Cerebellar Activity Affects Distal Cortical Physiology and Synaptic Plasticity in a Human Parietal-Motor Pathway...

Voluntary movement control depends on plasticity in several interconnected brain regions, including the cerebellum (CB), primary motor cortex (M1), and posterior parietal cortex (PPC). It is thought that one role of the CB is to regulate communication between PPC and M1, but causal evidence for this regulatory role in humans remains lacking. Here, we evaluated how transiently altering activity in CB via intermittent theta burst stimulation (iTBS) affects PPC-M1 connectivity and plasticity by assessing the effectiveness of subsequent Hebbian-like cortical paired associative stimulation (cPAS) to PPC and M1. Using a within-subject design, we administered four different single-session stimulation conditions to the CB and parietal-motor pathway of the motor network and measured the aftereffects on plasticity (both sexes). We administered iTBS to the right CB or right visual cortex, followed by cPAS of a parietal-motor circuit in the left hemisphere. In a subset of participants, we performed two additional control conditions to assess the effect of CB iTBS alone and Hebbian-like cPAS of the PPC-M1 circuit alone. We evaluated motor-evoked potentials (MEPs) using single-pulse transcranial magnetic stimulation as a measure of motor cortical excitability before and after each plasticity induction protocol. Cerebellar iTBS reduced cPAS-induced plasticity in the parietal-motor circuit, as evidenced by a decrease in MEPs. These responses were selective, as no decreases in excitability were observed during the control experiments. These findings suggest that CB activity can modify distal neural activity in a network-connected parietal-motor circuit through heterosynaptic metaplasticity.