  Targeted electrical stimulation of the brain perturbs neural networks and
modulates their rhythmic activity both at the site of stimulation and at remote
brain regions. Understanding, or even predicting, this neuromodulatory effect
is crucial for any therapeutic use of brain stimulation. To this end, we
analyzed the stimulation responses in 131 stimulation sessions across 66
patients with focal epilepsy recorded through intracranial EEG (iEEG). We
considered functional and structural connectivity features as predictors of the
response at every iEEG contact. Taking advantage of multiple recordings over
days, we also investigated how slow changes in interictal functional
connectivity (FC) ahead of the stimulation relate to stimulation responses. The
results reveal that, indeed, this long-term variability of FC exhibits strong
association with the stimulation-induced increases in delta and theta band
power. Furthermore, we show through cross-validation that long-term variability
of FC improves prediction of responses above the performance of spatial
predictors alone. These findings can enhance the patient-specific design of
effective neuromodulatory protocols for therapeutic interventions.
