Our new preprint coming out of UPSIDE demonstrates a miniaturized epidural focused ultrasound (eFUS) interface for deep-brain neuromodulation in awake, freely moving animals.
Instead of delivering focused ultrasound transcranially using an external transducer, we bring ultrasound directly to the surface of the brain.
At the heart of the system is a miniaturized (4.2 mm aperture) 2D piezoelectric transducer array integrated with a custom ASIC, allowing us to electronically steer and focus ultrasound at software-defined locations deep inside the brain — without mechanically moving the device.
Importantly for an implantable system, this is achieved with very low power consumption and minimal heating: the chip consumes only 12.25 mW/MPa/DC, while the temperature increase remains below 1°C at 10% duty cycle, even at the maximum driving voltage.
And most importantly: it works in vivo. In awake and freely moving rats, we electronically targeted the ventral tegmental area (VTA), a deep subcortical structure involved in the brain’s reward circuitry. eFUS stimulation produced a measurable increase in dopamine release in the nucleus accumbens, recorded in real time using fiber photometry, providing physiological evidence that our software-defined ultrasound focus can effectively modulate a deep-brain circuit.
Importantly, we also investigated the safety of the approach. Post-mortem histological analysis showed no inflammatory markers in the targeted brain regions. Mild tissue damage associated with the epidural placement of the device was observed, highlighting an important aspect of the implantation procedure that we aim to further improve in future generations of the system.
This opens a path towards a minimally invasive alternative to deep-brain stimulation (DBS) using focused ultrasound, with high-precision stimulation targets (~0.1 mm³) that can be defined and adjusted entirely through software.
For us, this is an important step towards a new class of implantable ultrasound interfaces capable of electronically addressing different locations deep inside the brain while remaining at its surface.
A special recognition goes to Lisa Ratz and Máté Döbrössy, who led the in vivo work and made it possible to take the eFUS technology into freely moving animal experiments. On the technology side, Hassan Rivandi, Gandhika K. Wardhana, Eshani Sarkar, Masoumeh Aqamolaei, Samuel Desmarais and Tiago L. Costa, worked on the development of the eFUS chip and system across its different stages — from the underlying integrated electronics and transducer technology to the final experimental platform. And a huge thank you to all the other co-authors, whose contributions and fruitful discussions throughout the four years of UPSIDE helped us get this far.
The preprint, “An electronically steerable epidural ultrasound interface for deep brain neuromodulation in freely moving rats,” is now available on bioRxiv:
An electronically steerable epidural ultrasound interface for deep brain neuromodulation in freely moving rats
We are now preparing the manuscript for submission to journal. Stay tuned!
