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Low-intensity transcranial focused ultrasound of the amygdala modulates neural activation during emotion processing

Kathryn C. Jenkins, Katherine Koning, Arman Mehzad, John LaRocco, Jagan Jimmy, Shiane Toleson, Kevin Reeves, Stephanie M. Gorka, K. Luan Phan

Frontiers in Neuroimaging 2025 · 10.3389/fnimg.2025.1580623

human healthyhealthyfmribehaviour

Abstract

Introduction Low-intensity focused ultrasound (LIFU) is a form of neuromodulation that offers increased depth of penetrance and improved spatial resolution over other non-invasive techniques, allowing for modulation of otherwise inaccessible subcortical structures that are implicated in neuropsychiatric pathologies. The amygdala is a target of great interest due to its involvement in numerous psychiatric conditions. While prior works have found that LIFU sonication of the amygdala can alter resting-state neural activation, only a few studies have investigated whether LIFU can selectively modulate the amygdala during task-based fMRI. Methods We aimed to address these gaps in literature in a cohort of 10 healthy individuals. We utilized the well-validated Emotional Face Assessment Task (EFAT), which is designed to robustly engage the amygdala. We selected the fusiform gyrus and the thalamus as our non-target regional comparison measures due to their roles in facial and emotional processing. In succession, participants completed a pre-LIFU baseline fMRI, received 10-min of LIFU neuromodulation, and then repeated the baseline fMRI. To test our hypothesis, we conducted paired-samples t-tests assessing changes in amygdala, fusiform gyrus, and thalamic activation from pre to post scan. Results We found that there was a significant decrease in left ( t (9) = 2.286; p = 0.024) and right ( t (9) = 2.240; p = 0.026) amygdala activation from pre-to-post sonication. Discussion Meanwhile, there were no differences in activation of the left or right fusiform gyrus or thalamus. Our results indicate that LIFU of the amygdala acutely dampens amygdala reactivity during active socio-emotional processing.

Abstract via europepmc.

Specieshuman
Subjects10 participants
Sessions per subject1
Randomisedno
Blindingnone
Sham / controlnone
Auditory controlnot reported
Readout timingoffline
Anaesthesianot applicable
Readoutsfmri, behaviour — Emotional Face Assessment Task (EFAT) BOLD ROI estimates (amygdala, fusiform, thalamus); task accuracy and reaction time
Direction of effectinhibitoryLeft and right amygdala activation to fearful/angry faces vs shapes decreased from pre to post sonication; fusiform gyrus and thalamus did not change.
Adverse eventsnone observedFollow-up phone call and side-effect questionnaire; 'No serious adverse events were reported by any participants.' Estimated thermal dose 0.18 CEM43 over the session.

Exposures

Exposure 1: LIFU of left amygdala

Target: amygdala — “left amygdala”
Device: BrainSonix · BrainSonix · Pulsar 1002 LIFU pulsation system with a 65 mm transducer ✓

Pulse timing
Waveformpulsed
Fundamental frequency (kHz)650✓✓✓
Pulse duration (ms)5✓✓✓
Pulse repetition frequency (Hz)10✓✓✓
Duty cycle (%)5pulse duration × PRF gives 5%✓✓✓
Sonication duration (s)30✓✓✓
Pressure and intensity, by domain
Free-field pressure (kPa)not reported
Free-field Isppa (W/cm²)not reported
Free-field Ispta (W/cm²)not reported
In-situ estimatenot reported
In-situ pressure (kPa)not reported
In-situ Isppa (W/cm²)not reported
In-situ Ispta (W/cm²)not reported
Ispta, domain unspecified (W/cm²)0.72✓✓✓⚑
Protocol, in the paper’s words

30-s trains of 650 kHz sonication at PRF 10 Hz with 30-s rest periods, 10 cycles over 10 min; pulse width 5 ms, duty cycle 5%.

Flags from extraction

  • exposures[0].unspecified_domain.ispta_w_cm2 — Stated as 720 mW/cm2 (converted to 0.72 W/cm2); domain not stated. No pressure or Isppa reported (MI 1.7 stated).
  • adverse_events — Paper says no serious adverse events; milder events are not explicitly excluded.
  • n_sessions_per_subject — Single-session pre/post design inferred from the procedure description; not stated as a number.
  • n_subjects — 15 enrolled, 10 included in analysis; the paper's abstract and methods give 10.
  • sham_type — Open-label single-arm; non-target regions used as controls, no sham.