TRANSCRANIAL FOCUSED ULTRASOUND FOR SEIZURE MODULATION: PARAMETER MAPPING IN THE INTRAHIPPOCAMPAL KAINIC ACID MOUSE MODEL USING FIBER PHOTOMETRY

Temporal lobe epilepsy (TLE) is the most prevalent type of focal epilepsy in adults. In TLE, the epileptogenic focus often lies within the hippocampus and is commonly associated with hippocampal sclerosis. Despite the available antiseizure medications, about one-third of patients remain drug-resistant. Alternatively, epileptic surgery offers an effective treatment option, although many patients are not eligible. To date, other options like invasive electrostimulation therapies can reduce seizures but require surgery, carry infection risk and show variable efficacy. Non-invasive electrostimulation approaches have limited spatial resolution, reduced efficacy on deeper structures, and lack cell-type specificity. These limitations underscore the need for safe, effective and targeted alternatives. Transcranial focused ultrasound (TUS) offers non-invasive neuromodulation with millimeter-scale focal resolution, the ability to target deep brain structures, and potential cell-type selectivity, making it an attractive candidate therapy for drug-resistant TLE. Although, previous findings show that TUS can reduce seizure activity, the mechanisms underlying hippocampal modulation and the optimal stimulation parameters remain unclear. This projects aims to evaluate the effects of different TUS parameters (frequency, duty cycle, pulse repetition frequency) on calcium dynamics of hippocampal neurons in healthy and epileptic mice, using fiber photometry. Fiber photometry with the GCaMP6s calcium indicator will monitor the real-time activity of excitatory neurons as a readout of circuit-level responses to different TUS parameters. Additionally, simultaneous depth electrode recordings will provide us insight into the effects of different TUS parameters on epileptic seizures. It is hypothesized that TUS stimulation exerts parameter-dependent effects on neuronal calcium dynamics and reduces epileptiform spike rates.