Predicting neural responses to intra- and extra-cranial electric brain stimulation by means of the reciprocity theorem

Electrical stimulation of nervous tissue is grounded in well-established biophysical principles, yet understanding its precise effect on neural activity remains challenging. This represents a major obstacle to both scientific and clinical applications of electrical brain stimulation.

We here show that the reciprocity theorem of electromagnetism can be applied more broadly than previously acknowledged, providing a framework for elucidating the effects of electrical brain stimulation on neurons. Through this new perspective, we account for the observed weak frequency-dependence of extracellular electrical stimulation–induced membrane potential changes, and demonstrate a 1/ r falloff for nearby and 1/ r ² falloff for distant neurons.

We also show that for transcranial electrical stimulation, the susceptibility of a neuron to the stimulation is directly proportional to the size of the current dipole moment resulting from somatic current input. The induced somatic membrane potential changes are small and exhibit weak spatial but strong orientation dependency across human neocortex.

The reciprocity-based approach to electrical stimulation reproduces a large body of previous experimental data, and provides new insights into how ES affects neurons.