A MINIATURIZED TRANSCRANIAL FOCUSED ULTRASOUND DEVICE FOR NEUROMODULATION RESEARCH

Transcranial focused ultrasound stimulation (tFUS) is a novel, noninvasive neuromodulation technique. Despite its potential, the underlying mechanisms require further investigation. This study aims to advance the field by designing a miniature transducer for use in pre-clinical studies. We developed a miniature US device and conducted in vitro studies to assess its effects at the cellular level. Experiments used hippocampal cell cultures, where current-clamp measurements were recorded. Voltage responses to current steps were measured before and after the US stimulation, and controlled with sham stimulation. In parallel, computational models based on the Hodgkin-Huxley formalism simulated the potential mechanisms underlying observed changes. Furthermore, we designed an in vivo experiment in rats using our device to modulate brain states during sleep. We implemented real-time sleep spindle detectors, supported by dedicated custom hardware, for guiding ultrasonic stimulation at spindle occurrence. Recordings revealed that brief US exposure cause long-term effects on membrane properties including increased voltage noise, increased resting potential, decreased spike latency and action potential amplitude. In silico modeling supported the hypothesis that observed electrical changes may be attributed to modifications in membrane permeability. Validation of sleep spindle detectors proved effective, and hardware for real-time EEG and stimulation was successfully established for rodent studies. Our results demonstrate the feasibility of tFUS for basic research, and provide evidence that long-term effects emerge following transient US stimulation. The integration of real-time signal processing and custom hardware lays the groundwork for future studies exploring the neuromodulatory impact of tFUS on brain state and learning in animal models.