Transcranial Focused Ultrasound Remotely Modulates Extrastriate Visual Cortex with Subregion Specificity

Low-intensity transcranial focused ultrasound (tFUS) has emerged as a powerful neuromodulation tool characterized by its deep penetration and precise spatial targeting to influence neural activity. Our study directed low-intensity tFUS stimulation onto a region of prefrontal cortex (the frontal eye field, or FEF) of a rhesus macaque to examine its impact on a remote site, the extrastriate visual cortex (area V4). This pair of cortical regions form a top-down modulatory circuit that has been studied extensively with electrical microstimulation. To measure the impact of tFUS stimulation, we recorded local field potentials (LFPs) and multi-unit spiking activities from a multi-electrode array implanted in the visual cortex. To deliver tFUS stimulation, we leveraged a customized 128-element random array ultrasound transducer with improved spatial targeting. We observed that tFUS stimulation in FEF produced modulation of V4 neuronal activity, either through enhancement or suppression, dependent on the pulse repetition frequency of the tFUS stimulation. Electronically steering the transcranial ultrasound focus through the targeted FEF cortical region produced changes in the level of modulation, indicating that the tFUS stimulation was spatially targeted within FEF. Modulation of V4 activity was confined to specific frequency bands, and this modulation was dependent on the presence or absence of a visual stimulus during tFUS stimulation. A control study targeting the insula produced no effect, emphasizing the region-specific nature of tFUS neuromodulation. Our findings shed light on the capacity of tFUS to modulate specific neural pathways and provide a comprehensive understanding of its potential applications for neuromodulation within brain networks.