Cerebellar-Motor Cortex Connectivity: One or Two Different Networks?

Anterior-posterior (AP) and posterior-anterior (PA) pulses of transcranial magnetic stimulation over the primary motor cortex (M1) appear to activate distinct interneuron networks that contribute differently to two varieties of physiological plasticity and motor behaviors (Hamada et al., 2014). The AP network is thought to be more sensitive to online manipulation of cerebellar (CB) activity using transcranial direct current stimulation. Here we probed CB-M1 interactions using cerebellar-brain inhibition (CBI) on young healthy female and male individuals. Transcranial magnetic stimulation (TMS) over the cerebellum produced maximal CBI of PA-evoked EMG responses at an inter-stimulus interval of 5ms (PA-CBI), whereas the maximum effect on AP responses was at 7ms (AP-CBI), suggesting that CB-M1 pathways with different conduction times interact with AP and PA networks. In addition, paired associative stimulation using ulnar nerve stimulation and PA TMS pulses over M1, a protocol used in human studies to induce cortical plasticity, reduced PA-CBI but not AP-CBI, indicating that cortical networks process cerebellar inputs in distinct ways. Finally, PA-CBI and AP-CBI were differentially modulated after performing two different types of motor learning tasks that are known to process cerebellar input in different ways. The data presented here are compatible with the idea that applying different TMS currents to the cerebral cortex may reveal cerebellar inputs to both the premotor cortex and M1. Overall, these results suggest there are two independent CB-M1networks that contribute uniquely to different motor behaviors.Significance StatementConnections between the cerebellum and primary motor cortex (M1) are essential for performing daily life activities, as damage to these pathways can result in faulty movements. Therefore, developing and understanding novel approaches to probe this pathway is critical to advancing our understanding of the pathophysiology of diseases involving the cerebellum. Here, we show evidence for two distinct cerebellar-cerebral interactions using cerebellar stimulation in combination with directional transcranial magnetic stimulation (TMS) over M1. These distinct cerebellar-cerebral interactions respond differently to physiological plasticity and to distinct motor learning tasks, which suggests they represent separate cerebellar inputs to the premotor cortex and M1. Overall, we show that directional TMS can probe two distinct cerebellar-cerebral pathways that likely contribute to independent processes of learning.