Contrast Gain Control Abnormalities in Idiopathic Generalized Epilepsy

Objective: The origin of neural hyperexcitability underlying idiopathic generalized epilepsy (IGE) is not known. The objective of this study is to identify evidence of hyperexcitability in precisely measured visual evoked responses and to understand the nature of changes in excitation and inhibition that lead to altered responses in human patients with IGE. Methods: Steady-state visual-evoked potentials (VEPs) to contrast reversing gratings were recorded over a wide range of stimulus contrast. VEPs were analyzed at the pattern reversal rate using spectral analysis. Ten patients with IGE and 13 healthy subjects participated. All subjects had normal visual acuity and had no history of photic-induced seizures or photoparoxysmal electroencephalograph (EEG) activity. Results: At a group level, the amplitude of visual responses did not saturate at high stimulus contrast in patients, as it did in the control subjects. This reflects an abnormality in neuronal gain control. The VEPs did not have sufficient power to reliably distinguish patients from controls at an individual level. Parametric modeling using a standard gain control framework showed that the abnormality lay in reduced inhibition from neighboring neurons rather than increased excitatory response to the stimulus. Interpretation: Visual evoked responses reveal changes in a fundamental mechanism regulating neuronal sensitivity. These changes may give rise to hyperexcitability underlying generalized epilepsy. ANN NEUROL 2011;70:574-582