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

PLoS Comput Biol. 2023 Apr 27;19(4):e1010736. doi: 10.1371/journal.pcbi.1010736. eCollection 2023 Apr.

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.

MeSH terms

  • Neuronal Plasticity / physiology
  • Neurons / physiology
  • Transcranial Direct Current Stimulation* / methods
  • Treatment Outcome

Grants and funding

We thank the National Research Council of Canada (NSERC GRANT RGPIN-2017-06662) (DT, AP, JL) as well as the Canadian Institute for Health Research (CIHR GRANT NO PJT-156164)(AH) for funding. AH acknowledges the support by the INRIA Action Exploratoire ‘A/D Drugs’. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.