Cortico-cortical evoked potentials (CCEPs) elicited by single-pulse electric stimulation
(SPES) are widely used to assess effective connectivity between cortical areas and
are also implemented in the presurgical evaluation of epileptic patients. Nevertheless,
the cortical generators underlying the various components of CCEPs in humans have
not yet been elucidated. Our aim was to describe the laminar pattern arising under
SPES evoked CCEP components (P1, N1, P2, N2, P3) and to evaluate the similarities
between N2 and the downstate of sleep slow waves. We used intra-cortical laminar microelectrodes
(LMEs) to record CCEPs evoked by 10 mA bipolar 0.5 Hz electric pulses in seven patients
with medically intractable epilepsy implanted with subdural grids. Based on the laminar
profile of CCEPs, the latency of components is not layer-dependent, however their
rate of appearance varies across cortical depth and stimulation distance, while the
seizure onset zone does not seem to affect the emergence of components. Early neural
excitation primarily engages middle and deep layers, propagating to the superficial
layers, followed by mainly superficial inhibition, concluding in a sleep slow wave-like
inhibition and excitation sequence.