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

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

“…However, neurophysiological, behavioral and therapeutic effects of DES remain quite variable and unpredictable [12][13][14][15][16][17]. This variability in efficacy likely results from complex interactions amongst multiple factors, including stimulation location, pulse width and duration, injected current, location relative to grey and white matter, and stimulation frequency [14,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33].…”

“…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][48][49][50][51][52][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][48][49][50][51][52][53].…”

“…Stimulation location, not surprisingly, has a substantial impact on both behavioral and physiological responses with differing clinical outcomes [14,28,42,51,[57][58][59][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].…”