An index to probe cortical excitability.

Cortical excitability can be defined as the cortex's responsiveness to incoming stimuli. It can be probed with brain stimulation, either globally and non-invasively, using transcranial magnetic stimulation (TMS) or locally through direct electrical stimulation of the cortex. Here, we establish a method to quantify cortical excitability over its dynamical range, applying stimulation of increasing intensities and recording growing cortical responses via intracranial (i)EEG from patients with pharmacoresistant epilepsy (so-called stimulation-response curves). Approach: We propose a practical framework for (i) identifying effective cortical connections of different strength using Spearman's rank correlation on the stimulation-response curve, (ii) characterizing their linear or non-linear dynamics using two- to five-parameter fits of the measured stimulation-response curve and (iii) extracting the excitability index (ExI), a unitless quantity between 0 and 1 - the area under the normalized stimulation-response curve - that estimates the excitability of a given cortico-cortical connection. The robustness of this framework was characterized in a series of sensitivity and power analysis, in which a dataset of 9024 single-trial stimulations among 12 participants was subsampled. Results: Across brain regions, we found a total of 974 (34.5%) effective connections (p<0.005 FDR-corrected, Spearman correlation). A majority showed a non-linear stimulation-response relationship (R^2=0.89+/-0.12), and a five-parameter sigmoid fit was necessary in >30% of cases, justifying the added complexity (Akaike information criterion). To illustrate the clinical relevance of the proposed approach, we analyze the change in excitability in 4 patients pre- and post-medication (0.5-1 mg clonazepam, intravenously). Significance: We present a framework to probe, measure, fit, and quantify the excitability of cortico-cortical connections in practice. Our proposed excitability index provides a simple way to measure and compare cortical excitability across recorded brain areas, participants and conditions.