Lybbert, C. | Search bioRxiv

bioRxiv2026

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 stimulation volumes, missing control conditions, and limited target validation. This study investigated the effects of FUS of the CLT in a non-human 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 pFDR [≥] 0.30). The largest observed effect was increased body movement under the unfocused paradigm (rrb = +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.

neuroscience↗

bioRxiv2022

The effects of physical and temporal certainty on locomotion with discrete underfoot perturbations

BackgroundAmbulation over complex terrain requires active control of foot placement to maintain a normal kinematic relationship between the center of mass and base of support. Recent investigations have suggested that foot placement location may be selected to anticipate shifts to the underfoot center of pressure. However, it is unclear whether temporal affordance and physical certainty contribute to the selection of a perturbation-specific anticipatory strategy. This study investigates anticipatory and reactive locomotor strategies for repeated underfoot perturbations with varying levels of temporal certainty, temporal affordance, and physical certainty. MethodsThirteen healthy adults walked with random underfoot perturbations from a mechanized shoe. Temporal certainty was challenged by presenting the perturbations with or without warning. Temporal affordance was challenged by adjusting the timing of a warning tone before the perturbation. Physical certainty was challenged with conditions that included only eversion perturbations, only inversion perturbations, or both eversion and inversion perturbations. Linear-mixed effects models assessed the effect of each condition on the percent change of margin of stability and step width, respectively. ResultsFor temporally uncertain perturbations and perturbations with one stride or less of affordance, we observed few changes to step width or margin of stability. As affordance increased to two strides, participants adopted a wider step width in anticipation of the perturbation (p = 0.001). Physical certainty had little effect on gait for the step of the perturbation, but participants recovered normal gait sooner when the physical nature of the perturbation was predictable (p < 0.001). DiscussionDespite having information about the timing and magnitude of upcoming perturbations, individuals do not develop perturbation specific feedforward strategies but instead rely on feedback control to recover normal gait after a perturbation. However, physical certainty appears to improve the efficiency of the feedback controller and allows individuals to recover normal gait sooner.

neuroscience↗