Riis Thomas S, Feldman Daniel A, Kwon Sarah S, Vonesh Lily C, Koppelmans Vincent, Brown Jefferson R, Solzbacher Daniela, Kubanek Jan, Mickey Brian J
Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah.
Department of Biomedical Engineering, University of Utah, Salt Lake City, Utah; Department of Radiology, University of Utah, Salt Lake City, Utah; Department of Psychiatry, Huntsman Mental Health Institute, University of Utah, Salt Lake City, Utah.
Biol Psychiatry. 2025 Apr 15;97(8):825-834. doi: 10.1016/j.biopsych.2024.09.029. Epub 2024 Oct 11.
Severe forms of depression have been linked to excessive subcallosal cingulate cortex (SCC) activity. Stimulation of the SCC with surgically implanted electrodes can alleviate depression, but current noninvasive techniques cannot directly and selectively modulate deep targets. We developed a new noninvasive neuromodulation approach that can deliver low-intensity focused ultrasonic waves to the SCC.
Twenty-two individuals with treatment-resistant depression participated in a randomized, double-blind, sham-controlled study. Ultrasonic stimulation was delivered to the bilateral SCC during concurrent functional magnetic resonance imaging to quantify target engagement. Mood state was measured with the Sadness subscale of the Positive and Negative Affect Schedule before and after 40 minutes of real or sham SCC stimulation. Change in depression severity was measured with the 6-item Hamilton Depression Rating Scale at 24 hours and 7 days.
Functional magnetic resonance imaging demonstrated a target-specific decrease in SCC activity during stimulation (p = .028, n = 16). In 7 of 16 participants, SCC neuromodulation was detectable at the individual participant level with a single 10-minute scan (p < .05, small-volume correction). Mood and depression scores improved more with real than with sham stimulation. In the per-protocol sample (n = 19), real stimulation was superior to sham for 6-item Hamilton Depression Rating Scale scores at 24 hours and for Sadness scores (both p < .05, d > 1). Nonsignificant trends were found in the intent-to-treat sample.
This small pilot study indicates that ultrasonic stimulation modulates SCC activity and can rapidly reduce depressive symptoms. The capability to noninvasively and selectively target deep brain areas creates new possibilities for the future development of circuit-directed therapeutics and for the analysis of deep-brain circuit function in humans.
重度抑郁症与胼胝体下扣带回皮质（SCC）活动过度有关。通过手术植入电极刺激SCC可缓解抑郁症，但目前的非侵入性技术无法直接且选择性地调节深部靶点。我们开发了一种新的非侵入性神经调节方法，可将低强度聚焦超声波传递至SCC。
22名难治性抑郁症患者参与了一项随机、双盲、假对照研究。在同步功能磁共振成像期间，将超声波刺激传递至双侧SCC以量化靶点参与情况。在进行40分钟的真实或假SCC刺激前后，使用正负情绪量表的悲伤分量表测量情绪状态。在24小时和7天时，用6项汉密尔顿抑郁量表测量抑郁严重程度的变化。
功能磁共振成像显示，刺激期间SCC活动出现靶点特异性降低（p = 0.028，n = 16）。在16名参与者中的7名中，通过单次10分钟扫描可在个体参与者水平检测到SCC神经调节（p < 0.05，小体积校正）。与假刺激相比，真实刺激使情绪和抑郁评分改善更明显。在符合方案样本（n = 19）中，真实刺激在24小时时的6项汉密尔顿抑郁量表评分和悲伤评分方面均优于假刺激（均p < 0.05，d > 1）。在意向性分析样本中发现无显著趋势。
这项小型试点研究表明，超声波刺激可调节SCC活动并能迅速减轻抑郁症状。非侵入性且选择性地靶向深部脑区的能力为未来定向环路治疗的发展以及人类深部脑环路功能分析创造了新的可能性。
