Microstructural and functional plasticity following repeated brain stimulation during cognitive training in older adults

Abstract

The combination of repeated behavioral training with transcranial direct current stimulation (tDCS) holds promise to exert beneficial effects on brain function beyond the trained task. However, little is known about the underlying mechanisms. We performed a monocenter, single-blind randomized, placebo-controlled trial comparing cognitive training to concurrent anodal tDCS (target intervention) with cognitive training to concurrent sham tDCS (control intervention), registered at ClinicalTrial.gov (Identifier NCT03838211). The primary outcome (performance in trained task) and secondary behavioral outcomes (performance on transfer tasks) were reported elsewhere. Here, underlying mechanisms were addressed by pre-specified analyses of multimodal magnetic resonance imaging before and after a three-week executive function training with prefrontal anodal tDCS in 48 older adults. Results demonstrate that training combined with active tDCS modulated prefrontal white matter microstructure which predicted individual transfer task performance gain. Training-plus-tDCS also resulted in microstructural grey matter alterations at the stimulation site, and increased prefrontal functional connectivity. We provide insight into the mechanisms underlying neuromodulatory interventions, suggesting tDCS-induced changes in fiber organization and myelin formation, glia-related and synaptic processes in the target region, and synchronization within targeted functional networks. These findings advance the mechanistic understanding of neural tDCS effects, thereby contributing to more targeted neural network modulation in future experimental and translation tDCS applications.

Information-based rhythmic transcranial magnetic stimulation accelerates learning during auditory working memory training

“…We propose that a combined protocol of longitudinal cognitive training and rhTMS can produce more durable results if we target the specific oscillatory network dynamics associated with working memory operations. This hypothesis is supported by evidence that repeated stimulation sessions can induce stable late-phase long-term potentiation, a potential mechanism underlying prolonged modulation of network activity and connectivity (Antonenko et al, 2023; Monte-Silva et al, 2013).…”

Uncorking the limitation—improving dual tasking using transcranial electrical stimulation and task training in the elderly: a systematic review

“…In the future, a more in-depth exploration of the montage of tES intervention should be conducted, despite specific positions or cortices, brain networks such as the frontoparietal network can also be targeted. Additionally, it is important to highlight that all included tES-only studies in this review utilized only a single intervention session, further investigation through multi-session interventions is recommended as it has been reported that repeated tES can induce long-term potential effects and boost cognitive enhancement and lasting up to 1 month ( Korai et al, 2021 ; Antonenko et al, 2023 ). In the realm of training studies or clinical rehabilitations, virtual reality techniques could be an optimized tool moving forward.…”

Online stimulation of prefrontal cortex during practice increases motor variability and modulates later cognitive transfer: a randomized, double-blinded & sham-controlled tDCS study

“…These transfer effects are also theorised to be tied to early phases of structural plasticity within overlapping networks[19]. The ‘neural overlap hypothesis’ has been supported by evidence from concurrent tDCS during cognitive training resulting in microstructural brain alterations alongside near-transfer behavioural effects [34,67]. Since the motor learning paradigm used in this study is capable of inducing structural grey and white matter changes in PFC and SMA regions [11,62,68,69], we further hypothesized it to potentially lead to cognitive transfer effects.…”

“…Although the neurophysiological effects of a single tDCS session are shown to last a few minutes to a couple of hours after the end of stimulation [30,31], it is nevertheless capable of inducing long-term structural plasticity in the form of rearranged synaptic networks and spinogenesis as established through animal models [32,33]. Similarly, in older adults, training combined with tDCS spread over multiple days was shown to modulate functional connectivity and microstructural brain alterations associated with cognitive performance gains [34]. In line with these findings, prefrontal tDCS applied during motor practice may therefore influence the balance learning-induced prefrontal neural changes that support ongoing balance performance; also affecting the transfer to cognitive tasks assessed after a time delay that outlasts the acute neurophysiological effects of tDCS.…”