Locomotion-dependent modulation of vestibular entries
An intriguing clinical phenomenon in patients with unilateral or bilateral peripheral vestibular deficits is that their balance and oculomotor impairments tend to diminish during locomotion, especially at higher walking speeds. This phenomenon can also be reproduced in healthy individuals under targeted vestibular perturbation, where locomotion leads to a general reduction, and even phase- and task-specific cancellation, of perturbation effects. These clinical and experimental findings suggest that during walking, vestibular inputs are selectively suppressed, and both balance and gaze stabilization shift from a vestibular-dependent to a locomotor-specific control mode tied to the ongoing motor program. Despite its clinical relevance, the neurophysiological basis of this locomotion-induced vestibular gating and strategy switch remains poorly understood. While studies in lower vertebrates have proposed plausible mechanisms, including processes in the brainstem, cerebellum, or at the spinal level, these have yet to be systematically explored in mammals. This French-German collaborative project aims to bridge the gap between clinical-experimental findings in humans and mechanistic insights from animal models through a bidirectional translational approach. In a back-translational direction (French partner), we will reproduce the human locomotor-vestibular phenotype in rats, a mammalian model with high translational relevance, by combining high-resolution behavioral monitoring of whole-body and gaze coordination (using IMUs and computer vision-based body tracking in combination with mobile eye tracking) with targeted vestibular neuromodulation (electrical and pharmacological). This will provide a platform for precise experimental validation using advanced neurophysiological techniques, such as optogenetic manipulation and local field potential recordings, to test regulatory principles hypothesized in lower vertebrates. In a forward-translational direction (German partner), we will test a promising mechanism suggested by animal studies: that during locomotion, gaze stabilization may be controlled in a feedforward manner via efference copies of locomotor commands generated in the spinal cord. This mechanism is expected to be most effective during locomotion, when the trunk and head are tightly coupled, i.e., when the trunk “knows” what the head is doing. Building on this hypothesis, we will assess whether the effect of targeted vestibular stimulation on eye movements during walking in healthy individuals depends on head–trunk coordination. In patients, we will map visual symptoms related to gaze stability in relation to head–trunk coordination patterns, with the goal of identifying compensatory strategies that suppress symptoms during gait and could serve as novel therapeutic targets. To enhance ecological validity, key experiments will be conducted during unconstrained locomotion in real-world environments. In summary, this project investigates how locomotor programs interact with vestibular sensorimotor regulation, from clinical observations in patients back to animal models, and from mechanistic insights in animals toward potential therapeutic applications in humans. Both project partners bring extensive expertise in vestibular physiology and locomotor research, along with complementary technical and analytical capabilities, which will be collaboratively shared to address the proposed research questions in a highly integrated and innovative manner.
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Imported from OpenAIRE Germany | Grant ANR-25-CE37-3712.
Open sourceOverview
Grant agreement ANR-25-CE37-3712 | LocoMoVE
Open sourceAn intriguing clinical phenomenon in patients with unilateral or bilateral peripheral vestibular deficits is that their balance and oculomotor impairments tend to diminish during locomotion, especially at higher walking speeds. This phenomenon can also be reproduced in healthy individuals under targeted vestibular perturbation, where locomotion leads to a general reduction, and even phase- and task-specific cancellation, of perturbation effects. These clinical and experimental findings suggest that during walking, vestibular inputs are selectively suppressed, and both balance and gaze stabilization shift from a vestibular-dependent to a locomotor-specific control mode tied to the ongoing motor program. Despite its clinical relevance, the neurophysiological basis of this locomotion-induced vestibular gating and strategy switch remains poorly understood. While studies in lower vertebrates have proposed plausible mechanisms, including processes in the brainstem, cerebellum, or at the spinal level, these have yet to be systematically explored in mammals. This French-German collaborative project aims to bridge the gap between clinical-experimental findings in humans and mechanistic insights from animal models through a bidirectional translational approach. In a back-translational direction (French partner), we will reproduce the human locomotor-vestibular phenotype in rats, a mammalian model with high translational relevance, by combining high-resolution behavioral monitoring of whole-body and gaze coordination (using IMUs and computer vision-based body tracking in combination with mobile eye tracking) with targeted vestibular neuromodulation (electrical and pharmacological). This will provide a platform for precise experimental validation using advanced neurophysiological techniques, such as optogenetic manipulation and local field potential recordings, to test regulatory principles hypothesized in lower vertebrates. In a forward-translational direction (German partner), we will test a promising mechanism suggested by animal studies: that during locomotion, gaze stabilization may be controlled in a feedforward manner via efference copies of locomotor commands generated in the spinal cord. This mechanism is expected to be most effective during locomotion, when the trunk and head are tightly coupled, i.e., when the trunk “knows” what the head is doing. Building on this hypothesis, we will assess whether the effect of targeted vestibular stimulation on eye movements during walking in healthy individuals depends on head–trunk coordination. In patients, we will map visual symptoms related to gaze stability in relation to head–trunk coordination patterns, with the goal of identifying compensatory strategies that suppress symptoms during gait and could serve as novel therapeutic targets. To enhance ecological validity, key experiments will be conducted during unconstrained locomotion in real-world environments. In summary, this project investigates how locomotor programs interact with vestibular sensorimotor regulation, from clinical observations in patients back to animal models, and from mechanistic insights in animals toward potential therapeutic applications in humans. Both project partners bring extensive expertise in vestibular physiology and locomotor research, along with complementary technical and analytical capabilities, which will be collaboratively shared to address the proposed research questions in a highly integrated and innovative manner.