Age-related changes in responsiveness to non-invasive brain stimulation neuroplasticity paradigms: A systematic review with meta-analysis.
Level 1 - systematic review of randomized trials
Systematic review with meta-analysis of experimental physiology studies
PubMed 38579515 · doi:10.1016/j.clinph.2024.03.002
What was done
Authors searched four databases (Medline, Embase, PsycINFO, and Scopus) through February 7, 2023, for studies evaluating the effect of age on neuroplasticity induced by non-invasive brain stimulation (NBS) applied to the primary motor cortex. The review included healthy adult studies measuring corticospinal excitability changes using motor-evoked potentials (MEPs). A total of 39 studies (40 experiments) across eight NBS paradigms were analyzed: paired associative stimulation (PAS; n = 12), intermittent theta burst stimulation (iTBS; n = 8), continuous theta burst stimulation (cTBS; n = 7), transcranial direct current stimulation (tDCS; n = 7), repetitive transcranial magnetic stimulation (rTMS; n = 2), transcranial alternating current stimulation (tACS; n = 2), quadripulse stimulation (QPS; n = 1), and i-wave periodic transcranial magnetic stimulation (iTMS; n = 1).
What was found
Pooled analysis of PAS experiments indicated that older adults have reduced post-stimulation neuroplastic responses compared to younger adults, accompanied by substantial heterogeneity. Findings across all other NBS modalities (iTBS, cTBS, tDCS, rTMS, tACS, QPS, and iTMS) and post-stimulation timepoints were mixed. The abstract reports no effect sizes, confidence intervals, or numerical outcome metrics for the meta-analytic estimates.
Why it matters
This review highlights that while aging may blunt paired associative stimulation-induced plasticity in the primary motor cortex, the broad assumption of a generalized, age-related decline in responsiveness across all non-invasive brain stimulation protocols is not robustly supported by current pooled data.
Limits
The abstract notes high inter- and intra-individual variability both within and across studies, making firm conclusions difficult. Several paradigms were represented by very few studies (e.g., QPS and iTMS had only one study each; rTMS and tACS had two). The analysis was restricted to healthy adults and motor-evoked potential measures in the primary motor cortex, limiting generalizability to clinical populations or non-motor cortical regions.
Cited by
- supports Neuroplasticity exists throughout the human lifespan.