Locomotion-dependent modulation of vestibular entries

• Applicant: Privatdozent Dr. Max Wühr
• Subject Area: Human Cognitive and Systems Neuroscience ; Experimental Models for the Understanding of Nervous System Diseases ; Experimental and Theoretical Network Neuroscience ; Clinical Neurology; Neurosurgery and Neuroradiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 569078105

An intriguing clinical phenomenon in patients with peripheral vestibular deficits is that their balance and oculomotor impairments tend to diminish during locomotion – especially at higher walking speeds. This effect 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 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, these remain largely unexplored in mammals. This French-German collaborative project aims to bridge the gap between clinical 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 whole-body and gaze coordination analysis with targeted vestibular neuromodulation. This will provide a platform to experimentally test regulatory principles proposed in lower vertebrates, using methods such as optogenetic manipulation and local field potential recordings. In a forward-translational direction (German partner), we will examine a mechanism suggested in animals: 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 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 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 instability in relation to head–trunk coordination patterns, aiming to identify compensatory strategies that suppress symptoms during gait and could inform novel therapeutic approaches. To enhance ecological validity, key experiments will be performed during unconstrained locomotion in real-world settings. 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 therapeutic applications in humans. Both partners bring complementary expertise in vestibular physiology and locomotor control and will jointly address the research questions in a highly integrated and innovative manner.

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partner: Guillaume Dugué, Ph.D.