Interdisciplinary Project I01

DISSECTING HYPOTHALAMIC CONTRIBUTIONS TO MOTOR URGE IN RESTLESS LEGS SYNDROME: A MULTIMODAL IMAGING STUDY

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Hypothalamic A11 network in restless legs syndrome

The figure schematically illustrates the proposed projections of the hypothalamic dopaminergic A11 region and their potential significance for Restless Legs Syndrome. Reduced dopaminergic inhibition by the A11 region could lead to the amplified or aberrant transmission of unpleasant sensory signals in this area.

The interdisciplinary project I01 investigates restless legs syndrome (RLS) as a model disorder of disturbed motor control, with a particular focus on internally driven motor urges and their regulation. Increasing evidence suggests that RLS arises from the interaction of multiple pathophysiological processes, including dopaminergic dysfunction, iron deficiency, altered arousal regulation, circadian dysregulation, and impaired inhibitory control. A central structure linking these mechanisms is the hypothalamus, which plays a key role in circadian rhythm regulation, motivation, arousal, and dopaminergic signalling. Importantly, animal studies have highlighted the relevance of hypothalamic A11 dopaminergic regions, whose disruption induces RLS-like motor phenotypes in mice, pointing to a crucial role of hypothalamic-spinal pathways in locomotor suppression. Despite its theoretical relevance, hypothalamic network function has not yet been systematically examined in human neuroimaging studies of RLS.

Beyond advancing the mechanistic understanding of RLS, the study establishes a translational model of internally driven motor dysregulation that closely aligns with the overarching goals of CRC 1451.

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