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.

Mapping human brain networks with cortico-cortical evoked potentials

“…Group analysis suggests that regions in the lateral prefrontal and superior parietal-regions implicated in the default mode network [93,94]-demonstrate strong indegree with net inward flow, whereas the pre-central, post-central and posterior temporal regions demonstrate strong outdegree with net outward flow. Moreover, regions involved in motor or language function-defined clinically by behavioural disruption elicited by high-frequency stimulation at specific electrodes-demonstrated strong outdegree with net outward flow [95,96]. These results provide evidence of consistent directional information flow between regions of the neocortex.…”

Physiology of functional and effective networks in epilepsy

“…In contrast, interventional approaches measure evoked responses to stimulation applied directly to the human brain to achieve the same end (Matsumoto et al, 2004;David et al, 2010;Entz et al, 2014;Keller et al, 2014a,b). Here we will focus on the latter, as it facilitates direct evaluation of connectivity in the human brain in patients with epilepsy, and is thus a powerful tool in studying both connectivity and seizure electrophysiology.…”

“…Indeed, stimulation parameters can vary widely both within and between studies. For example, studies focused upon defining connectivity (Matsumoto et al, 2004;Entz et al, 2014;Keller et al, 2014a) use 1 Hz stimulation frequencies, whereas studies focusing (Valentin et al, 2002;Lacruz et al, 2007) use much longer intervals (8-10 s). Stimulation intensity also varies considerably across the above-mentioned studies, with an application of current that ranges from 4 to 10 mA.…”

Closed-loop interaction with the cerebral cortex using a novel micro-ECoG-based implant: the impact of beta vs. gamma stimulation frequencies on cortico-cortical spectral responses

“…As they are perturbation-based, CCEPs can unequivocally show directed (causal) connectivity between remote areas [11,12], which is challenging to achieve by analysis of undisturbed brain dynamics. As of yet, the CCEP technique has been only rarely applied utilizing μECoG electrodes.…”

“…This well-established method allows one to unravel functional connectivity in the cortex [7][8][9][10][11][12] or subcortical regions [13], and recent studies used ECoG-based SPES in humans to investigate CCEPassociated changes in the spectral domain [14,15]. For reviews on studies investigating cortical connectivity by means of CCEPs see [16,17].…”