Optimized ultrasound neuromodulation for non-invasive control of behavior and physiology.

Authors: Murphy KR, Farrell JS, Bendig J, Mitra A, Luff C, Stelzer IA, Yamaguchi H, Angelakos CC, Choi M, Bian W, DiIanni T, Pujol EM, Matosevich N, Airan R, Gaudillière B, Konofagou EE, Butts-Pauly K, Soltesz I, de Lecea L

Focused ultrasound can non-invasively modulate neural activity, but whether effective stimulation parameters generalize across brain regions and cell types remains unknown. We used focused ultrasound coupled with fiber photometry to identify optimal neuromodulation parameters for four different arousal centers of the brain in an effort to yield overt changes in behavior. Applying coordinate descent, we found that optimal parameters for excitation or inhibition are highly distinct, the effects of which are generally conserved across brain regions and cell types. Optimized stimulations induced clear, target-specific behavioral effects, whereas non-optimized protocols of equivalent energy resulted in substantially less or no change in behavior. These outcomes were independent of auditory confounds and, contrary to expectation, accompanied by a cyclooxygenase-dependent and prolonged reduction in local blood flow and temperature with brain-region-specific scaling. These findings demonstrate that carefully tuned and targeted ultrasound can exhibit powerful effects on complex behavior and physiology.

Introduction

Purpose Transcranial ultrasound stimulation

Study Objective To identify optimized focused ultrasound stimulation parameters across multiple brain regions and cell types that reliably modulate neural activity and produce overt behavioral and physiological effects.

Disease model Healthy

Outcomes and Safety

Summary of Outcomes Carefully tuned focused ultrasound waveforms, identified by coordinate-descent screening and distinct for excitation versus inhibition (region- and cell-type-specific optimized parameter sets), produced robust, target-specific changes in neural activity and overt behavior across four arousal centers while non-optimized equal-energy protocols produced little or no behavioral change; these effective protocols were independent of auditory confounds but accompanied by a COX-dependent, prolonged reduction in local blood flow and temperature.

Safety-related matter Focused ultrasound produced a cyclooxygenase-dependent and prolonged reduction in local blood flow and temperature, scaling with brain region; the paper does not explicitly report other adverse effects.

Brain Region

Visualization unavailable

Ultrasound Parameters

Focal Characteristics Focal depth: None; Focal length: None; Aperture size: None

Treatment frequency multiple sessions

We are open to feedback. If you see a mistake or have a suggestion, please contact us.