrasound (tFUS) modulates the reward network: a pilot study
Xiaolong Peng, Dillon J. Connolly, Falon Sutton, John Robinson, Brenna Baker-Vogel, Edward B. Short, Bashar W. Badran
Frontiers in Human Neuroscience 2024, 18 · 10.3389/fnhum.2024.1359396
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.
Abstract via europepmc.
Exposures
Exposure 1: Active tFUS to left nucleus accumbens
Target: nucleus accumbens — “left NAc”
Device: BrainSonix · BrainSonix Corp. · BXPulsar 1002
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | 0.995 | ✓✓✓⚑ |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | 0.719 | ✓✓✓⚑ |
| Pressure, domain unspecified (kPa) | 720 | ✓✓✓⚑ |
Each tFUS-fMRI run consisted of a 30s tFUS “ON” block, followed by a 30s “OFF” block, and repeated ten times. 20 min of either active or sham tFUS was administered targeting the left NAc during concurrent fMRI acquisition (two, 10-min scans).
Flags from extraction
exposures[0].free_field.ispta_w_cm2— Domain (free field vs in situ) inferred from the standard AIUM ISPTA.0/ISPTA.3 subscript convention (0 and 0.3 dB/cm/MHz derating); the paper does not explicitly state that ISPTA.0 is a free-field value and ISPTA.3 an in-situ derated value.exposures[0].in_situ.ispta_w_cm2— Same subscript-convention inference as ISPTA.0 (method coded as derating).exposures[0].unspecified_domain.pressure_kpa— Paper reports peak rarefactional pressure (0.72 MPa) without stating whether it is a free-field or in-situ value.