The peripheral effect of direct current stimulation on brain circuits involving memory

An ongoing debate surrounding transcranial direct current stimulation (tDCS) of the scalp is whether it modulates brain activity both directly and in a regionally constrained manner enough to positively affect symptoms in patients with neurological disorders. One alternative explanation is that direct current stimulation affects neural circuits mainly indirectly, i.e., via peripheral nerves. Here, we report that noninvasive direct current stimulation indirectly affects neural circuits via peripheral nerves. In a series of studies, we show that direct current stimulation can cause activation of the greater occipital nerve (ON-tDCS) and augments memory via the ascending fibers of the occipital nerve to the locus coeruleus, promoting noradrenaline release. This noradrenergic pathway plays a key role in driving hippocampal activity by modifying functional connectivity supporting the consolidation of a memory event.