Focused Ultrasound Neuromodulation of the Central Lateral Thalamus in a Non-Human Primate Model of Disorders of Consciousness
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…
Objective of the study was to evaluate the impact of focused ultrasound neuromodulation (FUS) on central lateral thalamus (CLT) in a non-human primate model of disorders of consciousness (DOC). Previous research had been hampered by broad effective stimulation areas, missing control situations, and insufficient target confirmation. This investigation aimed to address those limitations by implementing more precise targeting and stricter control conditions.
Two male rhesus macaques underwent one-hour anesthesia sessions to simulate DOC. Both animals received bilateral CLT targets using a stereotactic mounting 256-element phased-array focused ultrasound system. The study tested focused and unfocused stimulation paradigms, as well as a spotlighting approach involving multiple targets in one of the animals. Arousal levels were assessed through EEG beta power, pulse oximetry, breathing rate, and movement, and compared between sonication and control sessions for each paradigm.
Statistical analysis using paired Wilcoxon signed-rank tests revealed no significant differences for any of the four measures across the three intervention strategies (pFDR [≥] 0.30). The most notable effect was an increase in body movement during the unfocused paradigm (rrb = +0.58), although this effect did not reach statistical significance.
Throughout the sessions and recovery periods, the animals maintained physiological stability, with no clinically significant alterations in heart rate, breathing rate, blood oxygen saturation, or other safety issues.
The findings indicate that FUS of the CLT did not elicit measurable changes in arousal under the tested parameters. The lack of adverse physiological effects confirms the safety of this FUS approach. Additionally, the study suggests that spatially distributed sonication, which results in broader stimulation volumes, may be more effective in producing arousal responses.
These results warrant further investigation into distributed network stimulation as an alternative to focal targeting. Future studies should continue to incorporate robust control conditions to accurately quantify the effects of FUS on the CLT.
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