Transcranial direct current stimulation (tDCS) modulates human behavior, neuronal patterns, and metabolite concentrations, with exciting potential for neurorehabilitation. However, the understanding of tDCS-induced alterations on the neuronal level is incomplete, and conclusions from young adults, in whom the majority of studies have been conducted, cannot be easily transferred to older populations. Here, we investigated tDCS-induced effects in older adults ( = 48; age range, 50-79 years) using magnetic resonance spectroscopy to quantify GABA levels as well as resting-state functional magnetic resonance imaging to assess sensorimotor network strength and interhemispheric connectivity. In a randomized, counterbalanced, crossover design, we applied anodal tDCS (atDCS), cathodal tDCS (ctDCS), and sham tDCS (stDCS) over the left sensorimotor region. We observed a significant reduction of GABA levels after atDCS compared with stDCS, reflecting the preserved neuromodulatory effect of atDCS in older adults. Moreover, resting-state functional coupling was decreased during atDCS compared with stDCS, most likely indicating augmented efficiency in brain network functioning. Increased levels of interhemispheric connectivity with age were diminished by atDCS, suggesting stimulation-induced functional decoupling. Further, the magnitude of atDCS-induced local plasticity was related to baseline functional network strength. Our findings provide novel insight into the neuronal correlates underlying tDCS-induced neuronal plasticity in older adults and thus might help to develop tDCS interventions tailored to the aging brain. Transcranial direct current stimulation (tDCS) modulates human behavior, neuronal patterns, and metabolite concentrations, with exciting potential for neurorehabilitation. However, the understanding of tDCS-induced alterations on the neuronal level is incomplete, and conclusions from young adults cannot be easily transferred to older populations. We used a systematic multimodal imaging approach to investigate the neurophysiological effects of tDCS in older adults and found stimulation-induced effects on GABA levels, reflecting augmented local plasticity and functional connectivity, suggesting modulation of network efficiency. Our findings may help to reconcile some of the recent reports on the variability of tDCS-induced effects, not only implicating age as a crucial modulating factor, but detailing its specific impact on the functionality of neural networks.

Transcranial direct current stimulation (tDCS) augments training-induced cognitive gains, an issue of particular relevance in the aging population. However, negative outcomes have been reported as well, and few studies so far have evaluated the impact of tDCS on episodic memory formation in elderly cohorts. The heterogeneity of previous findings highlights the importance of elucidating neuronal underpinnings of tDCS-induced modulations, and of determining individual predictors of a positive response. In the present study, we aimed to modulate episodic memory formation in 34 older adults with anodal tDCS (1 mA, 20 min) over left temporoparietal cortex. Participants were asked to learn novel associations between pictures and pseudowords, and episodic memory performance was subsequently assessed during immediate retrieval. Prior to experimental sessions, participants underwent resting-state functional magnetic resonance imaging. tDCS led to better retrieval performance and augmented learning curves. Hippocampo-temporoparietal functional connectivity was positively related to initial memory performance, and was positively associated with the magnitude of individual tDCS-induced enhancement. In sum, we provide evidence for brain stimulation-induced plasticity of episodic memory processes in older adults, corroborating and extending previous findings. Our results demonstrate that intrinsic network coupling may determine individual responsiveness to brain stimulation, and thus help to further explain variability of tDCS responsiveness in older adults.