In vivo epileptogenicity of focal cortical dysplasia: A direct cortical paired stimulation study

Purpose: Alternation of the intracortical inhibitory and excitatory mechanisms in focal cortical dysplasia (FCD) has not been well elucidated in vivo in humans. We investigated in vivo alternation of these mechanisms in epileptogenesis of FCD by means of paired-pulse direct cortical electrical stimulation. Methods: A 31-year-old man with FCD at the left foot primary somatosensory (SI) and motor areas who underwent invasive monitoring with subdural electrodes was studied. By means of subdural electrodes, paired-pulse electrical stimulation was performed at the epileptic focus (foot SI) and control cortex (hand SI) with interstimulus interval (ISI) of 1-100 ms. Instead of using motor evoked potentials to investigate the degree of cortical excitability in response to motor cortex stimulation, we evaluated the size change of corticocortical evoked potentials (CCEPs), which are elicited at the adjacent cortex by direct cortical stimulation via fiber projection and thus reflect direct and indirect excitation of corticocortical projection neurons at the site of stimulation. Results: During the interictal state, paired-pulse stimulation of the focus revealed abnormally enhanced intracortical inhibition at ISI of 1-10 ms (maximum, 22%) compared with control stimulation of the hand SI (ISI of 1-2 ms; maximum, 18%) (p < 0.01). While the patient was having the somatosensory aura that later evolved into the left-leg clonic seizure, single and paired stimulation at the focus showed increased cortical excitability (enlarged CCEP) and decreased intracortical inhibition, respectively. Conclusions: During the aura, interictally enhanced intracortical inhibition at the focus was replaced by increased cortical excitability and decreased intracortical inhibition, suggesting increased net intrinsic epileptogenicity during seizure generation in this patient with FCD.