title: The Concept of Effective Inflow: Application to Interictal Localization of the Epileptogenic Focus From iEEG.
abstract: Accurate determination of the epileptogenic focus is of paramount diagnostic and therapeutic importance in epilepsy. The current gold standard for focus localization is from ictal (seizure) onset and thus requires the occurrence and recording of multiple typical seizures of a patient. Localization of the focus from seizure-free (interictal) periods remains a challenging problem, especially in the absence of interictal epileptiform activity.
  
  
  
  By exploring the concept of effective inflow, we developed a focus localization algorithm (FLA) based on directed connectivity between brain sites. Subsequently, using the measure of generalized partial directed coherence over a broad frequency band in FLA for the analysis of interictal periods from long-term (days) intracranial electroencephalographic signals, we identified the brain region that is the most frequent receiver of maximal effective inflow from other brain regions.
  
  
  
  In six out of nine patients with temporal lobe epilepsy, the thus identified brain region was a statistically significant outlier (p < 0.01) and coincided with the clinically assessed epileptogenic focus. In the remaining three patients, the clinically assessed focus still exhibited the highest inflow, but it was not deemed an outlier (p > 0.01).
  
  
  
  These findings suggest that the epileptogenic focus is a region of intense influence from other regions interictally, possibly as a mechanism to keep it under control in seizure-free periods.
  
  
  
  The developed framework is expected to assist with the accurate epileptogenic focus localization, reduce hospital stay and healthcare cost, and provide guidance to treatment of epilepsy via resective surgery or neuromodulation.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Vlachos
authors.forename: Balu
authors.initials: B
authors.lastname: Krishnan
authors.forename: David M
authors.initials: DM
authors.lastname: Treiman
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Tsakalis
authors.forename: Dimitris
authors.initials: D
authors.lastname: Kugiumtzis
authors.forename: Leon D
authors.initials: LD
authors.lastname: Iasemidis
mesh_terms: D000465:Algorithms; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D063132:Connectome / Q000379:methods; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D000069280:Electrocorticography / Q000379:methods*; D004827:Epilepsy / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D008297:Male; D009415:Nerve Net / Q000503:physiopathology*; D009434:Neural Pathways / Q000503:physiopathology; D010363:Pattern Recognition, Automated / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity