An electronically steerable epidural ultrasound interface for deep brain neuromodulation in freely moving rats
- 1University Freiburg Medical Centre
Abstract
Low-intensity focused ultrasound (LI-FUS) clinical trials exploit either the neural activity modulating, or the blood-brain barrier opening, capacity of this stimulation modality. However, LI-FUS currently is applied only transcranially which means that it is conducive only for episodic and intermittent stimulation, although, clinical data shows that in numerous neurological and psychiatric applications, chronic and continuous stimulation is required for long-term, stable therapeutic effect. The paper presents experimental data on a novel and innovative approach describing an implantable, epidural focus ultrasound (eFUS) device, designed for continuous, chronic and multi-site steerable neuromodulation. The miniaturized eFUS 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. The system generates electronically steerable focused ultrasound with software-defined focal coordinates, sufficient to stimulate neuronal activity in deep brain structures. In vitro acoustic characterization confirmed accurate beam steering and focusing, while in vivo validation demonstrated reliable stimulation of a deep subcortical target with measurable physiological effects. eFUS-mediated targeting of the ventral tegmental area in awake and freely moving rats produced increase in dopamine release in the nucleus accumbens as confirmed using fiber photometry recordings. Post-mortem histological analysis of the target regions showed the absence of inflammatory markers, although the 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, and in vivo physiological evidence of neuromodulatory ability of a deep, subcortical brain structure.
Related
- Focused Ultrasound Neuromodulation of the Central Lateral Thalamus in a Non-Human Primate Model of Disorders of Consciousness
- Low-intensity ultrasound drives offline neuromodulation through passive membrane mechanisms in synaptically isolated hippocampal neurons
- Dose-dependent ultrasound neuromodulation of the human brain
- Ultra-high-efficacy Wireless Neuromodulation Using a Conductive Ring Interface
- Ultrasound neuromodulation hypotheses on the directionality of effects and community resource
BibTeX
@misc{ratz2026electronically,
title = {{An electronically steerable epidural ultrasound interface for deep brain neuromodulation in freely moving rats}},
author = {L. Ratz and H. Rivandi and G. K. Wardhana and E. Sarkar and M. Aqamolaei and Y. Tong and S. Desmarais and L. Sohail and P. D. Donaldson and V. Aloia and M. Arlotti and V. A. Coenen and D. G. Muratore and G. D. Spyropoulos and T. L. Costa and M. Dobrossy},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.10.750612},
url = {https://www.biorxiv.org/content/10.64898/2026.09.10.750612v1},
note = {Public domain},
}
RIS
TY - UNPB
TI - An electronically steerable epidural ultrasound interface for deep brain neuromodulation in freely moving rats
AU - L. Ratz
AU - H. Rivandi
AU - G. K. Wardhana
AU - E. Sarkar
AU - M. Aqamolaei
AU - Y. Tong
AU - S. Desmarais
AU - L. Sohail
AU - P. D. Donaldson
AU - V. Aloia
AU - M. Arlotti
AU - V. A. Coenen
AU - D. G. Muratore
AU - G. D. Spyropoulos
AU - T. L. Costa
AU - M. Dobrossy
PY - 2026
DA - 2026/09/10
PB - bioRxiv
DO - 10.64898/2026.09.10.750612
UR - https://www.biorxiv.org/content/10.64898/2026.09.10.750612v1
AB - Low-intensity focused ultrasound (LI-FUS) clinical trials exploit either the neural activity modulating, or the blood-brain barrier opening, capacity of this stimulation modality. However, LI-FUS currently is applied only transcranially which means that it is conducive only for episodic and intermittent stimulation, although, clinical data shows that in numerous neurological and psychiatric applications, chronic and continuous stimulation is required for long-term, stable therapeutic effect. The paper presents experimental data on a novel and innovative approach describing an implantable, epidural focus ultrasound (eFUS) device, designed for continuous, chronic and multi-site steerable neuromodulation. The miniaturized eFUS 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. The system generates electronically steerable focused ultrasound with software-defined focal coordinates, sufficient to stimulate neuronal activity in deep brain structures. In vitro acoustic characterization confirmed accurate beam steering and focusing, while in vivo validation demonstrated reliable stimulation of a deep subcortical target with measurable physiological effects. eFUS-mediated targeting of the ventral tegmental area in awake and freely moving rats produced increase in dopamine release in the nucleus accumbens as confirmed using fiber photometry recordings. Post-mortem histological analysis of the target regions showed the absence of inflammatory markers, although the 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, and in vivo physiological evidence of neuromodulatory ability of a deep, subcortical brain structure.
ER -