Focused Ultrasound Neuromodulation of the Central Lateral Thalamus in a Non-Human Primate Model of Disorders of Consciousness
Carter Lybbert, Caroline Garrett, Taylor Webb, Keisuke Tsunoda, Ruksana Begum, Jan Kubanek
2026 · 10.64898/2026.09.15.751608
Abstract
Objectives Disorders of consciousness (DOC) affect an estimated 200,000 patients in the United States. Effective treatment options have remained elusive. Focused ultrasound neuromodulation (FUS) of brain regions controlling consciousness, such as the central lateral thalamus (CLT), has emerged as a promising non-invasive treatment. However, prior studies have been limited by broad effective stimulation volumes, missing control conditions, and limited target validation. This study investigated the effects of FUS of the CLT in a nonhuman primate model of DOC with robust control conditions and more robust targeting than previous experiments. Materials and Methods Two male rhesus macaques underwent 1-hour propofol anesthesia sessions as a model of DOC. Bilateral CLT targets were sonicated using a stereotactically mounted 256-element phased-array focused ultrasound system. Focused and unfocused (random phases) paradigms were tested in both animals, and a spotlighting (sonicating multiple targets) paradigm was tested in one animal. Arousal was monitored via EEG beta power, pulse oximetry, breathing rate, and movement, and compared between sonication and control sessions for each paradigm. Results Paired Wilcoxon signed-rank tests showed no significant differences for any of the four measures across the three paradigms (all p FDR ≥ 0.30 ). The largest observed effect was increased body movement under the unfocused paradigm ( r rb = +0.58), though this did not reach statistical significance. Animals remained physiologically stable throughout sessions and recovery periods, with no clinically significant changes in heart rate, breathing rate, blood oxygen saturation, or other safety concerns. Conclusions Under the tested parameters, FUS of the CLT did not produce measurable changes in arousal. The absence of adverse physiological effects supports the safety of this FUS paradigm. The largest effect occurring under spatially distributed sonication, consistent with prior evidence that broader stimulation volumes produce stronger arousal responses, suggests that distributed network stimulation may warrant investigation as an alternative to focal targeting. Future studies should investigate this possibility and should include robust control conditions to properly quantify effects.
Abstract via europepmc.
Exposures
Exposure 1: Focused, unfocused (random phase) and spotlighting sonication of bilateral CLT under propofol
Target: thalamus — “central lateral thalamus (CLT)”
Device: not reported · Remus system, 256-element phased array
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 480 | ✓✓✓ |
| Pulse duration (ms) | not reportedimplied by duty cycle ÷ PRF: 10 ms (not stated by the paper) | ⚑ |
| Pulse repetition frequency (Hz) | 50 | ✓✓✓ |
| Duty cycle (%) | 50 | ✓✓✓ |
| Sonication duration (s) | 0.3 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementsingle value | |
| In-situ pressure (kPa) | 1,000 | ✓✓✓ |
| In-situ Isppa (W/cm²) | 32.3 | ✓✓✓ |
| In-situ Ispta (W/cm²) | 0.4, 1.6swept | ✓✓✓ |
Bilateral CLTs sonicated in alternating 3-minute blocks with a 3 s inter-stimulus interval between successive sonications of each CLT, 40 sonications per CLT per block; sonication or no sonication began 15 min into a 1-hour propofol session; one session per week. Paper states 300 ms pulse duration with 50% duty cycle and 50 Hz PRF.
Flags from extraction
exposures[0].timing.pulse_duration_ms— Paper states 300 ms pulse duration, but 50% duty cycle at 50 Hz PRF implies a 10 ms pulse; 300 ms may be the length of each sonication. Recorded as stated; burst rule unresolved.exposures[0].timing.sonication_duration_s— Not stated unambiguously; left not_reported.exposures[0].in_situ.method— In situ pressure said to be estimated from MR thermometry (intensity 21% of free field) by previously described methods; method label is a judgement.exposures[0].unspecified_domain.isppa_w_cm2— ISPPA 32.3 and ISPTA 1.6 W/cm2 (focused paradigm) are stated without a domain; spotlighting paradigm had ISPTA 0.4 W/cm2 at each position.sham_type— Control sessions had no sonication; unfocused paradigm used randomised element phases at the same energy.n_subjects— Spotlighting paradigm only in subject B.exposures[0].device.family— Remus system built by the authors' group but no manufacturer named for the transducer.