Selective control of synaptic plasticity in heterogeneous networks through transcranial alternating current stimulation (tACS)

Abstract

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.