Transcranial Focused Ultrasound Stimulation Targeting White Matter Inhibits Seizures in a Rat Model of Epilepsy
Huan Gao, Annabel Frake, Dominique M. Durand, Bin He
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2026 · 10.1109/tnsre.2025.3644273
Abstract
Transcranial focused ultrasound (tFUS) can noninvasively modulate sensory pathways, but the cell-type-specific mechanisms underlying excitatory or inhibitory effects remain unclear. Here, we investigate how tFUS applied to the somatosensory cortex (S1) influences S1 and posterior medial thalamic nucleus (POm) responses to hind paw vibration-tactile stimulation and which neuronal populations mediate these effects. Vibration-tactile stimulation evoked potentials (TEPs) and multi-unit activities (MUA) in S1 and POm were recorded from male rats. Optogenetic tagging was used to identify S1 CaMKII-positive, PV-positive, and SST-positive neurons, while waveform features were used to classify putative excitatory (i.e., regular-spiking units - RSUs) and inhibitory neurons (i.e., fast-spiking units - FSUs) in POm. We found that only S1 CaMKII-positive neurons and POm RSUs responded robustly to tactile stimulation. When tFUS was applied to S1, high pulse repetition frequency (PRF), high duty cycle, and high-pressure stimulation (etFUS) produced excitatory modulation of the sensory pathway, whereas low PRF, low duty cycle, and low-pressure stimulation (itFUS) induced inhibitory effects. Further analyses revealed that excitatory modulation was mediated by activation of S1 CaMKII-positive neurons, while the inhibitory effect arose from their deactivation. These findings demonstrate that tFUS exerts bidirectional, parameter-dependent modulation of a sensory pathway and highlight the critical role of CaMKII-positive neurons in mediating these effects. This study provides mechanistic insight into cell-type-specific neuromodulation by tFUS, particularly in bidirectional modulation of a sensory pathway, and informs the optimization of stimulation parameters for targeted therapeutic interventions.
Abstract via europepmc.
Exposures
Exposure 1: tFUS of corpus callosum
Target: corpus callosum — “corpus callosum (CC)”
Device: not reported · H276 128-element random array transducer; Verasonics Vantage 128 ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 1,500 | ✓✓✓ |
| Pulse duration (ms) | 20 | ✓✓✓ |
| Pulse repetition frequency (Hz) | 1 | ✓✓✓ |
| Duty cycle (%) | 2pulse duration × PRF gives 2% | ✓✓✓ |
| Sonication duration (s) | 3,750 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reportedsingle value | |
| In-situ pressure (kPa) | 127 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
20 ms pulses at 1 Hz (2% duty cycle) delivered continuously for ~62.5 minutes (3,750 pulses) to the corpus callosum during the condition block, followed by about 3 hours of post-stimulation recording.
Flags from extraction
n_subjects— 16 rats in epilepsy study (10 tFUS, 6 sham) plus 7 in a mechanism study (23 total); total includes sham animals.blinding— Only the seizure-labelling experimenter was stated blinded to time block.exposures[0].timing.sonication_duration_s— 3,750 pulses at 1 Hz (~62.5 min) converted to 3750 s; total stimulation is one hour block of pulses.exposures[0].in_situ.pressure_kpa— Legend states in situ pressure ~127 kPa; method of determination not described in main text.sham_type— Sham: no stimulation applied; mechanism not described.exposures[0].device.family— Maker of H276 transducer not named in the text.