LAUSR

Transcranial direct current stimulation (tDCS) is a variant of noninvasive neuromodulation, which promises treatment for brain diseases like major depressive disorder. In experiments, long-lasting aftereffects were observed, suggesting that persistent plastic changes are induced. The mechanism underlying the emergence of lasting aftereffects, however, remains elusive. Here we propose a model, which assumes that tDCS triggers a homeostatic response of the network involving growth and decay of synapses. The cortical tissue exposed to tDCS is conceived as a recurrent network of excitatory and inhibitory neurons, with synapses subject to homeostatically regulated structural plasticity. We systematically tested various aspects of stimulation, including electrode size and montage, as well as stimulation intensity and duration. Our results suggest that transcranial stimulation perturbs the homeostatic equilibrium and leads to a pronounced growth response of the network. The stimulated population eventually eliminates excitatory synapses with the unstimulated population, and new synapses among stimulated neurons are grown to form a cell assembly. Strong focal stimulation tends to enhance the connectivity within new cell assemblies, and repetitive stimulation with well-chosen duty cycles can increase the impact of stimulation even further. One long-term goal of our work is to help in optimizing the use of tDCS in clinical applications.Author SummaryNoninvasive brain stimulation techniques like tDCS have the potential to directly interfere with neural activity, but may also trigger activity-dependent plasticity. We propose a model to study the mechanism of tDCS and persistent aftereffects that may be induced as a consequence of homeostatic structural plasticity. Based on the idea that tDCS perturbs the ongoing activity of neurons, our model predicts that the stimulation also triggers a rearrangement of synapses among stimulated and unstimulated neurons, eventually leading to network remodeling and cell assembly formation. Focal and strong stimulation leads to stronger cell assemblies, and so does repetitive stimulation with optimized stimulation protocols. This is the first original work studying possible long-lasting aftereffects of transcranial stimulation at the mesoscopic neuronal network level using a computational model.