Closed-Loop Transcranial Ultrasound Stimulation for Real-Time Non-invasive Neuromodulation in vivo

The closed-loop brain stimulation technique plays a key role in neural network information processing and therapies of neurological diseases. Transcranial ultrasound stimulation (TUS) is an established neuromodulation method for the neural oscillation in animals or human. All available TUS systems provide brain stimulation in an open-loop pattern. In this study, we developed a closed-loop transcranial ultrasound stimulation (CLTUS) system for real-time non-invasive neuromodulation in vivo. We used the CLTUS system to modulate the neural activities of the hippocampus of a wild-type mouse based on the phase of the theta rhythm recorded at the ultrasound-targeted location. In addition, we modulated the hippocampus of a temporal lobe epilepsy (TLE) mouse. The ultrasound stimulation increased the absolute power and reduced the relative power of the theta rhythm, which were independent of the specific phase of the theta rhythm. Compared with those of a sham stimulation, the latency of epileptic seizures was significantly increased, while the epileptic seizure duration was significantly decreased under the CLTUS. The above results indicate that the CLTUS can be used to not only modulate the neural oscillation through the theta-phase-specific manipulation of the hippocampus but also effectively inhibit the seizure of a TLE mouse in time. CLTUS has large application potentials for the understanding of the causal relationship of neural circuits as well as for timely, effective, and non-invasive therapies of neurological diseases such as epilepsy and Parkinson’s disease.