A Probabilistic Approach to Functional Organization Based on Extraoperative Electrocortical Stimulation Mapping

Direct electrocortical stimulation (DES) is the gold standard for mapping eloquent cortex, yet existing functional atlases are limited by sampling biases and density-based methods that obscure a region's true functional probability. Consequently, interpatient variability and the functional contributions of nontraditional language areas, such as the middle frontal gyrus, remain poorly characterized, particularly in epilepsy populations where functional reorganization is common. We therefore developed a probabilistic functional atlas of extraoperative DES and applied data-driven methods to characterize the functional organization of language, motor, and sensory cortex.

This was a retrospective observational study of patients undergoing intracranial monitoring for drug-resistant epilepsy (2008-2023). Electrical stimulation was delivered to intracranial electrodes during language tasks, and language, motor, and sensory findings were recorded. Positive and negative stimulation sites were analyzed in standard patient space and using the Human Connectome Project parcellation atlas. A multilevel statistical framework, including probability mapping, bootstrapped region-of-interest analyses, and kernel density estimation, defined structure-function relationships. Generalized linear mixed-effects models assessed the influence of clinical variables on language disruption.

We analyzed 2,124 trials from 125 patients (mean age 30 years; 47% female). Instead of eloquent functions clustering into discrete canonical regions, they were distributed throughout the cortex along probabilistic continua. Language disruption demonstrated high interpatient variability with the middle frontal gyrus emerging as a high probability area for naming and speech arrest. Motor responses were not confined to the precentral gyrus but frequently extended into parietal association cortex. Clinically, early seizure onset (p = 0.006) and the presence of a temporal lobe lesion (p = 0.003) independently predicted a lower probability of language disruption in the temporal lobe.

This extraoperative DES atlas provides a comprehensive benchmark for understanding functional cortical organization in epilepsy. We add evidence to the growing literature that language and motor systems are more distributed and variable than classically described. Substantial interpatient variability underscores the necessity of individualized mapping to guide safe neurosurgical planning. Limitations include the retrospective design and sampling bias inherent to electrode placement.