Purpose

Corticocortical evoked potentials (CCEPs) resulting from single pulse electrical stimulation are increasingly used to understand seizure networks, as well as normal brain connectivity. However, we observed that when using depth electrodes, traditional measures of CCEPs amplitude using a referential montage can be falsely localizing, often to white matter.

Methods

We pooled 27 linear electrode arrays targeting the amygdala, hippocampus, or cingulate cortex from eight participants. Using postoperative imaging, we classified contacts as being in gray matter, white matter, or bordering each and measured the amplitude using the root-mean-squared deviation from baseline in a referential, common average, bipolar, or Laplacian montage.

Results

Of 27 electrode contacts, 25 (93%) had a significantly higher mean amplitude when in gray matter than in white matter using a Laplacian montage, which was significantly more than the 12 of 27 electrodes (44%) when using a referential montage ( P = 0.0003, Fisher exact test). The area under the curve for a receiver operating characteristic classifying contacts as gray or white matter was significantly higher for either the Laplacian (0.79) or the bipolar (0.72) montage when compared with either the common average (0.56) or the referential (0.51) montage ( P ≤ 0.005, bootstrap).

Conclusions

Both the Laplacian and bipolar montages were superior to the common average or referential montage in localizing CCEPs to gray matter. These montages may be more appropriate for interpreting CCEPs when using depth electrodes than the referential montage, which has typically been used in prior studies of CCEPs with subdural grids.

Mapping of cortical functions is critical for the best clinical care of patients undergoing epilepsy and tumor surgery, but also to better understand human brain function and connectivity. The purpose of this review is to explore existing and potential means of mapping higher cortical functions, including stimulation mapping, passive mapping, and connectivity analyses. We examine the history of mapping, differences between subdural and stereoelectroencephalographic approaches, and some risks and safety aspects, before examining different types of functional mapping. Much of this review explores the prospects for new mapping approaches to better understand other components of language, memory, spatial skills, executive, and socio-emotional functions. We also touch on brain-machine interfaces, philosophical aspects of aligning tasks to brain circuits, and the study of consciousness. We end by discussing multi-modal testing and virtual reality approaches to mapping higher cortical functions.

We report a case study of a surgical candidate, a 51-year-old woman with left temporal lobe epilepsy, who failed a left injection intracarotid amobarbital procedure (e.g., Wada test), scoring 0 of 8 items. This raised concerns for postoperative memory decline. However, the patient was uninterested in a neuromodulatory approach and wished to be reconsidered for surgery. A stereotactic laser amygdalohippocampotomy (SLAH) was considered, encouraging the need for an alternative test to evaluate risk of memory decline. We developed a novel approach to testing memory during stimulation of a depth electrode implanted in the hippocampus, i.e., an electric Wada. During multiple stimulation trials across a range of amplitudes, the patient scored up to 8 of 8 items, which suggested strong contralateral memory support. The surgical team proceeded with a radiofrequency ablation and a subsequent SLAH. The patient remains seizure-free at 12 months post SLAH with no evidence of verbal or visuospatial memory decline based on a post-surgical neuropsychological battery. We believe that this case study provides a proof of concept for the feasibility and possible utility of an electric version of the Wada procedure. Future studies are needed to develop an optimal paradigm and to validate this approach.