Phase clustering in epilepsy and migraine Phase clustering in transcranial magnetic stimulation-evoked EEG responses in juvenile myoclonic epilepsy and migraine. Running head: Phase clustering in epilepsy and migraine

Background: Epilepsy and migraine are paroxysmal neurological conditions associated with disturbances of cortical excitability. No useful biomarkers to monitor disease activity in these conditions are available. Phase clustering was previously described in electroencephalographic (EEG) responses to photic stimulation and may be a potential epilepsy biomarker. Objective: To investigate EEG phase clustering in response to transcranial magnetic stimulation (TMS), compare it to photic stimulation in controls and explore its potential as a biomarker of juvenile myoclonic epilepsy or migraine with aura. Methods: People with juvenile myoclonic epilepsy, migraine with aura and healthy controls underwent single-pulse TMS with concomitant EEG recording during the interictal period. We compared phase clustering after TMS with photic stimulation across the groups using permutation-based testing. Results: We included eight people with juvenile myoclonic epilepsy (five off medication, three on), 10 with migraine with aura and 37 controls. TMS and photic phase clustering spectra showed significant differences between epilepsy without medication and controls. Two phase clustering-based indices successfully captured these differences between groups. One participant was tested multiple times. In this case, the phase clustering-based indices were inversely correlated with the dose of anti-epileptic medication. Phase clustering did not differ between people with migraine and controls. Conclusion: We present methods to quantify phase clustering using TMS-EEG and show its potential value as of brain network activity in epilepsy. Our results suggest that the higher propensity to phase clustering is not shared between epilepsy and migraine. Phase clustering in epilepsy and migraine