A shape-morphing cortex-adhesive sensor for closed-loop transcranial ultrasound neurostimulation

Transcranial focused ultrasound has shown promising non-invasive therapeutic effects for drug-resistant epilepsy due to its spatial resolution and depth penetrability. However, current manual strategies, which use fixed neurostimulation protocols, cannot provide precise patient-specific treatment due to the absence of ultrasound wave-insensitive closed-loop neurostimulation devices. Here, we report a shape-morphing cortex-adhesive sensor for closed-loop transcranial ultrasound neurostimulation. The sensor consists of a catechol-conjugated alginate hydrogel adhesive, a stretchable 16-channel electrode array and a viscoplastic self-healing polymeric substrate, and is coupled to a pulse-controlled transcranial focused ultrasound device. It can provide conformal and robust fixation to curvy cortical surfaces, and we show that it is capable of stable neural signal recording in awake seizure rodents during transcranial focused ultrasound neurostimulation. The sensing performance allows real-time detection of preseizure signals with unexpected and irregular high-frequency oscillations, and we demonstrate closed-loop seizure control supervised by intact cortical activity under ultrasound stimulation in awake rodents. A sensor that consists of a catechol-conjugated alginate hydrogel adhesive, a stretchable 16-channel electrode array and a viscoplastic self-healing polymeric substrate, and is coupled to a pulse-controlled transcranial focused ultrasound device, can be used for closed-loop transcranial ultrasound neurostimulation.