Transcranial focused ultrasound modulates spiking, LFP, and BOLD activity in the primate thalamus

Transcranial-focused ultrasound (FUS) is a non-invasive neuromodulation technique capable of targeting deep brain regions with high precision. However, its mechanisms of action - particularly how it modulates neuronal activity and relates to fMRI BOLD signals - remain poorly understood. Using the macaque monkey thalamus and insular cortex as a model system, we show that low-intensity FUS evokes localized BOLD increases and preferentially modulates low-frequency (Delta, Theta, and Alpha) local field potentials and single-unit spiking in the ventroposterior lateral (VPL) nucleus, as well as through remote stimulation of the insular cortex. Compared with vibrotactile stimulation, FUS-evoked responses exhibit slower peak latencies. Importantly, we observe strong spatial correspondence between ultrasound-induced changes in spiking, LFP activity, and BOLD signals. These findings define the temporal and spatial characteristics of FUS neuromodulation and demonstrate the feasibility of precise, non-invasive targeting of deep brain circuits, supporting its translational potential for neuroscience and therapeutic applications.