Frequency and Timing‐Dependent Effects of Ultrasound on Neural Responses: Comparative Analysis With Whisker Stimulation in Rats

This study explores whether ultrasound can induce short-term synaptic plasticity (STP)-like effects at the systems level by modulating cortical excitability and sensory responsiveness. We designed a temporally shifted sensory paradigm to test how ultrasound frequency (1, 2, and 4 MHz), inter-stimulus interval (10, 25, and 100 ms), and stimulation order (ultrasound-whisker vs. whisker-ultrasound) affect cortical responses in the rat barrel cortex. Thirty Sprague-Dawley rats underwent an identical experimental protocol. Electrocorticography (ECoG) signals were recorded from the C2 barrel column, and neural responses were assessed by peak amplitude, latency, and power spectral density. Whisker stimulation alone evoked strong cortical responses, significantly greater than ultrasound stimulation. Notably, when ultrasound preceded whisker stimulation by 25 ms, subsequent whisker responses were significantly enhanced, suggesting the existence of a cortical "excitability window" for neuromodulation. This facilitation effect was absent with time intervals of 10 and 100 ms. Mechanistically, ultrasound may modulate membrane tension and activate mechanosensitive ion channels to transiently lower the activation threshold of cortical neurons. These findings reveal that ultrasound can temporally enhance cortical excitability and sensory responsiveness in a frequency- and timing-dependent manner. Our results provide systems-level evidence of STP-like neuromodulation and provide the potential of ultrasound as a noninvasive method for dynamic control of sensory processing.