Low-intensity focused ultrasound alters the latency and spatial patterns of sensory-evoked cortical responses in vivo

The use of transcranial, low intensity focused ultrasound (FUS) is an emerging neuromodulation technology that shows promise for both therapeutic and research applications. Compared with other noninvasive neuromodulation approaches, key technical advantages include high lateral resolution of stimulation and deep penetration depth. However, empirically observed effects in vivo are diverse; for example, variations in sonication location and waveform can alternatively elicit putatively inhibitory or excitatory effects. At a fundamental level, it is unclear how FUS alters the function of neural circuits at the site of sonication. To address this knowledge gap, we developed an approach to optically interrogate the spatiotemporal patterns of neural activity in the cortex directly at the acoustic focus, thereby offering a glimpse into the local effects of FUS on distributed populations of neurons in vivo. Our experiments probed electrical activity through the use of voltage sensitive dyes (VSDs) and, in transgenic GCaMP6f mice, monitored associated Ca2+ responses. Our results directly demonstrate that low-intensity FUS adjusts both the kinetics and spatial patterns of sensory receptive fields at the acoustic focus in vivo. Although our experimental configuration limits interpretation to population activity, the use of VSDs ensures that the detected alterations reflect activity in cortical neurons, unobscured by signals in subcortical or laterally distant cortical regions. More generally, this optical measurement paradigm can be implemented to observe FUS-induced alterations in cortical representation with higher lateral resolution spatial versatility than is practical through more conventional electrodebased measurements. Our findings suggest that reports of FUS-induced sensory modulation in human studies may partly reflect alterations cortical representation and reactivity.