Transcranial focused ultrasound of the amygdala modulates fear network activation and connectivity.

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.

First Acute-Course Electroconvulsive Therapy for Moderate-to-Severe Depression Benefits Patients With or Without Accompanying Baseline Cognitive Impairment.

BACKGROUND: Researchers are increasingly investigating therapeutic response associated with new patient subgroups as a way to improve electroconvulsive therapy (ECT) treatment outcomes and reduce adverse events. This study is the first to examine baseline cognitive impairment status as a predictor of clinical outcome in first acute-course ECT patients. METHODS: Baseline cognitive function at various thresholds and serial depressive symptom severity data from first-time ECT patients were examined using generalized linear mixed-effects models. RESULTS: Of 1345 patients who met the inclusion criteria, 617 had available data at their third assessment visit (~15th treatment visit). There was a robust improvement in depression symptoms over time (P < 0.0001), and cognitive function was not associated with baseline levels of depressive symptoms or serially measured change in self-reported symptom severity during acute-phase ECT. CONCLUSIONS: These results indicate that an acute course of ECT for the treatment of moderate-to-severe depression benefits patients with or without accompanying baseline cognitive impairment. These findings may be useful in informing shared decision-making discussions about ECT risks and expected benefits.