Summary

A bioRxiv preprint found no measurable change in arousal when focused ultrasound was applied to the central lateral thalamus of two anaesthetised rhesus macaques. The animals remained physiologically stable, while the authors propose testing more distributed stimulation in future studies.

A preprint posted on bioRxiv reports that focused ultrasound applied to the central lateral thalamus (CLT) produced no measurable change in arousal in two anaesthetised rhesus macaques. The animals remained physiologically stable during the experiments and recovery periods.

The study examined whether focused ultrasound neuromodulation could influence arousal in a non-human primate model of disorders of consciousness. The authors describe the CLT as a brain region involved in controlling consciousness and say that previous experiments have been limited by broad stimulation volumes, weak control conditions or insufficient target validation.

The findings are preliminary: they come from two male macaques in a preprint, and the absence of an arousal response applied to the tested stimulation parameters and experimental model.

How the experiment tested neuromodulation

Each macaque underwent one-hour sessions under propofol anaesthesia, which the researchers used as a model of a disorder-of-consciousness state. A stereotactically mounted focused-ultrasound system with a 256-element phased array was used to sonicate bilateral CLT targets.

The experiment included several stimulation conditions. In the focused condition, the ultrasound energy was directed at the selected targets. In the unfocused condition, the array used random phases rather than concentrating the acoustic energy at one point. A third, spotlighting condition, in which multiple targets were sonicated, was tested in one animal. The focused and unfocused paradigms were tested in both animals.

The researchers compared sonication sessions with control sessions while monitoring four measures associated with arousal and physiological state: EEG beta power, pulse oximetry, breathing rate and body movement. Statistical comparisons used paired Wilcoxon signed-rank tests, with correction for multiple comparisons.

No measurable arousal response under the tested parameters

None of the four measures showed a statistically significant difference across the three paradigms. The reported false-discovery-rate-adjusted results were all pFDR ≥ 0.30.

The largest observed effect was an increase in body movement during the unfocused paradigm, with a rank-biserial correlation of +0.58. That result did not reach statistical significance, so the study did not identify a measurable arousal response from the tested stimulation conditions.

The animals remained physiologically stable throughout the sessions and recovery periods. The researchers report no clinically significant changes in heart rate, breathing rate or blood-oxygen saturation, and no other safety concerns during the experiments.

The authors interpret the results as support for further testing of spatially distributed stimulation rather than only highly focal targeting. Their conclusion draws on the observation that broader stimulation volumes have produced stronger arousal responses in earlier work, although this study itself did not demonstrate such a response. Future experiments will need to test that approach with robust control conditions.

This work provides an early non-human primate assessment of CLT-focused ultrasound, not evidence of a treatment for people with disorders of consciousness. Its main contribution is the combination of targeted stimulation, unfocused and multi-target controls, and simultaneous behavioural, EEG and physiological monitoring in a small animal study.

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