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[Preprint]. 2024 Oct 12:2024.10.10.617091. [Version 1] doi: 10.1101/2024.10.10.617091

Microscopic deconstruction of cortical circuit stimulation by transcranial ultrasound

Théo Lemaire, Yi Yuan, Celia Gellman, Amy M LeMessurier, Sarah R Haiken Dray, Justin P Little, Robert C Froemke, Shy Shoham
PMCID: PMC11483041  PMID: 39415988

ABSTRACT

Transcranial Ultrasound Stimulation (TUS) can noninvasively and reversibly perturb neuronal activity, but the mechanisms by which ultrasound engages brain circuits to induce functional effects remain unclear. To elucidate these interactions, we applied TUS to the cortex of awake mice and concurrently monitored local neural activity at the acoustic focus with two-photon calcium imaging. We show that TUS evokes highly focal responses in three canonical neuronal populations, with cell-type-specific dose dependencies. Through independent parametric variations, we demonstrate that evoked responses collectively scale with the time-average intensity of the stimulus. Finally, using computational unmixing we propose a physiologically realistic cortical circuit model that predicts TUS-evoked responses as a result of both direct effects and local network interactions. Our results provide a first direct evidence of TUS’s focal effects on cortical activity and shed light on the complex circuit mechanisms underlying these effects, paving the way for TUS’s deployment in clinical settings.

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