The importance of assessing interactions between different circuits in primary motor cortex in Parkinson's disease.

Abstract In humans, the primary motor cortex (M1) plays a crucial role in voluntary movement control. M1 receives basal ganglia and cerebellar output, and its activity is regulated by multiple inhibitory and excitatory intracortical (i.e., local) circuits ( Di Lazzaro and Ziemann, 2013 ). In Parkinson’s disease (PD), paired-pulse transcranial magnetic stimulation (TMS) studies have demonstrated the impairment of specific intracortical M1 circuits, and these abnormalities are involved in the pathophysiology of motor dysfunction ( Bologna et al., 2018 , Guerra et al., 2021 , 2019). The most reliable alterations are reduced effectiveness of short-interval intracortical inhibition (SICI), suggesting impaired GABA-A-ergic neurotransmission ( Ammann et al., 2020 , Berardelli et al., 2008 ), and abnormally enhanced short-interval intracortical facilitation (SICF), possibly reflecting increased synchronization and hyperexcitability of glutamatergic interneurons in M1 ( Guerra et al., 2019 , Ni et al., 2013 , Shirota et al., 2019 , Ziemann, 2020 ). Changes in long-interval intracortical inhibition (LICI) have also been reported ( Berardelli et al., 2008 , 1996).