An electronically steerable epidural ultrasound interface for deep brain neuromodulation in freely moving rats

Low-intensity focused ultrasound (LI-FUS) is being tested clinically for neural activity modulation and blood-brain barrier opening, but current LI-FUS is applied only transcranially, limiting it to episodic and intermittent stimulation. Clinical data indicate that many neurological and psychiatric applications need chronic, continuous stimulation to achieve long-term stable therapeutic effects, motivating an implantable solution.

To address this, the paper presents an implantable epidural focused ultrasound (eFUS) device for continuous, chronic, and multi-site steerable neuromodulation. The miniaturized device consists of a two-dimensional piezoelectric transducer array directly integrated onto a custom ASIC, specifically engineered for proof-of-principle neuromodulation studies in the rat brain. It generates electronically steerable focused ultrasound with software-defined focal coordinates capable of stimulating neuronal activity in deep brain structures.

In vitro acoustic characterization confirmed accurate beam steering and focusing. In vivo validation demonstrated reliable stimulation of a deep subcortical target with measurable physiological effects. In awake, freely moving rats, eFUS targeting of the ventral tegmental area produced increased dopamine release in the nucleus accumbens, confirmed by fiber photometry recordings. Post-mortem histological analysis of target regions showed no inflammatory markers, although epidural placement of the eFUS device was associated with mild tissue damage.

Overall, the study provides in vitro data demonstrating the energy efficiency and steerability of the technology, plus in vivo physiological evidence of neuromodulatory ability in a deep subcortical brain structure. The approach aims to enable chronic, continuous, multi-site deep brain neuromodulation beyond what transcranial LI-FUS can deliver.