Targeting intracranial electrical stimulation to network regions defined within individuals causes network-level effects

Abstract Intracranial electrical stimulation (ES) is routinely used therapeutically, diagnostically, and to provide causal evidence in neuroscience studies. However, our understanding of the brain network-level effects of ES remains limited. We applied precision functional mapping (PFM), based on functional magnetic resonance imaging (fMRI), to define large-scale networks within individual epilepsy patients. We show that single-pulse electrical stimulation (SPES) and high-frequency electrical stimulation (HFES) are more likely to evoke within-network responses and elicit network-related behavioral effects, respectively, when applied near to a PFM-defined network region. Network-level effects were more likely when stimulating sites in white matter, in close proximity to the targeted network, and within a region predominantly occupied by the targeted network. Further, network-specific modulation may be achievable by applying lower current intensities at these sites. Our findings support that modulation of specific networks is achievable by targeting ES to a functional anatomic “sweet spot” that can be identified using PFM. Competing Interest Statement The authors have declared no competing interest. Footnotes Main: Formatting changes for margins, font, and spacing of figures, legends, and section headings. Corrections for one typo each in the introduction and conclusion. Author affiliations and funding sources updated. References section reformatted for correct capitalization and bolding. Supplemental: Formatting changes for margins, font, and spacing of figures and legends.