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Abstract

There is considerable individual variability in the reported effectiveness of non-invasive brain stimulation. This variability has often been ascribed to differences in the neuroanatomy and resulting differences in the induced electric field inside the brain. In this study, we addressed the question whether individual differences in the induced electric field can predict the neurophysiological and behavioral consequences of gamma band tACS. In a within-subject experiment, bi-hemispheric gamma band tACS and sham stimulation was applied in alternating blocks to the participants’ superior temporal lobe, while task-evoked auditory brain activity was measured with concurrent functional magnetic resonance imaging (fMRI) and a dichotic listening task. Gamma tACS was applied with different interhemispheric phase lags. In a recent study, we could show that anti-phase tACS (180° interhemispheric phase lag), but not in-phase tACS (0° interhemispheric phase lag), selectively modulates interhemispheric brain connectivity. Using a T1 structural image of each participant’s brain, an individual simulation of the induced electric field was computed. From these simulations, we derived two predictor variables: maximal strength (average of the 10,000 voxels with largest electric field values) and precision of the electric field (spatial correlation between the electric field and the task evoked brain activity during sham stimulation). We found considerable variability in the individual strength and precision of the electric fields. Importantly, the strength of the electric field over the right hemisphere predicted individual differences of tACS induced brain connectivity changes. Moreover, we found in both hemispheres a statistical trend for the effect of electric field strength on tACS induced BOLD signal changes. In contrast, the precision of the electric field did not predict any neurophysiological measure. Further, neither strength, nor precision predicted interhemispheric integration. In conclusion, we found evidence for the dose-response relationship between individual differences in electric fields and tACS induced activity and connectivity changes in concurrent fMRI. However, the fact that this relationship was stronger in the right hemisphere suggests that the relationship between the electric field parameters, neurophysiology, and behavior may be more complex for bi-hemispheric tACS.