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

Taylor Kuhn; Norman M Spivak; Bianca H Dang; Sergio Becerra; Sabrina E Halavi; Natalie Rotstein; Benjamin M Rosenberg; Sonja Hiller; Andrew Swenson; Luka Cvijanovic; Nolan Dang; Michael Sun; David Kronemyer; Rustin Berlow; Malina R Revett; Nanthia Suthana; Martin M Monti; Susan Bookheimer

doi:10.3389/fncir.2023.1120410

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

Front Neural Circuits. 2023 Apr 5:17:1120410. doi: 10.3389/fncir.2023.1120410. eCollection 2023.

Authors

Taylor Kuhn¹, Norman M Spivak^{1

2

3}, Bianca H Dang¹, Sergio Becerra¹, Sabrina E Halavi¹, Natalie Rotstein¹, Benjamin M Rosenberg⁴, Sonja Hiller¹, Andrew Swenson⁵, Luka Cvijanovic⁵, Nolan Dang¹, Michael Sun⁶, David Kronemyer¹, Rustin Berlow⁷, Malina R Revett¹, Nanthia Suthana^{1

2

4

8}, Martin M Monti^{1

2

4}, Susan Bookheimer¹

Affiliations

¹ Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, United States.
² Department of Neurosurgery, University of California, Los Angeles, Los Angeles, CA, United States.
³ UCLA-Caltech Medical Scientist Training Program, Los Angeles, CA, United States.
⁴ Department of Psychology, University of California, Los Angeles, Los Angeles, CA, United States.
⁵ Neuroscience Interdepartmental Program, University of California, Los Angeles, Los Angeles, CA, United States.
⁶ Department of Psychological and Brain Sciences, Dartmouth College, Hanover, NH, United States.
⁷ American Brain Stimulation Clinic, Del Mar, CA, United States.
⁸ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract

Background: Low intensity, transcranial focused ultrasound (tFUS) is a re-emerging brain stimulation technique with the unique capability of reaching deep brain structures non-invasively.

Objective/hypothesis: 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.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: amygdala; brain perfusion; entorhina cortex; functional connectivity; transcranial focused ultrasound.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Brain / diagnostic imaging
Brain / physiology
Brain Mapping* / methods
Humans
Magnetic Resonance Imaging / methods
Perfusion
Reflex, Startle*

Grants and funding

UCLA Staglin IMHRO Center for Cognitive Neuroscience Pilot Funding (TK). UCLA Semel Institute for Neuroscience and Behavior (TK). Alzheimer’s Association Zenith Award ZEN-20-643042: Modulation of Hippocampal Circuitry with Focused Ultrasound in MCI (SBo and TK).