Brain stimulation preferentially influences long-range projections

Advances in brain stimulation have made it possible to target smaller and smaller regions for electromagnetic stimulation, in the hopes of producing increasingly focal neural effects. However, the brain is extensively interconnected, and the neurons comprising those connections may themselves be particularly susceptible to neurostimulation. Here, we test this hypothesis by identifying long-range projections in single-unit recordings from nonhuman primates receiving transcranial alternating current stimulation. We find that putative long-range projections are more strongly affected by stimulation than other cells. Specifically, they are both more entrained on average and account for occurrences of extremely strong entrainment. Given that stimulation appears to target the edges, rather than nodes, of neural networks, it may be necessary to rethink how neurostimulation strategies are designed.