Quantifying auditory event-related responses in multichannel human intracranial recordings

Multichannel intracranial recordings are used increasingly to study the functional organization of human cortex. Intracranial recordings of event-related activity, or electrocorticography (ECoG), are based on high density electrode arrays implanted directly over cortex, combining good temporal and spatial resolution. Developing appropriate statistical methods for analyzing event-related responses in these high dimensional ECoG datasets remains a major challenge for clinical and systems neuroscience. We present a novel methodological framework that combines complementary, existing methods adapted for statistical analysis of auditory event-related responses in multichannel ECoG recordings. This analytic framework integrates single-channel (time-domain, time-frequency) and multichannel analyses of event-related ECoG activity to determine statistically significant evoked responses, induced spectral responses, and effective (causal) connectivity. Implementation of this quantitative approach is illustrated using multichannel ECoG data from recent studies of auditory processing in patients with epilepsy. Methods described include a time-frequency matching pursuit algorithm adapted for modeling brief, transient cortical spectral responses to sound, and a recently developed method for estimating effective connectivity using multivariate autoregressive modeling to measure brief event-related changes in multichannel functional interactions. A semi-automated spatial normalization method for comparing intracranial electrode locations across patients is also described. The individual methods presented are published and readily accessible. We discuss the benefits of integrating multiple complementary methods in a unified and comprehensive quantitative approach. Methodological considerations in the analysis of multichannel ECoG data, including corrections for multiple comparisons are discussed, as well as remaining challenges in the development of new statistical approaches.