Purpose: We routinely perform conjoint measurement of intracranial electrophysiology and brain neurochemistry in patients with medically intractable epilepsy undergoing intracranial EEG (icEEG) monitoring for possible epilepsy surgery. The conjoint measurement of these two modalities can be revealing of the presumed neurochemical basis of electrophysiological markers of human brain excitation and inhibition. This study focused on interictal electroencephalography (EEG) spikes. Interictal EEG spikes have traditionally been considered to be a marker of brain excitability in epilepsy, though some recent research has questioned this assumption. Here we correlated co-localized measurements of intracranially recorded interictal EEG spikes and basal extracellular glutamate concentrations, a well-established marker of excitation, in patients with intractable epilepsy.

Methods: Glutamate was quantified from brain microdialysate obtained from 30 combined depth icEEG electrode and microdialysis catheters placed in 15 patients. EEG spikes were counted, at the time when glutamate was documented, in two separate manners: (1) for the two icEEG electrode contacts on either side of the microdialysis membrane, and (2) for all contacts within the brain region where the dialysis probe was located.

Results:We observed the interictal icEEG spike rate was not directly proportional to basal glutamate; rather the icEEG spike rate was low when basal glutamate was high, and vice versa. A joint analysis of brain electrophysiology and neurochemistry thus indicates an inverse, rather than a direct, relationship between interictal icEEG spikes and brain extracellular glutamate.

Discussion: Interictal EEG spikes have traditionally been considered to be a marker of brain excitability. The lack of a direct relation between basal glutamate and icEEG spike rate, however, supports the suggestion that EEG spikes may not be reflective of brain excitability, but rather may be reflective of inhibition. To support the findings of this study and underscore the importance of the conjoint measurement of brain electrophysiology and neurochemistry we discuss observations of other studies of interictal EEG spikes, and observations from other studies of conjoint brain electrophysiology and neurochemistry performed by our group.

Conclusions: This study suggests that there is considerable value for in-vivo co-localized measurement of human brain electrophysiology and neurochemistry to improve our understanding of these two modalities, and for understanding the mechanism underlying medically intractable epilepsy.