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.

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.

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.

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.

伏隔核 (NAc) 是大脑奖励回路驱动奖励相关行为的关键节点。 NAc 失调已被证明会导致物质使用障碍 (SUD) 成瘾的病理标志，使其成为大脑刺激的潜在治疗靶点。经颅聚焦超声（tFUS）是一种新兴的非侵入性脑刺激方法，可以以高空间分辨率调节大脑深部区域。然而，目前没有证据表明 NAc 的大脑活动和奖励网络内的大脑功能连接如何通过 NAc 上的 tFUS 进行神经调节。

在这项初步研究中，我们利用功能磁共振成像 (fMRI) 进行了一项单盲、假对照临床试验，以研究 tFUS 通过 NAc 对 10 名健康成年人神经调节奖励网络的潜在机制。具体来说，该实验包括 20 分钟的并发 tFUS/fMRI 扫描以及 tFUS 前后两次 24 分钟的静息态 fMRI。

首先，我们的结果证明了 NAc 20 分钟 tFUS 的可行性和安全性。此外，我们的研究结果表明，与假手术相比，在 tFUS 期间，左侧 NAc 的双侧 NAc 受到抑制。最后，在左侧 NAc tFUS 后观察到 NAc 和内侧前额叶皮层 (mPFC) 之间的功能连接增加，但假手术组没有变化。

将 tFUS 传递至 NAc 可以调节奖励网络内的大脑激活和功能连接。这些初步研究结果表明，tFUS 可能成为一种有前途的神经调节工具，用于直接和非侵入性管理 NAc，并为 SUD 和其他涉及奖赏处理的脑部疾病的治疗提供新的思路。