Transcranial focused ultrasound of the amygdala modulates fear network activation and connectivity
Tina Chou, Thilo Deckersbach, Bastien Guerin, Karianne Sretavan Wong, Benjamin M. Borron, Anish Kanabar, Ashley N. Hayden, Marina P. Long, Mohammad Daneshzand, Edward F. Pace-Schott, Darin D. Dougherty
Brain Stimulation 2024, 17, 312-320 · 10.1016/j.brs.2024.03.004
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, η 2 = 0.16) during the fear task, and lower hippocampal (F(1,27) = 4.41, p = 0.05, η 2 = 0.14), and dorsal anterior cingulate cortex (F(1,27) = 6.26, p = 0.02; η 2 = 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.
Abstract via europepmc.
Exposures
Exposure 1: active tFUS of left amygdala
Target: amygdala — “left amygdala”
Device: BrainSonix · BrainSonix Corporation · BX Pulsar 1002 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 650 | ✓✓✓ |
| Pulse duration (ms) | 5 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 5pulse duration × PRF gives 5% | ✓✓✓ |
| Sonication duration (s) | 30 | ✓✓✓ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | deratingsingle value | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | 14.4 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓ |
In the MRI scanner, the active tFUS group received 20 min total of 30-s on and 30-s off blocks of sonication to the left amygdala; a specific amygdala sub-nucleus was not targeted.
Flags from extraction
n_subjects— Total enrolled was 30 (15 sham, 15 active); n_subjects reflects only the 15 participants who received active (real) tFUS, per the definition of 'subjects exposed to ultrasound'.n_sessions_per_subject— The paper describes a single scanning visit with pre/post tFUS measurements but never explicitly states the number of sessions per participant.