Selective Control of Synaptic Plasticity in Heterogeneous Networks Through Transcranial Alternating Current Stimulation (tACS)

Transcranial alternating current stimulation (tACS) represents a promising non-invasive treatment for an increasingly wide range of neurological and neuropsychiatric disorders. The ability to use periodically oscillating electric fields to non-invasively engage neural dynamics opens up the possibility of recruiting synaptic plasticity and to modulate brain function. However, despite consistent reports about tACS clinical effectiveness, strong state-dependence combined with the ubiquitous heterogeneity of cortical networks collectively results in high outcome variability. Introducing variations in intrinsic neuronal timescales, we explored how such heterogeneity influences stimulation-induced change in synaptic connectivity. We examined how spike timing dependent plasticity, at the level of cells, intra- and inter-laminar cortical networks, can be selectively and preferentially engaged by periodic stimulation. Using leaky integrate-and-fire neuron models, we analyzed cortical circuits comprised of multiple cell-types, alongside superficial multi-layered networks expressing distinct layer-specific timescales. Our results show that mismatch in neuronal timescales within and/or between cells-and the resulting variability in excitability, temporal integration properties and frequency tuning-enables selective and directional control on synaptic connectivity by tACS. Our work provides new vistas on how to recruit neural heterogeneity to guide brain plasticity using non-invasive stimulation paradigms.