Disuse-driven plasticity in the human thalamus and putamen

Cortico-striato-thalamo-cortical loops have been heavily studied because of their importance in movement disorders such as Parkinson’s Disease and tremor. Capturing plasticity effect in this circuit has been mainly successful using animals or using invasive electrophysiology in patients. Given the importance of the striatum and thalamus for motor control and skill learning, the current study leverages on an arm immobilization paradigm in humans with neuroimaging to induce disuse and explore human subcortical motor circuits plasticity. We employed an experimental paradigm involving upper-extremity immobilization for two weeks with daily resting-state functional connectivity (FC) and motor task-related fMRI. This approach of dense sampling of individuals, i.e Precision Functional Mapping (PFM), offers individual-specific insights and provides enough data to address the issue of low signal to noise ratio in the subcortex. Previously, we identified increased FC between somatomotor cortex and the cingulo-opercular network and emergence of disuse pulses in the cortex during casting. We expand our prior investigation to include analysis adapted to the signal characteristic of subcortical regions to capture disuse-driven plasticity in human subcortical circuits. Subcortical nodes, particularly the central thalamus and posterior putamen, exhibited strengthened FC during disuse and spontaneous activity pulses. Motor task fMRI validated that subcortical disuse-driven plasticity effects spatially correspond to the upper extremity movement execution circuitry, emphasizing the role of these structures in motor control and adaptation. In conclusion, our study highlights the involvement of the cortico-striato-thalamo-cortical loops in human motor plasticity and discuss similarities in findings with two research fields: Parkinson Disease (PD), suggesting a novel interpretation of PD neuroimaging finding; and sleep, particularly plasticity and sleep pressure regulated by the thalamus.