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Cortical plasticity, including long-term potentiation (LTP)-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS) protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS) in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI), a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS.Methods: SAI was first assessed by examining the modulation of motor evoked potentials (MEPs) in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 Hz every 200 ms for 2 s with 8 s between trains, repeated 20 times). MEP responses (120% resting motor threshold (RMT)) were assessed immediately after iTBS and 5, 10, and 20 min post-application.Results: Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n = 13 young and 10 older adults) showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS.Conclusion: Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS.

BackgroundThe deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging.MethodsWe used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31).ResultsWe found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions.ConclusionIndividual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging.

RÉSUMÉ La détérioration du système cholinergique lors du vieillissement normal semble contribuer au déclin de l'attention avec l'âge. Nous avons examiné l'effet potentiel de l'âge sur la performance au « Attention Network Test » (ANT) ainsi que sur la variabilité intra-individuelle dans la vitesse des réponses à une tâche go/no-go et à une tâche de temps de réaction (TR) à choix multiples chez un groupe de jeunes adultes et de personnes âgées en santé. Nous avons ensuite examiné si un marqueur neurophysiologique de l'activité cholinergique dérivé de la stimulation magnétique transcrânienne (i.e., inhibition afférente à courte latence; IACL) était associé à la performance. Les personnes âgées montraient un ralentissement au ANT ainsi qu'une plus grande variabilité intra-individuelle que les jeunes adultes à la tâche de TR à choix multiples, mais il n'y avait pas de différence liée à l'âge dans les scores reflétant les réseaux attentionnels du ANT (vigilance, orientation aux stimuli et contrôle exécutif). Les niveaux de IACL étaient diminués chez les personnes âgées, mais ils n'étaient pas associés à la performance. Il est possible que des relations entre le marqueur de l'activité cholinergique et l'attention émergent seulement en cas de déficits de neurotransmission sévères. D'autres mécanismes corticaux pourraient aussi être plus fortement associés aux fonctions liées à l'attention.

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