Abstract

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.

Highlights

  • Non-invasive transcranial magnetic stimulation (TMS) can be used to explore the neurophysiological mechanisms underlying synaptic plasticity in the human motor cortex through various repetitive protocols

  • Responses to intermittent theta burst stimulation (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 motor evoked potential (MEP) responses

  • short latency afferent inhibition (SAI) was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with long-term potentiation (LTP)-like plasticity as assessed with iTBS

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Summary

Introduction

Non-invasive transcranial magnetic stimulation (TMS) can be used to explore the neurophysiological mechanisms underlying synaptic plasticity in the human motor cortex through various repetitive protocols (rTMS). Initial reports on iTBS revealed robust facilitation of brain excitability (Huang et al, 2005), but considerable inter-individual variability has more recently been described with up to 50% of participants not exhibiting the expected facilitation of MEP responses (e.g., Player et al, 2012; Hamada et al, 2013; Vallence et al, 2013; Hinder et al, 2014; López-Alonso et al, 2014) Factors such as genetics, voluntary motor activity, sex, and physical exercise all contribute to this variability (Ridding and Ziemann, 2010). One study has examined age effects on iTBS responses in a small group of Frontiers in Aging Neuroscience www.frontiersin.org

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