PT  - JOURNAL ARTICLE
AU  - Morteza Mohammadjavadi
AU  - Patrick Peiyong Ye
AU  - Anping Xia
AU  - Julian Brown
AU  - Gerald Popelka
AU  - Kim Butts Pauly
TI  - Elimination of peripheral auditory pathway activation does not affect motor responses from ultrasound neuromodulation
AID  - 10.1101/428342
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 428342
4099  - http://biorxiv.org/content/early/2018/09/27/428342.short
4100  - http://biorxiv.org/content/early/2018/09/27/428342.full
AB  - 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. 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. 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. These results support the concept that tFUS-evoked motor responses are not a result of stimulation of the peripheral auditory system.