Cortico-muscular and cortico-cortical coherence changes resulting from Perampanel treatment in patients with cortical myoclonus

Objective To investigate the mechanisms by which Perampanel (PER) reduces the severity of action myoclonus, we studied on MEG signals the changes occurring in cortico-muscular coherence (CMC) and cortico-cortical connectivity in patients with progressive myoclonus epilepsies. Methods The subjects performed an isometric extension of the hand; CMC and cortico-cortical connectivity were assessed using autoregressive models and generalized partial-directed coherence. The contralateral (Co) sensors showing average CMC values >0.7 of the maximum (set to 1) were grouped as central (C) regions of interest (ROI), while adjacent sensors showing CMC values >0.3 were grouped as Surrounding (Sr) ROIs. Results Under PER treatment, CMC decreased on Co C and Sr ROIs, but also on homologous ipsilateral (Ip) ROIs; out-degrees and betweenness centrality increased in Co ROIs and decreased in Ip ROIs. The flow from Ip to Co ROIs and from activated muscles to Ip C ROI decreased. Conclusion The improvement of myoclonus corresponded to decreased CMC and recovered leadership of the cortical regions directly involved in the motor task, with a reduced interference of ipsilateral areas. Significance Our study highlights on mechanisms suitable to treating myoclonus and suggests the role of a reduced local synchronization together a better control of distant synaptic effects.