Intracranial electrical stimulation (iES) of the human brain has long been known to elicit a remarkable variety of perceptual, motor and cognitive effects, but the functional–anatomical basis of this heterogeneity remains poorly understood. We conducted a whole-brain mapping of iES-elicited effects, collecting first-person reports following iES at 1,537 cortical sites in 67 participants implanted with intracranial electrodes. We found that intrinsic network membership and the principal gradient of functional connectivity strongly predicted the type and frequency of iES-elicited effects in a given brain region. While iES in unimodal brain networks at the base of the cortical hierarchy elicited frequent and simple effects, effects became increasingly rare, heterogeneous and complex in heteromodal and transmodal networks higher in the hierarchy. Our study provides a comprehensive exploration of the relationship between the hierarchical organization of intrinsic functional networks and the causal modulation of human behaviour and experience with iES.
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The data that support the findings of this study are available from the corresponding authors upon request.
Custom code that supports the findings of this study is available from the corresponding authors upon request.
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The authors are grateful to the many patients who participated, without whom this research would have been impossible, as well as numerous funding agencies for generous support. K.C.R.F. was supported by a Postdoctoral Fellowship from the Natural Sciences and Engineering Research Council (NSERC) of Canada, and is currently supported by a Medical Scholars Research Fellowship from the Stanford University School of Medicine. L.S. is supported by the China Scholarship Council (201708110057) and National Natural Science Foundation of China (81701268). B.L.F. is supported by the National Institutes of Health (R00MH103479). A.K. was supported by a Banting Postdoctoral Fellowship from the Canadian Institutes of Health Research (CIHR). J.P. is supported by the National Institutes of Health (1P50MH109429). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
The authors declare no competing interests.
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For post-hoc individual network comparisons, statistical significance was set at p < .007 (α = .05 Bonferroni-corrected for seven multiple comparisons).
Seven-network parcellation: correlations between elicitation rate and principal gradient value across all reliability samples (Pearson’s r, [95% CIs]).
17-network parcellation: correlations between elicitation rate and principal gradient value across all reliability samples (Pearson’s r, [95% CIs]).
Frequency of effect types within each network.
Frequency of effect types within each network.
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Fox, K.C.R., Shi, L., Baek, S. et al. Intrinsic network architecture predicts the effects elicited by intracranial electrical stimulation of the human brain. Nat Hum Behav 4, 1039–1052 (2020). https://doi.org/10.1038/s41562-020-0910-1
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