Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans.

Authors: Kuhn T, Spivak NM, Dang BH, Becerra S, Halavi SE, Rotstein N, Rosenberg BM, Hiller S, Swenson A, Cvijanovic L, Dang N, Sun M, Kronemyer D, Berlow R, Revett MR, Suthana N, Monti MM, Bookheimer S

Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively. We sought to demonstrate that tFUS can selectively and accurately target and modulate deep brain structures in humans important for emotional functioning as well as learning and memory. We hypothesized that tFUS would result in significant longitudinal changes in perfusion in the targeted brain region as well as selective modulation of BOLD activity and BOLD-based functional connectivity of the target region. In this study, we collected MRI before, simultaneously during, and after tFUS of two deep brain structures on different days in sixteen healthy adults each serving as their own control. Using longitudinal arterial spin labeling (ASL) MRI and simultaneous blood oxygen level dependent (BOLD) functional MRI, we found changes in cerebral perfusion, regional brain activity and functional connectivity specific to the targeted regions of the amygdala and entorhinal cortex (ErC). tFUS selectively increased perfusion in the targeted brain region and not in the contralateral homolog or either bilateral control region. Additionally, tFUS directly affected BOLD activity in a target specific fashion without engaging auditory cortex in any analysis. Finally, tFUS resulted in selective modulation of the targeted functional network connectivity. We demonstrate that tFUS can selectively modulate perfusion, neural activity and connectivity in deep brain structures and connected networks. Lack of auditory cortex findings suggests that the mechanism of tFUS action is not due to auditory or acoustic startle response but rather a direct neuromodulatory process. Our findings suggest that tFUS has the potential for future application as a novel therapy in a wide range of neurological and psychiatric disorders associated with subcortical pathology.

Introduction

Purpose Transcranial ultrasound stimulation

Study Objective To demonstrate that low-intensity transcranial focused ultrasound (tFUS) can selectively target and modulate perfusion, neural activity, and functional connectivity of deep human brain structures (amygdala and entorhinal cortex).

Animal model / Human subject Homo sapiens (human); strain: N/A; age: adults (unspecified); sex: not specified

Disease model healthy

Targeted brain region(s) Amygdala And Entorhinal Cortex (Erc)

Outcomes and Safety

Summary of Outcomes Transcranial focused ultrasound (tFUS) to the amygdala or entorhinal cortex selectively increased ipsilateral regional perfusion and produced target-specific modulation of BOLD activity and functional connectivity — amygdala sonication (10 Hz, disruption paradigm) decreased amygdala-network FC, while entorhinal sonication (100 Hz, excitation paradigm) increased ErC BOLD and ErC–DLPFC connectivity — with no auditory-cortex engagement.

Safety-related matter No adverse events occurred in this study; participants were followed daily for three days after each tFUS session and reported no negative reactions, including physical discomfort or heightened anxiety. Prior literature and histological data cited indicate adverse events are rare and associated with intensities above approved human limits, with no tissue damage observed at intensities several-fold higher than used here, though the authors note additional safety work is needed.

Transcranial focused ultrasound selectively increases perfusion and modulates functional connectivity of deep brain regions in humans.

Introduction

Outcomes and Safety

Brain Region

Ultrasound Parameters