title: Evoked effective connectivity of the human neocortex.
abstract: The role of cortical connectivity in brain function and pathology is increasingly being recognized. While in vivo magnetic resonance imaging studies have provided important insights into anatomical and functional connectivity, these methodologies are limited in their ability to detect electrophysiological activity and the causal relationships that underlie effective connectivity. Here, we describe results of cortico-cortical evoked potential (CCEP) mapping using single pulse electrical stimulation in 25 patients undergoing seizure monitoring with subdural electrode arrays. Mapping was performed by stimulating adjacent electrode pairs and recording CCEPs from the remainder of the electrode array. CCEPs reliably revealed functional networks and showed an inverse relationship to distance between sites. Coregistration to Brodmann areas (BA) permitted group analysis. Connections were frequently directional with 43% of early responses and 50% of late responses of connections reflecting relative dominance of incoming or outgoing connections. The most consistent connections were seen as outgoing from motor cortex, BA6-BA9, somatosensory (SS) cortex, anterior cingulate cortex, and Broca's area. Network topology revealed motor, SS, and premotor cortices along with BA9 and BA10 and language areas to serve as hubs for cortical connections. BA20 and BA39 demonstrated the most consistent dominance of outdegree connections, while BA5, BA7, auditory cortex, and anterior cingulum demonstrated relatively greater indegree. This multicenter, large-scale, directional study of local and long-range cortical connectivity using direct recordings from awake, humans will aid the interpretation of noninvasive functional connectome studies.
authors.affiliation: Department of Neurosurgery, Hofstra North Shore LIJ School of Medicine and Feinstein Institute of Medical Research, Manhasset, New York, 11030; Institute of Cognitive Neuroscience and Psychology, Research Centre for Natural Sciences, Hungarian Academy of Sciences, Budapest, 1132, Hungary; Department of Functional Neurosurgery and Department of Epilepsy, National Institute of Clinical Neuroscience, Budapest, 1145, Hungary; Péter Pázmány Catholic University, Faculty of Information Technology and Bionics, Budapest, 1083, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Entz
authors.forename: Emília
authors.initials: E
authors.lastname: Tóth
authors.forename: Corey J
authors.initials: CJ
authors.lastname: Keller
authors.forename: Stephan
authors.initials: S
authors.lastname: Bickel
authors.forename: David M
authors.initials: DM
authors.lastname: Groppe
authors.forename: Dániel
authors.initials: D
authors.lastname: Fabó
authors.forename: Lajos R
authors.initials: LR
authors.lastname: Kozák
authors.forename: Loránd
authors.initials: L
authors.lastname: Erőss
authors.forename: István
authors.initials: I
authors.lastname: Ulbert
authors.forename: Ashesh D
authors.initials: AD
authors.lastname: Mehta
mesh_terms: D000293:Adolescent; D000328:Adult; D001931:Brain Mapping; D004567:Electrodes, Implanted; D004827:Epilepsy / Q000503:physiopathology / Q000601:surgery; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D007839:Functional Laterality; D006801:Humans; D021621:Imaging, Three-Dimensional; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000502:physiology* / Q000601:surgery; D009434:Neural Pathways / Q000502:physiology; D055815:Young Adult
keywords: Brodmann's areas; cortical stimulation; effective connectivity; epilepsy; evoked potentials