TMS-EEG reveals impaired intracortical interactions and coherence in Unverricht-Lundborg type progressive myoclonus epilepsy (EPM1).

Unverricht-Lundborg disease (EPM1) is an inherited neurodegenerative disorder, and the most common form of progressive myoclonus epilepsies. Its main symptoms, epileptic seizures and drug-resistant myoclonus, may be associated with neurophysiological evidence of abnormal cortical excitability or reduced inhibition. The aim of the present study was to utilize transcranial magnetic stimulation (TMS) to induce cortical responses measured with electroencephalography (EEG) in order to observe prevailing cortical excitability/inhibition changes, as well as power and coherence of the cortical oscillations in EPM1. We studied 7 genetically verified EPM1 patients (4 female; age 36±6 years) and 6 healthy control subjects (1 female; age 34±12 years). Navigated TMS was focused on the left primary motor cortex at the representation area of the right thumb. TMS-EEG responses were measured at 90% of the resting motor threshold intensity in 110-150 trials. We observed that P30 waveform following the TMS was significantly (p<0.05) increased in EPM1 patients suggesting increased cortico-cortical excitability, while the later N100/P180 waveform was significantly (p<0.05) decreased indicating reduced inhibition. In the event-related spectral perturbation (ERSP), we found that alpha, beta and gamma band oscillations following the TMS were significantly lower in power in the EPM1 patients compared to controls. In the alpha and beta bands, the inter-trial coherence (ITC) representing the degree of synchronization was also decreased in EPM1. Our results suggest abnormal reactivity in EPM1, and may indicate impaired cortico-cortical inhibition and attenuation of subsequent cortical circuits or the thalamic or subcortical nuclei.