Optically-generated focused ultrasound for noninvasive brain stimulation with ultrahigh precision

High precision neuromodulation is a powerful tool to decipher neurocircuits and treat neurological diseases. Current non-invasive neuromodulation methods offer limited precision at the millimeter level. Here, we report opticallygenerated focused ultrasound (OFUS) for non-invasive brain stimulation with ultrahigh precision. OFUS is generated by a soft optoacoustic pad (SOAP) fabricated through embedding candle soot nanoparticles in a curved polydimethylsiloxane film. SOAP generates a transcranial ultrasound focus at 15 MHz with an ultrahigh lateral resolution of 83 µm, which is two orders of magnitude smaller than that of conventional transcranial-focused ultrasound (tFUS). Here, we show effective OFUS neuromodulation in vitro with a single ultrasound cycle. We demonstrate submillimeter transcranial stimulation of the mouse motor cortex in vivo. An acoustic energy of 0.6 mJ/ cm², four orders of magnitude less than that of tFUS, is sufficient for successful OFUS neuromodulation. OFUS offers new capabilities for neuroscience studies and disease treatments by delivering a focus with ultrahigh precision non-invasively.

Yueming Li, Ying Jiang, Lu Lan, Xiaowei Ge, Ran Cheng, Yuewei Zhan, Guo Chen, Linli Shi, Runyu Wang, Nan Zheng, Chen Yang, Ji-Xin Cheng