Paired-pulse afferent modulation of TMS responses reveals a selective decrease in short latency afferent inhibition with age

Changes in motor cortical excitability were examined in 2 groups of participants, young (18-30 years of age, n = 25) and senior (65-82 years of age, n = 31), using paired-pulse afferent stimulation with transcranial magnetic stimulation (TMS). Motor evoked potentials (MEPs) elicited by TMS at suprathreshold intensity (120% motor threshold) were first recorded in unconditioned trials (TMS alone) and then in conditioned trials, in which TMS pulses were preceded by median nerve stimulation at 3 different interstimulus intervals (ISI; 20, 50, and 200 ms). Conditioning of MEP responses revealed a similar pattern of modulation in the 2 age groups, with 2 periods of inhibition at 20- and 200-ms ISIs, separated by a period in which MEPs tended to return to baseline at a 50-ms ISI. Afferent-induced inhibition at the short interval (i.e., SAI 20-ms ISI), was selectively reduced in seniors, with half of them showing either low or no MEP suppression. Age-associated changes in SAI level were also good predictors of performance on tests of processing speed and dexterity. The selective decrease in SAI exhibited by many seniors is consistent with reported alterations in intracortical inhibition with age. Our observations also highlight the potential value of SAI, as a putative marker of central cholinergic activity, in predicting declines in motor and cognitive function with age.