New Approach for Exploring Cerebral Functional Connectivity: Review of Cortico-cortical Evoked Potential

There has been a paradigm shift in the understanding of brain function. The intrinsic architecture of neuronal connections forms a key component of the cortical organization in our brain. Many imaging studies, such as noninvasive magnetic resonance imaging (MRI) studies, have now enabled visualization of the white matter fiber tracts interconnecting the functional cortical areas in the living brain. Although such a structural connectome is essential for understanding of cortical function, the anatomical information alone is not sufficient. Practically, few techniques allow the investigation of the excitatory and inhibitory mechanisms of the cortex in vivo in humans. Several attempts have been made to track neuronal connectivity by applying direct electrical stimuli to the brain in order to stimulate subdural and/or depth electrodes and record responses from the functionally connected cortex. In vivo single-pulse electrical stimulation (SPES) and/or cortico-cortical evoked potential (CCEP) were recently introduced to track various brain networks. This article reviews the concepts, significance, methods, mechanisms, limitations, and clinical applications of CCEP in the analysis of these dynamic connections.