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 computational simulations informed by human experimental data, 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.

A new perspective for evaluating the efficacy of tACS and tDCS in improving executive functions: A combined tES and fNIRS study

“…Separate enhancements of synaptic plasticity and oscillations in tES via endogenous voltage‐dependent Hebbian plasticity or nerve entrainment are thought to be important mechanisms that promote behavior (Pariz, 2023; Korai, 2021), and variation in hemodynamics reflects the degree of functional cortical activity according to the theory of neurovascular coupling (Pinti et al, 2020b). In the present study, fNIRS was used to measure the signal of the cortex during electrical stimulation without current interference due to its optical basis, and the activity on the right IFG and the frontal pole region in the resting state was continuously observed by fNIRS during the entire tES modulation process.…”

Amplifying post-stimulation oscillatory dynamics by engaging synaptic plasticity with periodic stimulation: a modelling study

“…Researchers, experimentally and theoretically, have addressed the numerous challenges related to the effects of these interventions on behaviour [4,5], brain function [6], as well as pathologies such as epilepsy [1,7], Parkinson [8], major depressive disorder (MDD) [9,10] and stroke [11,12]. Despite these promising results, it is still unclear how brain stimulation interventions shape endogenous brain dynamics [13][14][15][16] and the neural circuits that support them [17,18]. Indeed, brain stimulation outcomes remain variable: induced changes in neuron's excitability vary remarkably between stimulation sites, repeated trials, and subjects, oftentimes vanishing after stimulation offset [19][20][21][22].…”

“…One central challenge stems from biophysical heterogeneity. Indeed, the influence of time-varying PBS on neural activity and plasticity relies heavily on biophysical cellular properties, such as the membrane time constant (MTC) [18]. The MTC is a quantity that reflects the agility of neurons in response to time-varying stimuli [37], and dictates their varied frequency selectivity [18].…”

“…Indeed, the influence of time-varying PBS on neural activity and plasticity relies heavily on biophysical cellular properties, such as the membrane time constant (MTC) [18]. The MTC is a quantity that reflects the agility of neurons in response to time-varying stimuli [37], and dictates their varied frequency selectivity [18]. The MTC varies significantly across cortical layers, and brain areas, ranging from a few to tens of milliseconds [38,39].…”

“…The MTC varies significantly across cortical layers, and brain areas, ranging from a few to tens of milliseconds [38,39]. Such variability has been shown to mediate selective, direction-specific synaptic plasticity under tACS [18] and hence represents a promising candidate in supporting persistent post-stimulation effects. Indeed, stimulation-induced and MTC-dependent changes in neuronal spike timing, further modulated by endogenous oscillations, may solicit Hebbian spike-timing dependant plasticity (STDP) to support lasting changes in synaptic weights [17,18].…”