There is great interest in using quantitative methods to localize epileptic networks from intracranial EEG, a vital part of care for patients with drug resistant epilepsy (DRE). In particular, there is evidence that using interictal data for this purpose, which could eliminate the need to record seizures, has great potential to reduce morbidity from precipitated seizures and to decrease length of stay. How much of this data is required for this purpose, and from what state(s) of consciousness, is not known. In this study we analyzed interictal intracranial EEG (iEEG) data from 30 subjects and compared it against normative reference iEEG derived from 106 additional patients. We summarized brain activity and connectivity by computing spectral power and coherence in 6 frequency bands and computed z-scores relative to normal features within the same anatomical region. We used a validated algorithm to estimate the sleep or wake state. We applied a cross-validated random forest model to assign predicted abnormality value to each channel for each state of wakefulness. To determine the effectiveness of this approach for each unseen patient, we computed the area under the precision recall curve (AUPRC) between predicted abnormality within and outside of the resection zone. We further identified associations between predicted abnormalities and neuropsychological testing performance, highlighting applications of quantitative biomarkers to epilepsy comorbidities. We found that subjects with good seizure outcome (Engel 1) at 2 years had higher AUPRC than subjects with poor seizure outcome for predicted abnormalities in N2 sleep (Mann-Whitney test; pHolm=Bonferroni < 0.05). Combining features from wakefulness and NREM sleep best separated good and poor seizure outcome subgroups (Mann-Whitney test; pHolm=Bonferroni < 0.05, Cohen’s d = 1.62). Combinations of wake and sleep abnormalities and interictal spikes explained the variance in pre-surgical neuropsychological testing (R2 = 0.57-0.58).

E.C.C. performs consulting work for Epiminder, an EEG device company. The remaining authors have no conflicts of interest.

B.L. received funding from NINDS grants R01-NS-125137 and DP1-NS-122038, Jonathan and Bonnie Rothberg, the Mirowski Family Foundation and Neil and Barbara Smit. W.K.S.O received funding from NSF-GRFP DGE-1845298. N.S. was supported by the National Institute Of Neurological Disorders And Stroke of the National Institutes of Health under award number K99NS138680. K.A.D. received funding from NINDS R01-NS-116504. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. E.C.C. received support from the National Institute of Neurological Disorders and Stroke (NINDS; NINDS K23 NS121401-01A1) and the Burroughs Wellcome Fund.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The Institutional Review Board of the University of Pennsylvania gave ethical approval for this work.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes