A Noninvasive Focused Ultrasound-Evoked Electrophysiological Mapping Method with High Spatiotemporal Precision.

Achieving noninvasive functional brain mapping with submillimeter spatial and millisecond temporal resolution remains a major technical challenge. Existing modalities fail to meet both requirements simultaneously: fMRI offers high spatial resolution but suffers from hemodynamic delays, while EEG provides superior temporal resolution yet lacks spatial specificity. We present a cortical mapping method that integrates focused ultrasound (FUS) stimulation with local field potential (LFP) recordings for high-resolution electrophysiological mapping. A 5×5 Cartesian scanning grid was applied over the barrel cortex. FUS pulses (4 MHz, 1.6 MPa peak negative pressure, 1 Hz pulse repetition frequency) were sequentially delivered to each grid point, and peak LFP amplitudes were recorded at each site via a tungsten microelectrode to generate activation heatmap. Our method achieved approximately 0.45 mm spatial resolution and 10 ms temporal resolution in detecting FUS evoked LFP responses. The proposed FUS-LFP mapping paradigm enables high-resolution and time-precision visualization of cortical electrophysiological responses to noninvasive stimulation. This method provides a robust and scalable approach for probing evoked cortical responses and constructing functional brain maps, with promising translational relevance for preclinical neuroengineering.