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Causal Evidence for Left DLPFC Contributions to Working Memory, Attention, and Cognitive Control in Ageing: A cTBS/ERP Study

Leon-Correa, E.; Balani, A.; Qureshi, A.; Tse, D.; MAKRIS, S.

2026-01-15 neuroscience
10.64898/2026.01.15.699654 bioRxiv
Show abstract

Ageing is characterised by progressive neurodegeneration and marked declines in working memory (WM), a domain critically dependent on the integrity of the dorsolateral prefrontal cortex (DLPFC). Although non-invasive brain stimulation is widely used to target this region, the causal contribution of the DLPFC to WM performance in older adults remains insufficiently understood. Here, we applied continuous theta burst stimulation (cTBS) to transiently inhibit the left DLPFC in twenty healthy older adults and assessed the behavioural and neurophysiological consequences during verbal and visuospatial N-back tasks. Behaviourally, moderate learning effects emerged exclusively in the verbal task following vertex stimulation, whereas learning after DLPFC stimulation remained inconclusive. Performance in the visuospatial task showed no reliable evidence of learning across conditions, consistent with greater interindividual variability and age-related decline in spatial WM. Neurophysiologically, ERP amplitudes were stable across conditions; however, marked latency perturbations were observed. In the verbal task, P200 and N200 latencies robustly predicted performance, with P200 latency significantly prolonged after DLPFC inhibition, indicating disrupted early attentional gating. N200 and P300 latency modulations further suggested load-dependent compensatory strategies, reflecting adaptive slowing of cognitive control processes. In contrast, visuospatial performance was not reliably predicted by P200 latency, although N200 and P300 latencies remained informative, indicating domain-specific differences in DLPFC involvement. Taken together, these findings provide causal evidence that left DLPFC disruption selectively interferes with the temporal coordination of verbal WM, emphasising the central role of processing speed and compensatory dynamics in cognitive ageing. ERP latency markers emerge as sensitive indices of subtle stimulation-induced perturbations in older adults.

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