Cortical and subcortical mechanisms underlying movement generation and inhibition: a view through the mirror neuron system. (360G-Wellcome-102849_Z_13_Z)

The observation of the actions of others is central to our social lives. Action observation rarely triggers movements in ourselves, despite the presence of significant activity within the cortical motor network, including its corticospinal outputs. I propose that studying the mirror neuron system, which is active both during action-observation and action-execution, could offer novel insights into both the command signals that do characterise motor execution, and the mechanisms for suppression of unwanted movements, a key feature of human behaviour. Suppression may be exaggerated in Parkinson patients leading to the pathological slowing of movement. I will record single mirror neuron and local field potential (LFPs) activity in the cortical and subcortical motor network, during execution of skilled hand movements, during motionless observation of the same movement, and when movement is prepared but subsequently withheld. This will identify the motor system si gnals specifically associated with movement generation. I will search for the cortical and subcortical sources of movement inhibition that occurs during action-observation. In particular, I will investigate the role of cortical neurons projecting to the subthalamic nucleus (STN) through the hyperdirect pathway, since this projection may play a role in movement suppression, and may contribute to Parkinson disease (PD) pathophysiology. I will test the effects of Deep Brain Stimulation of STN on these neurons. My research will advance understanding of cortical activity evoked by action-observation as useful signals for brain-machine interfaces, and the mechanisms underlying the therapeutic effects of DBS for motor symptoms in PD.