The Photoparoxysmal Response Reflects Abnormal Early Visuomotor Integration in the Human Motor Cortex

- V-PAS100 increases MEPs more in PPR-positive patients than in HS.
- PPR-positive patients with and without IGE have similar responses to V-PAS.
- Facilitatory premotor-to-motor connections are comparable in HS and patients.
- After V-PAS, patients have abnormal inhibitory premotor-to-motor connectivity.
- PPR-positive patients have abnormal early visuomotor integration.

BackgroundVisual-paired associative stimulation (V-PAS) is a transcranial magnetic stimulation (TMS) technique able to investigate long-term potentiation (LTP) and depression (LTD)-like plasticity in the primary motor cortex (M1) arising through early visuomotor integration.Objective/hypothesisAbnormal early visuomotor integration might contribute to the pathophysiology of intermittent photic stimulation (IPS)-induced photoparoxysmal response (PPR).MethodsWe applied V-PAS in 25 healthy subjects (HS), 25 PPR-positive patients, with and without idiopathic generalized epilepsy (IGE), and 8 PPR-negative patients with IGE. V-PAS consisted of primary visual area activation achieved by visual evoked potentials coupled with TMS-induced M1 activation at 100 ms interstimulus interval (ISI) (V-PAS100). Before and after V-PAS, we measured changes in motor evoked potentials (MEPs). We compared MEPs after 1 Hz repetitive TMS (rTMS) and 0.25 Hz-V-PAS100. To examine possible V-PAS-induced after-effects at other ISIs, we delivered V-PAS at 40 (V-PAS40) and 140 ms ISIs (V-PAS140). To clarify whether V-PAS100 increases parieto-/premotor-to-M1 connectivity, before and after V-PAS100, we examined MEPs evoked by paired-pulse techniques.ResultsV-PAS100 increased MEPs more in PPR-positive patients than in HS. PPR-negative patients had normal response to V-PAS100. 1 Hz-rTMS, 0.25 Hz-V-PAS100 and V-PAS40 elicited similar responses in HS and PPR-positive patients, whereas V-PAS140 induced stronger after-effects in PPR-positive patients than HS. After V-PAS, MEPs elicited by facilitatory paired-pulse protocols decreased similarly in HS and PPR-positive patients. Conversely, MEPs elicited by inhibitory protocols decreased in HS, whereas in PPR-positive patients, they turned from inhibition to facilitation.ConclusionWe suggest that abnormal early visuomotor integration contributes to the pathophysiology of PPR.