Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
Brain Stimul. 2024 Mar-Apr;17(2):312-320. doi: 10.1016/j.brs.2024.03.004. Epub 2024 Mar 4.
BACKGROUND: Current noninvasive brain stimulation methods are incapable of directly modulating subcortical brain regions critically involved in psychiatric disorders. Transcranial Focused Ultrasound (tFUS) is a newer form of noninvasive stimulation that could modulate the amygdala, a subcortical region implicated in fear. OBJECTIVE: We investigated the effects of active and sham tFUS of the amygdala on fear circuit activation, skin conductance responses (SCR), and self-reported anxiety during a fear-inducing task. We also investigated amygdala tFUS' effects on amygdala-fear circuit resting-state functional connectivity. METHODS: Thirty healthy individuals were randomized in this double-blinded study to active or sham tFUS of the left amygdala. We collected fMRI scans, SCR, and self-reported anxiety during a fear-inducing task (participants viewed red or green circles which indicated the risk of receiving an aversive stimulus), as well as resting-state scans, before and after tFUS. RESULTS: Compared to sham tFUS, active tFUS was associated with decreased (pre to post tFUS) blood-oxygen-level-dependent fMRI activation in the amygdala (F(1,25) = 4.86, p = 0.04, η = 0.16) during the fear task, and lower hippocampal (F(1,27) = 4.41, p = 0.05, η = 0.14), and dorsal anterior cingulate cortex (F(1,27) = 6.26, p = 0.02; η = 0.19) activation during the post tFUS fear task. The decrease in amygdala activation was correlated with decreased subjective anxiety (r = 0.62, p = 0.03). There was no group effect in SCR changes from pre to post tFUS (F(1,23) = 0.85, p = 0.37). The active tFUS group also showed decreased amygdala-insula (F(1,28) = 4.98, p = 0.03) and amygdala-hippocampal (F(1,28) = 7.14, p = 0.01) rsFC, and increased amygdala-ventromedial prefrontal cortex (F(1,28) = 3.52, p = 0.05) resting-state functional connectivity. CONCLUSIONS: tFUS can change functional connectivity and brain region activation associated with decreased anxiety. Future studies should investigate tFUS' therapeutic potential for individuals with clinical levels of anxiety.
背景：目前的非侵入性脑刺激方法无法直接调节与精神疾病密切相关的皮质下脑区。经颅聚焦超声（tFUS）是一种较新的非侵入性刺激方式，它可以调节杏仁核，这是一个与恐惧有关的皮质下区域。 目的：我们研究了主动和假 tFUS 刺激左杏仁核对恐惧回路激活、皮肤电反应（SCR）和恐惧诱导任务期间自我报告的焦虑的影响。我们还研究了 tFUS 对杏仁核-恐惧回路静息状态功能连接的影响。 方法：30 名健康个体被随机分配到这项双盲研究中，接受主动或假 tFUS 刺激左杏仁核。我们在恐惧诱导任务期间采集 fMRI 扫描、SCR 和自我报告的焦虑（参与者观看红色或绿色圆圈，指示接受厌恶刺激的风险），以及 tFUS 前后的静息状态扫描。 结果：与假 tFUS 相比，主动 tFUS 与恐惧任务期间（t 至 post tFUS）杏仁核的血氧水平依赖 fMRI 激活减少（F（1，25）= 4.86，p = 0.04，η= 0.16）有关，以及海马（F（1，27）= 4.41，p = 0.05，η= 0.14）和背侧前扣带回皮层（F（1，27）= 6.26，p = 0.02；η= 0.19）的激活减少。杏仁核激活的减少与主观焦虑的降低相关（r = 0.62，p = 0.03）。从 t 至 post tFUS，SCR 变化无组间差异（F（1，23）= 0.85，p = 0.37）。主动 tFUS 组还表现出杏仁核-岛叶（F（1，28）= 4.98，p = 0.03）和杏仁核-海马（F（1，28）= 7.14，p = 0.01）的 rsFC 降低，以及杏仁核-腹侧前额叶皮层（F（1，28）= 3.52，p = 0.05）的静息状态功能连接增加。 结论：tFUS 可以改变与焦虑减轻相关的功能连接和脑区激活。未来的研究应该调查 tFUS 对有临床水平焦虑的个体的治疗潜力。
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