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Background: Disorders of gait are a very common feature of Parkinsons Disease. We examined how deep brain stimulation of the subthalamic nucleus (STN DBS) and dopaminergic medication affect gait and more specifically its rhythmicity. Objectives: We accurately quantified multiple gait parameters in Parkinsons patients during on and off stages of their treatment (levodopa or STN DBS) to compare and contrast the treatment-induced changes in gait. Methods: We studied 11 patients with STN DBS, 15 patients on levodopa and 42 healthy controls. They all completed the MDS-UPDRS part III along with a gait assessment protocol while wearing six nine-axis inertial measurement units (lumbar, sternal, and all four extremities). Results: Both medication and stimulation significantly improved stride length, while medication further significantly increased gait speed. In the lower limbs, both medication and stimulation had a normalising effect on lower limb angles, significantly increasing the foot strike angle and toe-off angle. Conclusions: STN DBS reduced the step to step variability in a range of lower limb gait parameters in PD, while antiparkinsonian medication had no significant effect. This suggests that STN stimulation, but not dopaminergic medication, has access to circuits that control gait rhythm, and that the resulting effect of stimulation on gait is beneficial. However, the results we observed for movement of the trunk and upper limbs were strikingly different to those seen in the lower limbs. We propose a hypothesis to explain why we observe these results, focusing on cholinergic pedunculopontine projections.

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Myelination has been increasingly implicated in the function and dysfunction of the adult human brain. Although it is known that axon myelination shapes axon physiology in animal models, it is unclear whether a similar principle applies in the living human brain, and at the level of whole axon bundles in white matter tracts. Here, we hypothesised that in humans, cortico-cortical interactions between two brain areas may be shaped by the amount of myelin in the white matter tract connecting them. As a test bed for this hypothesis, we use a well-defined interhemispheric premotor-to-motor circuit. We combined TMS-derived physiological measures of cortico-cortical interactions during action reprogramming with multimodal myelin markers (MT, R1, R2* and FA), in a large cohort of healthy subjects. We found that physiological metrics of premotor-to-motor interaction are broadly associated with multiple myelin markers, suggesting interindividual differences in tract myelination may play a role in motor network physiology. Moreover, we also demonstrate that myelination metrics link indirectly to action switching by influencing local primary motor cortex dynamics. These findings suggest that myelination levels in white matter tracts may influence millisecond-level cortico-cortical interactions during tasks. They also unveil a link between the physiology of the motor network and the myelination of tracts connecting its components, and provide a putative mechanism mediating the relationship between brain myelination and human behaviour.