Mechanical Displacement Correlates with Motor Response and Vascular Hemodynamic Changes induced by Focused Ultrasound (FUS) Neuromodulation in Craniotomized Mice

Focused ultrasound (FUS) has been shown capable of modulating both the peripheral and central nervous systems. Displacement and functional ultrasound (fUS) imaging has been shown to concurrently occur with FUS enabling mechanistic and functional monitoring of FUS neuromodulation. In this study, we investigated FUS-evoked mechanical displacement in the brain with subsequent neurovascular responses and their relationship with FUS-evoked motor responses and the relationship between displacement, neurovascular and motor responses. Displacement and cerebral blood volume (CBV) were measured in craniotomized and anesthetized mice while FUS elicited motor activation of hind limb and tail with electromyography (EMG) recorded. We demonstrated FUS-evoked target specific and dose-dependent motor activation with ~ 63 ms latency. We found that FUS elicits a localized ipsilateral CBV increase followed by a contralateral CBV increase. CBV starts rising at FUS onset and peaks at ~ 4 s with a peak amplitude of ~ 16 % at 3.39 MPa. In addition, we demonstrated that displacement correlates with FUS-evoked CBV and EMG responses. Lastly, we found high correlation between displacement, CBV, and EMG, which may indicate the FUS-elicited neurovascular and motor activation were dominantly mediated in a displacement-driven mechanism. Our findings thus demonstrate the acoustic radiation force-based mechanism of FUS motor modulation.