Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation

Morteza Mohammadjavadi; Patrick Peiyong Ye; Anping Xia; Julian Brown; Gerald Popelka; Kim Butts Pauly

doi:10.1016/j.brs.2019.03.005

Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation

Brain Stimul. 2019 Jul-Aug;12(4):901-910. doi: 10.1016/j.brs.2019.03.005. Epub 2019 Mar 6.

Authors

Morteza Mohammadjavadi¹, Patrick Peiyong Ye², Anping Xia³, Julian Brown⁴, Gerald Popelka⁵, Kim Butts Pauly⁶

Affiliations

¹ Department of Radiology, Stanford University, Stanford, CA, USA. Electronic address: mortezmj@stanford.edu.
² Department of Bioengineering, Stanford University, Stanford, CA, USA.
³ Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.
⁴ Howard Hughes Medical Institute, Department of Neurobiology, Stanford University, Stanford, CA, USA.
⁵ Department of Radiology, Stanford University, Stanford, CA, USA; Department of Otolaryngology-Head and Neck Surgery, Stanford University, Stanford, CA, USA.
⁶ Department of Radiology, Stanford University, Stanford, CA, USA; Department of Bioengineering, Stanford University, Stanford, CA, USA; Department of Electrical Engineering, Stanford University, Stanford, CA, USA.

Abstract

Background: Recent studies in a variety of animal models including rodents, monkeys, and humans suggest that transcranial focused ultrasound (tFUS) has considerable promise for non-invasively modulating neural activity with the ability to target deep brain structures. However, concerns have been raised that motor responses evoked by tFUS may be due to indirect activation of the auditory pathway rather than direct activation of motor circuits.

Objective: In this study, we sought to examine the involvement of peripheral auditory system activation from tFUS stimulation applied to elicit motor responses. The purpose was to determine to what extent ultrasound induced auditory artifact could be a factor in ultrasound motor neuromodulation.

Methods: In this study, tFUS-induced electromyography (EMG) signals were recorded and analyzed in wild-type (WT) normal hearing mice and two strains of genetically deaf mice to examine the involvement of the peripheral auditory system in tFUS-stimulated motor responses. In addition, auditory brainstem responses (ABRs) were measured to elucidate the effect of the tFUS stimulus envelope on auditory and motor responses. We also varied the tFUS stimulation duration to measure its effect on motor response duration.

Results: We show, first, that the sharp edges in a tFUS rectangular envelope stimulus activate the peripheral afferent auditory pathway and, second, that smoothing these edges eliminates the auditory responses without affecting the motor responses in normal hearing WT mice. We further show that by eliminating peripheral auditory activity using two different strains of deaf knockout mice, motor responses are the same as in normal hearing WT mice. Finally, we demonstrate a high correlation between tFUS pulse duration and EMG response duration.

Conclusion: These results support the concept that tFUS-evoked motor responses are not a result of stimulation of the peripheral auditory system.

Keywords: Auditory artifact; Auditory brainstem response; Motor response; Neuromodulation; Noninvasive brain stimulation; Ultrasound.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Acoustic Stimulation / methods*
Animals
Auditory Pathways / physiology*
Brain / physiology*
Brain Mapping / methods
Electromyography / methods
Female
Humans
Mice
Mice, Inbred C57BL
Mice, Knockout
Motor Activity / physiology*
Ultrasonic Waves*

Abstract

Publication types

MeSH terms

Grants and funding