Studying states and state transitions in the brain is challenging due to nonlinear, complex dynamics. In this research, we analyze the brain's response to non-invasive perturbations. Perturbation techniques offer a powerful method for studying complex dynamics, though their translation to human brain data is under-explored. This method involves applying small inputs, in this case via photic stimulation, to a system and measuring its response. Sensitivity to perturbations can forewarn a state transition. Therefore, biomarkers of the brain's perturbation response or “cortical excitability” could be used to indicate seizure transitions. However, perturbing the brain often involves invasive intracranial surgeries or expensive equipment such as transcranial magnetic stimulation (TMS) which is only accessible to a minority of patient groups, or animal model studies. Photic stimulation is a widely used diagnostic technique in epilepsy that can be used as a non-invasive perturbation paradigm to probe brain dynamics during routine electroencephalography (EEG) studies in humans. This involves changing the frequency of strobing light, sometimes triggering a photo-paroxysmal response (PPR), which is an electrographic event that can be studied as a state transition to a seizure state. We investigate alterations in the response to these perturbations in patients with genetic generalized epilepsy (GGE), with (n = 10) and without (n = 10) PPR, and patients with psychogenic non-epileptic seizures (PNES; n = 10), compared to resting controls (n = 10). Metrics of EEG time-series data were evaluated as biomarkers of the perturbation response including variance, autocorrelation, and phase-based synchrony measures. We observed considerable differences in all group biomarker distributions during stimulation compared to controls. In particular, variance and autocorrelation demonstrated greater changes in epochs close to PPR transitions compared to earlier stimulation epochs. Comparison of PPR and spontaneous seizure morphology found them indistinguishable, suggesting PPR is a valid proxy for seizure dynamics. Also, as expected, posterior channels demonstrated the greatest change in synchrony measures, possibly reflecting underlying PPR pathophysiologic mechanisms. We clearly demonstrate observable changes at a group level in cortical excitability in epilepsy patients as a response to perturbation in EEG data. Our work re-frames photic stimulation as a non-invasive perturbation paradigm capable of inducing measurable changes to brain dynamics.
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