Disuse-driven plasticity in the human thalamus and putamen.

Motor adaptation in cortico-striato-thalamo-cortical loops has been studied mainly in animals using invasive electrophysiology. Here, we leverage functional neuroimaging in humans to study motor circuit plasticity in the human subcortex. We employed an experimental paradigm that combined two weeks of upper-extremity immobilization with daily resting-state and motor task fMRI before, during, and after the casting period. We previously showed that limb disuse leads to decreased functional connectivity (FC) of the contralateral somatomotor cortex (SM1) with the ipsilateral somatomotor cortex, increased FC with the cingulo-opercular network (CON) as well as the emergence of high amplitude, fMRI signal pulses localized in the contralateral SM1, supplementary motor area and the cerebellum. From our prior observations, it remains unclear whether the disuse plasticity affects the thalamus and striatum. We extended our analysis to include these subcortical regions and found that both exhibit strengthened cortical FC and spontaneous fMRI signal pulses induced by limb disuse. The dorsal posterior putamen and the central thalamus, mainly CM, VLP and VIM nuclei, showed disuse pulses and FC changes that lined up with fmri task activations from the Human connectome project motor system localizer, acquired before casting for each participant. Our findings provide a novel understanding of the role of the cortico-striato-thalamo-cortical loops in human motor plasticity and a potential link with the physiology of sleep regulation. Additionally, similarities with FC observation from Parkinson Disease (PD) questions a pathophysiological link with limb disuse.
Competing Interests: Competing Interests A.N.V. and N.U.F.D. have a financial interest in Turing Medical Inc. and may benefit financially if the company is successful in marketing FIRMM motion monitoring software products. A.N.V. and N.U.F.D. may receive royalty income based on FIRMM technology developed at Washington University School of Medicine and Oregon Health and Sciences University and licensed to Turing Medical Inc. N.U.F.D. are co-founders of Turing Medical Inc. These potential conflicts of interest have been reviewed and are managed by Washington University School of Medicine, Oregon Health and Sciences University and the University of Minnesota. A.N.V. is now an employee of Turing Medical Inc. The other authors declare no competing interests.