Age-related changes in responsiveness to non-invasive brain stimulation neuroplasticity paradigms: a systematic review with meta-analysis

Objectives: We aimed to summarise and critically appraise the available evidence for the effect of age on responsiveness to non-invasive brain stimulation (NBS) paradigms delivered to the primary motor cortex. Methods: Four databases (Medline, Embase, PsycINFO and Scopus) were searched from inception to February 7, 2023. Studies investigating age group comparisons and associations between age and neuroplasticity induction from NBS paradigms were included. Only studies delivering neuroplasticity paradigms to the primary motor cortex and responses measured via motor-evoked potentials (MEPs) in healthy adults were considered. Results: 39 studies, encompassing 40 experiments and eight NBS paradigms were included: paired associative stimulation (PAS; n = 12), repetitive transcranial magnetic stimulation (rTMS; n = 2), intermittent theta burst stimulation (iTBS; n = 8), continuous theta burst stimulation (cTBS; n = 7), transcranial direct and alternating current stimulation ((tDCS; n = 7; tACS; n = 2)), quadripulse stimulation (QPS; n = 1) and i-wave periodic transcranial magnetic stimulation (iTMS; n = 1). Pooled findings from PAS paradigms suggested older adults have reduced post-paradigm responses, although there was considerable heterogeneity. Mixed results were observed across all other NBS paradigms and post-paradigm timepoints. Conclusions/significance: Whilst age-dependent reduction in corticospinal excitability is possible, there is extensive inter- and intra-individual variability both within and between studies, making it difficult to draw meaningful conclusions from pooled analyses.