Low-Intensity Focused Ultrasound Neuromodulation for Tic Disorder Therapy: Preclinical Validation With Clinically Relevant Parameters
Subeen Kim, Miseon Kang, Myunghyun J. Jeong, Yehhyun Jo, Jeongyeon Kim, Hyunjoo J. Lee
IEEE Transactions on Neural Systems and Rehabilitation Engineering 2025 · 10.1109/tnsre.2025.3629724
Abstract
Tourette syndrome (TS) is typically treated with pharmacological therapies, which often induce tolerance. Recently, neuromodulatory therapies, such as deep brain stimulation (DBS) and transcranial magnetic stimulation (TMS), have emerged as alternatives for tic disorders. However, these modalities are constrained by invasiveness and insufficient spatial resolution. To address these limitations, we employed low-intensity focused ultrasound (LIFU), an emerging noninvasive therapeutic modality previously applied in various neurological disorders, and established effective stimulation parameters that alleviated tic-like movements. We developed a bicuculline-induced mouse model of tic disorder and validated tic-like features through analyses of electrophysiological brain signals, neural activities, and behavior. We further applied a LIFU stimulation with clinically relevant parameters using a 250-kHz ultrasound transducer. Ultrasound stimulation targeting the secondary motor cortex (M2) significantly reduced the frequency of tic-like movements and pathological electrophysiological spikes by 51% and 87%, respectively. These findings suggest that LIFU brain stimulation alleviates tic symptoms in a preclinical model of TS. Given the clinical compatibility of our stimulation parameters, this approach provides a robust basis for translational research toward human applications in tic disorder treatment.
Abstract via europepmc.
Exposures
Exposure 1: M2 stimulation (STIM)
Target: motor cortex — “secondary motor cortex (M2)”
Device: other named manufacturer · Hagisonic Co., Ltd. · M710-SB ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 250 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 0.2 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 100 | ✓✓✓ |
| Duty cycle (%) | 2 | ✓✓✓ |
| Sonication duration (s) | not reported | ⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | 3.3 | ✓✓✓ |
| Free-field Ispta (W/cm²) | 0.065 | ✓✓✓⚑ |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
250 kHz, 100 Hz PRF, 2% duty cycle. The sonication lasted 20 minutes in total, with an inter-stimulus interval (ISI) of 10 s; duration of each train not stated.
Flags from extraction
exposures[0].free_field.ispta_w_cm2— Results/methods give Ispta 0.065 W/cm2; the Discussion gives 66 mW/cm2 for Ispta. Recorded the Methods value.exposures[0].timing.sonication_duration_s— Paper states the sonication lasted 20 minutes in total with a 10 s inter-stimulus interval, but not the duration of each train; left not_reported.exposures[0].timing.pulse_duration_ms— Pulse duration not stated; not computed from PRF and duty cycle.exposures[0].target.terms— Transducer positioned over M2 (AP +2, ML 0); mapped to motor_cortex since M2 has no dedicated target id.readout_timing— Timing of stimulation relative to EEG/behaviour recording is only shown in Fig. 2 (not in text); not stated whether measured online or offline.n_sessions_per_subject— Single session per mouse inferred; not explicitly stated.blinding— Investigators scoring behaviour and counting c-Fos cells were blinded; blinding of the stimulating experimenter not stated.sham_type— Sham: transducer on but held 10 mm above skull without gel.