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

Abstract

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.

Transcranial Focused Ultrasound Neuromodulation: A Review of the Excitatory and Inhibitory Effects on Brain Activity in Human and Animals

“…An early study by Min et al (2011) reported that low-intensity, pulsed FUS (690 kHz) sonication suppressed the number of epileptic signal bursts and severe epileptic behavior using an acute epilepsy model in animals. Yang et al (2020) delivered pulsed closed-loop transcranial ultrasound stimulation with a frequency of 500 kHz to the hippocampus to modulate neural oscillation and effectively inhibited the seizure of a temporal lobe epilepsy (TLE) mouse. The study of Chen et al (2020) reported that pulsed tFUS (500 kHz) effectively suppressed epileptic spikes in an acute epilepsy animal model and found that ultrasound pulsation interferes with neuronal activity.…”

Focusing in on the Future of Focused Ultrasound as a Translational Tool

“…EEG has inherently much better temporal resolution than BOLD fMRI (1 ms versus 700 ms), and changes in network connectivity can be much more readily assessed with EEG than with fMRI. Concurrent tFUS-EEG has a major advantage over electro-magnetic methods, such as TMS, since ultrasound produces very few artifacts in the EEG [ 39 ], lending itself nicely to closed-loop stimulation systems [ 40 ]. However, EEG is not the best tool for detecting subcortical change, so any tFUS studies targeting deeper targets should rely on fMRI instead.…”

Control of inflammation using non-invasive neuromodulation: past, present and promise

“…Since the first report of ultrasound as a therapeutic tool in the 1920s, it has been widely used in clinical practice and clinical/translational research for the treatment of various human malignancies ( 96–98 ) and pathologies including Parkinson’s disease ( 99 ), stroke ( 100 ), prostatic hyperplasia ( 101 ), renal masses ( 102 ), treatment of abdominal subcutaneous adipose tissue ( 103 ), bone repair ( 104 ), osteoarthritis ( 105 ) and carpal tunnel syndrome ( 106 ). Ultrasound waves are sound waves generated by cyclic mechanical vibrations with frequencies higher than the upper audible range for the human (>20 kHz).…”