The Aging Brain Recharged: High-Frequency rTMS Boosts Cortical Excitability and Cognition in Aging.

OBJECTIVES: This pilot study aimed to investigate whether high-frequency repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) can enhance cortical excitability (CE) and improve cognitive and emotional functioning in healthy older adults. We also explored whether CE, assessed through TMS-derived motor-evoked potentials (MEPs), could serve as a sensitive biomarker of neuroplasticity and cognitive resilience in aging (1). MATERIALS: Four cognitively healthy older adults (62–70 years) participated in a cross-over protocol including both active and sham high-frequency rTMS, with pre/post assessments of neuropsychological function and cortical excitability (2). METHOD: Each participant underwent a 12-week treatment protocol, one with high-frequency (10 Hz) rTMS and one with sham stimulation, in counterbalanced order and separated by a washout period. rTMS was delivered over the left DLPFC at 120% of individual resting motor threshold (rMT), guided by neuronavigation. CE was indexed via motor evoked potentials (MEPs) recorded from the right first dorsal interosseous muscle at baseline (T0) and post-treatment (T36). Cognitive, affective, and quality-of-life outcomes were assessed using a standardized neuropsychological battery. RESULTS: Participants who underwent active rTMS exhibited selective neurophysiological and behavioral improvements. In both cases, MEP amplitudes significantly increased post- intervention (e.g., MF: F(2,43) = 28.50, p < .001), indicating potentiated corticospinal excitability. These effects were absent in the sham condition. On a behavioral level, one participant (MF) showed marked improvements in executive function (ΔTMT-B: –20.7 sec), fatigue (ΔFAS: –6), and mood (ΔBDI-II: –2; ΔBAI: –2). The other active participant (AM) demonstrated stable high-level performance with modest executive enhancement (ΔTMT-B: –16.2 sec). No meaningful cognitive or neurophysiological changes emerged in the sham group, confirming the specificity of the effects observed following active stimulation. DISCUSSION: Our findings suggest that high-frequency rTMS can induce both neurophysiological and behavioral benefits in aging individuals. The co-occurrence of MEP amplitude increases and improved cognitive/emotional performance supports CE as a promising biomarker of neuroplastic responsiveness (3). Additionally, the differential effects between active and sham conditions confirm the specificity of the rTMS-induced changes and rule out practice effects. CONCLUSIONS: Despite the limited sample size, this study provides preliminary support for the use of CE as an objective and sensitive marker of brain plasticity in older adults. High-frequency rTMS targeting the left DLPFC may be a feasible strategy to promote cognitive resilience and emotional well-being in aging.