Understanding Electric Brain Stimulation Through the Reciprocity Theorem

Lee et al. recently reported robust, frequency-independent subthreshold membrane coupling to extracellular current stimulation across cell classes and brain regions, in both human and mice cortical slices. Specifically, small extracellular sinusoidal electrical stimulations (ES) at frequencies between 1-140 Hz induced a local oscillation in the extracellular potential, leading to sub-threshold (< 0.5 mV) sinusoidal potentials across the cell membrane of nearby cell bodies. Surprisingly, these induced changes in Vm did not decrease with frequency. This seems to imply that ES is a fundamentally different stimulus than equivalent intracellular stimulation that results in strong membrane filtering, caused by the frequency-dependent membrane capacitance. Here we would like to draw attention to the reciprocity theorem as a powerful and (to the best of our knowledge) as-of-yet-unused tool for understanding the effects of ES on neural dynamics, and this counterintuitive result in particular.