Multifocal tDCS modulates resting-state functional connectivity in older adults depending on induced electric field and baseline connectivity

Abstract

Background. Advancing age affects the brain's resting-state functional networks. Combining non-invasive brain stimulation (NIBS) with neuroimaging is a promising approach to modulate activity across resting-state functional systems and explore their true contribution to cognitive function in aging. However, substantial individual variability in the response to NIBS has been reported and, hence, identifying the individual predictors of NIBS-induced modulatory effects is crucial if we are to harness their potential.Methods. Thirty-one cognitively healthy older adults (71.68 ± 2.5 years; 19 females) underwent two different multifocal real tDCS conditions (C1 and C2) and a sham condition in a crossover design during a resting-state functional magnetic resonance imaging (rs-fMRI) acquisition. The real tDCS conditions were designed to induce two distinct electric field distribution patterns either targeting generalized cortical overactivity or a dissociation between the frontal areas and the posteromedial cortex. Stimulation was delivered through an MRI-compatible device using 8 small circular electrodes. Each individuals' anatomical T1-weighted MRI was used to generate a finite element model to define the individual electric field generated by each tDCS condition.Results. The two tDCS conditions modulated resting-state connectivity differently. C1 increased the coactivation of numerous functional couplings as compared to sham, however, a smaller amount of connections increased in C1 as compared to C2, while no differences between C2 and sham were appreciated. At the group level, C1-induced modulations primarily included temporo-occipital areas and distinct cerebellar regions. This functional pattern was anatomically consistent with the estimated distribution of the induced electric field in the C1 condition. Finally, at the individual level, the extent of tDCS-induced rs-fMRI modulation in C1 was predicted by baseline resting-state connectivity and simulation-based electric field magnitude. Discussion.Our results highlighted that multifocal tDCS procedures can effectively change neural dynamics in the elderly consistently with the spatial distribution of the estimated electric fields on the brain. Furthermore, we showed that specific brain factors that have been revealed to explain part of the individual variability to NIBS in young samples are also relevant in older adults. In accordance, designing multifocal tDCS configurations based on specific fMRI patterns appears to be a valuable approach to precisely adjust those complex neural dynamics sustaining cognition that are affected as a function of age. Furthermore, these innovative NIBS-based interventions should be individually-tailored based on subject-specific structural and functional data to ultimately boost their potential in aged populations. KeywordsAging, electrical modeling, finite element method, multifocal transcranial direct current stimulation, resting-state functional magnetic resonance imaging.

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

“…One of the factors limiting the therapeutic potential of tDCS is the high inter-subject variability of behavioural effects. It has been suggested that this might, at least in part, be due to the use of a standard extracranial current intensity across participants, which will inevitably lead to variability in the E-field applied in the cortex [ 21 , 30 , 56 – 58 ]. Supporting this theory, tDCS-induced behavioural outcomes such as improvements in working memory have been related to the applied E-field [ 59 ].…”

tDCS induced GABA change is associated with the simulated electric field in M1, an effect mediated by grey matter volume in the MRS voxel

“…One of the factors limiting the therapeutic potential of tDCS is the high inter-subject variability of behavioural effects. It has been suggested that this might, at least in part, be due to the use of a standard extracranial current intensity across participants, which will inevitably lead to variability in the E-field applied in the cortex (Abellaneda-Pérez et al, 2020; Kim et al, 2014; Laakso et al, 2015; Mezger et al,2021; Soleimani et al, 2021). Supporting this theory, tDCS-induced behavioural outcomes such as improvements in working memory have been related to the applied E-field (Albizu et al, 2020).…”