Local and Distant responses to single pulse electrical stimulation reflect different forms of connectivity

Abstract

Background: Measuring connectivity in the human brain can involve innumerable approaches using both noninvasive (fMRI, EEG) and invasive (intracranial EEG or iEEG) recording modalities, including the use of external probing stimuli, such as direct electrical stimulation. Objective/Hypothesis: To examine how different measures of connectivity correlate with one another, we compared 'passive' measures of connectivity during resting state conditions map to the more 'active' probing measures of connectivity with single pulse electrical stimulation (SPES). Methods: We measured the network engagement and spread of the cortico-cortico evoked potential (CCEP) induced by SPES at 53 total sites across the brain, including cortical and subcortical regions, in patients with intractable epilepsy (N=11) who were undergoing intracranial recordings as a part of their clinical care for identifying seizure onset zones. We compared the CCEP network to functional, effective, and structural measures of connectivity during a resting state in each patient. Functional and effective connectivity measures included correlation or Granger causality measures applied to stereoEEG (sEEGs) recordings. Structural connectivity was derived from diffusion tensor imaging (DTI) acquired before intracranial electrode implant and monitoring (N=8). Results: The CCEP network was most similar to the resting state voltage correlation network in channels near to the stimulation location. In contrast, the distant CCEP network was most similar to the DTI network. Other connectivity measures were not as similar to the CCEP network. 3 Conclusions: These results demonstrate that different connectivity measures, including those derived from active stimulation-based probing, measure different, complementary aspects of regional interrelationships in the brain.

Impact of stimulation location relative to grey and white matter on single pulse electrical stimulation responses in the human brain

“…A growing body of literature, however, has revealed consistent relationships between some stimulation parameters and neural responses across individuals [24,28,29]. This suggests that there are consistent, but only partially identified, maps for how the human brain responds to different stimulation parameters.…”

“…This suggests that there are consistent, but only partially identified, maps for how the human brain responds to different stimulation parameters. This is best reflected in isolated single pulse electrical stimulation (SPES, via macro-electrodes) where local cortico-cortico evoked potentials (CCEPs) usually show consistent waveforms divisible into N1 and N2 voltage peaks [29,47–53]. In addition, SPES have been extensively used to map brain connectivity including the effect of pathologies, such as epilepsy [52,54].…”

“…In addition, SPES have been extensively used to map brain connectivity including the effect of pathologies, such as epilepsy [52,54]. Various parameters affect the CCEP size and shape [29,47–53].…”

“…Stimulation location, not surprisingly, has a substantial impact on both behavioral and physiological responses with differing clinical outcomes [14,28,42,51,57–60]. The most therapeutically effective DES, whether inducing very focal or more widespread neural responses or engagement of the network to induce different states, is thought to generally engage white matter tracts [29,60], which has been supported by a recent study relating stimulation effects to white matter proximity [28]. Indeed, some experiments and modeling studies of electrode location, spacing, and orientation relative to subcortical regions and white matter tracts have suggested it is possible to map, and plan, DBS approaches to subcortical stimulation that predict optimal therapeutic effects [6,39,61,62].…”

“…Responses close to the site of stimulation are quite different from ones further away and their dependence on parameters may differ as well. For example, local stimulation responses appear to reflect functional connectivity while distant stimulation responses may better reflect structural (white matter tract) connectivity [29].…”