Differential effects of focused ultrasound neuromodulation in Parkinson’s disease mice versus healthy mice
Leqi Yang, Kevin Xu, Dingyue Zhang, Andrew Stark, Yimei Yue, Alexxai Kravitz, Yaoheng Yang, Hong Chen
Journal of Neural Engineering 2026 · 10.1088/1741-2552/ae4383
Abstract
Objective. Focused ultrasound (FUS) neuromodulation holds strong potential for treating neurological disorders, but most preclinical studies have been performed in healthy animal models. How disease states influence the FUS neuromodulation effects remains poorly understood, limiting clinical translation. Approach. We used Parkinson ' s disease (PD) as a model to compare the calcium and behavioral responses to FUS neuromodulation in healthy and diseased mice. The PD mouse model was the unilateral dopamine depletion model, induced by injecting 6-hydroxydopamine into the left middle forebrain bundle. FUS was targeted at the left external globus pallidus (GPe) in freely moving mice using a wearable device. Calcium activity in the GPe was monitored via fiber photometry, and motor behavior was assessed using video tracking. Main results. In unilateral PD mice, FUS significantly inhibited GPe calcium activity, and this inhibition lasted for ∼3 min after stimulation. This inhibition was accompanied by motor improvements as shown by a reduction in ipsilateral circling that lasted for at least 50 min after stimulation. In healthy mice, FUS did not significantly change the calcium activity in the GPe and rotational behavior during or after the FUS. Histological analysis revealed no evidence of neuronal damage, astrocytic activation, or microglial proliferation following the FUS. Significance. These findings demonstrate that FUS neuromodulation produces disease-state-dependent effects on calcium activity and behavior, emphasizing the importance of evaluating neuromodulation strategies in relevant disease models for clinical translation.
Abstract via europepmc.
Exposures
Exposure 1: FUS to left GPe (unilateral PD and healthy mice)
Target: globus pallidus externus — “left external globus pallidus (GPe)”
Device: custom-built · DeL Piezo Specialties (PZT ceramic resonator) · DL-43 ceramic resonator ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 3,200 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 50 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 10 | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 10 | ✓✓✓ |
| 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) | 1,600 | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
Frequency 3.2 MHz; duty cycle 50%; PRF 10 Hz; stimulus duration 10 s; interstimulus interval 30 s; four stimulations (total time 160 s), delivered with a wearable transducer in freely moving mice.
Flags from extraction
exposures[0].in_situ.pressure_kpa— 1.6 MPa is stated as peak negative pressure after skull attenuation; whether derived by measurement through ex vivo skulls or by derating is not stated, so method is not_reported.n_subjects— 69 is the total across six experiments including TH staining and baseline studies not all of which involved FUS; per-experiment sizes differ.exposures[0].timing.pulse_duration_ms— Pulse duration not stated; 'burst duration' of 10 s is the train length.anaesthesia— Mice briefly anaesthetised for transducer mounting and recovered 1 h before stimulation; temperature measurement was under isoflurane.