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bioRxiv · 10.1101/2025.03.27.645800

Enhanced Episodic Memory Following Putative Inhibition of the Amygdala via Transcranial Low-Intensity Focused Ultrasound

Doss, M. K.·Lambert, S. R.·Samaha, J.·Nemeroff, C. B.·Fonzo, G. A.·Dunsmoor, J. E.
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Abstract

The amygdala is considered crucial to the formation of emotional episodic memories, but causal evidence in humans is limited due to challenges in non-invasive neuromodulation of deep brain structures. In a double-blind, sham-controlled, repeated measures study, we examined whether transcranial low-intensity focused ultrasound (tFUS) targeting the left amygdala prior to the encoding of emotional and neutral pictures impacted memory for these pictures 24 hours later. We used a putative inhibitory tFUS protocol shown to attenuate amygdala blood-oxygenation- level-dependent signal, thus testing the hypothesis that pre-encoding amygdala inhibition diminishes emotional memory. Surprisingly, active vs. sham sonication enhanced multiple measures of neutral and emotional memory across two memory tests. A secondary test of amygdala function found that active sonication enhanced fear recognition in faces. Computational modeling further supported these results. These findings motivate a novel conceptualization of the amygdalas role in emotional episodic memory. Rather than enhancing memory via amplification of salient stimuli, the amygdala may instead act as a filter that attenuates the maintenance of non-salient stimuli in long-term memory. Finally, the potential to enhance memory serves as an impetus to test tFUS of the amygdala in disorders such as depression and posttraumatic disorder that exhibit comorbid hyperreactive amygdalae and memory impairments.

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Doss, M. K., Lambert, S. R., Samaha, J., Nemeroff, C. B., Fonzo, G. A., Dunsmoor, J. E.. 2025-03-31. Enhanced Episodic Memory Following Putative Inhibition of the Amygdala via Transcranial Low-Intensity Focused Ultrasound. https://doi.org/10.1101/2025.03.27.645800

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