2026 ECNP Congress

PS02-2178

Neurostimulation approaches to cognitive aging: effects of transcranial magnetic stimulation on working memory networks

Ana Francisca Aires — M. Lázaro · Unidade Local de Saúde do Algarve, Psychiatry, Faro, Portugal

2026 ECNP Congress

Introduction

Working memory decline is a hallmark of cognitive ageing, contributing to reduced independence, impaired daily functioning, and an increased risk of developing dementia. Non-invasive brain stimulation, particularly transcranial magnetic stimulation (TMS), offers a promising approach to modulate cortical excitability and functional connectivity. TMS has the potential to induce synaptic plasticity and alter neural networks that support cognition [1,3]. Several studies have investigated the effects of TMS on working memory performance in older adults; however, results remain inconsistent, reflecting substantial variability in stimulation protocols, cognitive tasks, participant characteristics, and underlying neurophysiological mechanisms [2]. Understanding these effects is essential for translating TMS into interventions aimed at preserving cognitive function in ageing populations.

Aims

This review systematically evaluates current evidence on the effects of TMS on working memory networks in older adults, with a focus on methodological differences, cognitive outcomes, and neurophysiological correlates. The review aims to identify patterns of efficacy, elucidate potential mechanisms of action, and provide recommendations for optimizing stimulation protocols in cognitive ageing research and clinical applications.

Methods

A systematic search of PubMed, Scopus, and Web of Science was conducted for studies published up to December 2025. Search terms included “transcranial magnetic stimulation,” “working memory,” “older adults,” and “cognitive ageing.” Studies were included if participants were aged ≥60 years, working memory was assessed as a primary or secondary outcome, and TMS was applied (single pulse, repetitive, or paired pulse). Exclusion criteria were case reports, studies lacking working memory outcomes, or interventions combining TMS with pharmacological agents. Extracted data included sample size, age range, TMS parameters (frequency, stimulation site, intensity, duration), cognitive tasks used, neuroimaging measures, and main findings.

Results

Eighteen studies met inclusion criteria (N = 522; mean age range 62–79). TMS protocols varied widely, with high-frequency repetitive TMS (rTMS; 5–20 Hz) targeting the left dorsolateral prefrontal cortex (DLPFC) being the most common. Working memory was evaluated using n-back tasks, digit span, and complex span measures. Seven studies reported significant improvements following high-frequency rTMS, particularly in 2-back accuracy and reaction time, whereas six studies reported no measurable cognitive benefits. Three studies employing intermittent theta burst stimulation (iTBS) demonstrated modest enhancements in frontoparietal connectivity but without robust behavioral improvements. Positive cognitive effects were consistently linked to high-frequency stimulation of the left DLPFC. Neuroimaging data suggested modulation of frontoparietal networks; however, small sample sizes, heterogeneity in tasks, and absence of sham controls limit generalizability. Overall, approximately 40% of studies showed measurable improvements, highlighting both the potential and inconsistency of TMS efficacy in older adults.

Conclusions

TMS appears capable of inducing modest improvements in working memory and enhancing frontoparietal network connectivity in older adults, particularly with high-frequency stimulation targeting the left DLPFC [1–3]. Nevertheless, variability in stimulation protocols, limited replication, and methodological constraints necessitate cautious interpretation. Future well-powered, standardized randomized controlled trials are required to determine optimal stimulation parameters, clarify underlying neural mechanisms, and evaluate clinical relevance for preserving cognitive function and independence in ageing populations.

References

  1. Luber B, Lisanby SH. Enhancement of human cognitive performance using transcranial magnetic stimulation (TMS). NeuroImage 2014;85:961–970.
  2. Chung SW, Hoy KE, Fitzgerald PB. Theta-burst stimulation: a new form of TMS treatment for depression? Depress Anxiety 2016;33:193–206.
  3. Pascual-Leone A, Amedi A, Fregni F, Merabet LB. The plastic human brain cortex. Annu Rev Neurosci 2005;28:377–401.