Abstract：
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, η2 = 0.16) during the fear task, and lower hippocampal (F(1,27) = 4.41, p = 0.05, η2 = 0.14), and dorsal anterior cingulate cortex (F(1,27) = 6.26, p = 0.02; η2 = 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.
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, η2 = 0.16) during the fear task, and lower hippocampal (F(1,27) = 4.41, p = 0.05, η2 = 0.14), and dorsal anterior cingulate cortex (F(1,27) = 6.26, p = 0.02; η2 = 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.
摘要：
背景：目前的非侵入性脑刺激方法不能直接调节严重参与精神疾病的皮质下脑区域。经颅聚焦超声（tFUS）是一种新型的非侵入性刺激，可以调节杏仁核，与恐惧有关的皮层下区域。
目的：我们研究了杏仁核的活性和假tFUS对恐惧回路激活的影响，皮肤电导反应（SCR），以及在引发恐惧的任务中自我报告的焦虑。我们还研究了杏仁核tFUS对杏仁核恐惧回路静息状态功能连通性的影响。
方法：在这项双盲研究中，将30名健康个体随机分为左杏仁核的活动或假tFUS。我们收集了功能磁共振成像扫描,SCR,和在引发恐惧的任务中自我报告的焦虑（参与者查看红色或绿色圆圈，表明接受厌恶刺激的风险），以及静息状态扫描，tfus之前和之后。
结果：与假tFUS相比，在恐惧任务期间，活动的tFUS与杏仁核中的血氧水平依赖性fMRI激活降低（从tFUS之前到tFUS之后）相关（F（1,25）=4.86，p=0.04，η2=0.16），和下海马(F(1,27)=4.41，p=0.05，η2=0.14)，tFUS后恐惧任务期间的背侧前扣带皮层（F（1,27）=6.26，p=0.02；η2=0.19）激活。杏仁核激活的减少与主观焦虑的减少相关(r=0.62,p=0.03)。从tFUS前后的SCR变化没有组效应(F(1,23)=0.85,p=0.37)。活动tFUS组还显示杏仁核-脑岛减少（F（1,28）=4.98，p=0.03）和杏仁核-海马减少（F（1,28）=7.14，p=0.01）rsFC，杏仁核-腹内侧前额叶皮质增加（F（1,28）=3.52，p=0.05）静息状态功能连接。
结论：tFUS可以改变与焦虑降低相关的功能连接和脑区激活。未来的研究应该调查tFUS对临床焦虑水平个体的治疗潜力。
目的：我们研究了杏仁核的活性和假tFUS对恐惧回路激活的影响，皮肤电导反应（SCR），以及在引发恐惧的任务中自我报告的焦虑。我们还研究了杏仁核tFUS对杏仁核恐惧回路静息状态功能连通性的影响。
方法：在这项双盲研究中，将30名健康个体随机分为左杏仁核的活动或假tFUS。我们收集了功能磁共振成像扫描,SCR,和在引发恐惧的任务中自我报告的焦虑（参与者查看红色或绿色圆圈，表明接受厌恶刺激的风险），以及静息状态扫描，tfus之前和之后。
结果：与假tFUS相比，在恐惧任务期间，活动的tFUS与杏仁核中的血氧水平依赖性fMRI激活降低（从tFUS之前到tFUS之后）相关（F（1,25）=4.86，p=0.04，η2=0.16），和下海马(F(1,27)=4.41，p=0.05，η2=0.14)，tFUS后恐惧任务期间的背侧前扣带皮层（F（1,27）=6.26，p=0.02；η2=0.19）激活。杏仁核激活的减少与主观焦虑的减少相关(r=0.62,p=0.03)。从tFUS前后的SCR变化没有组效应(F(1,23)=0.85,p=0.37)。活动tFUS组还显示杏仁核-脑岛减少（F（1,28）=4.98，p=0.03）和杏仁核-海马减少（F（1,28）=7.14，p=0.01）rsFC，杏仁核-腹内侧前额叶皮质增加（F（1,28）=3.52，p=0.05）静息状态功能连接。
结论：tFUS可以改变与焦虑降低相关的功能连接和脑区激活。未来的研究应该调查tFUS对临床焦虑水平个体的治疗潜力。
