Enhanced Episodic Memory Encoding Following Modulation of the Amygdala via Transcranial Low-intensity Focused Ultrasound
Manoj K. Doss, Sydney R. Lambert, Jason Samaha, Sai Prashanth Raja Sundaram, Charles B. Nemeroff, Gregory A. Fonzo, Joseph E. Dunsmoor
Journal of Cognitive Neuroscience 2026, 1-14 · 10.1162/jocn.a.2687
Abstract
The amygdala is considered crucial to the formation of emotional episodic memories, yet causal evidence in humans is limited due to challenges in noninvasive neuromodulation of deep brain structures. In a double-blind, sham-controlled, repeated-measures study, we tested whether transcranial low-intensity focused ultrasound (tFUS) targeting the left amygdala before encoding emotional and neutral pictures impacted memory for these pictures 24 hr later (n = 23). Using a putative inhibitory tFUS protocol previously shown to attenuate amygdala BOLD-dependent signal, we hypothesized that preencoding amygdala inhibition would impair emotional memory. Contrary to this hypothesis, active (vs. sham) sonication enhanced-or tended to enhance-memory for both neutral and emotional memory across two memory tests. As a secondary measure of amygdala modulation, participants completed a dynamic emotional facial recognition task (n = 20). Active tFUS selectively enhanced recognition of subtle fearful expressions. Computational modeling further supported tFUS-mediated memory and emotion recognition enhancements. Assuming that this tFUS protocol did indeed inhibit amygdala function, these findings suggest that rather than solely amplifying emotional salience, the amygdala may act as a filter that suppresses weaker, ambiguous signals. Inhibiting the amygdala may thus attenuate this gating function, thereby unmasking subtle affective cues and enhancing their processing into memory. Nevertheless, the purported inhibitory nature of this tFUS protocol requires further investigation. Should these findings replicate, they highlight the potential for tFUS as a translational tool to modulate affective processes for disorders such as depression and posttraumatic disorder characterized by impairments in emotional processing and memory.
Abstract via europepmc.
Exposures
Exposure 1: tFUS to left amygdala before encoding
Target: basolateral amygdala — “left amygdala (greatest modeled effect in anterior basolateral amygdala)”
Device: BrainSonix · Brainsonix · 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) | 640 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 14.4 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.72 | ✓✓✓ |
Sonication was delivered as 10 min total in 30-sec on/off blocks (continuous pulsing at 10-Hz PRF, 5% duty cycle during each 30-sec 'on' period) immediately before the encoding phase of the emotional episodic memory task.
Flags from extraction
randomised— Paper describes a double-blind, sham-controlled, within-subject design with counterbalanced sonication order, but does not explicitly state that arm order was randomized (only 'counterbalanced').auditory_control— Paper states sonication parameters are 'imperceptible' and the sham pad contains a foam layer, but does not describe any explicit auditory masking method to control for audible confounds.exposures[0].timing.sonication_duration_s— Sonication is delivered in 30-sec on/off blocks over a total 10-min session; the 30-sec 'on' block is treated as the length of one uninterrupted pulse train, with the overall session structure described in protocol_description.